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

Functional Medicine

Back Clinic Functional Medicine Team. Functional medicine is an evolution in the practice of medicine that better addresses the healthcare needs of the 21st century. By shifting the traditional disease-centered focus of medical practice to a more patient-centered approach, functional medicine addresses the whole person, not just an isolated set of symptoms.

Practitioners spend time with their patients, listening to their histories and looking at the interactions among genetic, environmental, and lifestyle factors that can influence long-term health and complex, chronic disease. In this way, functional medicine supports the unique expression of health and vitality for each individual.

By changing the disease-centered focus of medical practice to this patient-centered approach, our physicians are able to support the healing process by viewing health and illness as part of a cycle in which all components of the human biological system interact dynamically with the environment. This process helps to seek and identify genetic, lifestyle, and environmental factors that may shift a person’s health from illness to well-being.

Vertebral Artery Dissection Found During Chiropractic Examination

Vertebral Artery Dissection Found During Chiropractic Examination

by | Chiropractic, Clinical Case Reports, Clinical Case Series, Functional Medicine

Acknowledging the subsequent information below,�approximately more than 2 million people are injured in automobile accidents each year and among those incidents, the majority of the people involved are diagnosed with whiplash and/or neck injury by a healthcare professional. When the complex structure of the neck is subjected to trauma, tissue damage and other medical complications may occur. Vertebral artery dissection, or VAD, is characterized by a flap-like tear on the inner lining of the vertebral artery in charge of supplying blood to the brain. After the tear, blood can then enter the arterial wall and form a blood clot, thickening the artery wall and often impeding blood flow.

 

Through years of experience practicing chiropractic care,�VAD may often follow after trauma to the neck, such as that which occurs in an automobile accident, or whiplash injury. The symptoms of vertebral artery dissection include head and neck pain as well as intermittent or permanent stroke symptoms, such as difficulty speaking, impaired coordination and loss of vision. VAD, or vertebral artery dissection, is generally diagnosed with a contrast-enhanced CT or MRI scan.

 

Abstract

 

A 30-year-old woman presented to an emergency department with sudden onset of transient loss of left peripheral vision. Owing to a history of migraine headaches, she was released with a diagnosis of ocular migraine. Two days later, she sought chiropractic care for the chief symptom of severe neck pain. The chiropractor suspected the possibility of vertebral artery dissection (VAD). No manipulation was performed; instead, MR angiography (MRA) of the neck was obtained, which revealed an acute left VAD with early thrombus formation. The patient was placed on aspirin therapy. Repeat MRA of the neck 3?months later revealed resolution of the thrombus, without progression to stroke. This case illustrates the importance for all healthcare providers who see patients with neck pain and headache to be attentive to the symptomatic presentation of possible VAD in progress.

 

Background

 

Vertebral artery dissection (VAD) leading to stroke is an uncommon but potentially serious disorder. The incidence of stroke related to the vertebrobasilar system varies from 0.75 to 1.12/100?000 person-years. The pathological process in VAD typically involves dissection of the wall of the artery followed sometime later by thrombus formation, which may cause arterial occlusion or may lead to embolisation, causing occlusion of one or more of the distal branches off the vertebral artery, including the basilar artery, which can be catastrophic. VAD typically occurs in patients who have an inherent, transitory weakness in the arterial wall. In at least 80% of cases, the initial symptoms include neck pain with or without headache.

 

Many patients with VAD may in the early stages present to chiropractors seeking relief from neck pain and headache, without realising they are experiencing VAD. In many of these cases, the patient later develops a stroke. Until recently, it was assumed that the dissection (and subsequent stroke) was caused by cervical manipulative therapy (CMT). However, while early studies found an association between visits to a chiropractor and subsequent stroke related to VAD, recent data suggest that this relationship is not causal.

 

This case report is illustrative of the scenario in which a patient with an undiagnosed VAD in evolution consulted a chiropractor for neck pain and headache. After thorough history and examination, the chiropractor suspected VAD and did not perform CMT. Instead, the patient was referred for further evaluation, which detected a VAD in progress. Prompt diagnosis and anticoagulant treatment were thought to have averted progression to a stroke.

 

Case Presentation

 

A 30-year-old otherwise healthy woman consulted a chiropractor (DBF), reporting of right-sided neck pain in the suboccipital region. The patient reported that, 3?days previously, she had gone to the local hospital emergency department (ED) because of the sudden onset of loss of left peripheral vision. The visual symptoms interfered with her ability to see through her left eye; this was accompanied by �numbness� in her left eyelid. About 2?weeks prior to this ED visit, she had experienced an episode of acute left-sided neck pain with severe left-sided headache. She also related a history of migraine headache without prodrome. She was released from the ED with a tentative diagnosis of ocular migraine. She had never been previously diagnosed with ocular migraine, nor had she ever experienced any visual disturbances with her previous migraines.

 

Shortly after the left-sided ocular symptoms resolved, she suddenly developed right-sided neck pain without provocation, for which she sought chiropractic treatment. She also reported a transient episode of right-sided visual disturbance occurring that same day as well. This was described as sudden blurriness that was of short duration and resolved spontaneously earlier in the day of her presentation for chiropractic examination. When she presented for the initial chiropractic examination, she denied current visual disturbance. She said that she was not experiencing any numbness, paraesthesia or motor loss in the upper or lower extremities. She denied ataxia or difficulty with balance. Medical history was remarkable for childbirth 2� months prior to initial presentation. She stated that her migraine headaches were associated with her menstrual cycle. Family history was remarkable for a spontaneous ascending thoracic aortic aneurysm in her older sister, who was about 30?years of age when her aneurysm had occurred.

 

Investigations

 

Based on the history of sudden onset of severe upper cervical pain and headache with visual disturbance and ocular numbness, the DC was concerned about the possibility of early VAD. Urgent MR angiography (MRA) of the neck and head, along with MRI of the head, was ordered. No cervical spine examination or manipulation was performed because of the suspicion that the neck pain was related to VAD rather than to a �mechanical� cervical disorder.

 

MRA of the neck demonstrated that the left vertebral artery was small and irregular in calibre, extending from the C7 level cephalad to C2, consistent with dissection. There was a patent true lumen with a surrounding cuff of T1 hyper-intensity, consistent with dissection with subintimal thrombus within the false lumen (Figures 1 and ?2). MRI of the head with and without contrast, and MRA of the head without contrast, were both unremarkable. Specifically, there was no intracranial extension of dissection or evidence of infarction. MR perfusion of the brain revealed no focal perfusion abnormalities.

 

Figure 1 Axial Proton Density Image - Image 1

Figure 1: Axial proton density image demonstrates circumferential hyper-intensity surrounding the left cervical vertebral artery (representing the false lumen). Note decreased calibre of true lumen (black flow void) with respect to the right vertebral artery.

 

Figure 2 Axial Image from Three Dimensional Time of Flight MRA - Image 2

Figure 2: Axial image from three-dimensional time-of-flight MRA demonstrates T1 hypointense dissection flap separating the true lumen (lateral) from the false lumen (medial). MRA, MR angiography.

 

Differential Diagnosis

 

The ED released the patient with a tentative diagnosis of ocular migraine, due to her history of migraine headaches. However, the patient stated that the left-sided headache was atypical��like nothing I’ve ever experienced before.� Her previous migraines were associated with her menstrual cycle, but not with any vision changes. She had never been previously diagnosed with ocular migraine. MRA of the cervical region revealed that the patient actually had an acute dissection with thrombus formation in the left vertebral artery.

 

Treatment

 

Owing to the potential of impending stroke associated with an acute VAD with thrombus formation, the patient was admitted to the neurology stroke service for close neurological monitoring. During her admission, the patient did not experience any recurrence of neurological deficits and her headaches improved. She was discharged the following day with a diagnosis of left VAD and transient ischaemic attack. She was instructed to avoid vigorous exercise and trauma to the neck. Daily aspirin (325?mg) was prescribed, to be continued for 3�6?months after discharge.

 

Outcome and Follow-Up

 

After discharge from the stroke service, the patient had no recurrence of headache or visual disturbances, and her posterior neck pain symptoms resolved. Repeat imaging was performed 3?months after presentation, which demonstrated improved calibre of the cervical left vertebral artery with resolution of the thrombus within the false lumen (Figure 3). Imaging of the intracranial compartment remained normal, without evidence of interval infarction or perfusion asymmetry.

 

Figure 3 Maximum Intensity Projection MIP Images - Image 3

Figure 3: Maximum intensity projection (MIP) images from three-dimensional time-of-flight MRA (left image is at time of presentation and right image is at 3-month follow-up). The initial imaging demonstrates markedly diminutive calibre of the left vertebral artery

 

Discussion

 

The pathophysiological process of VAD is thought to start with degeneration of the tissues at the medial-adventitial border of the vertebral artery, leading to the development of microhaematomata within the wall of the artery and, eventually, arterial tear. This can lead to leakage of blood into the arterial wall, causing occlusion of the lumen with subsequent thrombus formation and embolisation, resulting in stroke related to one of the branches of the vertebral artery. This pathological process is similar to that of spontaneous carotid artery dissection, spontaneous thoracic aortic dissection and spontaneous coronary artery dissection. All these conditions tend to occur in younger adults and some have speculated that they may be part of a common inherited pathophysiological process. Notable in this case is the fact that the patient’s older sister had experienced a spontaneous thoracic aortic aneurysm (probably a dissection) at around the same age (30?years) as this patient was when she experienced her VAD.

 

While the dissection is often sudden, the luminal compromise and complications of VAD can develop gradually leading to variable symptoms and presentation, depending on the stage of the disease. The dissection itself, which develops some time before the onset of neural ischaemia, can cause stimulation of nociceptive receptors within the artery, producing pain that is most commonly felt in the upper cervical spine or head. Only after the pathophysiological process progresses to the point of complete arterial occlusion or thrombus formation with distal embolisation does the full manifestation of infarction occur. However, as illustrated in this case, neurological symptoms can develop early in the process, particularly in cases in which the true lumen demonstrates significant calibre decrease secondary to compression.

 

There are several interesting aspects to this case. First, it highlights the importance of spine clinicians being alert to the possibility that what may appear to be typical �mechanical� neck pain could be something potentially more sinister, such as VAD. The sudden onset of severe suboccipital pain, with or without headache, and accompanying brainstem related neurological symptoms, should alert the clinician to the possibility of VAD. As in the case reported here, patients with a history of migraine will typically describe the headache as different from their usual migraine. A careful neurological examination should be performed, looking for possible subtle neurological deficits, although the neurological examination will often be negative in the early stages of VAD.

 

Second, a triad of symptoms raised concern that the patient might be experiencing a VAD in progress. The symptom triad included: (1) spontaneous onset of severe upper cervical pain; (2) severe headache that was distinctly different from the patient’s usual migraine headaches; and (3) brainstem-related neurological symptoms (in the form of transient visual disturbance). Notably, careful neurological examination was negative. Nonetheless, the history was of sufficient concern to prompt immediate investigation.

 

When VAD is suspected but no frank signs of stroke are present, immediate vascular imaging is indicated. While the optimal imaging evaluation of VAD remains controversial, MRA or CTA are the diagnostic studies of choice given their excellent anatomic delineation and ability to evaluate for complications (including infarction and changes in brain perfusion). Some advocate the use of Doppler ultrasound; however, it has limited utility given the course of the vertebral artery in the neck and limited evaluation of the vertebral arteries cephalad to the origin. Additionally, ultrasound imaging is unlikely to allow visualisation of the dissection itself and thus can be negative in the absence of significant arterial occlusion.

 

Third, this case is interesting in light of the controversy about cervical manipulation as a potential �cause� of VAD. While case reports have presented patients who have experienced stroke related to VAD after cervical manipulation, and case�control studies have found a statistical association between visits to chiropractors and stroke related to VAD, further investigation has indicated that the association is not causal. Cassidy et al found that a patient who experiences stroke related to VAD is just as likely to have visited a primary care practitioner as to have visited a chiropractor prior to having the stroke. The authors suggested that the most likely explanation for the statistical association between visits to chiropractors and subsequent VAD is that a patient who experiences the initial symptoms of VAD (neck pain with or without headache) seeks medical attention for these symptoms (from a chiropractor, primary care practitioner, or another type of practitioner), then subsequently experiences the stroke, independent of any action taken by the practitioner.

 

It is important to note that, while there have been reported cases of carotid artery dissection after cervical manipulation, case�control studies have not found this association. The initial symptoms of carotid dissection (neurological symptoms, with neck and head pain less common than VAD), aortic dissection (sudden onset of severe, �tearing� pain) and coronary artery dissection (acute severe chest pain, ventricular fibrillation) are likely to cause the individual to immediately seek ED care, rather than seek chiropractic care. However, VAD has seemingly benign initial symptoms�neck pain and headache�which are symptoms that commonly cause patients to seek out chiropractic care. This may explain why only VAD is associated with visits to chiropractors, while these other types of dissections are not; patients with these other conditions, which have much more alarming symptoms, simply do not present to chiropractors.

 

This case is a good example of a patient with VAD in progress presenting to a chiropractor for the purpose of seeking relief from neck pain. Fortunately, the chiropractor was astute enough to ascertain that the patient’s symptoms were not suggestive of a �mechanical� cervical spine disorder, and appropriate diagnostic investigation was performed. However, if manipulation had been performed, the VAD that was already in progress from natural history may have been blamed on manipulation, after being detected on MRA imaging. Fortunately, in this case, the chiropractor was able to assist with early detection and treatment, and subsequently a stroke was likely averted.

 

Learning Points

 

  • A case is presented in which a patient saw a chiropractor, while seeking treatment for neck pain, and the history raised concern for possible vertebral artery dissection (VAD).
  • Rather than providing manipulative treatment, the chiropractor referred the patient for advanced imaging, which confirmed the diagnosis of VAD.
  • The case illustrates the importance of paying attention to subtle historical factors in patients with VAD.
  • It also serves as an example of a patient with a VAD in progress seeking the services of a chiropractor for the initial symptoms of the disorder.
  • In this case, early detection of the dissection occurred and the patient had a full recovery without any subsequent stroke.

 

Acknowledgments

 

The authors would like to acknowledge the assistance of Pierre Cote, DC, PhD, for his assistance with reviewing this manuscript.

 

Footnotes

 

Contributors: All the authors acknowledge that they have contributed the following to the submission of this manuscript: conception and design, drafting of the manuscript, critical revisions of the manuscript, literature review and references, and proof reading of the final manuscript.

 

Competing interests: None declared.

 

Patient consent: Obtained.

 

Provenance and peer review: Not commissioned; externally peer reviewed.

 

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

 

Cited 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

 

IMPORTANT TOPIC: EXTRA EXTRA: Treating Sciatica Pain

 

 

Blank
References
1.�Debette S, Leys D.�Cervical-artery dissections: predisposing factors, diagnosis, and outcome.�Lancet Neurol�2009;8:668�78.�doi:10.1016/S1474-4422(09)70084-5�[PubMed]
2.�Boyle E, Cote P, Grier AR et al.�Examining vertebrobasilar artery stroke in two Canadian provinces.�Spine�2008;33(4 Suppl):S170�5.�doi:10.1097/BRS.0b013e31816454e0�[PubMed]
3.�Lee VH, Brown RD Jr, Mandrekar JN et al.�Incidence and outcome of cervical artery dissection: a population-based study.�Neurology�2006;67:1809�12.�doi:10.1212/01.wnl.0000244486.30455.71[PubMed]
4.�Schievink WI.�Spontaneous dissection of the cartoid and vertebral arteries.�N Engl J Med�2001;344:898�906.�doi:10.1056/NEJM200103223441206�[PubMed]
5.�Volker W, Dittrich R, Grewe S et al.�The outer arterial wall layers are primarily affected in spontaneous cervical artery dissection.�Neurology�2011;76:1463�71.�doi:10.1212/WNL.0b013e318217e71c�[PubMed]
6.�Gottesman RF, Sharma P, Robinson KA et al.�Clinical characteristics of symptomatic vertebral artery dissection: a systematic review.�Neurologist�2012;18:245�54.�doi:10.1097/NRL.0b013e31826754e1[PMC free article]�[PubMed]
7.�Cassidy JD, Boyle E, Cote P et al.�Risk of vertebrobasilar stroke and chiropractic care: results of a population-based case-control and case-crossover study.�Spine�2008;33(4�Suppl):S176�83.�doi:10.1097/BRS.0b013e3181644600�[PubMed]
8.�Rothwell DM, Bondy SJ, Williams JI.�Chiropractic manipulation and stroke: a population-based case-control study.�Stroke�2001;32:1054�60.�doi:10.1161/01.STR.32.5.1054�[PubMed]
9.�Smith WS, Johnston SC, Skalabrin EJ et al.�Spinal manipulative therapy is an independent risk factor for vertebral artery dissection.�Neurology�2003;60:1424�8.�doi:10.1212/01.WNL.0000063305.61050.E6[PubMed]
10.�Volker W, Besselmann M, Dittrich R et al.�Generalized arteriopathy in patients with cervical artery dissection.�Neurology�2005;64:1508�13.�doi:10.1212/01.WNL.0000159739.24607.98�[PubMed]
11.�Evangelista A, Mukherjee D, Mehta RH et al.�Acute intramural hematoma of the aorta: a mystery in evolution.�Circulation�2005;111:1063�70.�doi:10.1161/01.CIR.0000156444.26393.80�[PubMed]
12.�Tweet MS, Hayes SN, Pitta SR et al.�Clinical features, management, and prognosis of spontaneous coronary artery dissection.�Circulation�2012;126:579�88.�doi:10.1161/CIRCULATIONAHA.112.105718[PubMed]
13.�Choi S, Boyle E, Cote P et al.�A population-based case-series of Ontario patients who develop a vertebrobasilar artery stroke after seeing a chiropractor.�J Manipulative Physiol Ther�2011;34:15�22.�doi:10.1016/j.jmpt.2010.11.001�[PubMed]
14.�Naggara O, Louillet F, Touze E et al.�Added value of high-resolution MR imaging in the diagnosis of vertebral artery dissection.�AJNR Am J Neuroradiol�2010;31:1707�12.�doi:10.3174/ajnr.A2165�[PubMed]
15.�Haynes MJ, Vincent K, Fischhoff C et al.�Assessing the risk of stroke from neck manipulation: a systematic review.�Int J Clin Pract�2012;66:940�7.�doi:10.1111/j.1742-1241.2012.03004.x[PMC free article]�[PubMed]
16.�Nebelsieck J, Sengelhoff C, Nassenstein I et al.�Sensitivity of neurovascular ultrasound for the detection of spontaneous cervical artery dissection.�J Clin Neurosci�2009;16:79�82.�doi:10.1016/j.jocn.2008.04.005�[PubMed]
17.�Bendick PJ, Jackson VP.�Evaluation of the vertebral arteries with duplex sonography.�J Vasc Surg1986;3:523�30.�doi:10.1016/0741-5214(86)90120-5�[PubMed]
18.�Murphy DR.�Current understanding of the relationship between cervical manipulation and stroke: what does it mean for the chiropractic profession?�Chiropr Osteopat�2010;18:22�doi:10.1186/1746-1340-18-22[PMC free article]�[PubMed]
19.�Engelter ST, Grond-Ginsbach C, Metso TM et al.�Cervical artery dissection: trauma and other potential mechanical trigger events.�Neurology�2013;80:1950�7.�doi:10.1212/WNL.0b013e318293e2eb�[PubMed]
20.�Peters M, Bohl J, Th�mke F et al.�Dissection of the internal carotid artery after chiropractic manipulation of the neck.�Neurology�1995;45:2284�6.�doi:10.1212/WNL.45.12.2284�[PubMed]
21.�Nadgir RN, Loevner LA, Ahmed T et al.�Simultaneous bilateral internal carotid and vertebral artery dissection following chiropractic manipulation: case report and review of the literature.�Neuroradiology2003;45:311�14.�doi:10.1007/s00234-003-0944-x�[PubMed]
22.�Dittrich R, Rohsbach D, Heidbreder A et al.�Mild mechanical traumas are possible risk factors for cervical artery dissection.�Cerebrovasc Dis�2007;23:275�81.�doi:10.1159/000098327�[PubMed]
23.�Chung CL, Cote P, Stern P et al.�The association between cervical spine manipulation and carotid artery dissection: a systematic review of the literature.�J Manipulative Physiol Ther�2014; doi:10.1016/j.jmpt.2013.09.005�doi:10.1016/j.jmpt.2013.09.005�[PubMed]
24.�Thomas LC, Rivett DA, Attia JR et al.�Risk factors and clinical features of craniocervical arterial dissection.�Man Ther�2011;16:351�6.�doi:10.1016/j.math.2010.12.008�[PubMed]
25.�Klineberg E, Mazanec D, Orr D et al.�Masquerade: medical causes of back pain.�Cleve Clin J Med2007;74:905�13.�doi:10.3949/ccjm.74.12.905�[PubMed]
Close Accordion
What are Case Reports & Case Series?

What are Case Reports & Case Series?

by | Clinical Case Reports, Clinical Case Series, Functional Medicine

The diagnosis of a variety of diseases has been effectively determined through clinical and experimental data. Research studies provide valuable information on the pathogenesis of many conditions and are often the primary source of information regarding new diseases or conditions. Case reports and case series are first level research studies, offering the most initial insights on a particular health issue through the personal experience of one or more people with a disease or condition. The following article describes the purpose of case reports and case series, and how they provide clinical and experimental data.

 

Learning Objectives

 

1. Case reports and case series describe the experience of one or more people with a disease.
2. Case reports and case series are often the first data alerting to a new disease or condition.
3. Case reports and case series have specific limitations:

  • a. Lack of a denominator to calculate rates of disease
  • b. Lack of a comparison group
  • c. Selecting study populations
  • d. Sampling variation

 

Case Reports and Case Series

 

Case reports and case series represent the most basic type of study design, in which researchers describe the experience of a single person (case report) or a group of people (case series). Typically, case reports and case series describe individuals who develop a particular new disease or condition. Case reports and case series can provide compelling reading because they present a detailed account of the clinical experience of individual study subjects. In contrast, studies that evaluate large numbers of individuals typically summarize the data using statistical measures, such as means and proportions.

 

Example 3.1. A case series describes 15 young women who develop breast cancer; 9 of these women report at least once weekly ingestion of foods packaged with the estrogenic chemical bisphenol A (BPA). Urine testing confirms the presence of BPA among all nine case women.

 

It is tempting to surmise from these data that BPA might be causally related to breast cancer. However, case reports/case series have important limitations that preclude inference of a causal relationship.

First, case reports/case series lack denominator data that are necessary to calculate the rate of disease. The denominator refers to the population from which the diseased subjects arose. For example, to calculate the incidence proportion or incidence rate of breast cancer among women exposed to BPA, the total number of women who were exposed to BPA or the total number of person-years at risk is needed.

 

Table 1 - Incidence Proportion & Incidence Rate

 

Disease rates are needed for comparison with historically reported disease rates, or with rates from a selected comparison group. Unfortunately, obtaining the necessary denominator data may not be easy. In this example, additional data sources are needed to determine the total number of BPA-exposed women from whom the breast cancer cases arose. The case series data alone cannot be used to calculate the rate of breast cancer because they do not include the total number of women who were exposed to BPA.

 

A second problem with case report/case series report data is the lack of a comparison group. The 60% prevalence of BPA exposure among women with breast cancer seems unusually high, but what is prevalence of BPA exposure among women without breast cancer? This comparison is critical for addressing the hypothesis that BPA might be a cause of breast cancer.

 

A third limitation of case reports/case series is that these studies often describe highly select individuals who may not represent the general population. For example, it is possible that the 15 breast cancer cases originated from a single hospital in a community with high levels of air pollution or other potential carcinogens. Under these conditions, a fair estimate of breast cancer incidence among non-BPA exposed women from the same community would be required to make an inference that BPA causes breast cancer.

 

A fourth limitation of case reports/case series is sampling variation. This concept will be explored in detail later in this book. The basic idea is that there is tremendous natural variation in disease development in humans. The fact that 9 of 15 women with breast cancer reported BPA exposure is interesting; however, this number may be very different in the next case series of 15 women with breast cancer simply due to chance. A precise estimate of the rate of a disease, independent from chance, can be obtained only by increasing the number of diseased subjects.

 

Recall the list of factors that are used to judge whether a factor may be a cause of disease:

 

1. Randomized evidence
2. Strength of association
3. Temporal relationship between exposure and outcome
4. Dose-response association
5. Biological plausibility

 

In general, case reports/case series rely almost exclusively on biological plausibility to make their case for causation. For the BPA and breast cancer case series, there is no randomized evidence, no measure of the strength of association between BPA and breast cancer, no reported dose�response association, and no evidence that BPA exposure preceded the development of breast cancer. The inference for causation derives completely from previous biological knowledge regarding the estrogenic effects of BPA.

 

Despite limitations of case series data, they may be highly suggestive of an important new association, disease process, or unintended side effect of a medication or treatment.

 

Example 3.2. In 2007, a case series described three cases of male prepubertal gynecomastia. The report included detailed information on each subjects� age, body size, serum levels of endogenous steroids, and known exposures to exogenous hormones. It was discovered that all three otherwise healthy boys had been exposed to some product containing lavender oil (lotion, shampoo, soap), and that in each case, the gynecomastia resolved upon discontinuation of the product. Subsequent in vitro studies demonstrated endocrine-disrupting activity of lavender oil. This novel case series data may lead to further investigations to determine whether lavender oil, a common ingredient in commercially available products, may be a cause of gynecomastia.

 

Example 3.3. A vaccine designed to prevent rotavirus infection was found to cause weakening of the intestinal muscle layers in animals. Following release of the vaccine, a number of cases of intussusception (when one portion of the bowel slides into the next) were reported in children who received the vaccine, with some fatal cases. The strong biological plausibility underlying this initial association, and knowledge that intussusception is otherwise rare in infants, was highly suggestive of a causal relationship and the vaccine was removed from the market.

 

Information referenced from B. Kestenbaum, Epidemiology and Biostatistics: An Introduction to Clinical Research, DOI 10.1007/978-0-387-88433-2_3, � Springer Science+Business Media, LLC 2009. The scope of our information is limited to chiropractic as well as to spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

 

Referenced 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

 

IMPORTANT TOPIC: EXTRA EXTRA: Treating Sciatica Pain

 

 

Management of Sciatica: Nonsurgical & Surgical Therapies

Management of Sciatica: Nonsurgical & Surgical Therapies

by | Chiropractic, Chiropractic Examination, Clinical Case Reports, Clinical Case Series, Functional Medicine, Sciatica

Consider the following, sciatica is a medical term used to describe a collective group of symptoms resulting from the irritation or compression of the sciatic nerve, generally due to an injury or aggravated condition. Sciatica is commonly characterized by radiating pain along the sciatic nerve, which runs down one or both legs from the lower back. The following case vignette discusses Mr. Winston’s medical condition, a 50-year-old bus driver who reported experiencing chronic, lower back and leg pain associated with sciatica during a 4-week time period. Ramya Ramaswami, M.B., B.S., M.P.H., Zoher Ghogawala, M.D., and James N. Weinstein, D.O., provide a comprehensive analysis of the various treatment options available to treat sciatica, including undergoing lumbar disk surgery and receiving nonsurgical therapy.

 

On a personal note, as a practicing doctor of chiropractic, choosing the correct treatment care for any type of injury or condition can be a personal and difficult decision. If the circumstances are favorable, the patient may determine what is the best form of treatment for their type of medical issue. While nonsurgical therapies, such as chiropractic care, can often be utilized to improve symptoms of sciatica, more severe cases of sciatica may require surgical interventions to treat the source of the issue. In most cases, nonsurgical therapies should be considered first, before turning to surgical therapies for sciatica.

 

Case Vignette

 

A Man with Sciatica Who is Considering Lumbar Disk Surgery

 

Ramya Ramaswami, M.B., B.S., M.P.H.

 

Mr. Winston, a 50-year-old bus driver, presented to your office with a 4-week history of pain in his left leg and lower back. He described a combination of severe sharp and dull pain that originated in his left buttock and radiated to the dorsolateral aspect of his left thigh, as well as vague aching over the lower lumbar spine. On examination, passive raising of his left leg off the table to 45 degrees caused severe pain that simulated his main symptom, and the pain was so severe that you could not lift his leg further. There was no leg or foot weakness. His body-mass index (the weight in kilograms divided by the square of the height in meters) was 35, and he had mild chronic obstructive pulmonary disease as a result of smoking one pack of cigarettes every day for 22 years. Mr. Winston had taken a leave of absence from his work because of his symptoms. You prescribed 150 mg of pregabalin per day, which was gradually increased to 600 mg daily because the symptoms had not abated.

 

Now, 10 weeks after the initial onset of his symptoms, he returns for an evaluation. The medication has provided minimal alleviation of his sciatic pain. He has to return to work and is concerned about his ability to complete his duties at his job. He undergoes magnetic resonance imaging, which shows a herniated disk on the left side at the L4�L5 root. You discuss options for the next steps in managing his sciatica. He is uncertain about invasive procedures such as lumbar disk surgery but feels limited by his symptoms of pain.

 

Treatment Options

 

Which of the following would you recommend for Mr. Winston?

 

  1. Undergo lumbar disk surgery.
  2. Receive nonsurgical therapy.

 

To aid in your decision making, each of these approaches is defended in a short essay by an expert in the field. Given your knowledge of the patient and the points made by the experts, which option would you choose?

 

Option 1: Undergo Lumbar Disk Surgery
Option 2: Receive Nonsurgical Therapy

 

1. Undergo Lumbar Disk Surgery

 

Zoher Ghogawala, M.D.

 

Mr. Winston�s case represents a common scenario in the management of symptomatic lumbar disk herniation. In this particular case, the patient�s symptoms and the physical examination are consistent with nerve-root compression and inflammation directly from an L4�L5 herniated disk on his left side. The patient does not have weakness but has ongoing pain and has been unable to work for the past 10 weeks despite receiving pregabalin. Two questions emerge: first, does lumbar disk surgery (microdiskectomy) provide outcomes that are superior to those with continued nonoperative therapy in patients with more than 6 weeks of symptoms; and second, does lumbar microdiskectomy improve the likelihood of return to work in patients with these symptoms?

 

The highest quality data on the topic come from the Spine Patient Outcomes Research Trial (SPORT). The results of the randomized, controlled trial are difficult to interpret because adherence to the assigned treatment strategy was suboptimal. Only half the patients who were randomly assigned to the surgery group actually underwent surgery within 3 months after enrollment, and 30% of the patients assigned to nonoperative treatment chose to cross over to the surgical group. In this study, the patients who underwent surgery had greater improvements in validated patient-reported outcomes. The treatment effect of microdiskectomy was superior to that of nonoperative treatment at 3 months, 1 year, and 2 years. Moreover, in an as-treated analysis, the outcomes among patients who underwent surgery were superior to those among patients who received nonoperative therapy. Overall, the results of SPORT support the use of microdiskectomy in this case.

 

Results of clinical trials are based on a comparison of treatment options in study populations and may or may not apply to individual patients. SPORT did not specify what type of nonoperative therapy was to be used. Physical therapy was used in 73% of the patients, epidural injections in 50%, and medical therapies (e.g., nonsteroidal antiinflammatory drugs) in more than 50%. In the case of Mr. Winston, pregabalin has been tried, but physical therapy and epidural glucocorticoid injections have not been attempted. Despite widespread use of physical therapy for the treatment of lumbar disk herniation, the evidence supporting its effectiveness is inconclusive, according to published guidelines of the North American Spine Society. On the other hand, there is evidence that transforaminal epidural glucocorticoid injection provides short-term relief (30 days) in patients with nerve-root symptoms directly related to a herniated disk. Overall, there is evidence, from SPORT and from a randomized trial from the Netherlands published in the Journal, that early surgery between 6 and 12 weeks after the onset of symptoms provides greater alleviation of leg pain and better overall pain relief than prolonged conservative therapy.

 

The ability to return to work has not been formally studied in comparisons of operative with nonoperative treatments for lumbar disk herniation. Registry data from the NeuroPoint-SD study showed that more than 80% of the patients who were working before disk herniation returned to work after surgery. The ability to return to work may be dependent on the type of vocation, since patients who are manual laborers may need more time to recover to reduce the risk of reherniation.

 

It is well recognized that many patients who have a symptomatic lumbar disk herniation will have improvement spontaneously over several months. Surgery can alleviate symptoms more quickly by immediately removing the offending disk herniation from the affected nerve root. The risk�benefit equation will vary among individual patients. In the case of Mr. Winston, obesity and mild pulmonary disease might increase the risk of complications from surgery, although in SPORT, 95% of surgical patients did not have any operative or postoperative complication. For Mr. Winston, a patient with pain that has persisted for more than 6 weeks, microdiskectomy is a rational option that is supported by high-quality evidence.

 

2. Receive Nonsurgical Therapy

 

James N. Weinstein, D.O.

 

This case involves a common presentation of low back pain radiating to the buttock and posterolateral thigh that might represent either referred mechanical pain or radiculopathy. Classic radiculopathy resulting from compression of a lower lumbar nerve root (L4, L5, or S1) results in pain that radiates distal to the knee and is often accompanied by weakness or numbness in the respective myotome or dermatome. In this case, the pain is proximal to the knee and is not associated with weakness or numbness. In SPORT, surgery resulted in faster recovery and a greater degree of improvement than nonoperative treatment in patients with pain that radiated distal to the knee and was accompanied by neurologic signs or symptoms. However, since Mr. Winston would not have met the inclusion criteria for SPORT, the results of diskectomy in this case would be somewhat unpredictable. He does not have radiculopathy that radiates below the knee, and he does not have weakness or numbness; nonoperative treatment should be exhausted before any consideration of a surgical procedure that in most cases has not been shown to be effective in patients with this type of presentation. In this issue of the Journal, Mathieson and colleagues report the results of a randomized, controlled trial that showed that pregabalin did not significantly alleviate pain related to sciatica. Mr. Winston has been treated only with pregabalin; therefore, other conservative options should be explored.

 

Saal and Saal reported that more than 80% of patients with radiculopathy associated with a lumbar disk herniation had improvement in a matter of months with exercise-based physical therapy. In the nonoperative SPORT cohort, patients had significant improvement from baseline, and approximately 60% of those with classic radiculopathy who initially received nonoperative treatment avoided surgery. Mr. Winston has had minimal treatment and has had symptoms for only 10 weeks. He should undergo a course of exercise-based physical therapy and a trial of a nonsteroidal antiinflammatory medication and may consider a lumbar epidural glucocorticoid injection. Although there is little evidence of the effectiveness of these nonoperative options alone, the combination of these treatments and the benign natural history of the patient�s condition could result in alleviation or resolution of symptoms. If these interventions � and time � do not resolve his symptoms, surgery could be considered as a final option, but it may not have long-term effectiveness and could in and of itself cause the possibility of more harm than good. Mr. Winston has risk factors, such as obesity and a history of smoking, that have been shown to contribute to poor surgical outcomes of certain spinal procedures.

 

Mr. Winston has symptoms of back pain that interfere with his quality of life. He would need to understand, through shared decision making, that a nonsurgical approach is likely to be more effective than surgery over time.

 

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

 

Cited 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

 

IMPORTANT TOPIC: EXTRA EXTRA: Treating Sciatica Pain

 

 

Blank
References

 

  • 1. Weinstein JN, Tosteson TD, Lurie JD, et al. Surgical vs nonoperative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT): a randomized trial. JAMA 2006;296:2441–2450

  • 2. Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical vs nonoperative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT) observational cohort. JAMA 2006;296:2451–2459

  • 3. Kreiner DS, Hwang SW, Easa JE, et al. An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy. Spine J 2014;14:180–191

  • 4. Ghahreman A, Ferch R, Bogduk N. The efficacy of transforaminal injection of steroids for the treatment of lumbar radicular pain. Pain Med 2010;11:1149–1168

  • 5. Peul WC, van Houwelingen HC, van den Hout WB, et al. Surgery versus prolonged conservative treatment for sciatica. N Engl J Med 2007;356:2245–2256

  • 6. Ghogawala Z, Shaffrey CI, Asher AL, et al. The efficacy of lumbar discectomy and single-level fusion for spondylolisthesis: results from the NeuroPoint-SD registry: clinical article. J Neurosurg Spine 2013;19:555–563

  • 7. Deyo RA, Weinstein JN. Low back pain. N Engl J Med 2001;344:363–370

  • 8. Lurie JD, Tosteson TD, Tosteson AN, et al. Surgical versus nonoperative treatment for lumbar disc herniation: eight-year results for the spine patient outcomes research trial. Spine (Phila Pa 1976) 2014;39:3–16

  • 9. Mathieson S, Maher CG, McLachlan AJ, et al. Trial of pregabalin for acute and chronic sciatica. N Engl J Med 2017;376:1111–1120

  • 10. Saal JA, Saal JS. Nonoperative treatment of herniated lumbar intervertebral disc with radiculopathy: an outcome study. Spine (Phila Pa 1976) 1989;14:431–437

  • 11. Pinto RZ, Maher CG, Ferreira ML, et al. Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis. BMJ 2012;344:e497–e497

  • 12. Pearson A, Lurie J, Tosteson T, et al. Who should have surgery for an intervertebral disc herniation? Comparative effectiveness evidence from the Spine Patient Outcomes Research Trial. Spine 2012;37:140–149

  • 13. Weeks WB, Weinstein JN. Patient-reported data can help people make better health care choices. Harvard Business Review. September 21, 2015

 

Close Accordion
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