ClickCease
+1-915-850-0900 spinedoctors@gmail.com
Select Page

Wellness

Clinic Wellness Team. A key factor to spine or back pain conditions is staying healthy. Overall wellness involves a balanced diet, appropriate exercise, physical activity, restful sleep, and a healthy lifestyle. The term has been applied in many ways. But overall, the definition is as follows.

It is a conscious, self-directed, and evolving process of achieving full potential. It is multidimensional, bringing together lifestyles both mental/spiritual and the environment in which one lives. It is positive and affirms that what we do is, in fact, correct.

It is an active process where people become aware and make choices towards a more successful lifestyle. This includes how a person contributes to their environment/community. They aim to build healthier living spaces and social networks. It helps in creating a person’s belief systems, values, and a positive world perspective.

Along with this comes the benefits of regular exercise, a healthy diet, personal self-care, and knowing when to seek medical attention. Dr. Jimenez’s message is to work towards being fit, being healthy, and staying aware of our collection of articles, blogs, and videos.

Nutritional Tips Every Chiropractic Patient Should Follow

Nutritional Tips Every Chiropractic Patient Should Follow

by | Nutrition

Nutritional Tips: Chiropractic care effectively and naturally treats a multitude of conditions and diseases. The overall premise is to return the body to its natural alignment by removing subluxations, which takes care of the root cause of many problems.

Spinal adjustments, however, aren�t necessarily the Holy Grail for total health. It’s essential for chiropractic patients to also make adjustments in their everyday lives. By doing so, they�ll maximize the effects of their chiropractic treatments, and experience better overall health in general.

Nutrition is one of the biggest factors and plays a large role in a patient’s recovery. The old adage “you are what you eat” is true. Feeding the body with vital vitamins and minerals promotes growth and healing. Filling up on fried, fatty foods does the opposite.

Let’s Look At Four Nutritional Tips Every Chiropractic Patient Should Follow:

Watch Your Calories

Individuals recovering from spinal or other injuries heal quicker when they avoid carrying excess weight. This is especially true if the injury has sidelined them from normal physical exercise.

Choose lean cuts of meat and fresh fruits and vegetables, and practice portion control. A diet with few excess calories offers the dual benefit of helping you avoid packing on the pounds, and helping you heal faster.

Pay Attention To Calcium Intake

Bones need calcium for strength, so it should be a priority to consume foods that are rich with it. According to healthconsciousness.com, the four most calcium-rich foods are dark leafy greens, low-fat cheese, milk, and yogurt.

If you are visiting a chiropractor for issues or conditions concerning your bones or nerves, he or she may recommend that you introduce these foods into your diet as soon as possible.

nutritional tipsMake Protein A Priority

Muscle injuries are one of the most popular reasons for chiropractic visits. Protein helps build and heal muscle tissue, helping it to renew itself back to a pre-injury state.

If your daily intake of protein is low, it can hinder the healing process and stand in the way of chiropractic visits giving you the maximum results. Fish and lean meats are the foods that offer the highest protein.

Other vegetarian options are tofu, soy beans, eggs, milk, and nuts. Help your muscles rebuild and heal by adding high protein foods into every meal menu.

Stay Hydrated

Why do most of us view water drinking with dread? Its not that bad! If you wish to promote healing, it’s imperative to drink enough water every day.

Water provides an entire slew of benefits, from transporting those important nutrients to where they need to be, to flushing harmful toxins out of the body. Aim for eight glasses of water a day, and try to drink it throughout the day.

Getting into this habit will boost overall health, and promote healing of injuries and other medical conditions.

While it’s a smart goal to try to ingest all the nutrients you need through food and drink, supplements are available to bridge the gap. Before beginning a supplement regimen, talk to you chiropractor for recommendations on the type and dosage that will aid and improve your unique situation.

You may also want to download a smartphone app to track your daily intake of calories, calcium, protein and liquid. There are many available, one being My Fitness Pal.

Easy and free to use, this is a powerful tool to keep you on the right nutritional track.

Making the commitment to chiropractic treatment is a big step in the right direction for your overall health and well-being. Incorporate these nutritional tips to your daily routine in order to get the most out of your chiropractic care.

Good Nutrition & Chiropractic Care Contribute To Overall Well-Being

Assessment and Treatment of Upper Trapezius

Assessment and Treatment of Upper Trapezius

by | Chiropractic, Functional Medicine, Injury Care

These assessment and treatment recommendations represent a synthesis of information derived from personal clinical experience and from the numerous sources which are cited, or are based on the work of researchers, clinicians and therapists who are named (Basmajian 1974, Cailliet 1962, Dvorak & Dvorak 1984, Fryette 1954, Greenman 1989, 1996, Janda 1983, Lewit 1992, 1999, Mennell 1964, Rolf 1977, Williams 1965).

 

Clinical Application of Neuromuscular Techniques: Upper Trapezius

 

Lewit (1999) simplifies the need to assess for shortness by stating, �The upper trapezius should be treated if tender and taut.� Since this is an almost universal state in modern life, it seems that everyone requires MET application to this muscle. Lewit also notes that a characteristic mounding of the muscle can often be observed when it is very short, producing the effect of �Gothic shoulders�, similar to the architectural supports of a Gothic church tower (see Fig. 2.13).

 

Assessment for Shortness of Upper Trapezius (13) (Fig. 4.30)

 

Figure 4 30 Assessment of the Relative Shortness of the Right Side Upper Trapezius Image 1

 

Figure 4.30 Assessment of the relative shortness of the right side upper trapezius. One side is compared with the other (for both the range of unforced motion and the nature of the end-feel of motion) to ascertain the side most in need of MET attention.

 

Test for upper trapezius for shortness (a) See scapulohumeral rhythm test (Ch. 5) which helps identify excessive activity or inappropriate tone in levator scapula and upper trapezius, which, because they are postural muscles, indicates shortness (Fig 5.13A, B). Greenman (1996) describes a functional �firing sequence� assessment which identifies general imbalance and dysfunction involving the upper and lower fixators of the shoulder (Fig. 4.31).

 

Figure 4 31 Palpation Assessment for Upper and Lower Fixators of the Shoulder Image 2

 

Figure 4.31 Palpation assessment for upper and lower fixators of the shoulder, including upper trapezius (Greenman 1996).

 

The patient is seated and the practitioner stands behind. The practitioner rests his right hand over the right shoulder area to assess firing sequence of muscles. The other hand can be placed either on the mid-thoracic region, mainly on the side being assessed, or spanning the lower back to palpate quadratus firing. The assessment should be performed at least twice so that various hand positions are used for different muscles (as in Fig. 4.31).

 

Greenman bases his description on Janda (1983), who notes the �correct� sequence for shoulder abduction, when seated, as involving: supraspinatus, deltoid, infraspinatus, middle and lower trapezius and finally contralateral quadratus. In dysfunctional states the most common substitutions are said to involve: shoulder elevation by levator scapulae and upper trapezius, as well as early firing by quadratus lumborum, ipsilateral and contralateral.

 

Inappropriate activity of the upper fixators results in shortness, and of the lower fixators in weakness and possible lengthening (see Ch. 2 for discussion of postural/phasic, etc. muscle characteristics).

 

Test for upper trapezius for shortness (b) The patient is seated and the practitioner stands behind with one hand resting on the shoulder of the side to be tested and stabilising it. The other hand is placed on the ipsilateral side of the head and the head/neck is taken into contralateral sidebending without force while the shoulder is stabilised (see Fig. 4.30).

 

The same procedure is performed on the other side with the opposite shoulder stabilised. A comparison is made as to which sidebending manoeuvre produced the greater range and whether the neck can easily reach 45� of side-flexion in each direction, which it should. If neither side can achieve this degree of sidebend, then both trapezius muscles may be short. The relative shortness of one, compared with the other, is evaluated.

 

Test for upper trapezius for shortness (c) The patient is seated and the practitioner stands behind with a hand resting over the muscle on the side to be assessed. The patient is asked to extend the arm at the shoulder joint, bringing the flexed arm/elbow backwards. If the upper trapezius is stressed on that side it will inappropriately activate during this movement. Since it is a postural muscle, shortness in it can then be assumed (see discussion of postural muscle characteristics in Ch. 3).

 

Test of upper trapezius for shortness (d) The patient is supine with the neck fully (but not forcefully) sidebent contralaterally (away from the side being assessed). The practitioner is standing at the head of the table and uses a cupped hand contact on the ipsilateral shoulder (i.e. on the side being tested) to assess the ease with which it can be depressed (moved caudally) (Fig. 4.32).

 

Figure 4 32 MET Treatment of Right Side Upper Trapezius Muscle Image 3

 

Figure 4.32 MET treatment of right side upper trapezius muscle. A Posterior fibres, B middle fibres, C anterior fibres. Note that stretching in this (or any of the alternative positions which access the middle and posterior fibres) is achieved following the isometric contraction by means of an easing of the shoulder away from the stabilised head, with no force being applied to the neck and head itself.

 

There should be an easy �springing� sensation as the practitioner pushes the shoulder towards the feet, with a soft end-feel to the movement. If depression of the shoulder is difficult or if there is a harsh, sudden end-point, upper trapezius shortness is confirmed.

 

This same assessment (always with full lateral flexion) should be performed with the head fully rotated away from the side being treated, half turned away from the side being treated, and slightly turned towards the side being treated, in order to respectively assess the relative shortness and functional efficiency of posterior, middle and anterior subdivisions of the upper portion of trapezius.

 

MET Treatment of Chronically Shortened Upper Trapezius

 

MET treatment of upper trapezius, method (a) (Fig. 4.32) In order to treat all the fibres of upper trapezius, MET needs to be applied sequentially. The upper trapezius is subdivided here into anterior, middle and posterior fibres. The neck should be placed into different positions of rotation, coupled with the sidebending as described in the assessment description above, for precise treatment of the various fibres.

 

The patient lies supine, arm on the side to be treated lying alongside the trunk, head/neck sidebent away from the side being treated to just short of the restriction barrier, while the practitioner stabilises the shoulder with one hand and cups the ear/mastoid area of the same side of the head with the other:

 

  • With the neck fully sidebent and fully rotated contralaterally, the posterior fibres of upper trapezius are involved in the contraction (see below). This will facilitate subsequent stretching of this aspect of the muscle.
  • With the neck fully sidebent and half rotated, the middle fibres are involved in the contraction.
  • With the neck fully sidebent and slightly rotated towards the side being treated the anterior fibres of upper trapezius are being treated.

 

The various contractions and subsequent stretches can be performed with practitioner�s arms crossed, hands stabilising the mastoid area and shoulder.

 

The patient introduces a light resisted effort (20% of available strength) to take the stabilised shoulder towards the ear (a shrug movement) and the ear towards the shoulder. The double movement (or effort towards movement) is important in order to introduce a contraction of the muscle from both ends simultaneously. The degree of effort should be mild and no pain should be felt. The contraction is sustained for 10 seconds (or so) and, upon complete relaxation of effort, the practitioner gently eases the head/neck into an increased degree of sidebending and rotation, where it is stabilised, as the shoulder is stretched caudally.

 

When stretching is introduced the patient can usefully assist in this phase of the treatment by initiating, on instruction, the stretch of the muscle (�as you breathe out please slide your hand towards your feet�). This reduces the chances of a stretch reflex being initiated. Once the muscle is being stretched, the patient relaxes and the stretch is held for 10�30 seconds.

 

CAUTION: No stretch should be introduced from the cranial end of the muscle as this could stress the neck. The head is stabilised at its side-flexion and rotation barrier.

 

Disagreement

 

There is some disagreement as to the head/neck rotation position as described in the treatment method above, which calls (for posterior and middle fibres) for sidebending and rotation away from the affected side.

 

Liebenson (1996), suggests that the patient �lies supine with the head supported in anteflexion and laterally flexed away and rotated towards the side of involvement�.

 

Lewit (1985b) suggests: �The patient is supine � the therapist fixes the shoulder from above with one hand, sidebending the head and neck with the other hand so as to take up the slack. He then asks the patient to look towards the side away from which the head is bent, resisting the patient�s automatic tendency to move towards the side of the lesion.� (This method is described below.)

 

The author has used the methods described above with good effect and urges readers to try these approaches as well as those of Liebenson and Lewit, and to evaluate results for themselves.

 

MET treatment of acutely shortened upper trapezius, method (b) Lewit suggests the use of eye movements to facilitate initiation of PIR before stretching, an ideal method for acute problems in this region.

 

The patient is supine, while the practitioner fixes the shoulder and the sidebent (away from the treated side) head and neck at the restriction barrier and asks the patient to look, with the eyes only (i.e. not to turn the head), towards the side away from which the neck is bent.

 

This eye movement is maintained, as is a held breath, while the practitioner resists the slight isometric contraction that these two factors (eye movement and breath) will have created.

 

On exhalation and complete relaxation, the head/neck is taken to a new barrier and the process repeated. If the shoulder is brought into the equation, this is firmly held as it attempts to lightly push into a shrug. After this 10 second contraction the muscle will have released somewhat and slack can again be taken out as the head is repositioned before a repetition of the procedure commences.

 

Dr. Alex Jimenez offers an additional assessment and treatment of the hip flexors as a part of a referenced clinical application of neuromuscular techniques by Leon Chaitow and Judith Walker DeLany. The scope of our information is limited to chiropractic and spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

 

By Dr. Alex Jimenez

 

Green-Call-Now-Button-24H-150x150-2-3.png

 

Additional Topics: Wellness

 

Overall health and wellness are essential towards maintaining the proper mental and physical balance in the body. From eating a balanced nutrition as well as exercising and participating in physical activities, to sleeping a healthy amount of time on a regular basis, following the best health and wellness tips can ultimately help maintain overall well-being. Eating plenty of fruits and vegetables can go a long way towards helping people become healthy.

 

blog picture of cartoon paperboy big news

 

WELLNESS TOPIC: EXTRA EXTRA: Managing Workplace Stress

 

 

Blank
References
1.�Ballou SK, Keefer L. Multicultural considerations in the diagnosis and management of irritable bowel syndrome: a selective summary.�Eur J Gastroenterol Hepatol.�2013;25:1127�1133.�[PubMed]
2.�Gonzales Gamarra RG, Ruiz S�nchez JG, Le�n Jim�nez F, Cubas Benavides F, D�az V�lez C. [Prevalence of irritable bowel syndrome in the adult population of the city of Chiclayo in 2011]�Rev Gastroenterol Peru.�2012;32:381�386.�[PubMed]
3.�Gwee KA, Lu CL, Ghoshal UC. Epidemiology of irritable bowel syndrome in Asia: something old, something new, something borrowed.�J Gastroenterol Hepatol.�2009;24:1601�1607.�[PubMed]
4.�Krogsgaard LR, Engsbro AL, Bytzer P. The epidemiology of irritable bowel syndrome in Denmark. A population-based survey in adults ? 50 years of age.�Scand J Gastroenterol.�2013;48:523�529.�[PubMed]
5.�Ibrahim NK, Battarjee WF, Almehmadi SA. Prevalence and predictors of irritable bowel syndrome among medical students and interns in King Abdulaziz University, Jeddah.�Libyan J Med.�2013;8:21287.[PMC free article]�[PubMed]
6.�Lee YY, Waid A, Tan HJ, Chua AS, Whitehead WE. Rome III survey of irritable bowel syndrome among ethnic Malays.�World J Gastroenterol.�2012;18:6475�6480; discussion p. 6479.�[PMC free article][PubMed]
7.�Ghoshal UC, Abraham P, Bhatt C, Choudhuri G, Bhatia SJ, Shenoy KT, Banka NH, Bose K, Bohidar NP, Chakravartty K, et al. Epidemiological and clinical profile of irritable bowel syndrome in India: report of the Indian Society of Gastroenterology Task Force.�Indian J Gastroenterol.�2008;27:22�28.�[PubMed]
8.�Bures J, Cyrany J, Kohoutova D, F�rstl M, Rejchrt S, Kvetina J, Vorisek V, Kopacova M. Small intestinal bacterial overgrowth syndrome.�World J Gastroenterol.�2010;16:2978�2990.�[PMC free article][PubMed]
9.�Dibaise JK, Young RJ, Vanderhoof JA. Enteric microbial flora, bacterial overgrowth, and short-bowel syndrome.�Clin Gastroenterol Hepatol.�2006;4:11�20.�[PubMed]
10.�Bouhnik Y, Alain S, Attar A, Flouri� B, Raskine L, Sanson-Le Pors MJ, Rambaud JC. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome.�Am J Gastroenterol.�1999;94:1327�1331.�[PubMed]
11.�Dukowicz AC, Lacy BE, Levine GM. Small intestinal bacterial overgrowth: a comprehensive review.�Gastroenterol Hepatol (N Y)�2007;3:112�122.�[PMC free article]�[PubMed]
12.�Posserud I, Stotzer PO, Bj�rnsson ES, Abrahamsson H, Simr�n M. Small intestinal bacterial overgrowth in patients with irritable bowel syndrome.�Gut.�2007;56:802�808.�[PMC free article]�[PubMed]
13.�Ghoshal U, Ghoshal UC, Ranjan P, Naik SR, Ayyagari A. Spectrum and antibiotic sensitivity of bacteria contaminating the upper gut in patients with malabsorption syndrome from the tropics.�BMC Gastroenterol.�2003;3:9.�[PMC free article]�[PubMed]
14.�Carrara M, Desideri S, Azzurro M, Bulighin GM, Di Piramo D, Lomonaco L, Adamo S. Small intestine bacterial overgrowth in patients with irritable bowel syndrome.�Eur Rev Med Pharmacol Sci.�2008;12:197�202.�[PubMed]
15.�Ghoshal UC, Ghoshal U, Das K, Misra A. Utility of hydrogen breath tests in diagnosis of small intestinal bacterial overgrowth in malabsorption syndrome and its relationship with oro-cecal transit time.�Indian J Gastroenterol.�2006;25:6�10.�[PubMed]
16.�Ghoshal UC, Kumar S, Mehrotra M, Lakshmi C, Misra A. Frequency of small intestinal bacterial overgrowth in patients with irritable bowel syndrome and chronic non-specific diarrhea.�J Neurogastroenterol Motil.�2010;16:40�46.�[PMC free article]�[PubMed]
17.�Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome.�Am J Gastroenterol.�2000;95:3503�3506.�[PubMed]
18.�Sachdeva S, Rawat AK, Reddy RS, Puri AS. Small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome: frequency and predictors.�J Gastroenterol Hepatol.�2011;26 Suppl 3:135�138.�[PubMed]
19.�Park H. The role of small intestinal bacterial overgrowth in the pathophysiology of irritable bowel syndrome.�J Neurogastroenterol Motil.�2010;16:3�4.�[PMC free article]�[PubMed]
20.�Ghoshal UC, Shukla R, Ghoshal U, Gwee KA, Ng SC, Quigley EM. The gut microbiota and irritable bowel syndrome: friend or foe?�Int J Inflam.�2012;2012:151085.�[PMC free article]�[PubMed]
21.�Brown AC. Ulcerative colitis, Crohn�s disease and irritable bowel syndrome patients need fecal transplant research and treatment.�J Crohns Colitis.�2014;8:179.�[PubMed]
22.�Sampath K, Levy LC, Gardner TB. Fecal transplantation: beyond the aesthetic.�Gastroenterology.�2013;145:1151�1153.�[PubMed]
23.�Grace E, Shaw C, Whelan K, Andreyev HJ. Review article: small intestinal bacterial overgrowth–prevalence, clinical features, current and developing diagnostic tests, and treatment.�Aliment Pharmacol Ther.�2013;38:674�688.�[PubMed]
24.�Yakoob J, Abbas Z, Khan R, Hamid S, Awan S, Jafri W. Small intestinal bacterial overgrowth and lactose intolerance contribute to irritable bowel syndrome symptomatology in Pakistan.�Saudi J Gastroenterol.�2011;17:371�375.�[PMC free article]�[PubMed]
25.�Gwee KA, Bak YT, Ghoshal UC, Gonlachanvit S, Lee OY, Fock KM, Chua AS, Lu CL, Goh KL, Kositchaiwat C, et al. Asian consensus on irritable bowel syndrome.�J Gastroenterol Hepatol.�2010;25:1189�1205.�[PubMed]
26.�Lacy BE, Gabbard SL, Crowell MD. Pathophysiology, evaluation, and treatment of bloating: hope, hype, or hot air?�Gastroenterol Hepatol (N Y)�2011;7:729�739.�[PMC free article]�[PubMed]
27.�Harder H, Serra J, Azpiroz F, Passos MC, Aguad� S, Malagelada JR. Intestinal gas distribution determines abdominal symptoms.�Gut.�2003;52:1708�1713.�[PMC free article]�[PubMed]
28.�Kumar S, Misra A, Ghoshal UC. Patients with irritable bowel syndrome exhale more hydrogen than healthy subjects in fasting state.�J Neurogastroenterol Motil.�2010;16:299�305.�[PMC free article][PubMed]
29.�Hungin AP, Mulligan C, Pot B, Whorwell P, Agr�us L, Fracasso P, Lionis C, Mendive J, Philippart de Foy JM, Rubin G, Winchester C, de Wit N. Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice — an evidence-based international guide.�Aliment Pharmacol Ther.�2013;38:864�886.�[PMC free article]�[PubMed]
30.�Attar A, Flouri� B, Rambaud JC, Franchisseur C, Ruszniewski P, Bouhnik Y. Antibiotic efficacy in small intestinal bacterial overgrowth-related chronic diarrhea: a crossover, randomized trial.�Gastroenterology.�1999;117:794�797.�[PubMed]
31.�Marcelino RT, Fagundes-Neto U. [Hydrogen test (H2) in the air expired for the diagnosis of small bowel bacterial overgrowth]�Arq Gastroenterol.�1995;32:191�198.�[PubMed]
32.�Santavirta J. Lactulose hydrogen and [14C]xylose breath tests in patients with ileoanal anastomosis.�Int J Colorectal Dis.�1991;6:208�211.�[PubMed]
33.�Ghoshal UC. How to interpret hydrogen breath tests.�J Neurogastroenterol Motil.�2011;17:312�317.[PMC free article]�[PubMed]
34.�Yang CY, Chang CS, Chen GH. Small-intestinal bacterial overgrowth in patients with liver cirrhosis, diagnosed with glucose H2 or CH4 breath tests.�Scand J Gastroenterol.�1998;33:867�871.�[PubMed]
35.�Ghoshal UC, Ghoshal U, Ayyagari A, Ranjan P, Krishnani N, Misra A, Aggarwal R, Naik S, Naik SR. Tropical sprue is associated with contamination of small bowel with aerobic bacteria and reversible prolongation of orocecal transit time.�J Gastroenterol Hepatol.�2003;18:540�547.�[PubMed]
36.�Lu CL, Chen CY, Chang FY, Lee SD. Characteristics of small bowel motility in patients with irritable bowel syndrome and normal humans: an Oriental study.�Clin Sci (Lond)�1998;95:165�169.�[PubMed]
37.�Sciarretta G, Furno A, Mazzoni M, Garagnani B, Malaguti P. Lactulose hydrogen breath test in orocecal transit assessment. Critical evaluation by means of scintigraphic method.�Dig Dis Sci.�1994;39:1505�1510.�[PubMed]
38.�Rao SS, Camilleri M, Hasler WL, Maurer AH, Parkman HP, Saad R, Scott MS, Simren M, Soffer E, Szarka L. Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies.�Neurogastroenterol Motil.�2011;23:8�23.[PubMed]
39.�Yu D, Cheeseman F, Vanner S. Combined oro-caecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath testing detects oro-caecal transit, not small intestinal bacterial overgrowth in patients with IBS.�Gut.�2011;60:334�340.�[PubMed]
40.�Rana SV, Sharma S, Sinha SK, Kaur H, Sikander A, Singh K. Incidence of predominant methanogenic flora in irritable bowel syndrome patients and apparently healthy controls from North India.�Dig Dis Sci.�2009;54:132�135.�[PubMed]
41.�Dridi B, Henry M, El Kh�chine A, Raoult D, Drancourt M. High prevalence of Methanobrevibacter smithii and Methanosphaera stadtmanae detected in the human gut using an improved DNA detection protocol.�PLoS One.�2009;4:e7063.�[PMC free article]�[PubMed]
42.�Chatterjee S, Park S, Low K, Kong Y, Pimentel M. The degree of breath methane production in IBS correlates with the severity of constipation.�Am J Gastroenterol.�2007;102:837�841.�[PubMed]
43.�Lunia MK, Sharma BC, Sachdeva S. Small intestinal bacterial overgrowth and delayed orocecal transit time in patients with cirrhosis and low-grade hepatic encephalopathy.�Hepatol Int.�2013;7:268�273.[PubMed]
44.�Resmini E, Parodi A, Savarino V, Greco A, Rebora A, Minuto F, Ferone D. Evidence of prolonged orocecal transit time and small intestinal bacterial overgrowth in acromegalic patients.�J Clin Endocrinol Metab.�2007;92:2119�2124.�[PubMed]
45.�Hamilton I, Worsley BW, Cobden I, Cooke EM, Shoesmith JG, Axon AT. Simultaneous culture of saliva and jejunal aspirate in the investigation of small bowel bacterial overgrowth.�Gut.�1982;23:847�853.[PMC free article]�[PubMed]
46.�Corazza GR, Sorge M, Strocchi A, Benati G, Di Sario A, Treggiari EA, Brusco G, Gasbarrini G. Non-absorbable antibiotics and small bowel bacterial overgrowth.�Ital J Gastroenterol.�1992;24:4�9.�[PubMed]
47.�Kuwahara T, Ogura Y, Oshima K, Kurokawa K, Ooka T, Hirakawa H, Itoh T, Nakayama-Imaohji H, Ichimura M, Itoh K, et al. The lifestyle of the segmented filamentous bacterium: a non-culturable gut-associated immunostimulating microbe inferred by whole-genome sequencing.�DNA Res.�2011;18:291�303.�[PMC free article]�[PubMed]
48.�Beumer RR, de Vries J, Rombouts FM. Campylobacter jejuni non-culturable coccoid cells.�Int J Food Microbiol.�1992;15:153�163.�[PubMed]
49.�Fromm H, Sarva RP, Ravitch MM, McJunkin B, Farivar S, Amin P. Effects of jejunoileal bypass on the enterohepatic circulation of bile acids, bacterial flora in the upper small intestine, and absorption of vitamin B12.�Metabolism.�1983;32:1133�1141.�[PubMed]
50.�Yoshida T, McCormick WC, Swell L, Vlahcevic ZR. Bile acid metabolism in cirrhosis. IV. Characterization of the abnormality in deoxycholic acid metabolism.�Gastroenterology.�1975;68:335�341.[PubMed]
51.�Bj�rneklett A, Fausa O, Midtvedt T. Bacterial overgrowth in jejunal and ileal disease.�Scand J Gastroenterol.�1983;18:289�298.�[PubMed]
52.�Vanner S. The small intestinal bacterial overgrowth. Irritable bowel syndrome hypothesis: implications for treatment.�Gut.�2008;57:1315�1321.�[PubMed]
53.�Kinross JM, von Roon AC, Holmes E, Darzi A, Nicholson JK. The human gut microbiome: implications for future health care.�Curr Gastroenterol Rep.�2008;10:396�403.�[PubMed]
54.�Clauw DJ. Fibromyalgia: an overview.�Am J Med.�2009;122:S3�S13.�[PubMed]
55.�Pimentel M, Wallace D, Hallegua D, Chow E, Kong Y, Park S, Lin HC. A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing.�Ann Rheum Dis.�2004;63:450�452.�[PMC free article]�[PubMed]
56.�Simr�n M, Stotzer PO. Use and abuse of hydrogen breath tests.�Gut.�2006;55:297�303.[PMC free article]�[PubMed]
57.�Gasbarrini A, Lauritano EC, Gabrielli M, Scarpellini E, Lupascu A, Ojetti V, Gasbarrini G. Small intestinal bacterial overgrowth: diagnosis and treatment.�Dig Dis.�2007;25:237�240.�[PubMed]
58.�Ghoshal UC, Srivastava D, Verma A, Misra A. Slow transit constipation associated with excess methane production and its improvement following rifaximin therapy: a case report.�J Neurogastroenterol Motil.�2011;17:185�188.�[PMC free article]�[PubMed]
59.�Bala L, Ghoshal UC, Ghoshal U, Tripathi P, Misra A, Gowda GA, Khetrapal CL. Malabsorption syndrome with and without small intestinal bacterial overgrowth: a study on upper-gut aspirate using 1H NMR spectroscopy.�Magn Reson Med.�2006;56:738�744.�[PubMed]
60.�Haboubi NY, Lee GS, Montgomery RD. Duodenal mucosal morphometry of elderly patients with small intestinal bacterial overgrowth: response to antibiotic treatment.�Age Ageing.�1991;20:29�32.�[PubMed]
61.�Shindo K, Machida M, Koide K, Fukumura M, Yamazaki R. Deconjugation ability of bacteria isolated from the jejunal fluid of patients with progressive systemic sclerosis and its gastric pH.�Hepatogastroenterology.�1998;45:1643�1650.�[PubMed]
62.�Wanitschke R, Ammon HV. Effects of dihydroxy bile acids and hydroxy fatty acids on the absorption of oleic acid in the human jejunum.�J Clin Invest.�1978;61:178�186.�[PMC free article]�[PubMed]
63.�Shanab AA, Scully P, Crosbie O, Buckley M, O�Mahony L, Shanahan F, Gazareen S, Murphy E, Quigley EM. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8.�Dig Dis Sci.�2011;56:1524�1534.�[PubMed]
64.�Ghoshal UC, Park H, Gwee KA. Bugs and irritable bowel syndrome: The good, the bad and the ugly.�J Gastroenterol Hepatol.�2010;25:244�251.�[PubMed]
65.�Barbara G, Stanghellini V, Brandi G, Cremon C, Di Nardo G, De Giorgio R, Corinaldesi R. Interactions between commensal bacteria and gut sensorimotor function in health and disease.�Am J Gastroenterol.�2005;100:2560�2568.�[PubMed]
66.�Cherbut C, Aub� AC, Blotti�re HM, Galmiche JP. Effects of short-chain fatty acids on gastrointestinal motility.�Scand J Gastroenterol Suppl.�1997;222:58�61.�[PubMed]
67.�Ramakrishna BS, Roediger WE. Bacterial short chain fatty acids: their role in gastrointestinal disease.�Dig Dis.�1990;8:337�345.�[PubMed]
68.�Dumoulin V, Moro F, Barcelo A, Dakka T, Cuber JC. Peptide YY, glucagon-like peptide-1, and neurotensin responses to luminal factors in the isolated vascularly perfused rat ileum.�Endocrinology.�1998;139:3780�3786.�[PubMed]
69.�Balsari A, Ceccarelli A, Dubini F, Fesce E, Poli G. The fecal microbial population in the irritable bowel syndrome.�Microbiologica.�1982;5:185�194.�[PubMed]
70.�Nobaek S, Johansson ML, Molin G, Ahrn� S, Jeppsson B. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome.�Am J Gastroenterol.�2000;95:1231�1238.�[PubMed]
71.�Cummings JH, Macfarlane GT. The control and consequences of bacterial fermentation in the human colon.�J Appl Bacteriol.�1991;70:443�459.�[PubMed]
72.�Camilleri M. Probiotics and irritable bowel syndrome: rationale, mechanisms, and efficacy.�J Clin Gastroenterol.�2008;42 Suppl 3 Pt 1:S123�S125.�[PubMed]
73.�Spiller R. Probiotics: an ideal anti-inflammatory treatment for IBS?�Gastroenterology.�2005;128:783�785.�[PubMed]
74.�Ford AC, Spiegel BM, Talley NJ, Moayyedi P. Small intestinal bacterial overgrowth in irritable bowel syndrome: systematic review and meta-analysis.�Clin Gastroenterol Hepatol.�2009;7:1279�1286.�[PubMed]
75.�Cuoco L, Salvagnini M. Small intestine bacterial overgrowth in irritable bowel syndrome: a retrospective study with rifaximin.�Minerva Gastroenterol Dietol.�2006;52:89�95.�[PubMed]
76.�Di Stefano M, Corazza GR. Treatment of small intestine bacterial overgrowth and related symptoms by rifaximin.�Chemotherapy.�2005;51 Suppl 1:103�109.�[PubMed]
77.�Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP. Rifaximin therapy for patients with irritable bowel syndrome without constipation.�N Engl J Med.�2011;364:22�32.�[PubMed]
78.�Hwang L, Low K, Khoshini R, Melmed G, Sahakian A, Makhani M, Pokkunuri V, Pimentel M. Evaluating breath methane as a diagnostic test for constipation-predominant IBS.�Dig Dis Sci.�2010;55:398�403.�[PubMed]
79.�Low K, Hwang L, Hua J, Zhu A, Morales W, Pimentel M. A combination of rifaximin and neomycin is most effective in treating irritable bowel syndrome patients with methane on lactulose breath test.�J Clin Gastroenterol.�2010;44:547�550.�[PubMed]
80.�Bengmark S. Colonic food: pre- and probiotics.�Am J Gastroenterol.�2000;95:S5�S7.�[PubMed]
81.�Quigley EM, Quera R. Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics.�Gastroenterology.�2006;130:S78�S90.�[PubMed]
82.�Xiao SD, Zhang DZ, Lu H, Jiang SH, Liu HY, Wang GS, Xu GM, Zhang ZB, Lin GJ, Wang GL. Multicenter, randomized, controlled trial of heat-killed Lactobacillus acidophilus LB in patients with chronic diarrhea.�Adv Ther.�2003;20:253�260.�[PubMed]
83.�O’Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, O�Sullivan GC, Kiely B, Collins JK, Shanahan F, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles.�Gastroenterology.�2005;128:541�551.�[PubMed]
84.�Tsuchiya J, Barreto R, Okura R, Kawakita S, Fesce E, Marotta F. Single-blind follow-up study on the effectiveness of a symbiotic preparation in irritable bowel syndrome.�Chin J Dig Dis.�2004;5:169�174.[PubMed]
85.�Kim YG, Moon JT, Lee KM, Chon NR, Park H. [The effects of probiotics on symptoms of irritable bowel syndrome]�Korean J Gastroenterol.�2006;47:413�419.�[PubMed]
86.�Park JS, Yu JH, Lim HC, Kim JH, Yoon YH, Park HJ, Lee SI. [Usefulness of lactulose breath test for the prediction of small intestinal bacterial overgrowth in irritable bowel syndrome]�Korean J Gastroenterol.�2010;56:242�248.�[PubMed]
87.�Mann NS, Limoges-Gonzales M. The prevalence of small intestinal bacterial vergrowth in irritable bowel syndrome.�Hepatogastroenterology.�2009;56:718�721.�[PubMed]
88.�Scarpellini E, Giorgio V, Gabrielli M, Lauritano EC, Pantanella A, Fundar� C, Gasbarrini A. Prevalence of small intestinal bacterial overgrowth in children with irritable bowel syndrome: a case-control study.�J Pediatr.�2009;155:416�420.�[PubMed]
89.�Nucera G, Gabrielli M, Lupascu A, Lauritano EC, Santoliquido A, Cremonini F, Cammarota G, Tondi P, Pola P, Gasbarrini G, et al. Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth.�Aliment Pharmacol Ther.�2005;21:1391�1395.�[PubMed]
90.�Reddymasu SC, Sostarich S, McCallum RW. Small intestinal bacterial overgrowth in irritable bowel syndrome: are there any predictors?�BMC Gastroenterol.�2010;10:23.�[PMC free article]�[PubMed]
91.�Lombardo L, Foti M, Ruggia O, Chiecchio A. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy.�Clin Gastroenterol Hepatol.�2010;8:504�508.�[PubMed]
92.�Parodi A, Dulbecco P, Savarino E, Giannini EG, Bodini G, Corbo M, Isola L, De Conca S, Marabotto E, Savarino V. Positive glucose breath testing is more prevalent in patients with IBS-like symptoms compared with controls of similar age and gender distribution.�J Clin Gastroenterol.�2009;43:962�966.[PubMed]
93.�Rana SV, Sinha SK, Sikander A, Bhasin DK, Singh K. Study of small intestinal bacterial overgrowth in North Indian patients with irritable bowel syndrome: a case control study.�Trop Gastroenterol.�2008;29:23�25.�[PubMed]
94.�Majewski M, McCallum RW. Results of small intestinal bacterial overgrowth testing in irritable bowel syndrome patients: clinical profiles and effects of antibiotic trial.�Adv Med Sci.�2007;52:139�142.[PubMed]
95.�Lupascu A, Gabrielli M, Lauritano EC, Scarpellini E, Santoliquido A, Cammarota G, Flore R, Tondi P, Pola P, Gasbarrini G, et al. Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in irritable bowel syndrome.�Aliment Pharmacol Ther.�2005;22:1157�1160.[PubMed]
Close Accordion
Research Studies on SIBO in Irritable Bowel Syndrome

Research Studies on SIBO in Irritable Bowel Syndrome

by | Chiropractic, Functional Medicine

Irritable bowel syndrome, or IBS, is a prevalent condition characterized by abdominal pain or discomfort, bloating, connected to altered stool form (such as diarrhea and constipation) as well as passage. Approximately 4 percent to 30 percent of individuals world-wide suffer from IBS. Small intestinal bacterial overgrowth, or SIBO, which was clinically demonstrated in patients with structural abnormalities in the gut, such as ileo-transverse anastomosis, stricture, fistula, slow motility and reduced gut defense, may also be characterized by abdominal pain or discomfort, bloating, flatulence and loose motion. It’s been recognized that SIBO may occur in the absence of structural abnormalities. These patients may be incorrectly diagnosed with IBS, or irritable bowel syndrome.

 

How common is SIBO diagnosed in IBS?

 

Small intestinal bacterial overgrowth has been described as the excessive presence of bacteria, forming 105 units per milliliter on culture of their intestine aspirate. As this is an invasive test, lots of noninvasive techniques like lactulose and glucose hydrogen breath tests (LHBT and GHBT) are broadly used to diagnose SIBO. This issue has been recognized among people with IBS. In a variety of research studies, frequency of SIBO among patients presenting IBS varied from 4 percent to 78 percent, according to Table ?1, more so among patients with diarrhea-predominant IBS. Not only quantitative increase (SIBO) but qualitative change from the gut bacteria (dysbiosis) was reported among patients with IBS. Research studies utilizing antibiotics and probiotics have caused disagreement to care for this disease with lately transplantation which led to a paradigm shift. Nonetheless, it’s essential to understand the wide-variability in frequency of SIBO among people with IBS. A wide-variability in frequency may indicate it is vital to evaluate the evidence carefully to determine whether the association between IBS and SIBO is under-projected in previous research studies.

 

Table 1 Summary of Prevalence of SIBO in IBS Image 1

 

The research studies are examined by people on discordance with the connection between IBS and SIBO as well as their strength and weakness, such as evidence on exploitation of gut flora on indications of IBS and other issues.

 

Assessment of Studies on SIBO in IBS

 

Table ?1 summarizes the outcomes among patients with IBS from research studies on individuals with SIBO. As can be noted in the table, the frequency of people with IBS and SIBO varied from 4 percent to 78 percent and from 1 percent and 40 percent among controls. Frequency of individuals with SIBO and IBS was greater than among controls. It might be concluded that SIBO is correlated with IBS. It’s essential to assess the explanations in various research studies.

 

Critical Evaluation of Studies on SIBO in IBS

 

Can IBS phenotype determine frequency of SIBO?

 

IBS is a state that’s heterogeneous. The sub-types may be diarrhea or constipation-predominant or may be alternating. Patients with diarrhea-predominant IBS have organic cause including SIBO compared to other types of IBS. In a study on 129 patients with non-diarrheal IBS, 73 with long-term diarrhea, for example diarrhea-predominant IBS, and 51 healthy controls, frequency of SIBO with GHBT was 11 (8.5 percent), 16 (22 percent) and 1 (2%), respectively. Similar findings are reported in various studies. Diarrheal IBS needs to be evaluated in comparison to other sorts of IBS for SIBO. Research studies that contained percentage of individuals are extremely likely to reveal frequency of SIBO.

 

Bloating is a symptom commonly reported among patients with IBS. Frequency of bloating has been reported to vary from Asia by 26 percent to 83 percent in research studies on IBS. The pathogenesis of bloating may be correlated with increased quantity of gas in the gut, its abnormal source and improved gut sense in response to distension of the gut. Patients with SIBO may have increased amount of gas inside the gut, so it’s plausible to believe IBS patients with bloating that is noticeable are expected to have SIBO. There is limited data with this specific circumstance. Evidence also demonstrated that both fasting along with post-substrate (e.g., sugar, lactulose) breath hydrogen is considerably higher compared to individuals with IBS compared to controls. Probiotics and antibiotics, which are demonstrated to reduce gas, are demonstrated to ease bloating. It has been noted that treatment can revert hydrogen breath tests back to normal. Patients with IBS, flatulence and bloating should be evaluated for SIBO. More data is involved with this issue.

 

Can techniques used to diagnose SIBO determine its frequency?

 

Several techniques are used to diagnose SIBO; including GHBT LHBT,14C breath test, and culture of aspirate. The principle of hydrogen breath tests is summarized in Figure 1. Dietary carbohydrates produce hydrogen in the gut. In patients with SIBO, the bacteria in the small bowel ferment these carbohydrates, producing hydrogen, which gets absorbed and is exhaled in the breath.

 

Figure 1 Outline of Principle of Method and Interpretation of Glucose and Lactulose Hydrogen Breath Tests Image 2

Figure 1

 

Hydrogen breath test involves giving patients a load of carbohydrate (generally in the sort of glucose and lactulose) and measuring expired hydrogen concentrations in a period of time. Identification of SIBO using hydrogen breath test depends upon the bodily principle of patients with SIBO, glucose may be fermented by bacteria in the intestine resulting in production of hydrogen gas that is consumed and exhaled in expired air (Figure ?1, A1). By contrast, lactulose, which may function as a non-absorbable disaccharide, will produce an early summit due to fermentation in the small intestine (normally within 90-min) or two summit (as a consequence of small intestine fermentation and minute from colon), if SIBO is present (Figure ?1, B2 and B3). There are limits in hydrogen breath test for identification of SIBO. There may be similarities in patients with problems and SIBO employing rapid transit making differentiation difficult. An ancient summit can be positive in people with gut transit time. By way of instance, in a study from India, median oro-cecal transit interval was 65 minutes (variety 40-110 moments) in healthy subjects. In another study from Taiwan, mean transit interval was 85 min. It’s been substantiated in Western individuals recently by simultaneously using LHBT and radio-nuclide method to gauge gut transport. Double summit standards for evaluation of SIBO using LHBT is quite insensitive. Sensitivity of GHBT to diagnose SIBO is 44 percent contemplating the culture of gut aspirate as a regular standard. As a result, it’s estimated that the researchers who used a historic summit standards in LHBT could discover a greater frequency of SIBO among people with IBS along with controls. In contrast, those who would use either GHBT or double summit benchmark in LHBT might locate a minimum frequency of SIBO alike in patients with IBS and controls. It is well worth noting from Table ?1 that the frequency of SIBO among people with IBS and controls on LHBT (early summit standards) varied from 34.5 percent to 78 percent and 7 percent to 40 percent, respectively; in contrast with the frequency GHBT varied from 8.5 percent to 46 percent and 2 percent to 18percent.

 

Fifteen percent of people might have methanogenic flora in the gut. Methanobrevibacter smithii, Methanobrevibacter stadmanae and perhaps several of those coliform bacteria are methanogens. In these areas, only hydrogen breath tests may not diagnose SIBO, estimation of methane may also be demanded (Figure ?1). Table ?1 shows that 8.5 percent to 26 percent of IBS sufferers and 0 percent to 25 percent of controls exhaled methane inside their breath. Whether methane was not expected in them, SIBO could not have been diagnosed. Methane was not estimated, which could have resulted in underestimation of frequency of SIBO as outlined in a proportion of the research study. Methane production in excess is connected to constipation. Consequently, methane estimation in breath, which is inaccessible in several commercially available hydrogen breath test machines, is particularly vital in patients employing constipation-predominant IBS. Some could have slow transit through the small intestine making prolonged testing as a lot of hours required and many people may not want to undergo such testing. However, a period of testing for them may overlook SIBO’s identification.

 

The jejunal aspirate culture has traditionally been used as the gold standard to diagnose SIBO, according to Figure ?2. On the other hand, the limitations of this test include invasiveness in addition to the challenges posed by attempting to civilization all strains and species. In fact, usage of air during endoscopy might lead to a false negative impact as anaerobes do not rise when these are exposed to oxygen. Furthermore, a massive percentage of germs are not cultured. By contrast, single lumen catheter passed through the nose or through the biopsy channel of endoscope, may lead to contamination with oro-pharyngeal flora supplying false positive result. Therefore, we left a double-lumen catheter to prevent these oro-pharyngeal contamination (Figure ?2). Studies on SIBO one of patients with IBS using qualitative civilization of small bowel aspirate are scanty (Table ?1). A study by Posserud et al reported that a frequency of SIBO of 4 percent among people with IBS. Taking the result of study using GHBT, the sensitivity of 44 percent to diagnose the intestine aspirate appears to have the incidence of SIBO . More studies are essential on this issue.

 

Figure 2 Outline of Method of Culturing Bacteria and Counting the Colonies Image 3

Figure 2

 

Figure 3 Bile Acid Breath Test Involving Bile Acid and Glycocholic Acid Image 4

Figure 3

 

13C and�14C based tests have also been developed based on the bacterial metabolism of D-xylose (Figure ?3). Of acids containing13C and�14C may be used to diagnose SIBO. The glycocholic acid breath test contains the managing of the bile acid14C glycocholic acid, as well as the discovery of14CO2, which may be increased in SIBO (Figure 3), according to the clinical and experimental data from the various research studies on SIBO associated with IBS. While evidence may appear conclusive, further research studies may be required to properly determine the results.

 

Information referenced from the National Center for Biotechnology Information (NCBI) and the National University of Health Sciences. The scope of our information is limited to chiropractic and spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

 

By Dr. Alex Jimenez

 

Green-Call-Now-Button-24H-150x150-2-3.png

 

Additional Topics: Wellness

 

Overall health and wellness are essential towards maintaining the proper mental and physical balance in the body. From eating a balanced nutrition as well as exercising and participating in physical activities, to sleeping a healthy amount of time on a regular basis, following the best health and wellness tips can ultimately help maintain overall well-being. Eating plenty of fruits and vegetables can go a long way towards helping people become healthy.

 

blog picture of cartoon paperboy big news

 

WELLNESS TOPIC: EXTRA EXTRA: Managing Workplace Stress

 

 

Blank
References
1.�Ballou SK, Keefer L. Multicultural considerations in the diagnosis and management of irritable bowel syndrome: a selective summary.�Eur J Gastroenterol Hepatol.�2013;25:1127�1133.�[PubMed]
2.�Gonzales Gamarra RG, Ruiz S�nchez JG, Le�n Jim�nez F, Cubas Benavides F, D�az V�lez C. [Prevalence of irritable bowel syndrome in the adult population of the city of Chiclayo in 2011]�Rev Gastroenterol Peru.�2012;32:381�386.�[PubMed]
3.�Gwee KA, Lu CL, Ghoshal UC. Epidemiology of irritable bowel syndrome in Asia: something old, something new, something borrowed.�J Gastroenterol Hepatol.�2009;24:1601�1607.�[PubMed]
4.�Krogsgaard LR, Engsbro AL, Bytzer P. The epidemiology of irritable bowel syndrome in Denmark. A population-based survey in adults ? 50 years of age.�Scand J Gastroenterol.�2013;48:523�529.�[PubMed]
5.�Ibrahim NK, Battarjee WF, Almehmadi SA. Prevalence and predictors of irritable bowel syndrome among medical students and interns in King Abdulaziz University, Jeddah.�Libyan J Med.�2013;8:21287.[PMC free article]�[PubMed]
6.�Lee YY, Waid A, Tan HJ, Chua AS, Whitehead WE. Rome III survey of irritable bowel syndrome among ethnic Malays.�World J Gastroenterol.�2012;18:6475�6480; discussion p. 6479.�[PMC free article][PubMed]
7.�Ghoshal UC, Abraham P, Bhatt C, Choudhuri G, Bhatia SJ, Shenoy KT, Banka NH, Bose K, Bohidar NP, Chakravartty K, et al. Epidemiological and clinical profile of irritable bowel syndrome in India: report of the Indian Society of Gastroenterology Task Force.�Indian J Gastroenterol.�2008;27:22�28.�[PubMed]
8.�Bures J, Cyrany J, Kohoutova D, F�rstl M, Rejchrt S, Kvetina J, Vorisek V, Kopacova M. Small intestinal bacterial overgrowth syndrome.�World J Gastroenterol.�2010;16:2978�2990.�[PMC free article][PubMed]
9.�Dibaise JK, Young RJ, Vanderhoof JA. Enteric microbial flora, bacterial overgrowth, and short-bowel syndrome.�Clin Gastroenterol Hepatol.�2006;4:11�20.�[PubMed]
10.�Bouhnik Y, Alain S, Attar A, Flouri� B, Raskine L, Sanson-Le Pors MJ, Rambaud JC. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome.�Am J Gastroenterol.�1999;94:1327�1331.�[PubMed]
11.�Dukowicz AC, Lacy BE, Levine GM. Small intestinal bacterial overgrowth: a comprehensive review.�Gastroenterol Hepatol (N Y)�2007;3:112�122.�[PMC free article]�[PubMed]
12.�Posserud I, Stotzer PO, Bj�rnsson ES, Abrahamsson H, Simr�n M. Small intestinal bacterial overgrowth in patients with irritable bowel syndrome.�Gut.�2007;56:802�808.�[PMC free article]�[PubMed]
13.�Ghoshal U, Ghoshal UC, Ranjan P, Naik SR, Ayyagari A. Spectrum and antibiotic sensitivity of bacteria contaminating the upper gut in patients with malabsorption syndrome from the tropics.�BMC Gastroenterol.�2003;3:9.�[PMC free article]�[PubMed]
14.�Carrara M, Desideri S, Azzurro M, Bulighin GM, Di Piramo D, Lomonaco L, Adamo S. Small intestine bacterial overgrowth in patients with irritable bowel syndrome.�Eur Rev Med Pharmacol Sci.�2008;12:197�202.�[PubMed]
15.�Ghoshal UC, Ghoshal U, Das K, Misra A. Utility of hydrogen breath tests in diagnosis of small intestinal bacterial overgrowth in malabsorption syndrome and its relationship with oro-cecal transit time.�Indian J Gastroenterol.�2006;25:6�10.�[PubMed]
16.�Ghoshal UC, Kumar S, Mehrotra M, Lakshmi C, Misra A. Frequency of small intestinal bacterial overgrowth in patients with irritable bowel syndrome and chronic non-specific diarrhea.�J Neurogastroenterol Motil.�2010;16:40�46.�[PMC free article]�[PubMed]
17.�Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome.�Am J Gastroenterol.�2000;95:3503�3506.�[PubMed]
18.�Sachdeva S, Rawat AK, Reddy RS, Puri AS. Small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome: frequency and predictors.�J Gastroenterol Hepatol.�2011;26 Suppl 3:135�138.�[PubMed]
19.�Park H. The role of small intestinal bacterial overgrowth in the pathophysiology of irritable bowel syndrome.�J Neurogastroenterol Motil.�2010;16:3�4.�[PMC free article]�[PubMed]
20.�Ghoshal UC, Shukla R, Ghoshal U, Gwee KA, Ng SC, Quigley EM. The gut microbiota and irritable bowel syndrome: friend or foe?�Int J Inflam.�2012;2012:151085.�[PMC free article]�[PubMed]
21.�Brown AC. Ulcerative colitis, Crohn�s disease and irritable bowel syndrome patients need fecal transplant research and treatment.�J Crohns Colitis.�2014;8:179.�[PubMed]
22.�Sampath K, Levy LC, Gardner TB. Fecal transplantation: beyond the aesthetic.�Gastroenterology.�2013;145:1151�1153.�[PubMed]
23.�Grace E, Shaw C, Whelan K, Andreyev HJ. Review article: small intestinal bacterial overgrowth–prevalence, clinical features, current and developing diagnostic tests, and treatment.�Aliment Pharmacol Ther.�2013;38:674�688.�[PubMed]
24.�Yakoob J, Abbas Z, Khan R, Hamid S, Awan S, Jafri W. Small intestinal bacterial overgrowth and lactose intolerance contribute to irritable bowel syndrome symptomatology in Pakistan.�Saudi J Gastroenterol.�2011;17:371�375.�[PMC free article]�[PubMed]
25.�Gwee KA, Bak YT, Ghoshal UC, Gonlachanvit S, Lee OY, Fock KM, Chua AS, Lu CL, Goh KL, Kositchaiwat C, et al. Asian consensus on irritable bowel syndrome.�J Gastroenterol Hepatol.�2010;25:1189�1205.�[PubMed]
26.�Lacy BE, Gabbard SL, Crowell MD. Pathophysiology, evaluation, and treatment of bloating: hope, hype, or hot air?�Gastroenterol Hepatol (N Y)�2011;7:729�739.�[PMC free article]�[PubMed]
27.�Harder H, Serra J, Azpiroz F, Passos MC, Aguad� S, Malagelada JR. Intestinal gas distribution determines abdominal symptoms.�Gut.�2003;52:1708�1713.�[PMC free article]�[PubMed]
28.�Kumar S, Misra A, Ghoshal UC. Patients with irritable bowel syndrome exhale more hydrogen than healthy subjects in fasting state.�J Neurogastroenterol Motil.�2010;16:299�305.�[PMC free article][PubMed]
29.�Hungin AP, Mulligan C, Pot B, Whorwell P, Agr�us L, Fracasso P, Lionis C, Mendive J, Philippart de Foy JM, Rubin G, Winchester C, de Wit N. Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice — an evidence-based international guide.�Aliment Pharmacol Ther.�2013;38:864�886.�[PMC free article]�[PubMed]
30.�Attar A, Flouri� B, Rambaud JC, Franchisseur C, Ruszniewski P, Bouhnik Y. Antibiotic efficacy in small intestinal bacterial overgrowth-related chronic diarrhea: a crossover, randomized trial.�Gastroenterology.�1999;117:794�797.�[PubMed]
31.�Marcelino RT, Fagundes-Neto U. [Hydrogen test (H2) in the air expired for the diagnosis of small bowel bacterial overgrowth]�Arq Gastroenterol.�1995;32:191�198.�[PubMed]
32.�Santavirta J. Lactulose hydrogen and [14C]xylose breath tests in patients with ileoanal anastomosis.�Int J Colorectal Dis.�1991;6:208�211.�[PubMed]
33.�Ghoshal UC. How to interpret hydrogen breath tests.�J Neurogastroenterol Motil.�2011;17:312�317.[PMC free article]�[PubMed]
34.�Yang CY, Chang CS, Chen GH. Small-intestinal bacterial overgrowth in patients with liver cirrhosis, diagnosed with glucose H2 or CH4 breath tests.�Scand J Gastroenterol.�1998;33:867�871.�[PubMed]
35.�Ghoshal UC, Ghoshal U, Ayyagari A, Ranjan P, Krishnani N, Misra A, Aggarwal R, Naik S, Naik SR. Tropical sprue is associated with contamination of small bowel with aerobic bacteria and reversible prolongation of orocecal transit time.�J Gastroenterol Hepatol.�2003;18:540�547.�[PubMed]
36.�Lu CL, Chen CY, Chang FY, Lee SD. Characteristics of small bowel motility in patients with irritable bowel syndrome and normal humans: an Oriental study.�Clin Sci (Lond)�1998;95:165�169.�[PubMed]
37.�Sciarretta G, Furno A, Mazzoni M, Garagnani B, Malaguti P. Lactulose hydrogen breath test in orocecal transit assessment. Critical evaluation by means of scintigraphic method.�Dig Dis Sci.�1994;39:1505�1510.�[PubMed]
38.�Rao SS, Camilleri M, Hasler WL, Maurer AH, Parkman HP, Saad R, Scott MS, Simren M, Soffer E, Szarka L. Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies.�Neurogastroenterol Motil.�2011;23:8�23.[PubMed]
39.�Yu D, Cheeseman F, Vanner S. Combined oro-caecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath testing detects oro-caecal transit, not small intestinal bacterial overgrowth in patients with IBS.�Gut.�2011;60:334�340.�[PubMed]
40.�Rana SV, Sharma S, Sinha SK, Kaur H, Sikander A, Singh K. Incidence of predominant methanogenic flora in irritable bowel syndrome patients and apparently healthy controls from North India.�Dig Dis Sci.�2009;54:132�135.�[PubMed]
41.�Dridi B, Henry M, El Kh�chine A, Raoult D, Drancourt M. High prevalence of Methanobrevibacter smithii and Methanosphaera stadtmanae detected in the human gut using an improved DNA detection protocol.�PLoS One.�2009;4:e7063.�[PMC free article]�[PubMed]
42.�Chatterjee S, Park S, Low K, Kong Y, Pimentel M. The degree of breath methane production in IBS correlates with the severity of constipation.�Am J Gastroenterol.�2007;102:837�841.�[PubMed]
43.�Lunia MK, Sharma BC, Sachdeva S. Small intestinal bacterial overgrowth and delayed orocecal transit time in patients with cirrhosis and low-grade hepatic encephalopathy.�Hepatol Int.�2013;7:268�273.[PubMed]
44.�Resmini E, Parodi A, Savarino V, Greco A, Rebora A, Minuto F, Ferone D. Evidence of prolonged orocecal transit time and small intestinal bacterial overgrowth in acromegalic patients.�J Clin Endocrinol Metab.�2007;92:2119�2124.�[PubMed]
45.�Hamilton I, Worsley BW, Cobden I, Cooke EM, Shoesmith JG, Axon AT. Simultaneous culture of saliva and jejunal aspirate in the investigation of small bowel bacterial overgrowth.�Gut.�1982;23:847�853.[PMC free article]�[PubMed]
46.�Corazza GR, Sorge M, Strocchi A, Benati G, Di Sario A, Treggiari EA, Brusco G, Gasbarrini G. Non-absorbable antibiotics and small bowel bacterial overgrowth.�Ital J Gastroenterol.�1992;24:4�9.�[PubMed]
47.�Kuwahara T, Ogura Y, Oshima K, Kurokawa K, Ooka T, Hirakawa H, Itoh T, Nakayama-Imaohji H, Ichimura M, Itoh K, et al. The lifestyle of the segmented filamentous bacterium: a non-culturable gut-associated immunostimulating microbe inferred by whole-genome sequencing.�DNA Res.�2011;18:291�303.�[PMC free article]�[PubMed]
48.�Beumer RR, de Vries J, Rombouts FM. Campylobacter jejuni non-culturable coccoid cells.�Int J Food Microbiol.�1992;15:153�163.�[PubMed]
49.�Fromm H, Sarva RP, Ravitch MM, McJunkin B, Farivar S, Amin P. Effects of jejunoileal bypass on the enterohepatic circulation of bile acids, bacterial flora in the upper small intestine, and absorption of vitamin B12.�Metabolism.�1983;32:1133�1141.�[PubMed]
50.�Yoshida T, McCormick WC, Swell L, Vlahcevic ZR. Bile acid metabolism in cirrhosis. IV. Characterization of the abnormality in deoxycholic acid metabolism.�Gastroenterology.�1975;68:335�341.[PubMed]
51.�Bj�rneklett A, Fausa O, Midtvedt T. Bacterial overgrowth in jejunal and ileal disease.�Scand J Gastroenterol.�1983;18:289�298.�[PubMed]
52.�Vanner S. The small intestinal bacterial overgrowth. Irritable bowel syndrome hypothesis: implications for treatment.�Gut.�2008;57:1315�1321.�[PubMed]
53.�Kinross JM, von Roon AC, Holmes E, Darzi A, Nicholson JK. The human gut microbiome: implications for future health care.�Curr Gastroenterol Rep.�2008;10:396�403.�[PubMed]
54.�Clauw DJ. Fibromyalgia: an overview.�Am J Med.�2009;122:S3�S13.�[PubMed]
55.�Pimentel M, Wallace D, Hallegua D, Chow E, Kong Y, Park S, Lin HC. A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing.�Ann Rheum Dis.�2004;63:450�452.�[PMC free article]�[PubMed]
56.�Simr�n M, Stotzer PO. Use and abuse of hydrogen breath tests.�Gut.�2006;55:297�303.[PMC free article]�[PubMed]
57.�Gasbarrini A, Lauritano EC, Gabrielli M, Scarpellini E, Lupascu A, Ojetti V, Gasbarrini G. Small intestinal bacterial overgrowth: diagnosis and treatment.�Dig Dis.�2007;25:237�240.�[PubMed]
58.�Ghoshal UC, Srivastava D, Verma A, Misra A. Slow transit constipation associated with excess methane production and its improvement following rifaximin therapy: a case report.�J Neurogastroenterol Motil.�2011;17:185�188.�[PMC free article]�[PubMed]
59.�Bala L, Ghoshal UC, Ghoshal U, Tripathi P, Misra A, Gowda GA, Khetrapal CL. Malabsorption syndrome with and without small intestinal bacterial overgrowth: a study on upper-gut aspirate using 1H NMR spectroscopy.�Magn Reson Med.�2006;56:738�744.�[PubMed]
60.�Haboubi NY, Lee GS, Montgomery RD. Duodenal mucosal morphometry of elderly patients with small intestinal bacterial overgrowth: response to antibiotic treatment.�Age Ageing.�1991;20:29�32.�[PubMed]
61.�Shindo K, Machida M, Koide K, Fukumura M, Yamazaki R. Deconjugation ability of bacteria isolated from the jejunal fluid of patients with progressive systemic sclerosis and its gastric pH.�Hepatogastroenterology.�1998;45:1643�1650.�[PubMed]
62.�Wanitschke R, Ammon HV. Effects of dihydroxy bile acids and hydroxy fatty acids on the absorption of oleic acid in the human jejunum.�J Clin Invest.�1978;61:178�186.�[PMC free article]�[PubMed]
63.�Shanab AA, Scully P, Crosbie O, Buckley M, O�Mahony L, Shanahan F, Gazareen S, Murphy E, Quigley EM. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8.�Dig Dis Sci.�2011;56:1524�1534.�[PubMed]
64.�Ghoshal UC, Park H, Gwee KA. Bugs and irritable bowel syndrome: The good, the bad and the ugly.�J Gastroenterol Hepatol.�2010;25:244�251.�[PubMed]
65.�Barbara G, Stanghellini V, Brandi G, Cremon C, Di Nardo G, De Giorgio R, Corinaldesi R. Interactions between commensal bacteria and gut sensorimotor function in health and disease.�Am J Gastroenterol.�2005;100:2560�2568.�[PubMed]
66.�Cherbut C, Aub� AC, Blotti�re HM, Galmiche JP. Effects of short-chain fatty acids on gastrointestinal motility.�Scand J Gastroenterol Suppl.�1997;222:58�61.�[PubMed]
67.�Ramakrishna BS, Roediger WE. Bacterial short chain fatty acids: their role in gastrointestinal disease.�Dig Dis.�1990;8:337�345.�[PubMed]
68.�Dumoulin V, Moro F, Barcelo A, Dakka T, Cuber JC. Peptide YY, glucagon-like peptide-1, and neurotensin responses to luminal factors in the isolated vascularly perfused rat ileum.�Endocrinology.�1998;139:3780�3786.�[PubMed]
69.�Balsari A, Ceccarelli A, Dubini F, Fesce E, Poli G. The fecal microbial population in the irritable bowel syndrome.�Microbiologica.�1982;5:185�194.�[PubMed]
70.�Nobaek S, Johansson ML, Molin G, Ahrn� S, Jeppsson B. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome.�Am J Gastroenterol.�2000;95:1231�1238.�[PubMed]
71.�Cummings JH, Macfarlane GT. The control and consequences of bacterial fermentation in the human colon.�J Appl Bacteriol.�1991;70:443�459.�[PubMed]
72.�Camilleri M. Probiotics and irritable bowel syndrome: rationale, mechanisms, and efficacy.�J Clin Gastroenterol.�2008;42 Suppl 3 Pt 1:S123�S125.�[PubMed]
73.�Spiller R. Probiotics: an ideal anti-inflammatory treatment for IBS?�Gastroenterology.�2005;128:783�785.�[PubMed]
74.�Ford AC, Spiegel BM, Talley NJ, Moayyedi P. Small intestinal bacterial overgrowth in irritable bowel syndrome: systematic review and meta-analysis.�Clin Gastroenterol Hepatol.�2009;7:1279�1286.�[PubMed]
75.�Cuoco L, Salvagnini M. Small intestine bacterial overgrowth in irritable bowel syndrome: a retrospective study with rifaximin.�Minerva Gastroenterol Dietol.�2006;52:89�95.�[PubMed]
76.�Di Stefano M, Corazza GR. Treatment of small intestine bacterial overgrowth and related symptoms by rifaximin.�Chemotherapy.�2005;51 Suppl 1:103�109.�[PubMed]
77.�Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP. Rifaximin therapy for patients with irritable bowel syndrome without constipation.�N Engl J Med.�2011;364:22�32.�[PubMed]
78.�Hwang L, Low K, Khoshini R, Melmed G, Sahakian A, Makhani M, Pokkunuri V, Pimentel M. Evaluating breath methane as a diagnostic test for constipation-predominant IBS.�Dig Dis Sci.�2010;55:398�403.�[PubMed]
79.�Low K, Hwang L, Hua J, Zhu A, Morales W, Pimentel M. A combination of rifaximin and neomycin is most effective in treating irritable bowel syndrome patients with methane on lactulose breath test.�J Clin Gastroenterol.�2010;44:547�550.�[PubMed]
80.�Bengmark S. Colonic food: pre- and probiotics.�Am J Gastroenterol.�2000;95:S5�S7.�[PubMed]
81.�Quigley EM, Quera R. Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics.�Gastroenterology.�2006;130:S78�S90.�[PubMed]
82.�Xiao SD, Zhang DZ, Lu H, Jiang SH, Liu HY, Wang GS, Xu GM, Zhang ZB, Lin GJ, Wang GL. Multicenter, randomized, controlled trial of heat-killed Lactobacillus acidophilus LB in patients with chronic diarrhea.�Adv Ther.�2003;20:253�260.�[PubMed]
83.�O’Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, O�Sullivan GC, Kiely B, Collins JK, Shanahan F, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles.�Gastroenterology.�2005;128:541�551.�[PubMed]
84.�Tsuchiya J, Barreto R, Okura R, Kawakita S, Fesce E, Marotta F. Single-blind follow-up study on the effectiveness of a symbiotic preparation in irritable bowel syndrome.�Chin J Dig Dis.�2004;5:169�174.[PubMed]
85.�Kim YG, Moon JT, Lee KM, Chon NR, Park H. [The effects of probiotics on symptoms of irritable bowel syndrome]�Korean J Gastroenterol.�2006;47:413�419.�[PubMed]
86.�Park JS, Yu JH, Lim HC, Kim JH, Yoon YH, Park HJ, Lee SI. [Usefulness of lactulose breath test for the prediction of small intestinal bacterial overgrowth in irritable bowel syndrome]�Korean J Gastroenterol.�2010;56:242�248.�[PubMed]
87.�Mann NS, Limoges-Gonzales M. The prevalence of small intestinal bacterial vergrowth in irritable bowel syndrome.�Hepatogastroenterology.�2009;56:718�721.�[PubMed]
88.�Scarpellini E, Giorgio V, Gabrielli M, Lauritano EC, Pantanella A, Fundar� C, Gasbarrini A. Prevalence of small intestinal bacterial overgrowth in children with irritable bowel syndrome: a case-control study.�J Pediatr.�2009;155:416�420.�[PubMed]
89.�Nucera G, Gabrielli M, Lupascu A, Lauritano EC, Santoliquido A, Cremonini F, Cammarota G, Tondi P, Pola P, Gasbarrini G, et al. Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth.�Aliment Pharmacol Ther.�2005;21:1391�1395.�[PubMed]
90.�Reddymasu SC, Sostarich S, McCallum RW. Small intestinal bacterial overgrowth in irritable bowel syndrome: are there any predictors?�BMC Gastroenterol.�2010;10:23.�[PMC free article]�[PubMed]
91.�Lombardo L, Foti M, Ruggia O, Chiecchio A. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy.�Clin Gastroenterol Hepatol.�2010;8:504�508.�[PubMed]
92.�Parodi A, Dulbecco P, Savarino E, Giannini EG, Bodini G, Corbo M, Isola L, De Conca S, Marabotto E, Savarino V. Positive glucose breath testing is more prevalent in patients with IBS-like symptoms compared with controls of similar age and gender distribution.�J Clin Gastroenterol.�2009;43:962�966.[PubMed]
93.�Rana SV, Sinha SK, Sikander A, Bhasin DK, Singh K. Study of small intestinal bacterial overgrowth in North Indian patients with irritable bowel syndrome: a case control study.�Trop Gastroenterol.�2008;29:23�25.�[PubMed]
94.�Majewski M, McCallum RW. Results of small intestinal bacterial overgrowth testing in irritable bowel syndrome patients: clinical profiles and effects of antibiotic trial.�Adv Med Sci.�2007;52:139�142.[PubMed]
95.�Lupascu A, Gabrielli M, Lauritano EC, Scarpellini E, Santoliquido A, Cammarota G, Flore R, Tondi P, Pola P, Gasbarrini G, et al. Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in irritable bowel syndrome.�Aliment Pharmacol Ther.�2005;22:1157�1160.[PubMed]
Close Accordion
Prostate Cancer, Nutrition And Dietary Interventions

Prostate Cancer, Nutrition And Dietary Interventions

by | Cancer Health, Nutrition

Prostate Cancer: Abstract

Prostate cancer (PCa) remains a leading cause of mortality in US men and the prevalence continues to rise world-wide especially in countries where men consume a �Western-style� diet. Epidemiologic, preclinical and clinical studies suggest a potential role for dietary intake on the incidence and progression of PCa. ‘This minireview provides an overview of recent published literature with regard to nutrients, dietary factors, dietary patterns and PCa incidence and progression. Low carbohydrates intake, soy protein, omega-3 (w-3) fat, green teas, tomatoes and tomato products and zyflamend showed promise in reducing PCa risk or progression. A higher saturated fat intake and a higher ?-carotene status may increase risk. A �U� shape relationship may exist between folate, vitamin C, vitamin D and calcium with PCa risk. Despite the inconsistent and inconclusive findings, the potential for a role of dietary intake for the prevention and treatment of PCa is promising. The combination of all the beneficial factors for PCa risk reduction in a healthy dietary pattern may be the best dietary advice. This pattern includes rich fruits and vegetables, reduced refined carbohydrates, total and saturated fats, and reduced cooked meats. Further carefully designed prospective trials are warranted.

Keywords: Diet, Prostate cancer, Nutrients, Dietary pattern, Lifestyle, Prevention, Treatment, Nutrition, Dietary intervention, Review

Introduction: Prostate Cancer

Prostate cancer (PCa) is the second most common cancer in men, with nearly a million new cases diagnosed worldwide per year [1], with approximately a six-fold higher incidence in Western than in non-Western countries. Diet, lifestyle, environmental and genetic factors are hypothesized to play a role in these differences. This review focuses on the latest evidence of the potential role of dietary factors on PCa and includes epidemiologic and clinical trial evidence for the impact of protein, fat, carbohydrate, fiber, phytochemicals, other food components, whole foods and dietary patterns on PCa incidence, development and/or progression. Data from meta-analyses or well-designed randomized trials and prospective studies are emphasized in this review. It should be noted that studies of dietary intake or nutrition and cancer are often subject to various limitations and thus complicate interpretation of results. For example, when a study is designed to examine the effect of the amount of fat intake, alteration in fat intake inevitably will change intake of protein and/or carbohydrate, and may change the intake of other nutrients as well. As a result, it is difficult to attribute the effect to change in fat intake alone. In addition, the impact of macronutrients potentially involves aspects of both absolute quantity and the type of macronutrients consumed. Both aspects may potentially affect cancer initiation and/or development independently, but they are not always distinguishable in research designs. Though this topic was recently reviewed [2], given the extensive new literature on the topic, an updated review is presented herein and a summary table is provided for a quick reference (Table 1).

Nutrients Carbohydrates Given the hypothesis that insulin is a growth factor for PCa, it has been hypothesized that reducing carbohydrates and thus lowering serum insulin may slow PCa growth [3]. Indeed, in animal models, either a no-carbohydrate ketogenic diet (NCKD) [4,5] or a low-carbohydrate diet (20% kcal as carbohydrate) has favorable effects on slowing prostate tumor growth [6,7]. In human studies, one�study found that high intake of refined carbohydrates was associated with increased risk of PCa [7]. In addition to the amount of carbohydrates, type of carbohydrates may impact on PCa but research has been inconclusive. The potential to reduce PCa risk and progression via impacting carbohydrate metabolism is actively being investigated with Metformin. Metformin reduced PCa cell proliferation and delayed progression in vitro and in vivo, respectively [8-10] and reduced incident risk and mortality in humans [11-13]. Two single arm clinical trials also showed a positive effect of metformin in affecting markers of PCa proliferation and progression [14,15]. However, other retrospective cohort studies have not supported an effect of metformin on recurrence or incident risk of PCa [16-22]. Despite the potential for reducing either total or simple carbohydrates in benefiting PCa control, evidence is lacking from randomized controlled trials (RCT). Two randomized trials are on-going examining the impact of a low-carbohydrate diet (approximately 5% kcal) on the PSA doubling time among PCa patients post radical prostatectomy (NCT01763944) and on glycemic response among patients initiating androgen deprivation therapy (ADT) (NCT00932672 ). Findings from these trials will shed light on the effect of carbohydrate intake on markers of PCa progression and the role of reduced carbohydrate intake on offsetting the side effects of ADT.

Protein

The ideal level of protein intake for optimal overall health or prostate health is unclear. Despite the popularity of low carbohydrate diets that are high in protein, recent human studies reported that low protein intake was associated with lower risk for cancer and overall mortality among men 65 and younger. Among men older than 65, low protein intake was associated with a higher risk for cancer and overall mortality [23]. In animal models the ratio between protein and carbohydrate impacted on cardiometabolic health, aging and longevity [24]. The role of dietary protein and the protein to carbohydrate ratio on PCa development and progression requires further study.

Animal-Based Proteins

Studying protein intake, like all aspects of nutritional science, can be challenging. For example, animal meat, which is a source of protein in Western diets, is composed not only of protein, but also of fat, cholesterol, minerals and other nutrients. The amount of these nutrients including fatty acids may vary from one animal meat to the other. Previous studies in human have shown that consumption of skinless poultry, which is lower in cholesterol and saturated fat than many red meats, was not associated with the recurrence or progression of PCa [25]. However, consumption of baked poultry was inversely associated with advanced PCa [26,27], while cooked red meat was associated with increased advanced PCa risk [26,27]. Thus, how the food is prepared may modify its impact on PCa risk and progression. Overall, fish consumption may be associated with reduced PCa mortality, but high temperature cooked fish may contribute to PCa carcinogenesis [28]. Thus, it may be advisable to consume fish regularly but cooking temperature should be kept moderate.

Dairy-Based Protein

Another common protein source is dairy products, such as milk, cheese and yogurt. Previous studies have shown that dairy increased overall PCa risk but not with aggressive or lethal PCa [29,30]. In addition, both whole milk and low-fat milk consumption were reported to either promote or delay PCa progression [29,31]. In the Physicians Health follow up cohort with 21,660 men, total dairy consumption was found to be associated with increased PCa incidence [32]. In particular, low fat or skim milk increased low grade PCa, whereas whole milk increased fatal PCa risk. Though the exact component(s) of dairy products driving these associations is unknown, the high concentrations of saturated fat and calcium may be involved. A cross-sectional study of 1798 men showed that dairy protein was positively associated with serum IGF-1 [33] levels which may stimulate initiation or progression of PCa. Thus, further research is needed to clarify the relationship between dairy intake and PCa. There is insufficient data to provide recommendations specifically related to dairy or dairy protein and PCa risk or progression.

Plant-Based Proteins

Soy and soy-based products are rich in protein and phytoestrogens that may facilitate PCa prevention, but its role on PCa is unclear. In a study in mice, intake of soy products was associated with decreased hepatic aromatase, 5?-reductase, expression of androgen receptor and its regulated genes, FOXA1, urogenital tract weight and PCa tumor progression [34]. A recent randomized trial of 177 men with high-risk disease after radical prostatectomy found that soy protein supplementation for two years had no effect on risk of PCa recurrence [35]. Although epidemiological and pre-clinical studies [36,37] support a potential role for soy/soy isoflavones in PCa risk reduction or progression, a meta-analysis did not find significant impact of soy intake in PSA levels, sex hormone-binding globulin, testosterone, free testosterone, estradiol or dihydrotestosterone [38]. Another RCT in patients before prostatectomy also did not find any effect of soy isoflavone supplement up to six weeks on PSA, serum total testosterone, free testosterone, total estrogen, estradiol or total cholesterol [39]. Since most RCTs�conducted have been small and of short duration, further examination is needed.

Many studies have continued to examine the primary isoflavone in soy, genistein, and its effect on PCa. The potential for genistein to inihibit PCa cell detachment, invasion and metastasis is reported [40]. Genistein may modify glucose update and glucose transporter (GLUT) expression in PCa cells [41], or exert its anti-tumor effect by down regulating several microRNAs [42]. Studies using tumor cells and animal models suggest genistein may compete with and block endogenous estrogens from binding to the estrogen receptor, thereby inhibiting cellular proliferation, growth, and inducing differentiation and, specifically, genistein may inhibit cell detachment, protease production, cell invasion and thus prevent metastasis [36,40,43]. However, neither plasma nor urinary genistein levels were associated with PCa risk in case control studies [44,45]. In a phase 2 placebo-controlled RCT with 47 men, supplementation of 30 mg genistein for three to six weeks significantly reduced androgen-related markers of PCa progression [46]. In addition, genistein may be beneficial in improving cabazitaxel chemotherapy in metastatic castration-resistant PCa [37]. Clinical studies are warranted to further examine the role of soy and soy isoflavones for PCa prevention or treatment. A definitive recommendation regarding protein intake for PCa prevention or treatment is not available yet.

Fat

Research findings examining fat consumption with PCa risk or progression are conflicting. Both the total absolute intake [47] of dietary fat and the relative fatty acid composition may independently relate to PCa initiation and/or progression. While animal studies repeatedly show that reducing dietary fat intake slows tumor growth [48-50] and high fat diets, especially animal fat and corn oil increase PCa progression [51], human data are less consistent. Case�control studies and cohort studies have shown either no association between total fat consumption and PCa risk [52-55] or an inverse association between fat intake and PCa survival, particularly among men with localized PCa [47]. In addition, a cross-sectional study showed that fat intake expressed as percent of total calorie intake was positively associated with PSA levels in 13,594 men without PCa [56]. Given these conflicting data, it is possible that the type of fatty acid [56] rather than total amount may play an important role in PCa development and progression. A study found plasma saturated fatty acids to be positively associated with PCa risk in a prospective cohort of 14,514 men of the Melbourne Collaborative Cohort Study [57]. In addition, another study found that eating more plant-based fat was associated with reduced PCa risk [58]. These studies support the current dietary guideline of eating less animal-based fat and more plant-based fat.

The data regarding omega-6 (w-6) and omega-3 (w-3) polyunsaturated fatty acid (PUFA) consumption and PCa risk are also conflicting. While there are data to support a link between increased w-6 PUFA intake (mainly derived from corn oil) and risk of overall and high-grade PCa [57,59], not all data support such a link [60]. In fact, a greater polyunsaturated fat intake was associated with a lower all cause mortality among men with nonmetastatic PCa in the Health Professionals Follow-up study [58]. The postulated mechanism linking w-6 PUFAs and PCa risk is the conversion of arachidonic acid (w-6 PUFA) to eicosanoids (prostaglandin E-2, hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids) leading to inflammation and cellular growth [61]. Conversely, w-3 PUFAs, which are found primarily in cold water oily fish, may slow growth of PCa through a number of mechanisms [61-63]. In a study of 48 men with low risk PCa under active surveillance, repeat biopsy in six months showed that prostate tissue w-3 fatty acids, especially eicosapentaenoic acid (EPA), may protect against PCa progression [64]. In vitro and animal studies suggest that w-3 PUFAs induce anti-inflammatory, pro-apoptotic, antiproliferative and anti-angiogenic pathways [65,66]. Moreover, a mouse study comparing various types of fat found that only the fish oil diet (that is, omega-3 based diet) slowed PCa growth relative to other dietary fats [67]. In regards to human data, a phase II randomized trial showed that a low-fat diet with w-3 supplementation four to six weeks prior to radical prostatectomy decreased PCa proliferation and cell cycle progression (CCP) score [62,68]. A low-fat fish oil diet resulted in decreased 15(S)- hydroxyeicosatetraenoic acid levels and lowered CCP score relative to a Western diet [69]. The potential benefits of omega-3 fatty acids from fish are supported by epidemiological literature showing that w-3 fatty acid intake was inversely associated with fatal PCa risk [70,71]. Despite the promise of omega-3 fatty acids, not all studies agree. Supplementing 2 g alpha-linolenic acid (ALA) per day for 40 months in 1,622 men with PSA <4 ng/ml did not change their PSA [72]. However, another study found that a high blood serum n-3 PUFA and docosapentaenoic acid (DPA) was associated with reduced total PCa risk while high serum EPA and docosahexaenoic acid (DHA) was possibly associated with increased high-grade PCa risk [73]. Further research is required to understand better the role of omega-3 PUFAs in PCa prevention or treatment.

Cholesterol

Many pre-clinical studies have shown that the accumulation of cholesterol contributes to the progression of PCa [74-76]. It was suggested that a high cholesterol in Lin et al. BMC Medicine (2015) 13:3 Page 5 of 15 circulation may be a risk factor for solid tumors, primarily through the upregulation of cholesterol synthesis, inflammatory pathways [77] and intratumoral steroidogenesis [78]. According to a recent study with 2,408 men scheduled for biopsy, serum cholesterol was independently associated with prediction of PCa risk [79]. Consistent with the cholesterol findings, usage of the cholesterol lowering drug statin post radical prostatectomy (RP) was significantly associated with reduced risk of biochemical recurrence in 1,146 radical prostatectomy patients [80]. Another study also showed that statins may reduce PCa risk by lowering progression [81]. Although the mechanism has not been established, more recent studies also showed that a low high-density lipoprotein (HDL) cholesterol level was associated with a higher risk for PCa and, thus, a higher HDL was protective [81-84]. These findings support the notion that a heart-healthy dietary intervention that lowers cholesterol may benefit prostate health also.

Vitamins & Minerals

Herein we will review the recent data on vitamins A, B complex, C, D, E, and K and selenium. In the two large clinical trials: the Carotene and Retinol Efficacy Trial (CARET; PCa was a secondary outcome) and the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health prospective cohort study, excessive multivitamin supplementation was associated with a higher risk of developing aggressive PCa, particularly among those taking individual ?-carotene supplements [85,86]. Similarly, high serum ?-carotene levels were associated with a higher risk for PCa among 997 Finnish men in the Kuopio Ischaemic Heart Disease Risk Factor cohort [87]. However, ?-carotene supplement was not found to affect risk for lethal PCa during therapy [88], or in the Danish prospective cohort study of 26,856 men [89]. Circulating retinol also was not associated with PCa risk in a large case�control study [90]. Thus, the association between vitamin A and PCa is still unclear.

Preclinical evidence suggests folate depletion may slow tumor growth, while supplementation has no effect on growth or progression, but may directly lead to epigenetic changes via increases in DNA methylation [91]. Two meta-analyses also showed that circulating folate levels were positively associated with an increased risk of PCa [92,93], while dietary or supplemental folate had no effect on PCa risk [94] in a cohort study with 58,279 men in the Netherlands [95] and a case�control study in Italy and Switzerland [96]. In fact, one study of a cohort of men undergoing radical prostatectomy at several Veterans Administration facilities across the US even showed that higher serum folate levels were associated with lower PSA and, thus, lower risk for biochemical failure [97]. Another study using data from the 2007 to 2010 National Health and Nutrition Examination Survey showed that a higher folate status may be protective against elevated PSA levels among 3,293 men, 40-years old and older, without diagnosed PCa [98]. It was suggested that folate may play a dual role in prostate carcinogenesis and, thus, the complex relationship between folate and PCa awaits further investigation [99].

Despite the potential role of vitamin C (ascorbic acid) as an antioxidant in anticancer therapy, trials examining dietary intake or supplementation of vitamin C are few. A RCT showed no effect of vitamin C intake on PCa risk [89]. Furthermore, vitamin C at high doses may act more as a pro-oxidant than antioxidant, complicating the research design and interpretation.

The primary active form of vitamin D, 1,25 dihydroxyvitamin D3 (calcitriol) aids in proper bone formation, induces differentiation of some immune cells, and inhibits pro-tumor pathways, such as proliferation and angiogenesis, and has been suggested to benefit PCa risk [100]; however, findings continue to be inconclusive. More recent studies found that increased serum vitamin D levels were associated with decreased PCa risk [101,102]. Further, supplementing vitamin D may slow PCa progression or induce apoptosis in PCa cells [103-105]. Other studies, however, reported either no impact of vitamin D supplement on PSA [106] or no effect of vitamin D status on PCa risk [107,108]. Some studies contrarily reported that a lower vitamin D status was associated with a lower PCa risk in older men [109], or a higher serum vitamin D was associated with a higher PCa risk [110,111]. A study even suggested that a �U� shaped relationship may exist between vitamin D status and PCa and the optimal range of circulating vitamin D for PCa prevention may be narrow [112]. This is consistent with the findings for other nutrients that a greater intake of a favorable nutrient may not always be better.

A recent study showed that the association between vitamin D and PCa was modulated by vitamin D-binding protein [113] which may have partially explained the previous inconsistent findings. Further, a meta-analysis investigating the association between Vitamin D receptor (VDR) polymorphisms (BsmI and FokI) and PCa risk reported no relationship with PCa risk [114]. Thus, the role of vitamin D in PCa remains unclear.

In a large randomized trial with a total of 14,641 US male physicians ?50-years old, participants randomly received 400 IU of vitamin E every other day for an overall mean of 10.3 (13.8) years. Vitamin E supplementation had no immediate or long-term effects on the risk of total cancers or PCa [115]. However, a moderate dose of vitamin E supplement (50 mg or about 75 IU) resulted in lower PCa risk among 29,133 Finnish male smokers [116]. Multiple preclinical studies suggest vitamin E slows tumor growth, partly due to inhibiting DNA synthesis and inducing�apoptotic pathways [117]. Unfortunately, human studies have been less than supportive. Two observational studies (the Cancer Prevention Study II Nutrition Cohort and the NIH-AARP Diet and Health Study) both showed no association between vitamin E supplementation and PCa risk [118,119]. However, a higher serum ?-tocopherol but not the ?-tocopherol level was associated with decreased risk of PCa [120,121] and the association may be modified by genetic variations in vitamin E related genes [122]. On the contrary, a prospective randomized trial, the Selenium and Vitamin E Cancer Prevention Trial (SELECT), showed vitamin E supplementation significantly increased PCa risk [123] and that a higher plasma ?-tocopherol level may interact with selenium supplements to increase high grade PCa risk [124]. This finding is consistent with a case-cohort study of 1,739 cases and 3,117 controls that showed vitamin E increased PCa risk among those with low selenium status but not those with high selenium status [125]. Thus, more research is needed to examine the association between vitamin E and PCa and the dose effect and interaction with other nutrients should be considered.

Vitamin K has been hypothesized to help prevent PCa by reducing bioavailable calcium. Preclinical studies show the combination of vitamins C and K have potent antitumor activity in vitro and act as chemo- and radiosensitizers in vivo [126]. To date, few studies have investigated this, although one study using the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort found an inverse relationship between vitamin K (as menaquinones) intake and PCa incidence [127]. Little to no preclinical studies have been conducted to examine the role of calcium with PCa. Retrospective and meta-analyses suggest increased or reduced PCa risk with increased calcium intake, while others suggest no association [128,129]. Another study suggests a �U�-shaped association, where very low calcium levels or supplementation are both associated with PCa [130].

Selenium, on the other hand, has been hypothesized to prevent PCa. While in vitro studies suggested that selenium inhibited angiogenesis and proliferation while inducing apoptosis [131], results from SELECT showed no benefit of selenium alone or in combination with vitamin E for PCa chemoprevention [123]. Further, selenium supplementation did not benefit men with low selenium status but increased the risk of high-grade PCa among men with high selenium status in a randomly selected cohort of 1,739 cases with high-grade (Gleason 7�10) PCa and 3,117 controls [125]. A prospective Netherlands Cohort Study, which included 58,279 men, 55- to 69-years old, also showed that toenail selenium was associated with a reduced risk of advanced PCa [132]. Further research is needed to clarify the role of selenium with PCa.

Phytochemicals

Along with vitamins and minerals [2], plants contain phytochemicals with potential anti-cancer effects. Typically not considered essential compounds, phytochemicals have antioxidant and anti-inflammatory properties.

Silibinin is a polyphenolic flavonoid found in the seeds of milk thistle. It has been shown in vitro and in vivo to inhihit PCa growth by targeting epidermal growth factor receptor (EGFR), IGF-1 receptor (IGF-1R), and nuclear factor-kappa B (NF-kB) pathways [133,134]. A recent study showed that silibinin may be useful in PCa prevention by inhibiting TGF?2 expression and cancerassociated fibroblast (CAF)-like biomarkers in the human prostate stromal cells [135]. Thus, silibinin is a promising candidate as a PCa chemopreventive agent that awaits further research.

Curcumin is used as food additive in Asia and as an herbal medicine for inflammation [136]. In vitro, curcumin inhibits the pro-inflammatory protein NF-?B while inducing apoptosis through increased expression of proapoptotic genes [137]. In vivo, curcumin slows PCa growth in mice while sensitizing tumors to chemo- and radiotherapies [136]; however, no human trial has examined its impact on PCa.

Pomegranate

The peel and fruit of pomegranates and walnuts are rich in ellagitannins (punicalagins). These phytochemicals are readily metabolized to the active form ellagic acid by gut flora [138]. Preclinical experiments show ellagitannins inhibit PCa proliferation and angiogenesis under hypoxic conditions and induce apoptosis [137,138]. In prospective trials in men with a rising PSA after primary treatment, pomegranate juice or POMx, a commercially available pomegranate extract, increased the PSA doubling time relative to baseline [139,140], although no trials included a placebo group. Results are pending from a prospective placebo RCT using pomegranate extract in men with a rising PSA. However, in a placebo controlled trial, two pills of POMx daily for up to four weeks prior to radical prostatectomy had no impact on tumor pathology or oxidative stress or any other tumor measures [141].

Green Tea

Green tea contains a number of antioxidant polyphenols including catechins, such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), (?)-epicatechin-3-gallate (ECG) and (?)-epicatechin. Preclinical studies suggest EGCG inhibits PCa growth, induces intrinsic and extrinsic apoptotic pathways and decreases inflammation by inhibiting NFkB [137]. Furthermore, the antioxidant properties of EGCG are 25 to 100 times more potent than vitamins C and E [131]. In a prospective randomized preprostatectomy trial, men consuming brewed green tea Lin et al. BMC Medicine (2015) 13:3 Page 7 of 15 prior to surgery had increased levels of green tea polyphenols in their prostate tissue [142]. In a small proof-ofprinciple trial with 60 men, daily supplementation of 600 mg green tea catechin extract reduced PCa incidence by 90% (3% versus 30% in the placebo group) [143]. Another small trial also showed that EGCG supplement resulted in a significant reduction in PSA, hepatocyte growth factor and vascular endothelial growth factor in men with PCa [144]. These studies suggest green tea polyphenols may lower PCa incidence and reduce PCa progression but more research is needed to confirm and clarify its mechanism [137,143,145].

Resveratrol

While most in vitro studies suggest resveratrol inhibits PCa growth [146-148], resveratrol suppresses tumor growth in some [137] but not all animal models [149], possibly due to limited bioavailability [150,151]. To date, there are no clinical trials investigating the preventive or therapeutic effects of resveratrol on PCa.

Zyflamend

Zyflamend is an anti-inflammatory mixture of herbs that has been shown to reduce PCa progression by lowering the expression of markers including pAKT, PSA, histone deacetylases and androgen receptor in animal models and PCa cell line [152-154]. Despite its anti-cancer potential [155], very few studies have been conducted in humans [156,157]. In an open-label Phase I trial of 23 patients with high-grade prostatic intraepithelial neoplasia, Zyflamend alone or in conjunction with other dietary supplements for 18 months reduced the risk for developing PCa [156]. More RCTs in humans are needed to confirm the efficacy and clinical application of this herbal supplement.

Other Whole Foods Fruits & Vegetables

Fruits and vegetables are rich sources of vitamins, minerals and phytochemicals. Several epidemiologic studies found inverse relationships between total fruit and vegetable intake [158], and cruciferous vegetable intake and PCa risk [159,160]. Allium vegetables, such as garlic, leeks, chives, and shallots, contain multiple sulfurous phytochemicals that were suggested to enhance the immune system, inhibit cell growth, modulate expression of androgen-responsive genes and induce apoptosis [161]. Although the number of published studies is limited, both preclinical and epidemiologic data suggest allium vegetable intake may be protective against PCa, particularly localized disease [162]. A randomized trial with 199 men also found that a blend supplement of pomegranate, green tea, broccoli and turmeric significantly reduced the rate of rise in PSA in men with PCa [163].

Tomatoes & Tomato Products

A number of studies have examined the association between tomatoes and tomato products with PCa but the findings are inconclusive. The antioxidant lycopene, which is rich in tomatoes, has also been studied specifically for its impact on PCa. In vitro, lycopene halts the cell cycle in several PCa cell lines and decreases IGF-1 signaling by inducing IGF-1 binding proteins [131]. While some animal studies found lycopene specifically slows PCa growth [164] or reduces PCa epithelial cells at stages of initiation, promotion and progression [165], two studies found conflicting findings between tomato paste and lycopene [166,167]. Prospective human studies found higher lycopene consumption [168,169] or higher serum levels were associated with lower PCa risk [170], but others have not [171,172]. Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PCa at six-month follow-up biopsy (P = 0.003) [173]. Two short-term preprostatectomy trials using tomato sauce or lycopene supplementation demonstrated lycopene uptake in prostate tissue and antioxidant and potential anticancer effects [174,175]. While several clinical trials suggested an inverse relationship between lycopene supplementation, PSA levels and decreases in cancerrelated symptoms [171,176], no large-scale randomized trials have tested the role of lycopene or tomato products on PCa prevention or treatment.

Coffee

Coffee contains caffeine and several unidentified phenolic compounds that may serve as antioxidants. Epidemiological studies suggest an inverse relationship between coffee consumption and PCa risk, mainly for advanced or lethal stage disease, and the findings were independent of caffeine content [177,178]. Although several epidemiological studies [179-182] found no association between coffee consumption and PCa risk, a recent meta-analysis of prospective studies concluded that coffee consumption may reduce PCa risk [183]. The potential mechanism(s) and pathway(s) involved are unknown but may include antioxidant, anti-inflammatory effects, glucose and insulin metabolism, and potential impact on IGF-I and circulating sex hormones.

Dietary Patterns

Even though many single nutrients or food factors have been examined for their impact or association with PCa risk or progression, the results have largely been inconclusive. A potential reason for the inconsistency is the fact that the impact of single nutrient or food factor may be too small to be detected. In addition, nutrients naturally existing in foods often are highly correlated and may interact with each other and, thus, affect the impact on PCa. Thus, dietary pattern analysis has received an increasing Lin et al. BMC Medicine (2015) 13:3 Page 8 of 15 interest but research has been limited and the existing results have been inconclusive. In a cohort of 293,464 men, a high dietary quality, as indicated by the Healthy Eating Index (HEI) score, was associated with a lower risk of total PCa risk [70]. The Mediterranean diet, which is high in vegetables, olive oil, complex carbohydrates, lean meats and antioxidants, is consistently recommended to patients for prevention of cardiovascular disease and obesity [184], and may show promise in PCa prevention [185]. Fish and omega-3 fatty acid consumption in the Mediterranean pattern were significantly and inversely associated with fatal PCa risk. In addition, adherence to the Mediterranean diet after diagnosis of non-metastatic PCa was associated with lower overall mortality [186]. Whereas, a Western pattern with high intakes of red meats, processed meats, fried fish, chips, high-fat milk and white bread, was associated with a higher risk for PCa [187].

Furthermore, Asian countries with high consumption of omega-3 PUFAs, soy and green tea-based phytochemicals, have lower PCa incidences versus countries consuming a �Western-style� diet [188]. However, not all studies [189-191] supported an association between certain dietary pattern and risk of PCa. It is possible that the methodology used in identifying dietary patterns may not have captured all the dietary factors associated with PCa risk. Alternatively, each dietary pattern may contain both beneficial and harmful components resulting in an overall null association. More research is needed to continue searching for dietary patterns that combine most of the beneficial nutrients/food factors for PCa and limit most of the negative nutrients/ food factors.

Future Direction For Clinical Trials

Based on the multitude of epidemiologic, preclinical and clinical trials described in this review, dietary interventions for the prevention and treatment of PCa hold great promise. In addition, several dietary factors and vitamins/supplements may be associated with PCa risk and/ or progression of disease. Prospective randomized trials are clearly indicated to identify specific nutrients or combination therapies for the prevention and treatment of PCa.

Recently, active surveillance (AS) has emerged as a viable option for men with lower risk PCa. Men on AS are motivated to adhere to diet and lifestyle modifications [192], making this subset a good target for dietary intervention and quality of life trials [193]. PCa survivors who are more active and report �healthy� eating habits (that is, consuming low-fat, low-refined carbohydrate diets rich in fruits and vegetables) have better overall quality of life versus their inactive, unhealthy counterparts [194]. Thus, more randomized trials are warranted to determine the overall long-term effects of dietary intervention in this population. Specifically, key questions to address in future trials are: 1) Can dietary interventions delay the need for treatment in men on AS; 2) Can dietary interventions prevent recurrence for men after treatment; 3) Can dietary interventions delay progression among men with recurrent disease and, thus, delay the need for hormonal therapy; 4) Can dietary interventions reduce the side effects of PCa treatments including hormonal therapy and newer targeted therapies; and 5) Is there any role for dietary interventions alone or combined with targeted therapies in men on hormonal therapy to prevent castrate-resistance or after the emergence of castrate resistance disease? Because increasing evidence shows that metabolic abnormalities increase risk for PCa, lifestyle intervention that improves metabolic profile is a win-win option for PCa prevention and treatment [195,196].

Conclusions: Prostate Cancer

Future research is required to determine the ideal diet for PCa prevention or treatment. However, several dietary factors and some dietary patterns hold promise in reducing PCa risk or progression and are consistent with current dietary guidelines for Americans [197]. For counseling patients on diet for primary and secondary PCa prevention, many believe �heart healthy equals prostate healthy.� Thus, given the current inconclusive results, the best dietary advice for PCa prevention or management seems to include: increasing fruits and vegetables, replacing refined carbohydrates with whole grains, reducing total and saturated fat, reducing overcooked meats and consuming a moderate amount of calories or reducing carbohydrates with a primary goal of obtaining and maintaining a healthy body weight.

Competing interests The authors declare that they have no competing interests.

Authors� contributions P-HL and SF conducted the review, P-HL drafted the manuscript and SF and WA edited and provided critical input. All authors read and approved the final manuscript.

Acknowledgements Funding was provided by grants 1K24CA160653 (Freedland), NIH P50CA92131 (W. Aronson). This manuscript is the result of work supported with resources and the use of facilities at the Veterans Administration Medical Center, West Los Angeles (W. Aronson).

Author details 1 Department of Medicine, Division of Nephrology, Duke University Medical Center, Box 3487, Durham, NC 27710, USA. 2 Urology Section, Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA. 3 Department of Urology, UCLA School of Medicine, Los Angeles, CA, USA. 4 Urology Section, Department of Surgery, Durham Veterans Affairs Medical Center, Division of Urology, Durham, NC, USA. 5 Duke Prostate Center, Departments of Surgery and Pathology, Duke University Medical Center, Durham, NC, USA.

 

blank
References:

1. Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, Bray F:
International variation in prostate cancer incidence and mortality rates.
Eur Urol 2012, 61:1079�1092.
2. Masko EM, Allott EH, Freedland SJ: The relationship between nutrition and
prostate cancer: is more always better? Eur Urol 2013, 63:810�820.
3. Mavropoulos JC, Isaacs WB, Pizzo SV, Freedland SJ: Is there a role for a
low-carbohydrate ketogenic diet in the management of prostate cancer?
Urology 2006, 68:15�18.
4. Freedland SJ, Mavropoulos J, Wang A, Darshan M, Demark-Wahnefried W,
Aronson WJ, Cohen P, Hwang D, Peterson B, Fields T, Pizzo SV, Isaacs WB:
Carbohydrate restriction, prostate cancer growth, and the insulin-like
growth factor axis. Prostate 2008, 68:11�19.
5. Mavropoulos JC: Buschemeyer WC 3rd, Tewari AK, Rokhfeld D, Pollak M,
Zhao Y, Febbo PG, Cohen P, Hwang D, Devi G, Demark-Wahnefried W,
Westman EC, Peterson BL, Pizzo SV, Freedland SJ: The effects of varying
dietary carbohydrate and fat content on survival in a murine LNCaP
prostate cancer xenograft model. Cancer Prev Res (Phila Pa) 2009,
2:557�565.
6. Masko EM, Thomas JA 2nd, Antonelli JA, Lloyd JC, Phillips TE, Poulton SH,
Dewhirst MW, Pizzo SV, Freedland SJ: Low-carbohydrate diets and
prostate cancer: how low is �low enough�? Cancer Prev Res (Phila) 2010,
3:1124�1131.
7. Drake I, Sonestedt E, Gullberg B, Ahlgren G, Bjartell A, Wallstrom P, Wirf�lt E:
Dietary intakes of carbohydrates in relation to prostate cancer risk: a
prospective study in the Malmo Diet and Cancer cohort. Am J Clin Nutr
2012, 96:1409�1418.
8. Zhang J, Shen C, Wang L, Ma Q, Xia P, Qi M, Yang M, Han B: Metformin
inhibits epithelial-mesenchymal transition in prostate cancer cells:
Involvement of the tumor suppressor miR30a and its target gene SOX4.
Biochem Biophys Res Commun 2014, 452:746�752.
9. Lee SY, Song CH, Xie YB, Jung C, Choi HS, Lee K: SMILE upregulated by
metformin inhibits the function of androgen receptor in prostate cancer
cells. Cancer Lett 2014, 354:390�397.
10. Demir U, Koehler A, Schneider R, Schweiger S, Klocker H: Metformin antitumor
effect via disruption of the MID1 translational regulator complex
and AR downregulation in prostate cancer cells. BMC Cancer 2014, 14:52.
11. Margel D: Metformin to prevent prostate cancer: a call to unite. Eur Urol
2014. doi:10.1016/j.eururo.2014.05.012. [Epub ahead of time]
12. Margel D, Urbach DR, Lipscombe LL, Bell CM, Kulkarni G, Austin PC, Fleshner
N: Metformin use and all-cause and prostate cancer-specific mortality
among men with diabetes. J Clin Oncol 2013, 31:3069�3075.
13. Tseng CH: Metformin significantly reduces incident prostate cancer risk
in Taiwanese men with type 2 diabetes mellitus. Eur J Cancer 2014,
50:2831�2837.
14. Joshua AM, Zannella VE, Downes MR, Bowes B, Hersey K, Koritzinsky M,
Schwab M, Hofmann U, Evans A, van der Kwast T, Trachtenberg J, Finelli A,
Fleshner N, Sweet J, Pollak M: A pilot �window of opportunity�
neoadjuvant study of metformin in localised prostate cancer. Prostate
Cancer Prostatic Dis 2014, 17:252�258.
15. Rothermundt C, Hayoz S, Templeton AJ, Winterhalder R, Strebel RT, Bartschi
D, Pollak M, Lui L, Endt K, Schiess R, R�schoff JH, Cathomas R, Gillessen S:
Metformin in Chemotherapy-naive Castration-resistant Prostate Cancer:
A Multicenter Phase 2 Trial (SAKK 08/09). Eur Urol 2014, 66:468�474.
16. Allott EH, Abern MR, Gerber L, Keto CJ, Aronson WJ, Terris MK, Kane CJ,
Amling CL, Cooperberg MR, Moorman PG, Freedland SJ: Metformin does
not affect risk of biochemical recurrence following radical
prostatectomy: results from the SEARCH database. Prostate Cancer
Prostatic Dis 2013, 16:391�397.
17. Rieken M, Kluth LA, Xylinas E, Fajkovic H, Becker A, Karakiewicz PI, Herman
M, Lotan Y, Seitz C, Schramek P, Remzi M, Loidl W, Pummer K, Lee RK,
Faison T, Scherr DS, Kautzky-Willer A, Bachmann A, Tewari A, Shariat SF:
Association of diabetes mellitus and metformin use with biochemical
recurrence in patients treated with radical prostatectomy for prostate
cancer. World J Urol 2014, 32:999�1005.
18. Margel D, Urbach D, Lipscombe LL, Bell CM, Kulkarni G, Austin PC, Fleshner
N: Association between metformin use and risk of prostate cancer and
its grade. J Natl Cancer Inst 2013, 105:1123�1131.
19. Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A:
Metformin therapy and risk of cancer in patients with type 2 diabetes:
systematic review. PLoS One 2013, 8:e71583.
20. Kaushik D, Karnes RJ, Eisenberg MS, Rangel LJ, Carlson RE, Bergstralh EJ:
Effect of metformin on prostate cancer outcomes after radical
prostatectomy. Urol Oncol 2014, 32:43 e41�47.
21. Bensimon L, Yin H, Suissa S, Pollak MN, Azoulay L: The use of metformin in
patients with prostate cancer and the risk of death. Cancer Epidemiol
Biomarkers Prev 2014, 23:2111�2118.
22. Tsilidis KK, Capothanassi D, Allen NE, Rizos EC, Lopez DS, van Veldhoven K,
Sacerdote C, Ashby D, Vineis P, Tzoulaki I, Ioannidis JP: Metformin does not
affect cancer risk: a cohort study in the U.K. Clinical Practice Research
Datalink analyzed like an intention-to-treat trial. Diabetes Care 2014,
37:2522�2532.
23. Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F,
Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J, Passarino G, Kennedy BK,
Wei M, Cohen P, Crimmins EM, Longo VD: Low protein intake is associated
with a major reduction in IGF-1, cancer, and overall mortality in the 65
and younger but not older population. Cell Metab 2014, 19:407�417.
24. Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC,
Warren A, Huang X, Pichaud N, Melvin RG, Gokarn R, Khalil M, Turner N,
Cooney GJ, Sinclair DA, Raubenheimer D, Le Couteur DG, Simpson SJ: The
ratio of macronutrients, not caloric intake, dictates cardiometabolic
health, aging, and longevity in ad libitum-fed mice. Cell Metab 2014,
19:418�430.
25. Richman EL, Stampfer MJ, Paciorek A, Broering JM, Carroll PR, Chan JM:
Intakes of meat, fish, poultry, and eggs and risk of prostate cancer
progression. Am J Clin Nutr 2010, 91:712�721.
26. Joshi AD, John EM, Koo J, Ingles SA, Stern MC: Fish intake, cooking
practices, and risk of prostate cancer: results from a multi-ethnic
case�control study. Cancer Causes Control 2012, 23:405�420.
27. Joshi AD, Corral R, Catsburg C, Lewinger JP, Koo J, John EM, Ingles SA,
Stern MC: Red meat and poultry, cooking practices, genetic susceptibility
and risk of prostate cancer: results from a multiethnic case�control
study. Carcinogenesis 2012, 33:2108�2118.
28. Catsburg C, Joshi AD, Corral R, Lewinger JP, Koo J, John EM, Ingles SA,
Stern MC: Polymorphisms in carcinogen metabolism enzymes, fish
intake, and risk of prostate cancer. Carcinogenesis 2012, 33:1352�1359.
29. Pettersson A, Kasperzyk JL, Kenfield SA, Richman EL, Chan JM, Willett WC,
Stampfer MJ, Mucci LA, Giovannucci EL: Milk and dairy consumption
among men with prostate cancer and risk of metastases and prostate
cancer death. Cancer Epidemiol Biomarkers Prev 2012, 21:428�436.
30. Deneo-Pellegrini H, Ronco AL, De Stefani E, Boffetta P, Correa P,
Mendilaharsu M, Acosta G: Food groups and risk of prostate cancer: a
case�control study in Uruguay. Cancer Causes Control 2012, 23:1031�1038.
31. Park SY, Murphy SP, Wilkens LR, Stram DO, Henderson BE, Kolonel LN:
Calcium, vitamin D, and dairy product intake and prostate cancer risk:
the Multiethnic Cohort Study. Am J Epidemiol 2007, 166:1259�1269.
32. Song Y, Chavarro JE, Cao Y, Qiu W, Mucci L, Sesso HD, Stampfer MJ,
Giovannucci E, Pollak M, Liu S, Ma J: Whole milk intake is associated with
prostate cancer-specific mortality among U.S. male physicians. J Nutr Feb
2013, 143:189�196.
33. Young NJ, Metcalfe C, Gunnell D, Rowlands MA, Lane JA, Gilbert R, Avery
KN, Davis M, Neal DE, Hamdy FC, Donovan J, Martin RM, Holly JM: A crosssectional
analysis of the association between diet and insulin-like growth
factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-2, and IGFBP-3 in men in
the United Kingdom. Cancer Causes Control 2012, 23:907�917.
34. Christensen MJ, Quiner TE, Nakken HL, Lephart ED, Eggett DL, Urie PM:
Combination effects of dietary soy and methylselenocysteine in a mouse
model of prostate cancer. Prostate 2013, 73:986�995.
35. Bosland MC, Kato I, Zeleniuch-Jacquotte A, Schmoll J, Enk Rueter E,
Melamed J, Kong MX, Macias V, Kajdacsy-Balla A, Lumey LH, Xie H, Gao W,
Walden P, Lepor H, Taneja SS, Randolph C, Schlicht MJ, Meserve-Watanabe
H, Deaton RJ, Davies JA: Effect of soy protein isolate supplementation on
biochemical recurrence of prostate cancer after radical prostatectomy: a
randomized trial. JAMA 2013, 310:170�178.
36. Chiyomaru T, Yamamura S, Fukuhara S, Yoshino H, Kinoshita T, Majid S, Saini
S, Chang I, Tanaka Y, Enokida H, Seki N, Nakagawa M, Dahiya R: Genistein
inhibits prostate cancer cell growth by targeting miR-34a and oncogenic
HOTAIR. PLoS One 2013, 8:e70372.
37. Zhang S, Wang Y, Chen Z, Kim S, Iqbal S, Chi A, Ritenour C, Wang YA, Kucuk
O, Wu D: Genistein enhances the efficacy of cabazitaxel chemotherapy
in metastatic castration-resistant prostate cancer cells. Prostate 2013,
73:1681�1689.38. van Die MD, Bone KM, Williams SG, Pirotta MV: Soy and soy isoflavones in
prostate cancer: a systematic review and meta-analysis of randomized
controlled trials. BJU Int 2014, 113:E119�E130.
39. Hamilton-Reeves JM, Banerjee S, Banerjee SK, Holzbeierlein JM, Thrasher JB,
Kambhampati S, Keighley J, Van Veldhuizen P: Short-term soy isoflavone
intervention in patients with localized prostate cancer: a randomized,
double-blind, placebo-controlled trial. PLoS One 2013, 8:e68331.
40. Pavese JM, Krishna SN, Bergan RC: Genistein inhibits human prostate
cancer cell detachment, invasion, and metastasis. Am J Clin Nutr 2014,
100:431S�436S.
41. Gonzalez-Menendez P, Hevia D, Rodriguez-Garcia A, Mayo JC, Sainz RM:
Regulation of GLUT transporters by flavonoids in androgen-sensitive and
-insensitive prostate cancer cells. Endocrinology 2014, 155:3238�3250.
42. Hirata H, Hinoda Y, Shahryari V, Deng G, Tanaka Y, Tabatabai ZL, Dahiya R:
Genistein downregulates onco-miR-1260b and upregulates sFRP1 and
Smad4 via demethylation and histone modification in prostate cancer
cells. Br J Cancer 2014, 110:1645�1654.
43. Handayani R, Rice L, Cui Y, Medrano TA, Samedi VG, Baker HV, Szabo NJ,
Shiverick KT: Soy isoflavones alter expression of genes associated with
cancer progression, including interleukin-8, in androgen-independent
PC-3 human prostate cancer cells. J Nutr 2006, 136:75�82.
44. Travis RC, Allen NE, Appleby PN, Price A, Kaaks R, Chang-Claude J, Boeing H,
Aleksandrova K, Tj�nneland A, Johnsen NF, Overvad K, Ram�n Quir�s J,
Gonz�lez CA, Molina-Montes E, S�nchez MJ, Larra�aga N, Casta�o JM,
Ardanaz E, Khaw KT, Wareham N, Trichopoulou A, Karapetyan T, Rafnsson
SB, Palli D, Krogh V, Tumino R, Vineis P, Bueno-de-Mesquita HB, Stattin P,
Johansson M, et al: Prediagnostic concentrations of plasma genistein and
prostate cancer risk in 1,605 men with prostate cancer and 1,697
matched control participants in EPIC. Cancer Causes Control 2012,
23:1163�1171.
45. Jackson MD, McFarlane-Anderson ND, Simon GA, Bennett FI, Walker SP:
Urinary phytoestrogens and risk of prostate cancer in Jamaican men.
Cancer Causes Control 2010, 21:2249�2257.
46. Lazarevic B, Hammarstr�m C, Yang J, Ramberg H, Diep LM, Karlsen SJ,
Kucuk O, Saatcioglu F, Task�n KA, Svindland A: The effects of short-term
genistein intervention on prostate biomarker expression in patients with
localised prostate cancer before radical prostatectomy. Br J Nutr 2012,
108:2138�2147.
47. Epstein MM, Kasperzyk JL, Mucci LA, Giovannucci E, Price A, Wolk A,
H�kansson N, Fall K, Andersson SO, Andr�n O: Dietary fatty acid intake and
prostate cancer survival in Orebro County, Sweden. Am J Epidemiol 2012,
176:240�252.
48. Kobayashi N, Barnard RJ, Said J, Hong-Gonzalez J, Corman DM, Ku M,
Doan NB, Gui D, Elashoff D, Cohen P, Aronson WJ: Effect of low-fat diet on
development of prostate cancer and Akt phosphorylation in the Hi-Myc
transgenic mouse model. Cancer Res 2008, 68:3066�3073.
49. Ngo TH, Barnard RJ, Cohen P, Freedland S, Tran C, deGregorio F, Elshimali
YI, Heber D, Aronson WJ: Effect of isocaloric low-fat diet on human
LAPC-4 prostate cancer xenografts in severe combined immunodeficient
mice and the insulin-like growth factor axis. Clin Cancer Res 2003,
9:2734�2743.
50. Huang M, Narita S, Numakura K, Tsuruta H, Saito M, Inoue T, Horikawa Y,
Tsuchiya N, Habuchi T: A high-fat diet enhances proliferation of
prostate cancer cells and activates MCP-1/CCR2 signaling. Prostate 2012,
72:1779�1788.
51. Chang SN, Han J, Abdelkader TS, Kim TH, Lee JM, Song J, Kim KS, Park JH,
Park JH: High animal fat intake enhances prostate cancer progression
and reduces glutathione peroxidase 3 expression in early stages of
TRAMP mice. Prostate 2014, 74:1266�1277.
52. Bidoli E, Talamini R, Bosetti C, Negri E, Maruzzi D, Montella M, Franceschi S,
La Vecchia C: Macronutrients, fatty acids, cholesterol and prostate cancer
risk. Ann Oncol 2005, 16:152�157.
53. Park SY, Murphy SP, Wilkens LR, Henderson BE, Kolonel LN: Fat and meat
intake and prostate cancer risk: the multiethnic cohort study. Int J Cancer
2007, 121:1339�1345.
54. Wallstrom P, Bjartell A, Gullberg B, Olsson H, Wirfalt E: A prospective study
on dietary fat and incidence of prostate cancer (Malmo, Sweden).
Cancer Causes Control 2007, 18:1107�1121.
55. Crowe FL, Key TJ, Appleby PN, Travis RC, Overvad K, Jakobsen MU,
Johnsen NF, Tj�nneland A, Linseisen J, Rohrmann S, Boeing H, Pischon T,
Trichopoulou A, Lagiou P, Trichopoulos D, Sacerdote C, Palli D, Tumino R,
Krogh V, Bueno-de-Mesquita HB, Kiemeney LA, Chirlaque MD, Ardanaz E,
S�nchez MJ, Larra�aga N, Gonz�lez CA, Quir�s JR, Manjer J, Wirf�lt E, Stattin
P, et al: Dietary fat intake and risk of prostate cancer in the European
Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 2008,
87:1405�1413.
56. Ohwaki K, Endo F, Kachi Y, Hattori K, Muraishi O, Nishikitani M, Yano E:
Relationship between dietary factors and prostate-specific antigen in
healthy men. Urol Int 2012, 89:270�274.
57. Bassett JK, Severi G, Hodge AM, MacInnis RJ, Gibson RA, Hopper JL,
English DR, Giles GG: Plasma phospholipid fatty acids, dietary fatty acids
and prostate cancer risk. Int J Cancer 2013, 133:1882�1891.
58. Richman EL, Kenfield SA, Chavarro JE, Stampfer MJ, Giovannucci EL, Willett
WC, Chan JM: Fat intake after diagnosis and risk of lethal prostate cancer
and all-cause mortality. JAMA Intern Med 2013, 173:1318�1326.
59. Williams CD, Whitley BM, Hoyo C, Grant DJ, Iraggi JD, Newman KA, Gerber
L, Taylor LA, McKeever MG, Freedland SJ: A high ratio of dietary n-6/n-3
polyunsaturated fatty acids is associated with increased risk of prostate
cancer. Nutr Res 2011, 31:1�8.
60. Chua ME, Sio MC, Sorongon MC, Dy JS: Relationship of dietary intake of
omega-3 and omega-6 fatty acids with risk of prostate cancer
development: a meta-analysis of prospective studies and review of
literature. Prostate Cancer 2012, 2012:826254.
61. Berquin IM, Edwards IJ, Kridel SJ, Chen YQ: Polyunsaturated fatty acid
metabolism in prostate cancer. Cancer Metastasis Rev 2011, 30:295�309.
62. Aronson WJ, Kobayashi N, Barnard RJ, Henning S, Huang M, Jardack PM, Liu
B, Gray A, Wan J, Konijeti R, Freedland SJ, Castor B, Heber D, Elashoff D, Said
J, Cohen P, Galet C: Phase II prospective randomized trial of a low-fat diet
with fish oil supplementation in men undergoing radical prostatectomy.
Cancer Prev Res (Phila) 2011, 4:2062�2071.
63. Hughes-Fulford M, Li CF, Boonyaratanakornkit J, Sayyah S: Arachidonic acid
activates phosphatidylinositol 3-kinase signaling and induces gene
expression in prostate cancer. Cancer Res 2006, 66:1427�1433.
64. Moreel X, Allaire J, Leger C, Caron A, Labonte ME, Lamarche B, Julien P,
Desmeules P, T�tu B, Fradet V: Prostatic and dietary omega-3 fatty acids
and prostate cancer progression during active surveillance. Cancer Prev
Res (Phila) 2014, 7:766�776.
65. Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D,
Steward W, Dennison A: The effect of omega-3 FAs on tumour angiogenesis
and their therapeutic potential. Eur J Cancer 2009, 45:2077�2086.
66. Gu Z, Suburu J, Chen H, Chen YQ: Mechanisms of omega-3 polyunsaturated
fatty acids in prostate cancer prevention. Biomed Res Int 2013, 2013:824563.
67. Lloyd JC, Masko EM, Wu C, Keenan MM, Pilla DM, Aronson WJ, Chi JT,
Freedland SJ: Fish oil slows prostate cancer xenograft growth relative to
other dietary fats and is associated with decreased mitochondrial and
insulin pathway gene expression. Prostate Cancer Prostatic Dis 2013,
16:285�291.
68. Williams CM, Burdge G: Long-chain n-3 PUFA: plant v. marine sources.
Proc Nutr Soc 2006, 65:42�50.
69. Galet C, Gollapudi K, Stepanian S, Byrd JB, Henning SM, Grogan T, Elashoff
D, Heber D, Said J, Cohen P, Aronson WJ: Effect of a low-fat fish oil diet
on proinflammatory eicosanoids and cell-cycle progression score in
men undergoing radical prostatectomy. Cancer Prev Res (Phila) 2014,
7:97�104.
70. Bosire C, Stampfer MJ, Subar AF, Park Y, Kirkpatrick SI, Chiuve SE, Hollenbeck
AR, Reedy J: Index-based dietary patterns and the risk of prostate cancer
in the NIH-AARP diet and health study. Am J Epidemiol 2013, 177:504�513.
71. Aronson WJ, Barnard RJ, Freedland SJ, Henning S, Elashoff D, Jardack PM,
Cohen P, Heber D, Kobayashi N: Growth inhibitory effect of low fat diet
on prostate cancer cells: results of a prospective, randomized dietary
intervention trial in men with prostate cancer. J Urol 2010, 183:345�350.
72. Brouwer IA, Geleijnse JM, Klaasen VM, Smit LA, Giltay EJ, de Goede J,
Heijboer AC, Kromhout D, Katan MB: Effect of alpha linolenic acid
supplementation on serum prostate specific antigen (PSA): results from
the alpha omega trial. PLoS One 2013, 8:e81519.
73. Chua ME, Sio MC, Sorongon MC, Morales ML Jr: The relevance of serum
levels of long chain omega-3 polyunsaturated fatty acids and prostate
cancer risk: A meta-analysis. Can Urol Assoc J 2013, 7:E333�E343.
74. Yue S, Li J, Lee SY, Lee HJ, Shao T, Song B, Cheng L, Masterson TA, Liu X,
Ratliff TL, Cheng JX: Cholesteryl ester accumulation induced by PTEN loss
and PI3K/AKT activation underlies human prostate cancer
aggressiveness. Cell Metab 2014, 19:393�406.

75. Sun Y, Sukumaran P, Varma A, Derry S, Sahmoun AE, Singh BB: Cholesterolinduced
activation of TRPM7 regulates cell proliferation, migration,
and viability of human prostate cells. Biochim Biophys Acta 1843,
2014:1839�1850.
76. Murai T: Cholesterol lowering: role in cancer prevention and treatment.
Biol Chem 2014. doi:10.1515/hsz-2014-0194. [Epub ahead of time]
77. Zhuang L, Kim J, Adam RM, Solomon KR, Freeman MR: Cholesterol
targeting alters lipid raft composition and cell survival in prostate cancer
cells and xenografts. J Clin Invest 2005, 115:959�968.
78. Mostaghel EA, Solomon KR, Pelton K, Freeman MR, Montgomery RB:
Impact of circulating cholesterol levels on growth and intratumoral
androgen concentration of prostate tumors. PLoS One 2012,
7:e30062.
79. Morote J, Celma A, Planas J, Placer J, de Torres I, Olivan M, Carles J,
Revent�s J, Doll A: Role of serum cholesterol and statin use in the risk of
prostate cancer detection and tumor aggressiveness. Int J Mol Sci 2014,
15:13615�13623.
80. Allott EH, Howard LE, Cooperberg MR, Kane CJ, Aronson WJ, Terris MK,
Amling CL, Freedland SJ: Postoperative statin use and risk of biochemical
recurrence following radical prostatectomy: results from the Shared
Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int 2014,
114:661�666.
81. Jespersen CG, Norgaard M, Friis S, Skriver C, Borre M: Statin use and risk of
prostate cancer: A Danish population-based case�control study,
1997�2010. Cancer Epidemiol 2014, 38:42�47.
82. Meyers CD, Kashyap ML: Pharmacologic elevation of high-density
lipoproteins: recent insights on mechanism of action and atherosclerosis
protection. Curr Opin Cardiol 2004, 19:366�373.
83. Xia P, Vadas MA, Rye KA, Barter PJ, Gamble JR: High density lipoproteins
(HDL) interrupt the sphingosine kinase signaling pathway. A possible
mechanism for protection against atherosclerosis by HDL. J Biol Chem
1999, 274:33143�33147.
84. Kotani K, Sekine Y, Ishikawa S, Ikpot IZ, Suzuki K, Remaley AT: High-density
lipoprotein and prostate cancer: an overview. J Epidemiol 2013,
23:313�319.
85. Soni MG, Thurmond TS, Miller ER 3rd, Spriggs T, Bendich A, Omaye ST:
Safety of vitamins and minerals: controversies and perspective. Toxicol
Sci 2010, 118:348�355.
86. Neuhouser ML, Barnett MJ, Kristal AR, Ambrosone CB, King I, Thornquist M,
Goodman G: (n-6) PUFA increase and dairy foods decrease prostate
cancer risk in heavy smokers. J Nutr 2007, 137:1821�1827.
87. Karppi J, Kurl S, Laukkanen JA, Kauhanen J: Serum beta-carotene in relation
to risk of prostate cancer: the Kuopio Ischaemic Heart Disease Risk
Factor study. Nutr Cancer 2012, 64:361�367.
88. Margalit DN, Kasperzyk JL, Martin NE, Sesso HD, Gaziano JM, Ma J, Stampfer
MJ, Mucci LA: Beta-carotene antioxidant use during radiation therapy
and prostate cancer outcome in the Physicians� Health Study. Int J Radiat
Oncol Biol Phys 2012, 83:28�32.
89. Roswall N, Larsen SB, Friis S, Outzen M, Olsen A, Christensen J, Dragsted LO,
Tj�nneland A: Micronutrient intake and risk of prostate cancer in a
cohort of middle-aged, Danish men. Cancer Causes Control 2013,
24:1129�1135.
90. Gilbert R, Metcalfe C, Fraser WD, Donovan J, Hamdy F, Neal DE, Lane JA,
Martin RM: Associations of circulating retinol, vitamin E, and 1,25-
dihydroxyvitamin D with prostate cancer diagnosis, stage, and grade.
Cancer Causes Control 2012, 23:1865�1873.
91. Bistulfi G, Foster BA, Karasik E, Gillard B, Miecznikowski J, Dhiman VK,
Smiraglia DJ: Dietary folate deficiency blocks prostate cancer progression
in the TRAMP model. Cancer Prev Res (Phila) 2011, 4:1825�1834.
92. Collin SM: Folate and B12 in prostate cancer. Adv Clin Chem 2013,
60:1�63.
93. Tio M, Andrici J, Cox MR, Eslick GD: Folate intake and the risk of prostate
cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic
Dis 2014, 17:213�219.
94. Vollset SE, Clarke R, Lewington S, Ebbing M, Halsey J, Lonn E, Armitage J,
Manson JE, Hankey GJ, Spence JD, Galan P, B�naa KH, Jamison R, Gaziano
JM, Guarino P, Baron JA, Logan RF, Giovannucci EL, den Heijer M, Ueland
PM, Bennett D, Collins R, Peto R, B-Vitamin Treatment Trialists’ Collaboration:
Effects of folic acid supplementation on overall and site-specific cancer
incidence during the randomised trials: meta-analyses of data on 50,000
individuals. Lancet 2013, 381:1029�1036.
95. Verhage BA, Cremers P, Schouten LJ, Goldbohm RA, van den Brandt PA:
Dietary folate and folate vitamers and the risk of prostate cancer
in The Netherlands Cohort Study. Cancer Causes Control 2012,
23:2003�2011.
96. Tavani A, Malerba S, Pelucchi C, Dal Maso L, Zucchetto A, Serraino D, Levi F,
Montella M, Franceschi S, Zambon A, La Vecchia C: Dietary folates and
cancer risk in a network of case�control studies. Ann Oncol 2012,
23:2737�2742.
97. Moreira DM, Banez LL, Presti JC Jr, Aronson WJ, Terris MK, Kane CJ, Amling
CL, Freedland SJ: High serum folate is associated with reduced
biochemical recurrence after radical prostatectomy: results from the
SEARCH Database. Int Braz J Urol 2013, 39:312�318. discussion 319.
98. Han YY, Song JY, Talbott EO: Serum folate and prostate-specific antigen in
the United States. Cancer Causes Control 2013, 24:1595�1604.
99. Rycyna KJ, Bacich DJ, O’Keefe DS: Opposing roles of folate in prostate
cancer. Urology 2013, 82:1197�1203.
100. Gilbert R, Martin RM, Beynon R, Harris R, Savovic J, Zuccolo L, Bekkering GE,
Fraser WD, Sterne JA, Metcalfe: Associations of circulating and dietary
vitamin D with prostate cancer risk: a systematic review and dose�
response meta-analysis. Cancer Causes Control 2011, 22:319�340.
101. Schenk JM, Till CA, Tangen CM, Goodman PJ, Song X, Torkko KC, Kristal AR,
Peters U, Neuhouser ML: Serum 25-hydroxyvitamin d concentrations and
risk of prostate cancer: results from the Prostate Cancer Prevention Trial.
Cancer Epidemiol Biomarkers Prev 2014, 23:1484�1493.
102. Schwartz GG: Vitamin D, in blood and risk of prostate cancer: lessons
from the Selenium and Vitamin E Cancer Prevention Trial and the
Prostate Cancer Prevention Trial. Cancer Epidemiol Biomarkers Prev 2014,
23:1447�1449.
103. Giangreco AA, Vaishnav A, Wagner D, Finelli A, Fleshner N, Van der Kwast T,
Vieth R, Nonn L: Tumor suppressor microRNAs, miR-100 and -125b, are
regulated by 1,25-dihydroxyvitamin D in primary prostate cells and in
patient tissue. Cancer Prev Res (Phila) 2013, 6:483�494.
104. Hollis BW, Marshall DT, Savage SJ, Garrett-Mayer E, Kindy MS, Gattoni-Celli S:
Vitamin D3 supplementation, low-risk prostate cancer, and health
disparities. J Steroid Biochem Mol Biol 2013, 136:233�237.
105. Sha J, Pan J, Ping P, Xuan H, Li D, Bo J, Liu D, Huang Y: Synergistic effect
and mechanism of vitamin A and vitamin D on inducing apoptosis of
prostate cancer cells. Mol Biol Rep 2013, 40:2763�2768.
106. Chandler PD, Giovannucci EL, Scott JB, Bennett GG, Ng K, Chan AT, Hollis
BW, Emmons KM, Fuchs CS, Drake BF: Null association between Vitamin D
and PSA levels among black men in a Vitamin D supplementation trial.
Cancer Epidemiol Biomarkers Prev 2014, 23:1944�1947.
107. Skaaby T, Husemoen LL, Thuesen BH, Pisinger C, Jorgensen T, Roswall N,
Larsen SC, Linneberg A: Prospective population-based study of the
association between serum 25-hydroxyvitamin-D levels and the
incidence of specific types of cancer. Cancer Epidemiol Biomarkers Prev
2014, 23:1220�1229.
108. Holt SK, Kolb S, Fu R, Horst R, Feng Z, Stanford JL: Circulating levels of
25-hydroxyvitamin D and prostate cancer prognosis. Cancer Epidemiol
2013, 37:666�670.
109. Wong YY, Hyde Z, McCaul KA, Yeap BB, Golledge J, Hankey GJ, Flicker L:
In older men, lower plasma 25-hydroxyvitamin D is associated with
reduced incidence of prostate, but not colorectal or lung cancer.
PLoS One 2014, 9:e99954.
110. Xu Y, Shao X, Yao Y, Xu L, Chang L, Jiang Z, Lin Z: Positive association
between circulating 25-hydroxyvitamin D levels and prostate cancer risk:
new findings from an updated meta-analysis. J Cancer Res Clin Oncol
2014, 140:1465�1477.
111. Meyer HE, Robsahm TE, Bjorge T, Brustad M, Blomhoff R: Vitamin D, season,
and risk of prostate cancer: a nested case�control study within
Norwegian health studies. Am J Clin Nutr 2013, 97:147�154.
112. Kristal AR, Till C, Song X, Tangen CM, Goodman PJ, Neuhauser ML, Schenk
JM, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL,
Klein EA: Plasma vitamin D and prostate cancer risk: results from the
Selenium and Vitamin E Cancer Prevention Trial. Cancer Epidemiol
Biomarkers Prev 2014, 23:1494�1504.
113. Weinstein SJ, Mondul AM, Kopp W, Rager H, Virtamo J, Albanes D:
Circulating 25-hydroxyvitamin D, vitamin D-binding protein and risk of
prostate cancer. Int J Cancer 2013, 132:2940�2947.
114. Guo Z, Wen J, Kan Q, Huang S, Liu X, Sun N, Li Z: Lack of association
between vitamin D receptor gene FokI and BsmI polymorphisms and�prostate cancer risk: an updated meta-analysis involving 21,756 subjects. Tumour Biol 2013, 34:3189�3200115. Wang L, Sesso HD, Glynn RJ, Christen WG, Bubes V, Manson JE, Buring JE,
Gaziano JM: Vitamin E and C supplementation and risk of cancer in men:
posttrial follow-up in the Physicians� Health Study II randomized trial.
Am J Clin Nutr 2014, 100:915�923.
116. Virtamo J, Taylor PR, Kontto J, Mannisto S, Utriainen M, Weinstein SJ,
Huttunen J, Albanes D: Effects of alpha-tocopherol and beta-carotene
supplementation on cancer incidence and mortality: 18-year
postintervention follow-up of the Alpha-tocopherol, Beta-carotene
Cancer Prevention Study. Int J Cancer 2014, 135:178�185.
117. Basu A, Imrhan V: Vitamin E and prostate cancer: is vitamin E succinate a
superior chemopreventive agent? Nutr Rev 2005, 63:247�251.
118. Lawson KA, Wright ME, Subar A, Mouw T, Hollenbeck A, Schatzkin A,
Leitzmann MF: Multivitamin use and risk of prostate cancer in the
National Institutes of Health-AARP Diet and Health Study. J Natl Cancer
Inst 2007, 99:754�764.
119. Calle EE, Rodriguez C, Jacobs EJ, Almon ML, Chao A, McCullough ML,
Feigelson HS, Thun MJ: The American Cancer Society Cancer Prevention
Study II Nutrition Cohort: rationale, study design, and baseline
characteristics. Cancer 2002, 94:2490�2501.
120. Weinstein SJ, Peters U, Ahn J, Friesen MD, Riboli E, Hayes RB, Albanes D:
Serum alpha-tocopherol and gamma-tocopherol concentrations and
prostate cancer risk in the PLCO Screening Trial: a nested case�control
study. PLoS One 2012, 7:e40204.
121. Cui R, Liu ZQ, Xu Q: Blood alpha-tocopherol, gamma-tocopherol levels
and risk of prostate cancer: a meta-analysis of prospective studies.
PLoS One 2014, 9:e93044.
122. Major JM, Yu K, Weinstein SJ, Berndt SI, Hyland PL, Yeager M, Chanock S,
Albanes D: Genetic variants reflecting higher vitamin e status in men are
associated with reduced risk of prostate cancer. J Nutr May 2014,
144:729�733.
123. Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ,
Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther
PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE,
Meyskens FL Jr, Baker LH: Vitamin E and the risk of prostate cancer: the
Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011,
306:1549�1556.
124. Albanes D, Till C, Klein EA, Goodman PJ, Mondul AM, Weinstein SJ, aylor PR,
Parnes HL, Gaziano JM, Song X, Fleshner NE, Brown PH, Meyskens FL Jr,
Thompson IM: Plasma tocopherols and risk of prostate cancer in the
Selenium and Vitamin E Cancer Prevention Trial (SELECT). Cancer Prev Res
(Phila) 2014, 7:886�895.
125. Kristal AR, Darke AK, Morris JS, Tangen CM, Goodman PJ, Thompson IM,
Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Lippman SM,
Klein EA: Baseline selenium status and effects of selenium and vitamin e
supplementation on prostate cancer risk. J Natl Cancer Inst 2014,
106:djt456.
126. Jamison JM, Gilloteaux J, Taper HS, Summers JL: Evaluation of the in vitro
and in vivo antitumor activities of vitamin C and K-3 combinations
against human prostate cancer. J Nutr 2001, 131:158S�160S.
127. Nimptsch K, Rohrmann S, Kaaks R, Linseisen J: Dietary vitamin K intake
in relation to cancer incidence and mortality: results from the
Heidelberg cohort of the European Prospective Investigation into
Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr 2010,
91:1348�1358.
128. Ma RW, Chapman K: A systematic review of the effect of diet in prostate
cancer prevention and treatment. J Hum Nutr Diet 2009, 22:187�199.
quiz 200�182.
129. Bristow SM, Bolland MJ, MacLennan GS, Avenell A, Grey A, Gamble GD, Reid
IR: Calcium supplements and cancer risk: a meta-analysis of randomised
controlled trials. Br J Nutr 2013, 110:1384�1393.
130. Williams CD, Whitley BM, Hoyo C, Grant DJ, Schwartz GG, Presti JC Jr, Iraggi
JD, Newman KA, Gerber L, Taylor LA, McKeever MG, Freedland SJ: Dietary
calcium and risk for prostate cancer: a case�control study among US
veterans. Prev Chronic Dis 2012, 9:E39.
131. Hori S, Butler E, McLoughlin J: Prostate cancer and diet: food for thought?
BJU Int 2011, 107:1348�1359.
132. Geybels MS, Verhage BA, van Schooten FJ, Goldbohm RA, van den Brandt
PA: Advanced prostate cancer risk in relation to toenail selenium levels.
J Natl Cancer Inst 2013, 105:1394�1401.
133. Singh RP, Agarwal R: Prostate cancer chemoprevention by silibinin: bench
to bedside. Mol Carcinog 2006, 45:436�442.
134. Ting H, Deep G, Agarwal R: Molecular mechanisms of silibinin-mediated
cancer chemoprevention with major emphasis on prostate cancer.
AAPS J 2013, 15:707�716.
135. Ting HJ, Deep G, Jain AK, Cimic A, Sirintrapun J, Romero LM, Cramer SD,
Agarwal C, Agarwal R: Silibinin prevents prostate cancer cell-mediated
differentiation of naive fibroblasts into cancer-associated fibroblast
phenotype by targeting TGF beta2. Mol Carcinog 2014. doi:10.1002/
mc.22135. [Epub ahead of time]
136. Goel A, Aggarwal BB: Curcumin, the golden spice from Indian saffron, is a
chemosensitizer and radiosensitizer for tumors and chemoprotector and
radioprotector for normal organs. Nutr Cancer 2010, 62:919�930.
137. Khan N, Adhami VM, Mukhtar H: Apoptosis by dietary agents for
prevention and treatment of prostate cancer. Endocr Relat Cancer 2010,
17:R39�R52.
138. Heber D: Pomegranate ellagitannins. In Herbal Medicine: Biomolecular and
Clinical Aspects. 2nd edition. Edited by Benzie IF, Wachtel-Galor S. Boca
Raton, FL: CRC Press; 2011.
139. Pantuck AJ, Leppert JT, Zomorodian N, Aronson W, Hong J, Barnard RJ,
Seeram N, Liker H, Wang H, Elashoff R, Heber D, Aviram M, Ignarro L,
Belldegrun A: Phase II study of pomegranate juice for men with rising
prostate-specific antigen following surgery or radiation for prostate
cancer. Clin Cancer Res 2006, 12:4018�4026.
140. Paller CJ, Ye X, Wozniak PJ, Gillespie BK, Sieber PR, Greengold RH, Stockton
BR, Hertzman BL, Efros MD, Roper RP, Liker HR, Carducci MA: A randomized
phase II study of pomegranate extract for men with rising PSA following
initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis
2013, 16:50�55.
141. Freedland SJ, Carducci M, Kroeger N, Partin A, Rao JY, Jin Y, Kerkoutian S,
Wu H, Li Y, Creel P, Mundy K, Gurganus R, Fedor H, King SA, Zhang Y,
Heber D, Pantuck AJ: A double-blind, randomized, neoadjuvant study of
the tissue effects of POMx pills in men with prostate cancer before
radical prostatectomy. Cancer Prev Res (Phila) 2013, 6:1120�1127.
142. Wang P, Aronson WJ, Huang M, Zhang Y, Lee RP, Heber D, Henning SM:
Green tea polyphenols and metabolites in prostatectomy tissue:
implications for cancer prevention. Cancer Prev Res (Phila) 2010,
3:985�993.
143. Kurahashi N, Sasazuki S, Iwasaki M, Inoue M, Tsugane S: Green tea
consumption and prostate cancer risk in Japanese men: a prospective
study. Am J Epidemiol 2008, 167:71�77.
144. McLarty J, Bigelow RL, Smith M, Elmajian D, Ankem M, Cardelli JA: Tea
polyphenols decrease serum levels of prostate-specific antigen,
hepatocyte growth factor, and vascular endothelial growth factor in
prostate cancer patients and inhibit production of hepatocyte growth
factor and vascular endothelial growth factor in vitro. Cancer Prev Res
(Phila) 2009, 2:673�682.
145. Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A:
Chemoprevention of human prostate cancer by oral administration of
green tea catechins in volunteers with high-grade prostate intraepithelial
neoplasia: a preliminary report from a one-year proof-of-principle study.
Cancer Res 2006, 66:1234�1240.
146. Fraser SP, Peters A, Fleming-Jones S, Mukhey D, Djamgoz MB: Resveratrol:
inhibitory effects on metastatic cell behaviors and voltage-gated Na(+)
channel activity in rat prostate cancer in vitro. Nutr Cancer 2014,
66:1047�1058.
147. Oskarsson A, Spatafora C, Tringali C, Andersson AO: Inhibition of CYP17A1
activity by resveratrol, piceatannol, and synthetic resveratrol analogs.
Prostate 2014, 74:839�851.
148. Ferruelo A, Romero I, Cabrera PM, Arance I, Andres G, Angulo JC: Effects of
resveratrol and other wine polyphenols on the proliferation, apoptosis
and androgen receptor expression in LNCaP cells. Actas Urol Esp Jul-Aug
2014, 38:397�404.
149. Osmond GW, Masko EM, Tyler DS, Freedland SJ, Pizzo S: In vitro and in vivo
evaluation of resveratrol and 3,5-dihydroxy-4?-acetoxy-trans-stilbene in
the treatment of human prostate carcinoma and melanoma. J Surg Res
2013, 179:e141�e148.
150. Baur JA, Sinclair DA: Therapeutic potential of resveratrol: the in vivo
evidence. Nat Rev Drug Discov 2006, 5:493�506.
151. Klink JC, Tewari AK, Masko EM, Antonelli J, Febbo PG, Cohen P, Dewhirst
MW, Pizzo SV, Freedland SJ: Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell-line specific manner, through paradoxical effects on oncogenic pathways. Prostate 2013, 73:754�762.

152. Huang EC, Zhao Y, Chen G, Baek SJ, McEntee MF, Minkin S, Biggerstaff JP,
Whelan J: Zyflamend, a polyherbal mixture, down regulates class I and
class II histone deacetylases and increases p21 levels in castrate-resistant
prostate cancer cells. BMC Complement Altern Med 2014, 14:68.
153. Huang EC, McEntee MF, Whelan J: Zyflamend, a combination of herbal
extracts, attenuates tumor growth in murine xenograft models of
prostate cancer. Nutr Cancer 2012, 64:749�760.
154. Yan J, Xie B, Capodice JL, Katz AE: Zyflamend inhibits the expression and
function of androgen receptor and acts synergistically with bicalutimide
to inhibit prostate cancer cell growth. Prostate 2012, 72:244�252.
155. Kunnumakkara AB, Sung B, Ravindran J, Diagaradjane P, Deorukhkar A, Dey
S, Koca C, Tong Z, Gelovani JG, Guha S, Krishnan S, Aggarwal BB: Zyflamend
suppresses growth and sensitizes human pancreatic tumors to
gemcitabine in an orthotopic mouse model through modulation of
multiple targets. Int J Cancer 2012, 131:E292�E303.
156. Capodice JL, Gorroochurn P, Cammack AS, Eric G, McKiernan JM, Benson
MC, Stone BA, Katz AE: Zyflamend in men with high-grade prostatic
intraepithelial neoplasia: results of a phase I clinical trial. J Soc Integr
Oncol 2009, 7:43�51.
157. Rafailov S, Cammack S, Stone BA, Katz AE: The role of Zyflamend, an
herbal anti-inflammatory, as a potential chemopreventive agent against
prostate cancer: a case report. Integr Cancer Ther 2007, 6:74�76.
158. Askari F, Parizi MK, Jessri M, Rashidkhani B: Fruit and vegetable intake in
relation to prostate cancer in Iranian men: a case�control study.
Asian Pac J Cancer Prev 2014, 15:5223�5227.
159. Liu B, Mao Q, Cao M, Xie L: Cruciferous vegetables intake and risk of
prostate cancer: a meta-analysis. Int J Urol 2012, 19:134�141.
160. Richman EL, Carroll PR, Chan JM: Vegetable and fruit intake after
diagnosis and risk of prostate cancer progression. Int J Cancer 2012,
131:201�210.
161. Hsing AW, Chokkalingam AP, Gao YT, Madigan MP, Deng J, Gridley G,
Fraumeni JF Jr: Allium vegetables and risk of prostate cancer: a
population-based study. J Natl Cancer Inst 2002, 94:1648�1651.
162. Chan R, Lok K, Woo J: Prostate cancer and vegetable consumption.
Mol Nutr Food Res 2009, 53:201�216.
163. Thomas R, Williams M, Sharma H, Chaudry A, Bellamy P: A double-blind,
placebo-controlled randomised trial evaluating the effect of a
polyphenol-rich whole food supplement on PSA progression in men
with prostate cancer-the UK NCRN Pomi-T study. Prostate Cancer Prostatic
Dis 2014, 17:180�186.
164. Yang CM, Lu IH, Chen HY, Hu ML: Lycopene inhibits the proliferation of
androgen-dependent human prostate tumor cells through activation of
PPARgamma-LXRalpha-ABCA1 pathway. J Nutr Biochem 2012, 23:8�17.
165. Qiu X, Yuan Y, Vaishnav A, Tessel MA, Nonn L, van Breemen RB: Effects of
lycopene on protein expression in human primary prostatic epithelial
cells. Cancer Prev Res (Phila) 2013, 6:419�427.
166. Boileau TW, Liao Z, Kim S, Lemeshow S, Erdman JW Jr, Clinton SK: Prostate
carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated
rats fed tomato powder, lycopene, or energy-restricted diets. J Natl
Cancer Inst 2003, 95:1578�1586.
167. Konijeti R, Henning S, Moro A, Sheikh A, Elashoff D, Shapiro A, Ku M,
Said JW, Heber D, Cohen P, Aronson WJ: Chemoprevention of prostate
cancer with lycopene in the TRAMP model. Prostate 2010, 70:1547�1554.
168. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC: A prospective
study of tomato products, lycopene, and prostate cancer risk. J Natl
Cancer Inst 2002, 94:391�398.
169. Zu K, Mucci L, Rosner BA, Clinton SK, Loda M, Stampfer MJ, Giovannucci E:
Dietary lycopene, angiogenesis, and prostate cancer: a prospective
study in the prostate-specific antigen era. J Natl Cancer Inst 2014,
106:djt430.
170. Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, Stampfer
MJ: Lower prostate cancer risk in men with elevated plasma lycopene
levels: results of a prospective analysis. Cancer Res 1999, 59:1225�1230.
171. Kristal AR, Till C, Platz EA, Song X, King IB, Neuhouser ML, Ambrosone CB,
Thompson IM: Serum lycopene concentration and prostate cancer risk:
results from the Prostate Cancer Prevention Trial. Cancer Epidemiol
Biomarkers Prev 2011, 20:638�646.
172. Kirsh VA, Mayne ST, Peters U, Chatterjee N, Leitzmann MF, Dixon LB, Urban
DA, Crawford ED, Hayes RB: A prospective study of lycopene and tomato
product intake and risk of prostate cancer. Cancer Epidemiol Biomarkers
Prev 2006, 15:92�98.
173. Mariani S, Lionetto L, Cavallari M, Tubaro A, Rasio D, De Nunzio C, Hong
GM, Borro M, Simmaco M: Low prostate concentration of lycopene is
associated with development of prostate cancer in patients with highgrade
prostatic intraepithelial neoplasia. Int J Mol Sci 2014, 15:1433�1440.
174. Kucuk O, Sarkar FH, Djuric Z, Sakr W, Pollak MN, Khachik F, Banerjee M,
Bertram JS, Wood DP Jr: Effects of lycopene supplementation in patients
with localized prostate cancer. Exp Biol Med (Maywood) 2002, 227:881�885.
175. Chen L, Stacewicz-Sapuntzakis M, Duncan C, Sharifi R, Ghosh L, van
Breemen R, Ashton D, Bowen PE: Oxidative DNA damage in prostate
cancer patients consuming tomato sauce-based entrees as a whole-food
intervention. J Natl Cancer Inst 2001, 93:1872�1879.
176. van Breemen RB, Sharifi R, Viana M, Pajkovic N, Zhu D, Yuan L, Yang Y,
Bowen PE, Stacewicz-Sapuntzakis M: Antioxidant effects of lycopene in
African American men with prostate cancer or benign prostate hyperplasia:
a randomized, controlled trial. Cancer Prev Res (Phila) 2011, 4:711�718.
177. Shafique K, McLoone P, Qureshi K, Leung H, Hart C, Morrison DS: Coffee
consumption and prostate cancer risk: further evidence for inverse
relationship. Nutr J 2012, 11:42.
178. Wilson KM, Kasperzyk JL, Rider JR, Kenfield S, van Dam RM, Stampfer MJ,
Giovannucci E, Mucci LA: Coffee consumption and prostate cancer risk
and progression in the Health Professionals Follow-up Study. J Natl
Cancer Inst 2011, 103:876�884.
179. Bosire C, Stampfer MJ, Subar AF, Wilson KM, Park Y, Sinha R: Coffee
consumption and the risk of overall and fatal prostate cancer in the
NIH-AARP Diet and Health Study. Cancer Causes Control 2013, 24:1527�1534.
180. Arab L, Su LJ, Steck SE, Ang A, Fontham ET, Bensen JT, Mohler JL: Coffee
consumption and prostate cancer aggressiveness among African and
Caucasian Americans in a population-based study. Nutr Cancer 2012,
64:637�642.
181. Phillips RL, Snowdon DA: Association of meat and coffee use with cancers
of the large bowel, breast, and prostate among Seventh-Day Adventists:
preliminary results. Cancer Res 1983, 43:2403 s�2408s.
182. Hsing AW, McLaughlin JK, Schuman LM, Bjelke E, Gridley G, Wacholder S,
Chien HT, Blot WJ: Diet, tobacco use, and fatal prostate cancer: results
from the Lutheran Brotherhood Cohort Study. Cancer Res 1990,
50:6836�6840.
183. Cao S, Liu L, Yin X, Wang Y, Liu J, Lu Z: Coffee consumption and risk of
prostate cancer: a meta-analysis of prospective cohort studies.
Carcinogenesis 2014, 35:256�261.
184. Nordmann AJ, Suter-Zimmermann K, Bucher HC, Shai I, Tuttle KR,
Estruch R, Briel M: Meta-analysis comparing Mediterranean to low-fat
diets for modification of cardiovascular risk factors. Am J Med 2011,
124:841�851. e842.
185. Kapiszewska M: A vegetable to meat consumption ratio as a relevant
factor determining cancer preventive diet. The Mediterranean versus
other European countries. Forum Nutr 2006, 59:130�153.
186. Kenfield SA, Dupre N, Richman EL, Stampfer MJ, Chan JM, Giovannucci EL:
Mediterranean diet and prostate cancer risk and mortality in the Health
Professionals Follow-up Study. Eur Urol 2014, 65:887�894.
187. Ambrosini GL, Fritschi L, de Klerk NH, Mackerras D, Leavy J: Dietary patterns
identified using factor analysis and prostate cancer risk: a case control
study in Western Australia. Ann Epidemiol 2008, 18:364�370.
188. Baade PD, Youlden DR, Krnjacki LJ: International epidemiology of prostate
cancer: geographical distribution and secular trends. Mol Nutr Food Res
2009, 53:171�184.
189. Muller DC, Severi G, Baglietto L, Krishnan K, English DR, Hopper JL, Giles GG:
Dietary patterns and prostate cancer risk. Cancer Epidemiol Biomarkers Prev
2009, 18:3126�3129.
190. Tseng M, Breslow RA, DeVellis RF, Ziegler RG: Dietary patterns and prostate
cancer risk in the National Health and Nutrition Examination Survey
Epidemiological Follow-up Study cohort. Cancer Epidemiol Biomarkers Prev
2004, 13:71�77.
191. Wu K, Hu FB, Willett WC, Giovannucci E: Dietary patterns and risk of
prostate cancer in U.S. men. Cancer Epidemiol Biomarkers Prev 2006,
15:167�171.
192. Daubenmier JJ, Weidner G, Marlin R, Crutchfield L, Dunn-Emke S, Chi C,
Gao B, Carroll P, Ornish D: Lifestyle and health-related quality of life of
men with prostate cancer managed with active surveillance. Urology
2006, 67:125�130.

193. Parsons JK, Newman VA, Mohler JL, Pierce JP, Flatt S, Marshall J: Dietary
modification in patients with prostate cancer on active surveillance: a
randomized, multicentre feasibility study. BJU Int 2008, 101:1227�1231.
194. Mosher CE, Sloane R, Morey MC, Snyder DC, Cohen HJ, Miller PE,
Demark-Wahnefried W: Associations between lifestyle factors and quality
of life among older long-term breast, prostate, and colorectal cancer
survivors. Cancer 2009, 115:4001�4009.
195. Bhindi B, Locke J, Alibhai SM, Kulkarni GS, Margel DS, Hamilton RJ, Finelli A,
Trachtenberg J, Zlotta AR, Toi A, Hersey KM, Evans A, van der Kwast TH,
Fleshner NE: Dissecting the association between metabolic syndrome
and prostate cancer risk: analysis of a large clinical cohort. Eur Urol 2014.
doi:10.1016/j.eururo.2014.01.040. [Epub ahead of time]
196. Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Parretta E,
Lenzi A, Giugliano D: Effect of metabolic syndrome and its components
on prostate cancer risk: meta-analysis. J Endocrinol Invest 2013,
36:132�139.
197. U.S. Department of Agriculture and U.S. Department of Health and
Human Services. Dietary Guidelines for Americans, 2010. 7th edition.
Washington, DC: U.S. Government Printing Office, December, 2010.

Close Accordion
Assessment and Treatment of the Pectoralis Major and Latissimus Dorsi

Assessment and Treatment of the Pectoralis Major and Latissimus Dorsi

by | Chiropractic, Conditions Treated, Functional Medicine, Injury Care

These assessment and treatment recommendations represent a synthesis of information derived from personal clinical experience and from the numerous sources which are cited, or are based on the work of researchers, clinicians and therapists who are named (Basmajian 1974, Cailliet 1962, Dvorak & Dvorak 1984, Fryette 1954, Greenman 1989, 1996, Janda 1983, Lewit 1992, 1999, Mennell 1964, Rolf 1977, Williams 1965).

 

Clinical Application of Neuromuscular Techniques: Pectoralis Major and Latissimus Dorsi

 

Assessment of Shortened Pectoralis Major and Latissimus Dorsi

 

Latissimus and pectoral test (a) Observation is as accurate as most palpation for evidence of pectoralis major shortening. The patient will have a rounded shoulder posture � especially if the clavicular aspect is involved.

 

Or

 

The patient lies supine with upper arms on the table, hands resting palm down on the lower abdomen. The practitioner observes from the head and notes whether either shoulder is held in an anterior position in relation to the thoracic cage. If one or both shoulders are forward of the thorax, pectoralis muscles are short (Fig. 4.24).

 

Figure 4 24 Observation Assessment for Pectoral Shortness Image 1

 

Figure 4.24 Observation assessment in which pectoral shortness on the right is suggested by the inability of the shoulder to rest on the table.

 

Latissimus and pectoral test (b) The patient lies supine with the head several feet from the top edge of the table, and is asked to rest the arms, extended above the head, on the treatment surface, palms upwards (Fig. 4.25).

 

Figure 4 25 Assessment of Shortness in Pectoralis Major and Latissimus Dorsi Image 2

 

Figure 4.25 Assessment of shortness in pectoralis major and latissimus dorsi. Visual assessment is used: if the arm on the tested side is unable to rest along its full length, shortness of pectoralis major is probable; if there is obvious deviation of the elbow laterally, probable latissimus shortening is indicated.

 

If these muscles are normal, the arms should be able to easily reach the horizontal when directly above the shoulders, and also to be in contact with the surface for almost all of the length of the upper arms, with no arching of the back or twisting of the thorax.

 

If either arm cannot reach the vertical above the shoulder, but is held laterally, elbow pulled outwards, then latissimus dorsi is probably short on that side. If an arm cannot rest with the dorsum of the upper arm in contact with the table surface without effort, then pectoral fibres are almost certainly short.

 

Pectoralis major test. Assessment of shortness in pectoralis major (Fig. 4.26) Assessment of the subclavicular portion of pectoralis major involves abduction of the arm to 90� (Lewit 1985b). In this position the tendon of pectoralis major at the sternum should not be found to be unduly tense, even with maximum abduction of the arm, unless the muscle is short.

 

Figure 4 26 Palpation Assessment for Shortness of Subclavicular Portion of Pectoralis Major Image 3

 

Figure 4.26 Palpation assessment for shortness of subclavicular portion of pectoralis major.

 

For assessment of sternal attachment the arm is brought into elevation and abduction as the muscle, as well as the tendon on the greater tubercle of the humerus, is palpated. If the sternal fibres have shortened, tautness will be visible and tenderness of the tissues under palpation will be reported.

 

Pectoralis Major Test: Assessment for Strength of Pectoralis Major

 

Patient is supine with arm in abduction at the shoulder joint and medially rotated (palm is facing down) with the elbow extended. The practitioner stands at the head and secures the opposite shoulder with one hand to prevent any trunk torsion and contacts the dorsum of the distal humerus, on the tested side, with the other.

 

The patient attempts to lift the arm and to adduct it across the chest, against resistance, as strength is assessed in the sternal fibres.

 

Different arm positions can be used to assess clavicular and costal fibres: for example with an angle of abduction/elevation of 135� costal and abdominal fibres will be involved; with abduction/elevation of 45� the clavicular fibres will be assessed. The practitioner should palpate to ensure that the �correct� fibres contract when assessments are being made.

 

If this postural muscle tests as weak it may be useful to use Norris�s (1999) approach of strengthening it by means of a slowly applied isotonic eccentric (isolytic) contraction, before proceeding to an MET stretching procedure.

 

MET Treatment of Short Pectoralis Major

 

Pectoralis major MET method (a) (Fig. 4.27A, B) The patient lies supine with the arm abducted in a direction which produces the most marked evidence of pectoral shortness (assessed by palpation and visual evidence of the particular fibres involved as described in tests above). The more elevated the arm (i.e. the closer to the head), the more focus there will be on costal and abdominal fibres. With a lesser degree of abduction (to around 45�), the focus is more on the clavicular fibres. Between these two extremes lies the position which influences the sternal fibres most directly.

 

Figure 4 27A MET Treatment of Pectoral Muscle Abdominal Attachment Image 4

 

Figure 4.27A MET treatment of pectoral muscle � abdominal attachment. Note that the fibres being treated are those which lie in line with the long axis of the humerus.

 

 

Figure 4.27B An alternative hold for application of MET to pectoral muscle � sternal attachment. Note that the patient needs to be close to the edge of the table in order to allow the arm to be taken towards the floor once the slack has been removed, during the stretching phase after the isometric contraction.

 

The patient lies as close to the side of the table as possible so that the abducted arm can be brought below the horizontal level in order to apply gravitational pull and passive stretch to the fibres, as appropriate. The practitioner stands on the side to be treated and grasps the humerus.

 

A useful arm hold, which depends upon the relative size of the patient and the practitioner, involves the practitioner grasping the anterior aspect of the patient�s flexed upper arm just above the elbow, while the patient cups the practitioner�s elbow and holds this contact throughout the procedure (see Fig. 4.27B).

 

The patient�s hand is placed on the contact (attachments of shortened fibres) area on the thorax so that the hand acts as a �cushion�. This is both more physically comfortable and also prevents physical contact with emotionally sensitive areas such as breast tissue. The practitioner�s thenar or hyperthenar eminence is placed over the patient�s �cushion� hand in order to stabilise the area during the contraction and stretch, preventing movement of it.

 

Commencing with the patient�s arm in a position which takes the affected fibres to just short of their restriction barrier (for a chronic problem), the patient introduces a light contraction (20% of strength) involving adduction against resistance from the practitioner, for 7�10 seconds.

 

As a rule the long axis of the patient�s upper arm should be in a straight line with the fibres being treated. If a trigger point has previously been identified in pectoralis, the practitioner should ensure � by means of palpation if necessary, or by observation � that the fibres housing the triggers are involved in the contraction.

 

As the patient exhales following complete relaxation of the area, a stretch through the new barrier is activated by the patient and maintained by the practitioner. Stretch is achieved via the positioning and leverage of the arm as the contact hand on the thorax acts as a stabilising point only.

 

The stretch needs to be one in which the arm is first pulled away (distracted) from the thorax, with the patient�s assistance (�ease your arm away from your shoulder�), before the stretch is introduced which involves the humerus being taken below the horizontal (�ease your arm towards the floor�).

 

During the stretching phase it is important for the entire thorax to be stabilised. No rolling or twisting of the thorax in the direction of the stretch should be permitted. The stretching procedure should be thought of as having two phases: first the slack being removed by distracting the arm away from the contact/stabilising hand on the thorax; second, movement of the arm towards the floor, initiated by the practitioner bending his knees.

 

Stretching (after an isometric contraction) should be repeated two or three times in each position. All attachments should be treated, which calls for the use of different arm positions, as discussed above, each with different stabilising (�cushion�) contacts as the various fibre directions and attachments are isolated.

 

Pectoralis major MET method (b) (Fig. 4.28) The patient is prone with face in a face hole or cradle. Her right arm is abducted to 90� and the elbow flexed to 90� palm towards the floor, with the upper arm supported by the table. The practitioner stands at waist level, facing cephalad, and places his non-table-side hand palm to palm with the patient�s so that the patient�s forearm is in contact with the ventral surface of the practitioner�s forearm. The practitioner�s table-side hand rests on the patient�s right scapula area, ensuring that no trunk rotation occurs.

 

Figure 4 28 MET for Pectoralis Major in Prone Position Image 6

 

Figure 4.28 MET for pectoralis major in prone position.

 

The practitioner eases the patient�s arm into extension at the shoulder until he senses the first sign of resistance from pectoralis. It is important when extending the arm in this way to ensure that no trunk rotation occurs and that the anterior surface of the shoulder remains in contact with the table throughout.

 

The patient is asked, using no more than 20% of strength, to bring her arm towards the floor and across her chest, with the elbow taking the lead in this attempted movement, which is completely resisted by the practitioner. The practitioner ensures that the patient�s arm remains parallel with the floor throughout the isometric contraction.

 

Following release of the contraction effort, and on an exhalation, the arm is taken into greater extension, with the patient�s assistance, and held at stretch for not less than 20 seconds.

 

This procedure is repeated two or three times, slackening the muscle slightly from its end-range before each subsequent contraction to reduce discomfort and for ease of application of the contraction.

 

Variations in pectoralis fibre involvement can be achieved by altering the angle of abduction � with a more superior angle (around 140�) the lower sternal and costal fibres, and with a lesser angle (around 45�) the clavicular fibres will be committed.

 

Pectoralis major MET method (c) Bilateral MET stretching of pectoralis major (sternocostal aspects) involves having the patient supine, knees and hips flexed, in order to provide stability to the spinal regions, preventing lumbar lordosis. A shallow but firm cushion should be placed between the scapulae, allowing a better excursion of the shoulders during this stretch. The chin should be tucked in and, if more comfortable, a small cushion placed under the neck. Ideally a strap/belt should be used to fix the thorax to the table, but this is not essential.

 

The practitioner stands at the head of the table and grasps the patient�s elbows or forearms, which are flexed, laterally rotated and held in a position to induce the most taut aspects of the muscles to become prominent.

 

Starting from such a barrier or short of it (acute/chronic), the patient is asked to contract the muscles by bringing the arms upwards and towards the table for 10 seconds or so during a held breath.

 

Following the contraction and complete relaxation, the arms are taken to a new or through the restriction barrier, as appropriate, during an exhalation. Repeat as necessary several times more.

 

Pectoralis major MET method (d) By adopting the same positions � but with the arms of the patient more laterally placed so that they are laterally rotated and in 90� abduction from the shoulder (upper arms are straight out sideways from the shoulder) and there is 90� flexion at the elbows, with the practitioner contacting the area just proximal to the flexed elbows � a more direct stretch of the clavicular insertions of the muscle can be achieved, using all the same contraction and stretch elements as in (b) above.

 

Latissimus Dorsi Test for Shortness

 

To screen latissimus dorsi (12), the standing patient is asked to bend forwards and allow the arms to hang freely from the shoulders as she holds a half-bend position, trunk parallel with the floor.

 

If the arms are hanging other than perpendicular to the floor there is probably some muscular restriction involved, and if this involves latissimus the arms will be held closer to the legs than perpendicular (if they hang markedly forward of such a position then trapezius shortening is probable, see below).

 

To screen latissimus in this position, one side at a time, the practitioner stands in front of the patient (who remains in this half-bend position) and, stabilising the scapula area with one hand, grasps the arm at elbow level and gently draws the tested side (straight) arm forwards. It should, without undue effort or excessive bind in the tissues being held, allow itself to be taken to a position where the elbow is higher than the level of the back of the head. If this is not possible, then latissimus is short.

 

MET Treatment of Short Latissimus Dorsi

 

Short latissimus dorsi MET method (a) The patient lies supine with the feet crossed (the side to be treated crossed under the non-treated side leg at the ankle). The patient is arranged in a light sidebend away from the side to be treated so that the pelvis is towards that side, and the feet and head away from that side. The heels are placed just off the edge of the table, so anchoring the lower extremities.

 

The patient places her arm on the side to be treated behind her neck, as the practitioner, standing on the side opposite that to be treated, slides his cephalad hand under the patient�s shoulders to grasp the treated side axilla. The patient grasps the practitioner�s cephalad arm at the elbow, making this contact more secure. The patients treated side elbow should point superiorly. The practitioner�s caudad hand is placed on the anterior superior iliac spine on the side being treated.

 

The patient is instructed to very lightly take the pointed elbow towards the sacrum and also to lightly try to bend backwards and towards the treated side. This should produce a light isometric contraction in latissimus dorsi on the side to be treated. After 7 seconds they are asked to relax completely as the practitioner transfers his body weight from the cephalad leg to the caudad leg, to sidebend the patient. Simultaneously the practitioner stands more erect and leans in a caudad direction.

 

This effectively lifts the patient�s thorax from the table surface and introduces a stretch into latissimus (especially if the patient has maintained a grasp on the practitioner�s elbow and the practitioner has a firm hold on the patient�s axilla).

 

This stretch is held for 15�30 seconds allowing a lengthening of shortened musculature in the region. (Note: starting position is as for Fig. 4.22.) Repeat as necessary.

 

Short latissimus dorsi MET method (b) The patient is side-lying, affected side up. The arm is taken into abduction to the point of resistance, so that it is possible to visualise, or palpate, the insertion of the shortened fibres on the lateral chest wall.

 

The condition is treated in either the acute or chronic mode of MET, at or short of the barrier, as appropriate.

 

As shown in Figure 4.29, the practitioner stands near the head of the patient, slightly behind, and holds the upper arm in the chosen position while applying the other hand to stabilise the posterior thorax area, or the pelvic crest, from where the stretch will be made.

 

Figure 4 29 Treatment of Latissimus Dorsi Image 7

 

Figure 4.29 Treatment of latissimus dorsi. A variety of different positions are required for the stabilising hand (on the chest wall as well as on the crest of the pelvis) to allow for precise application of stretches of fibres with different attachments, following the sequence of isometric contractions.

 

A build-up of tension should be palpated under the stabilising hand as the patient introduces an isometric contraction by attempting to bring the arm towards the ceiling, backwards and down (towards their own lower spine) against firm resistance, using only a modest amount of effort (20%) and holding the breath if appropriate (see notes on breathing, Box 4.2).

 

After 7�10 seconds, both the effort and breath are released and the patient relaxes completely, at which time the practitioner introduces stretch to or through the barrier (acute/chronic), bringing the humerus into greater adduction while applying a stretching/stabilising contact on the trunk (with separate contractions and stretches for each contact) anywhere between the lateral chest wall and the crest of the pelvis.

 

A downward movement of the humerus, towards the floor, assists the stretch following a separation of the practitioner�s two contact hands to remove all slack. As in the stretch of pectoralis major, there should be two phases � a distraction, taking out the slack, and a movement towards the floor of the practitioner, by flexing the knees � to induce a safe stretch. Repeat as necessary.

 

Ultimately, it should be possible to achieve complete elevation of the arm without stress or obvious shortness in latissimus fibres so that the upper arm can rest alongside the ear of the supine patient.

 

Dr. Alex Jimenez offers an additional assessment and treatment of the hip flexors as a part of a referenced clinical application of neuromuscular techniques by Leon Chaitow and Judith Walker DeLany. The scope of our information is limited to chiropractic and spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

 

By Dr. Alex Jimenez

 

Green-Call-Now-Button-24H-150x150-2-3.png

 

Additional Topics: Wellness

 

Overall health and wellness are essential towards maintaining the proper mental and physical balance in the body. From eating a balanced nutrition as well as exercising and participating in physical activities, to sleeping a healthy amount of time on a regular basis, following the best health and wellness tips can ultimately help maintain overall well-being. Eating plenty of fruits and vegetables can go a long way towards helping people become healthy.

 

blog picture of cartoon paperboy big news

 

WELLNESS TOPIC: EXTRA EXTRA: Managing Workplace Stress

 

 

Regulation of Gene Expression by Fatty Acids for IBD

Regulation of Gene Expression by Fatty Acids for IBD

by | Functional Medicine, Gastro Intestinal Health, Gut and Intestinal Health, Nutrition

Dietary fat has several essential functions in the human body. First, it functions as a supply of energy and structural components for the cells and second, it functions as a regulator of gene expression, which influences lipid, carbohydrate, and protein metabolism, along with cell growth and differentiation. The effects of fatty acids on gene expression are cell-specific and influenced by structure and metabolism. Fatty acids interact with the genome. They regulate PPAR, and the activity or nuclear abundance like SREBP. Fatty acids bind directly with one another to regulate gene expression.

 

What’s the role of fatty acids towards disease pathogenesis?

 

Alternately, fatty acids behave on gene expression through their effects on specific enzyme-mediated pathways, such as cyclooxygenase, lipoxygenase, protein kinase C, or sphingomyelinase signal transduction pathways, or through pathways that require changes in tissue lipid to lipid raft composition which affect G-protein receptor or tyrosine kinase-linked receptor signaling. Additional definition of these fatty acid-regulated pathways can offer insight into the role dietary fat plays in human health as well as the beginning and growth of many chronic diseases, such as coronary artery disease and atherosclerosis, dyslipidemia and inflammation, obesity and diabetes, cancer, major depressive disorders, and schizophrenia. The effects of fatty acids on gene expression, however, have been widely described on inflammatory bowel disease, or IBD.

 

Fatty Acids and Gene Expression

 

The effect of fatty acids on gene expression was previously determined to result mainly from changes in tissue phospholipids or eicosanoid production. More recently, the discovery of nuclear receptors; such as peroxisome proliferator-activated receptors, or PPARs, and their regulation by fatty acids, has significantly altered this view. PPARs are ligand activated transcription factors that upon heterodimerization with the retinoic X receptor, or RXR, comprehend PPAR response elements in the promoter regions of different genes, that have an impact on gene transcription. PPARs bind various ligands, including nonsteroidal anti inflammatory medications, or NSAIDS, thiazolidinediones (antidiabetic agents) along with PUFAs and their metabolites. Several subtypes of the receptor are recognized (?,?,?) and are expressed in several different cells. PPAR? is extracted from the adrenal gland, with most of its numbers observed in the colon.

 

PPAR? has been implicated in the regulation of inflammation, and it has become a potential therapeutic goal in treating inflammatory diseases, such as IBD. It has been suggested that people with ulcerative colitis, or UC, have a mucosal deficit in PPAR? that could bring about the development of their own disease. Analysis of the mRNA and proteins within colonic biopsies demonstrated decreased levels of PPAR? in UC patients in comparison with Crohn’s patients or healthy subjects.

 

Using colon cancer lines, it has been demonstrated that PPAR ligands attenuate cytokine gene expression by inhibiting NF-?B via an I?B determined mechanism. Further research studies imply that PPAR activators inhibit COX2 by interruption with NF-?B. PPARs impair interactions with STAT and other signaling pathways as well as the AP-1 signaling pathway.

 

Animal studies support using PPAR for autoimmune inflammation. Inflammation decreased by ligands for PPAR. The direction of PPAR and RXR agonists synergistically reduced TNBS-induced colitis, together with improved macroscopic and histologic scores, reductions in TNF? and IL-1? mRNA, and diminished NF-?B DNA binding actions. Though clinical evidence is limited, the results of an open source research study with rosiglitazone, a PPAR? ligand as therapy for UC, demonstrated that 27 percent of patients achieved remission after 12 weeks of therapy. Thus, PPAR? ligands may represent a cure for UC, where double-blind, placebo-controlled, randomized trials have been warranted.

 

Of substantial curiosity, the capability to regulate PPAR nutritionally has been examined. Dietary PUFA demonstrated an impact during the regulation of transcription factors on gene expression. Fatty acid regulation of PPAR was originally detected by Gottlicher et al.. A choice of fatty acids, like eicosanoids, and metabolites are proven to activate PPAR. Both PPAR? and PPAR? bind mono- and polyunsaturated fatty acids. Thus, the anti inflammatory effects of n3 PUFA may entail PPAR and its interruption with NF?B, rather than only changes in eicosanoid synthesis.

 

Conclusion

 

Fatty acids regulate gene expression involved in lipid and energy metabolism. Polyunsaturated fatty acids, or PUFA, though not saturated or polyunsaturated FA, suppress the induction of lipogenic genes by inhibiting their expression and processing of SREBP-1c. This impact of PUFA suggests that SREBP-1c may regulate the synthesis of fatty acids to glycerolipids, among others. PPARalpha has a role in the adaptation to fasting by inducing ketogenesis in mitochondria. During fasting, fatty acids are considered as ligands of PPARalpha. Dietary PUFA, except for 18:2 n-6, are extremely prone to induce fatty acid oxidation enzymes through PPARalpha because of specific mechanisms. Signaling functions of PPARalpha pPARalpha is needed for controlling the synthesis of fatty acids. Further research is needed to conclude the full effects of fatty acids in relation to the regulation of transcription factors for gene expression in inflammatory bowel disease, or IBD.

 

Information referenced from the National Center for Biotechnology Information (NCBI) and the National University of Health Sciences. The scope of our information is limited to chiropractic and spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

 

By Dr. Alex Jimenez

 

Green-Call-Now-Button-24H-150x150-2-3.png

 

Additional Topics: Wellness

 

Overall health and wellness are essential towards maintaining the proper mental and physical balance in the body. From eating a balanced nutrition as well as exercising and participating in physical activities, to sleeping a healthy amount of time on a regular basis, following the best health and wellness tips can ultimately help maintain overall well-being. Eating plenty of fruits and vegetables can go a long way towards helping people become healthy.

 

blog picture of cartoon paperboy big news

 

WELLNESS TOPIC: EXTRA EXTRA: Managing Workplace Stress

 

 

Blank
References
1.�Liu Y, van Kruiningen HJ, West AB, Cartun RW, Cortot A, Colombel JF. Immunocytochemical evidence of Listeria, Escherichia coli, and Streptococcus antigens in Crohn’s disease.�Gastroenterology.�1995;108:1396�1404.�[PubMed]
2.�Sartor R.�Microbial factors in the pathogenesis of Crohn’s disease, ulcerative colitis and experimental intestinal inflammation.�Baltimore: Williams & Wilkins; 1995.
3.�Wakefield AJ, Ekbom A, Dhillon AP, Pittilo RM, Pounder RE. Crohn’s disease: pathogenesis and persistent measles virus infection.�Gastroenterology.�1995;108:911�916.�[PubMed]
4.�Sartor RB. Current concepts of the etiology and pathogenesis of ulcerative colitis and Crohn’s disease.�Gastroenterol Clin North Am.�1995;24:475�507.�[PubMed]
5.�Sartor RB. Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases.�Am J Gastroenterol.�1997;92:5S�11S.�[PubMed]
6.�MacDermott RP. Alterations in the mucosal immune system in ulcerative colitis and Crohn’s disease.�Med Clin North Am.�1994;78:1207�1231.�[PubMed]
7.�Podolsky DK. Inflammatory bowel disease (1)�N Engl J Med.�1991;325:928�937.�[PubMed]
8.�Podolsky DK. Inflammatory bowel disease (2)�N Engl J Med.�1991;325:1008�1016.�[PubMed]
9.�Yang H, Rotter J.�The genetics of inflammatory disease.�Baltimore: Williams & Wilkins; 1994.
10.�Wurzelmann JI, Lyles CM, Sandler RS. Childhood infections and the risk of inflammatory bowel disease.�Dig Dis Sci.�1994;39:555�560.�[PubMed]
11.�Knoflach P, Park BH, Cunningham R, Weiser MM, Albini B. Serum antibodies to cow’s milk proteins in ulcerative colitis and Crohn’s disease.�Gastroenterology.�1987;92:479�485.�[PubMed]
12.�De Palma GD, Catanzano C. Removable self-expanding metal stents: a pilot study for treatment of achalasia of the esophagus.�Endoscopy.�1998;30:S95�S96.�[PubMed]
13.�Bernstein CN, Ament M, Artinian L, Ridgeway J, Shanahan F. Milk tolerance in adults with ulcerative colitis.�Am J Gastroenterol.�1994;89:872�877.�[PubMed]
14.�Matsui T, Iida M, Fujishima M, Imai K, Yao T. Increased sugar consumption in Japanese patients with Crohn’s disease.�Gastroenterol Jpn.�1990;25:271.�[PubMed]
15.�Kelly DG, Fleming CR. Nutritional considerations in inflammatory bowel diseases.�Gastroenterol Clin North Am.�1995;24:597�611.�[PubMed]
16.�Geerling BJ, Dagnelie PC, Badart-Smook A, Russel MG, Stockbr�gger RW, Brummer RJ. Diet as a risk factor for the development of ulcerative colitis.�Am J Gastroenterol.�2000;95:1008�1013.�[PubMed]
17.�Dudrick SJ, Latifi R, Schrager R. Nutritional management of inflammatory bowel disease.�Surg Clin North Am.�1991;71:609�623.�[PubMed]
18.�D’Odorico A, Bortolan S, Cardin R, D’Inca’ R, Martines D, Ferronato A, Sturniolo GC. Reduced plasma antioxidant concentrations and increased oxidative DNA damage in inflammatory bowel disease.�Scand J Gastroenterol.�2001;36:1289�1294.�[PubMed]
19.�Reimund JM, Hirth C, Koehl C, Baumann R, Duclos B. Antioxidant and immune status in active Crohn’s disease. A possible relationship.�Clin Nutr.�2000;19:43�48.�[PubMed]
20.�Romagnuolo J, Fedorak RN, Dias VC, Bamforth F, Teltscher M. Hyperhomocysteinemia and inflammatory bowel disease: prevalence and predictors in a cross-sectional study.�Am J Gastroenterol.�2001;96:2143�2149.�[PubMed]
21.�Lewis JD, Fisher RL. Nutrition support in inflammatory bowel disease.�Med Clin North Am.�1994;78:1443�1456.�[PubMed]
22.�Azcue M, Rashid M, Griffiths A, Pencharz PB. Energy expenditure and body composition in children with Crohn’s disease: effect of enteral nutrition and treatment with prednisolone.�Gut.�1997;41:203�208.[PMC free article]�[PubMed]
23.�Mingrone G, Capristo E, Greco AV, Benedetti G, De Gaetano A, Tataranni PA, Gasbarrini G. Elevated diet-induced thermogenesis and lipid oxidation rate in Crohn disease.�Am J Clin Nutr.�1999;69:325�330.[PubMed]
24.�Bjarnason I, Macpherson A, Mackintosh C, Buxton-Thomas M, Forgacs I, Moniz C. Reduced bone density in patients with inflammatory bowel disease.�Gut.�1997;40:228�233.�[PMC free article]�[PubMed]
25.�Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM. Growth and clinical course of children with Crohn’s disease.�Gut.�1993;34:939�943.�[PMC free article]�[PubMed]
26.�Fischer JE, Foster GS, Abel RM, Abbott WM, Ryan JA. Hyperalimentation as primary therapy for inflammatory bowel disease.�Am J Surg.�1973;125:165�175.�[PubMed]
27.�Reilly J, Ryan JA, Strole W, Fischer JE. Hyperalimentation in inflammatory bowel disease.�Am J Surg.�1976;131:192�200.�[PubMed]
28.�Ganem D, Schneider RJ. Hepadnaviridae: The viruses and their replication. In: Knipe DM, Howley PM, editors.�Fields Virology. Volume 2.�Philadelphia: Lippincott, Williams & Wilkins; 2001. pp. 2923�2969.
29.�Jones VA, Dickinson RJ, Workman E, Wilson AJ, Freeman AH, Hunter JO. Crohn’s disease: maintenance of remission by diet.�Lancet.�1985;2:177�180.�[PubMed]
30.�Suzuki I, Kiyono H, Kitamura K, Green DR, McGhee JR. Abrogation of oral tolerance by contrasuppressor T cells suggests the presence of regulatory T-cell networks in the mucosal immune system.�Nature.�1986;320:451�454.�[PubMed]
31.�Ostro MJ, Greenberg GR, Jeejeebhoy KN. Total parenteral nutrition and complete bowel rest in the management of Crohn’s disease.�JPEN J Parenter Enteral Nutr.�1985;9:280�287.�[PubMed]
32.�Matuchansky C. Parenteral nutrition in inflammatory bowel disease.�Gut.�1986;27 Suppl 1:81�84.[PMC free article]�[PubMed]
33.�Payne-James JJ, Silk DB. Total parenteral nutrition as primary treatment in Crohn’s disease–RIP?�Gut.�1988;29:1304�1308.�[PMC free article]�[PubMed]
34.�Shiloni E, Coronado E, Freund HR. Role of total parenteral nutrition in the treatment of Crohn’s disease.�Am J Surg.�1989;157:180�185.�[PubMed]
35.�Dickinson RJ, Ashton MG, Axon AT, Smith RC, Yeung CK, Hill GL. Controlled trial of intravenous hyperalimentation and total bowel rest as an adjunct to the routine therapy of acute colitis.�Gastroenterology.�1980;79:1199�1204.�[PubMed]
36.�McIntyre PB, Powell-Tuck J, Wood SR, Lennard-Jones JE, Lerebours E, Hecketsweiler P, Galmiche JP, Colin R. Controlled trial of bowel rest in the treatment of severe acute colitis.�Gut.�1986;27:481�485.[PMC free article]�[PubMed]
37.�Greenberg GR, Fleming CR, Jeejeebhoy KN, Rosenberg IH, Sales D, Tremaine WJ. Controlled trial of bowel rest and nutritional support in the management of Crohn’s disease.�Gut.�1988;29:1309�1315.[PMC free article]�[PubMed]
38.�Hughes CA, Bates T, Dowling RH. Cholecystokinin and secretin prevent the intestinal mucosal hypoplasia of total parenteral nutrition in the dog.�Gastroenterology.�1978;75:34�41.�[PubMed]
39.�Stratton RJ, Smith TR. Role of enteral and parenteral nutrition in the patient with gastrointestinal and liver disease.�Best Pract Res Clin Gastroenterol.�2006;20:441�466.�[PubMed]
40.�O’Sullivan M, O’Morain C. Nutrition in inflammatory bowel disease.�Best Pract Res Clin Gastroenterol.�2006;20:561�573.�[PubMed]
41.�Gonz�lez-Huix F, Fern�ndez-Ba�ares F, Esteve-Comas M, Abad-Lacruz A, Cabr� E, Acero D, Figa M, Guilera M, Humbert P, de Le�n R. Enteral versus parenteral nutrition as adjunct therapy in acute ulcerative colitis.�Am J Gastroenterol.�1993;88:227�232.�[PubMed]
42.�Voitk AJ, Echave V, Feller JH, Brown RA, Gurd FN. Experience with elemental diet in the treatment of inflammatory bowel disease. Is this primary therapy?�Arch Surg.�1973;107:329�333.�[PubMed]
43.�Axelsson C, Jarnum S. Assessment of the therapeutic value of an elemental diet in chronic inflammatory bowel disease.�Scand J Gastroenterol.�1977;12:89�95.�[PubMed]
44.�Lochs H, Steinhardt HJ, Klaus-Wentz B, Zeitz M, Vogelsang H, Sommer H, Fleig WE, Bauer P, Schirrmeister J, Malchow H. Comparison of enteral nutrition and drug treatment in active Crohn’s disease. Results of the European Cooperative Crohn’s Disease Study. IV.�Gastroenterology.�1991;101:881�888.[PubMed]
45.�Malchow H, Steinhardt HJ, Lorenz-Meyer H, Strohm WD, Rasmussen S, Sommer H, Jarnum S, Brandes JW, Leonhardt H, Ewe K. Feasibility and effectiveness of a defined-formula diet regimen in treating active Crohn’s disease. European Cooperative Crohn’s Disease Study III.�Scand J Gastroenterol.�1990;25:235�244.�[PubMed]
46.�O’Brien CJ, Giaffer MH, Cann PA, Holdsworth CD. Elemental diet in steroid-dependent and steroid-refractory Crohn’s disease.�Am J Gastroenterol.�1991;86:1614�1618.�[PubMed]
47.�Okada M, Yao T, Yamamoto T, Takenaka K, Imamura K, Maeda K, Fujita K. Controlled trial comparing an elemental diet with prednisolone in the treatment of active Crohn’s disease.�Hepatogastroenterology.�1990;37:72�80.�[PubMed]
48.�O’Mor�in C, Segal AW, Levi AJ. Elemental diet as primary treatment of acute Crohn’s disease: a controlled trial.�Br Med J (Clin Res Ed)�1984;288:1859�1862.�[PMC free article]�[PubMed]
49.�Raouf AH, Hildrey V, Daniel J, Walker RJ, Krasner N, Elias E, Rhodes JM. Enteral feeding as sole treatment for Crohn’s disease: controlled trial of whole protein v amino acid based feed and a case study of dietary challenge.�Gut.�1991;32:702�707.�[PMC free article]�[PubMed]
50.�Rocchio MA, Cha CJ, Haas KF, Randall HT. Use of chemically defined diets in the management of patients with acute inflammatory bowel disease.�Am J Surg.�1974;127:469�475.�[PubMed]
51.�Saverymuttu S, Hodgson HJ, Chadwick VS. Controlled trial comparing prednisolone with an elemental diet plus non-absorbable antibiotics in active Crohn’s disease.�Gut.�1985;26:994�998.�[PMC free article][PubMed]
52.�Teahon K, Bjarnason I, Pearson M, Levi AJ. Ten years’ experience with an elemental diet in the management of Crohn’s disease.�Gut.�1990;31:1133�1137.�[PMC free article]�[PubMed]
53.�Teahon K, Smethurst P, Pearson M, Levi AJ, Bjarnason I. The effect of elemental diet on intestinal permeability and inflammation in Crohn’s disease.�Gastroenterology.�1991;101:84�89.�[PubMed]
54.�Heuschkel RB, Menache CC, Megerian JT, Baird AE. Enteral nutrition and corticosteroids in the treatment of acute Crohn’s disease in children.�J Pediatr Gastroenterol Nutr.�2000;31:8�15.�[PubMed]
55.�Sanderson IR, Boulton P, Menzies I, Walker-Smith JA. Improvement of abnormal lactulose/rhamnose permeability in active Crohn’s disease of the small bowel by an elemental diet.�Gut.�1987;28:1073�1076.[PMC free article]�[PubMed]
56.�Sanderson IR, Udeen S, Davies PS, Savage MO, Walker-Smith JA. Remission induced by an elemental diet in small bowel Crohn’s disease.�Arch Dis Child.�1987;62:123�127.�[PMC free article]�[PubMed]
57.�Ruemmele FM, Roy CC, Levy E, Seidman EG. Nutrition as primary therapy in pediatric Crohn’s disease: fact or fantasy?�J Pediatr.�2000;136:285�291.�[PubMed]
58.�O’Morain C, O’Sullivan M. Nutritional support in Crohn’s disease: current status and future directions.�J Gastroenterol.�1995;30 Suppl 8:102�107.�[PubMed]
59.�Rigaud D, Cosnes J, Le Quintrec Y, Ren� E, Gendre JP, Mignon M. Controlled trial comparing two types of enteral nutrition in treatment of active Crohn’s disease: elemental versus polymeric diet.�Gut.�1991;32:1492�1497.�[PMC free article]�[PubMed]
60.�Royall D, Wolever TM, Jeejeebhoy KN. Evidence for colonic conservation of malabsorbed carbohydrate in short bowel syndrome.�Am J Gastroenterol.�1992;87:751�756.�[PubMed]
61.�Giaffer MH, North G, Holdsworth CD. Controlled trial of polymeric versus elemental diet in treatment of active Crohn’s disease.�Lancet.�1990;335:816�819.�[PubMed]
62.�Verma S, Kirkwood B, Brown S, Giaffer MH. Oral nutritional supplementation is effective in the maintenance of remission in Crohn’s disease.�Dig Liver Dis.�2000;32:769�774.�[PubMed]
63.�Levine GM, Deren JJ, Steiger E, Zinno R. Role of oral intake in maintenance of gut mass and disaccharide activity.�Gastroenterology.�1974;67:975�982.�[PubMed]
64.�Weser E, Heller R, Tawil T. Stimulation of mucosal growth in the rat ileum by bile and pancreatic secretions after jejunal resection.�Gastroenterology.�1977;73:524�529.�[PubMed]
65.�Fell JM, Paintin M, Arnaud-Battandier F, Beattie RM, Hollis A, Kitching P, Donnet-Hughes A, MacDonald TT, Walker-Smith JA. Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn’s disease.�Aliment Pharmacol Ther.�2000;14:281�289.�[PubMed]
66.�Souba WW, Smith RJ, Wilmore DW. Glutamine metabolism by the intestinal tract.�JPEN J Parenter Enteral Nutr.�1985;9:608�617.�[PubMed]
67.�Windmueller HG, Spaeth AE. Uptake and metabolism of plasma glutamine by the small intestine.�J Biol Chem.�1974;249:5070�5079.�[PubMed]
68.�Higashiguchi T, Hasselgren PO, Wagner K, Fischer JE. Effect of glutamine on protein synthesis in isolated intestinal epithelial cells.�JPEN J Parenter Enteral Nutr.�1993;17:307�314.�[PubMed]
69.�Burke DJ, Alverdy JC, Aoys E, Moss GS. Glutamine-supplemented total parenteral nutrition improves gut immune function.�Arch Surg.�1989;124:1396�1399.�[PubMed]
70.�Souba WW, Herskowitz K, Klimberg VS, Salloum RM, Plumley DA, Flynn TC, Copeland EM. The effects of sepsis and endotoxemia on gut glutamine metabolism.�Ann Surg.�1990;211:543�549; discussion 543-551;.�[PMC free article]�[PubMed]
71.�Den Hond E, Hiele M, Peeters M, Ghoos Y, Rutgeerts P. Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn’s disease.�JPEN J Parenter Enteral Nutr.�1999;23:7�11.�[PubMed]
72.�Akobeng AK, Miller V, Stanton J, Elbadri AM, Thomas AG. Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn’s disease.�J Pediatr Gastroenterol Nutr.�2000;30:78�84.�[PubMed]
73.�Jacobs LR, Lupton JR. Effect of dietary fibers on rat large bowel mucosal growth and cell proliferation.�Am J Physiol.�1984;246:G378�G385.�[PubMed]
74.�Spaeth G, Berg RD, Specian RD, Deitch EA. Food without fiber promotes bacterial translocation from the gut.�Surgery.�1990;108:240�246; discussion 246-247;.�[PubMed]
75.�Roediger WE, Moore A. Effect of short-chaim fatty acid on sodium absorption in isolated human colon perfused through the vascular bed.�Dig Dis Sci.�1981;26:100�106.�[PubMed]
76.�Sakata T. Stimulatory effect of short-chain fatty acids on epithelial cell proliferation in the rat intestine: a possible explanation for trophic effects of fermentable fibre, gut microbes and luminal trophic factors.�Br J Nutr.�1987;58:95�103.�[PubMed]
77.�Roediger WE. The colonic epithelium in ulcerative colitis: an energy-deficiency disease?�Lancet.�1980;2:712�715.�[PubMed]
78.�Chapman MA, Grahn MF, Boyle MA, Hutton M, Rogers J, Williams NS. Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis.�Gut.�1994;35:73�76.[PMC free article]�[PubMed]
79.�Den Hond E, Hiele M, Evenepoel P, Peeters M, Ghoos Y, Rutgeerts P. In vivo butyrate metabolism and colonic permeability in extensive ulcerative colitis.�Gastroenterology.�1998;115:584�590.�[PubMed]
80.�Simpson EJ, Chapman MA, Dawson J, Berry D, Macdonald IA, Cole A. In vivo measurement of colonic butyrate metabolism in patients with quiescent ulcerative colitis.�Gut.�2000;46:73�77.[PMC free article]�[PubMed]
81.�Tappenden KA, Thomson AB, Wild GE, McBurney MI. Short-chain fatty acid-supplemented total parenteral nutrition enhances functional adaptation to intestinal resection in rats.�Gastroenterology.�1997;112:792�802.�[PubMed]
82.�Senagore AJ, MacKeigan JM, Scheider M, Ebrom JS. Short-chain fatty acid enemas: a cost-effective alternative in the treatment of nonspecific proctosigmoiditis.�Dis Colon Rectum.�1992;35:923�927.[PubMed]
83.�Segain JP, Raingeard de la Bl�ti�re D, Bourreille A, Leray V, Gervois N, Rosales C, Ferrier L, Bonnet C, Blotti�re HM, Galmiche JP. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn’s disease.�Gut.�2000;47:397�403.�[PMC free article]�[PubMed]
84.�Aslan A, Triadafilopoulos G. Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study.�Am J Gastroenterol.�1992;87:432�437.�[PubMed]
85.�Shoda R, Matsueda K, Yamato S, Umeda N. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan.�Am J Clin Nutr.�1996;63:741�745.�[PubMed]
86.�Vilaseca J, Salas A, Guarner F, Rodr�guez R, Mart�nez M, Malagelada JR. Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis.�Gut.�1990;31:539�544.�[PMC free article]�[PubMed]
87.�Campos FG, Waitzberg DL, Habr-Gama A, Logullo AF, Noronha IL, Jancar S, Torrinhas RS, F�rst P. Impact of parenteral n-3 fatty acids on experimental acute colitis.�Br J Nutr.�2002;87 Suppl 1:S83�S88.[PubMed]
88.�Loeschke K, Ueberschaer B, Pietsch A, Gruber E, Ewe K, Wiebecke B, Heldwein W, Lorenz R. n-3 fatty acids only delay early relapse of ulcerative colitis in remission.�Dig Dis Sci.�1996;41:2087�2094.[PubMed]
89.�Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of an enteric-coated fish-oil preparation on relapses in Crohn’s disease.�N Engl J Med.�1996;334:1557�1560.�[PubMed]
90.�Hawthorne AB, Daneshmend TK, Hawkey CJ, Belluzzi A, Everitt SJ, Holmes GK, Malkinson C, Shaheen MZ, Willars JE. Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial.�Gut.�1992;33:922�928.�[PMC free article]�[PubMed]
91.�Hillier K, Jewell R, Dorrell L, Smith CL. Incorporation of fatty acids from fish oil and olive oil into colonic mucosal lipids and effects upon eicosanoid synthesis in inflammatory bowel disease.�Gut.�1991;32:1151�1155.�[PMC free article]�[PubMed]
92.�Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma)�J Biol Chem.�1995;270:12953�12956.�[PubMed]
93.�Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA. Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs.�J Biol Chem.�1997;272:3406�3410.�[PubMed]
94.�Delerive P, Furman C, Teissier E, Fruchart J, Duriez P, Staels B. Oxidized phospholipids activate PPARalpha in a phospholipase A2-dependent manner.�FEBS Lett.�2000;471:34�38.�[PubMed]
95.�Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM, et al. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma.�Proc Natl Acad Sci USA.�1997;94:4318�4323.�[PMC free article]�[PubMed]
96.�Forman BM, Chen J, Evans RM. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta.�Proc Natl Acad Sci USA.�1997;94:4312�4317.�[PMC free article]�[PubMed]
97.�Mans�n A, Guardiola-Diaz H, Rafter J, Branting C, Gustafsson JA. Expression of the peroxisome proliferator-activated receptor (PPAR) in the mouse colonic mucosa.�Biochem Biophys Res Commun.�1996;222:844�851.�[PubMed]
98.�Desreumaux P, Ernst O, Geboes K, Gambiez L, Berrebi D, M�ller-Alouf H, Hafraoui S, Emilie D, Ectors N, Peuchmaur M, et al. Inflammatory alterations in mesenteric adipose tissue in Crohn’s disease.�Gastroenterology.�1999;117:73�81.�[PubMed]
99.�Su CG, Wen X, Bailey ST, Jiang W, Rangwala SM, Keilbaugh SA, Flanigan A, Murthy S, Lazar MA, Wu GD. A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response.�J Clin Invest.�1999;104:383�389.�[PMC free article]�[PubMed]
100.�Ricote M, Huang J, Fajas L, Li A, Welch J, Najib J, Witztum JL, Auwerx J, Palinski W, Glass CK. Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein.�Proc Natl Acad Sci USA.�1998;95:7614�7619.�[PMC free article]�[PubMed]
101.�Staels B, Koenig W, Habib A, Merval R, Lebret M, Torra IP, Delerive P, Fadel A, Chinetti G, Fruchart JC, et al. Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators.�Nature.�1998;393:790�793.�[PubMed]
102.�Marx N, Bourcier T, Sukhova GK, Libby P, Plutzky J. PPARgamma activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARgamma as a potential mediator in vascular disease.�Arterioscler Thromb Vasc Biol.�1999;19:546�551.�[PubMed]
103.�Delerive P, Martin-Nizard F, Chinetti G, Trottein F, Fruchart JC, Najib J, Duriez P, Staels B. Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway.�Circ Res.�1999;85:394�402.�[PubMed]
104.�Sakai M, Matsushima-Hibiya Y, Nishizawa M, Nishi S. Suppression of rat glutathione transferase P expression by peroxisome proliferators: interaction between Jun and peroxisome proliferator-activated receptor alpha.�Cancer Res.�1995;55:5370�5376.�[PubMed]
105.�Zhou YC, Waxman DJ. STAT5b down-regulates peroxisome proliferator-activated receptor alpha transcription by inhibition of ligand-independent activation function region-1 trans-activation domain.�J Biol Chem.�1999;274:29874�29882.�[PubMed]
106.�Desreumaux P, Dubuquoy L, Nutten S, Peuchmaur M, Englaro W, Schoonjans K, Derijard B, Desvergne B, Wahli W, Chambon P, et al. Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimer. A basis for new therapeutic strategies.�J Exp Med.�2001;193:827�838.�[PMC free article]�[PubMed]
107.�Lewis JD, Lichtenstein GR, Stein RB, Deren JJ, Judge TA, Fogt F, Furth EE, Demissie EJ, Hurd LB, Su CG, et al. An open-label trial of the PPAR-gamma ligand rosiglitazone for active ulcerative colitis.�Am J Gastroenterol.�2001;96:3323�3328.�[PubMed]
108.�G�ttlicher M, Widmark E, Li Q, Gustafsson JA. Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor.�Proc Natl Acad Sci USA.�1992;89:4653�4657.[PMC free article]�[PubMed]
Close Accordion
Assessment and Treatment of Quadratus Lumborum

Assessment and Treatment of Quadratus Lumborum

by | Chiropractic, Conditions Treated, Functional Medicine, Injury Care

These assessment and treatment recommendations represent a synthesis of information derived from personal clinical experience and from the numerous sources which are cited, or are based on the work of researchers, clinicians and therapists who are named (Basmajian 1974, Cailliet 1962, Dvorak & Dvorak 1984, Fryette 1954, Greenman 1989, 1996, Janda 1983, Lewit 1992, 1999, Mennell 1964, Rolf 1977, Williams 1965).

 

Clinical Application of Neuromuscular Techniques: Quadratus Lumborum

 

Assessment of Shortness in Quadratus Lumborum (Figure 4.21)

 

Figure 4 21 Palpation Assessment for Quadratus Lumborum Overactivity Image 1

 

Figure 4.21 Palpation assessment for quadratus lumborum overactivity. The muscle is palpated, as is gluteus medius, during abduction of the leg. The correct firing sequence should be gluteus, followed at around 25� elevation by quadratus. If there is an immediate �grabbing� action by quadratus it indicates overactivity, and therefore stress, so shortness can be assumed (see details of similar functional assessments in Ch. 5).

 

Review Lewit�s functional palpation test described under the heading assessment and treatment of tensor fascia lata.

 

When the leg of the side-lying patient is abducted, and the practitioner�s palpating hand senses that quadratus becomes involved in this process before the leg has reached at least 25� of elevation, then it is clear that quadratus is overactive. If it has been overactive for any length of time then it is almost certainly hypertonic and short, and a need for MET can be assumed.

 

Quadratus lumborum test (a) (See also Fig. 5.11A, B.) The patient is side-lying and is asked to take the upper arm over the head to grasp the top edge of the table, �opening out� the lumbar area. The practitioner stands facing the back of the patient, and has easy access for palpation of quadratus lumborum�s lateral border � a major trigger point site (Travell & Simons 1992) � with the cephalad hand.

 

Activity of quadratus is tested (palpated for) with the cephalad hand as the leg is abducted, while also palpating gluteus medius with the caudad hand. If the muscles act simultaneously, or if quadratus fires first, then it is stressed, probably short, and will benefit from stretching.

 

Quadratus lumborum test (b) The patient stands, back towards crouching practitioner. Any leg length disparity (based on pelvic crest height) is equalised by using a book or pad under the short leg side heel. With the patient�s feet shoulder-width apart, a pure sidebending is requested, so that the patient runs a hand down the lateral thigh/calf. (Normal level of sidebending excursion allows the fingertips to reach to just below the knee.) (See Fig. 3.2A, B, C.)

 

The side to which the fingertips travel furthest is assessed. If sidebending to one side is limited then quadratus on the opposite side is probably short. Combined evidence from palpation (test a) and this sidebending test indicate whether or not it is necessary to treat quadratus.

 

Box 4.8 Notes on Quadratus Lumborum

 

  • Norris (2000) describes the divided roles in which quadratus is involved: The quadratus lumborum has been shown to be significant as a stabiliser in lumbar spine movements (McGill et al 1996) while tightening has also been described (Janda 1983). It seems likely that the muscle may act functionally differently in its medial and lateral portions, with the medial portion being more active as a stabiliser of the lumbar spine, and the lateral more active as a mobiliser [see stabiliser/mobiliser discussion Ch. 2]. Such subdivision is seen in a number of other muscles for example the gluteus medius where the posterior fibres are more posturally involved (Jull 1994) the internal oblique where the posterior fibres attaching to the lateral raphe are considered stabilisers (Bergmark 1989) the external oblique where the lateral fibres work during flexion in parallel with the rectus abdominis (Kendall et al 1993).
  • Janda (1983) observes that, when the patient is sidebending (as in method (b)) �when the lumbar spine appears straight, with compensatory motion occurring only from the thoracolumbar region upwards, tightness of quadratus lumborum may be suspected�. This �whole lumbar spine� involvement differs from a segmental restriction which would probably involve only a part of the lumbar spine.
  • Quadratus fibres merge with the diaphragm (as do those of psoas), which makes involvement in respiratory dysfunction a possibility since it plays a role in exhalation, both via this merging and by its attachment to the 12th rib.
  • Shortness of quadratus, or the presence of trigger points, can result in pain in the lower ribs and along the iliac crest if the lateral fibres are affected. Shortness of the medial fibres, or the presence of trigger points, can produce pain in the sacroiliac joint and the buttock.
  • Bilateral contraction produces extension and unilateral contraction produces extension and sidebending to the same side.
  • The important transition region, the lumbodorsal junction (LDJ), is the only one in the spine in which two mobile structures meet, and dysfunction results in alteration of the quality of motion between these structures (upper and lower trunk/dorsal and lumbar spines). In dysfunction there is often a degree of spasm or tightness in the muscles which stabilise the region, notably: psoas and erector spinae of the thoracolumbar region, as well as quadratus lumborum and rectus abdominis.
  • Symptomatic differential diagnosis of muscle involvement at the LDJ is possible as follows: psoas involvement usually triggers abdominal pain if severe and produces flexion of the hip and the typical antalgesic posture of lumbago; erector spinae involvement produces low back pain at its caudad end of attachment and interscapular pain at its thoracic attachment (as far up as the mid-thoracic level); quadratus lumborum involvement causes lumbar pain and pain at the attachment of the iliac crest and lower ribs; and rectus abdominis contraction may mimic abdominal pain and result in pain at the attachments at the pubic symphysis and the xiphoid process, as well as forwardbending of the trunk and restricted ability to extend the spine.

 

There is seldom pain at the site of the lesion in LDJ dysfunction. Lewit (1992) points out that even if a number of these muscles are implicated, it is seldom necessary, using PIR methods, to treat them all since, as the muscles most involved (discovered by tests for shortness, overactivity, sensitivity and direct palpation) are stretched and normalised, so will others begin automatically to normalise.

 

MET for Shortness in Quadratus Lumborum (�banana�)

 

Quadratus lumborum MET method (a) (Fig. 4.22) The patient lies supine with the feet crossed (the side to be treated crossed under the non-treated side leg) at the ankle. The patient is arranged in a light sidebend, away from the side to be treated, so that the pelvis is towards that side, and the feet and head away from that side (�banana shaped�). As this sidebend is being achieved the affected quadratus can be palpated for bind so that the barrier is correctly identified.

 

Figure 4 22 MET Treatment of Quadratus Lumborum Utilizing Banana Position Image 2

 

Figure 4.22 MET treatment of quadratus lumborum utilising �banana� position.

 

The patient�s heels are placed just off the side of the table, anchoring the lower extremities and pelvis. The patient places the arm of the side to be treated behind her neck as the practitioner, standing on the side opposite that to be treated, slides his cephalad hand under the patient�s shoulders to grasp the treated side axilla. The patient grasps the practitioner�s cephalad arm at the elbow, with the treated side hand, making the contact more secure.

 

The patient�s treated side elbow should, at this stage, be pointing superiorly. The practitioner�s caudad hand is placed firmly but carefully on the anterior superior iliac spine, on the side to be treated. The patient is instructed to very lightly sidebend towards the treated side. This should produce an isometric contraction in quadratus lumborum on the side to be treated.

 

After 7 seconds the patient is asked to relax completely, and then to sidebend towards the nontreated side, as the practitioner simultaneously transfers his bodyweight from the cephalad leg to the caudad leg and leans backwards slightly, in order to sidebend the patient. This effectively stretches quadratus lumborum. The stretch is held for 15�20 seconds, allowing a lengthening of shortened musculature in the region. Repeat as necessary.

 

Quadratus lumborum MET method (b) (Fig 4.23) The practitioner stands behind the side-lying patient, at waist level. The patient has the uppermost arm extended over the head to firmly grasp the top end of the table and, on an inhalation, abducts the uppermost leg until the practitioner palpates strong quadratus activity (elevation of around 30� usually).

 

Figure 4 23 MET Treatment of Quadratus Lumborum Image 3

 

Figure 4.23 MET treatment of quadratus lumborum. Note that it is important after the isometric contraction (sustained raised/abducted leg) that the muscle be eased into stretch, avoiding any defensive or protective resistance which sudden movement might produce. For this reason, body weight rather than arm strength should be used to apply traction.

 

The patient holds the leg (and, if appropriate, the breath, see Box 4.2) isometrically in this manner, allowing gravity to provide resistance. After the 10-second (or so) contraction, the patient allows the leg to hang slightly behind him over the back of the table. The practitioner straddles this and, cradling the pelvis with both hands (fingers interlocked over crest of pelvis), leans back to take out all slack and to �ease the pelvis away from the lower ribs� during an exhalation.

 

The stretch should be held for between 10 and 30 seconds. (The method will only be successful if the patient is grasping the top edge of the table, so providing a fixed point from which the practitioner can induce stretch.)

 

Contraction followed by stretch is repeated once or twice more with raised leg in front of, and once or twice with raised leg behind the trunk in order to activate different fibres. The direction of stretch should be varied so that it is always in the same direction as the long axis of the abducted leg. This calls for the practitioner changing from the back to the front of the table for the best results. When the leg hangs to the back of the trunk the long fibres of the muscle are mainly affected; and when the leg hangs forward of the body the diagonal fibres are mainly involved.

 

Quadratus lumborum MET method (c) Gravity-induced postisometric relaxation of quadratus lumborum � self-treatment (See Fig. 3.2A�C and captions) The patient stands, legs apart, bending sideways. The patient inhales and slightly raises the trunk (a few centimetres) at the same time as looking (with the eyes only) away from the side to which side-flexion is taking place. On exhalation, the sidebend is allowed to slowly go further to its elastic limit, while the patient looks towards the floor, in the direction of the side-flexion. (Care is needed that very little, if any, forward or backward bending is taking place at this time.) This sequence is repeated a number of times.

 

Eye positions influence the tendency to flex and sidebend (eyes look down) and extend (eyes look up) (Lewit 1999). Gravity-induced stretches of this sort require holding the stretch position for at least as long as the contraction, and ideally longer. More repetitions may be needed with a large muscle such as quadratus, and home stretches should be advised several times daily. Quadratus lumborum MET method (d) The side-lying treatment of latissimus dorsi described below also provides an effective quadratus stretch when the stabilising hand rests on the pelvic crest (see Fig. 4.29).

 

Dr. Alex Jimenez offers an additional assessment and treatment of the hip flexors as a part of a referenced clinical application of neuromuscular techniques by Leon Chaitow and Judith Walker DeLany. The scope of our information is limited to chiropractic and spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

 

By Dr. Alex Jimenez

 

Green-Call-Now-Button-24H-150x150-2-3.png

 

Additional Topics: Wellness

 

Overall health and wellness are essential towards maintaining the proper mental and physical balance in the body. From eating a balanced nutrition as well as exercising and participating in physical activities, to sleeping a healthy amount of time on a regular basis, following the best health and wellness tips can ultimately help maintain overall well-being. Eating plenty of fruits and vegetables can go a long way towards helping people become healthy.

 

blog picture of cartoon paperboy big news

 

WELLNESS TOPIC: EXTRA EXTRA: Managing Workplace Stress