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.
Food:�Genes that determine illness are triggered by what we put into our bodies, literally what we eat. Our cells are literally created out of the foods we put into our bodies. Like most people do, we are likely eating nutrient-poor foods that create damaged dysfunctional cells. When we learn to eat foods that nourish the body, our cells repair themselves, and the new cells created will be optimal functioning cells.
Unhealthy foods create chronic inflammation, which is destructive to the body. Inflammation is normally the body�s healthy response to injury or infection. However, when inflammation becomes chronic, from constant assault on the gut by consuming the wrong foods, inflammation becomes the cause of destructive diseases, i.e. Lupus, Rheumatoid Arthritis, Colitis and other inflammatory diseases.
Disclosure
Terry Wahls, MD disclosed no relevant financial relationships with any commercial interest.
The two routes by which diet can influence our health:
(A) the metabolism of our cells and
(B) the population of our gut microbiota.
Paolo Riccio, and Rocco Rossano ASN Neuro
2015;7:1759091414568185
Copyright � by SAGE Publications Inc, or the American Society for Neurochemistry, unless otherwise noted.
Manuscript content on this site is licensed under Creative Commons Licenses.
1. Review of MS patient survival on a Swank low saturated fat diet. Nutrition. 2003 Feb;19(2):161-2. Review.
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Low-Fat, Plant-Based Diet In Multiple Sclerosis: A Randomized
Controlled Trial
This was a randomized-controlled, assessor- blinded, one-year long study
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Pharmacol Ther. 1997 Aug;11(4):735-40.
4. Zachos M, Tondeur M, Griffiths AM. Enteral nutritional therapy for induction of remission in Crohn�s disease. Cochrane Database Syst Rev, 2007
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oral prednisolone. Postgrad Med J. 2007 Feb;83(976):128-31
6. Podas T, Nightingale JM, Oldham R, et al, Is rheumatoid arthritis a disease that starts in the intestine? A pilot study comparing an elemental diet with
oral prednisolone. Postgrad Med J. 2007 Feb;83(976):128-31
Exclusion Diets
Eliminated specific protein sources � RA Sx ?
Raw vegan, vegan and gluten free vegan
Systematic review of 14 RCTs
Dietary benefits uncertain
Small studies with risk of bias
1. Kjeldsen-Kragh J, Haugen M, Borchgrevink CF, Laerum E, Eek M, Mowinkel P, Hovi K, F�rre O. Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet. 1991 Oct 12;338(8772):899-902.
2. Kjeldsen-Kragh J, Haugen M, Borchgrevink CF, F�rre Vegetarian diet for patients with rheumatoid arthritis–status: two years after introduction of the diet. Clin Rheumatol. 1994 Sep;13(3):475-82
3. McDougall J, Bruce B, Spiller G, et al, Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis. J Altern Complement Med. 2002 Feb;8(1):71-5
4. Hafstro?m I, Ringertz B, Spa?ngberg A, et. al, A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford). 2001 Oct;40(10):1175-9.
5. Hagen KB, Byfuglien MG, Falzon L, et, al. Dietary interventions for rheumatoid arthritis. Cochrane Database Syst Rev. 2009 Jan 21;(1):
6. Smedslund G, Byfuglien MG, Olsen SU, et. al, Effectiveness and safety of dietary interventions for rheumatoid arthritis: a systematic review of
randomized controlled trials. J Am Diet Assoc. 2010 May;110(5):727-35
Exclusion Diets
Atopic dermatitis improved n=20
UC � fewer symptoms n=18
Crohn�s food sensitivities identified in half n=42
Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in MS – Inducing antibodies reacting with myelin oligodendrocyte glycoprotein (MOG) and Cerebellar peptides
Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0.836) across 27 countries and 29 populations.
�By eliminating lectins, which adversely influence both enterocyte and lymphocyte structure and function, it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RA.�
1. Lindeberg, S., Jo?nsson, T., Granfeldt, Y. et al. Diabetologia (2007) 50: 1795. doi:10.1007/s00125-007-0716-y
2. O?sterdahl M, Kocturk T, Koochek A, Wa?ndell PE. Effects of a short-term intervention with a paleolithic diet in healthy volunteers. European Journal of
Clinical Nutrition. 2007;62(5):682�685. doi:10.1038/sj.ejcn.1602790.
3. Jo?nsson T, Granfeldt Y, Ahre?n B, et al. Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study. Cardiovascular Diabetology. 2009;8:35. doi:10.1186/1475-2840-8-35.
4. Frassetto LA, Schloetter M, Mietus-Synder M, Morris RC, Sebastian A. Metabolic and physiologic improvements from consuming a paleolithic, hunter- gatherer type diet. European Journal of Clinical Nutrition. 2009;63(8):947�955. doi:10.1038/ejcn.2009.4.
5. Halberg N, Henriksen M, So?derhamn N, et. al, Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol (1985). 2005 Dec;99(6):2128-36.
6. Ryberg M, Sandberg S, Mellberg C, et al. A Palaeolithic-type diet causes strong tissue-specific effects on ectopic fat deposition in obese postmenopausal women. Journal of Internal Medicine. 2013;274(1):67�76. doi:10.1111/joim.12048.
7. Ruiz-Nu?n?ez B, Dijck-Brouwer DAJ, Muskiet FAJ. The relation of saturated fatty acids with low-grade inflammation and cardiovascular disease. The Journal of Nutritional Biochemistry. January 2016. doi:10.1016/j.jnutbio.2015.12.007.
8. Otten J, Stomby A, Waling M, et al. Benefits of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control: A randomized controlled trial in individuals with type 2 diabetes. Diabetes/Metabolism Research and Reviews. January 2016. doi:10.1002/dmrr.2828.
9. Konijeti GG1, Kim N, Lewis JD, Groven S, Chandrasekaran A. Efficacy of the Autoimmune Protocol Diet for Inflammatory Bowel Disease. Inflamm Bowel Dis. 2017 Aug 29. doi: 10.1097/MIB.0000000000001221.
10. Spreadbury I. Comparison with ancestral diets suggests dense acellular carbohydrates promote an inflammatory microbiota, and may be the primary dietary cause of leptin resistance and obesity. Diabetes Metab Syndr Obes. 2012;5:175-89.
11. Eaton SB, Konner MJ, Cordain L. Diet-dependent acid load, Paleolithic nutrition, and evolutionary health promotion. Am J Clin Nutr. 2010;91:295-7. Andersson A, et al. Whole?grain foods do not affect insulin sensitivity or markers of lipid peroxidation and inflammation in healthy, moderately overweight subjects. J Nutr.2007 Jun;137(6):1401?7.
12. Tighe P, et al. Effect of increased consumption of whole ? grain foods on blood pressure and other cardiovascular risk markers in healthy middle?aged persons: a randomized controlled trial. Am J Clin Nutr. 2010 Oct;92(4):733?40.
13. Brownlee IA, et al. Markers of cardiovascular risk are not changed by increased whole?grain intake: the WHOLEheart study, a randomised, controlled dietary intervention. Br J Nutr. 2010 Jul;104(1):125?34.
14. Masters RC, et al. Whole and refined grain intakes are related to inflammatory protein concentrations in human plasma. J Nutr. 2010 Mar;140(3):587?94.
15. Katcher HI, et al. The effects of a whole grain-enriched hypocaloric diet on cardiovascular disease risk factors in men and women with metabolic syndrome. Am J Clin Nutr. 2008 Jan;87(1):79?90.
Nutrient Triage
Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage.
Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose response meta-analysis of prospective cohort studies.
16 studies – 833,234 participants
Risk Of All Cause Mortality Associated With Servings/Day Of Fruit & Vegetables
Dose-Response Relation Between Fruit & Vegetable Consumption & Risk Of All Cause Mortality
BMJ. 2014; 349: g4490.
1. Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimer’s Disease. Med Cell Longev.2015;2015:781938
2. Learning and memory promoting effects of crude garlic extract. Indian J Exp Biol.2013 Dec;51(12):1094-100.
3. Enhancement of the neuroprotective activity of Hericium erinaceus mycelium co-cultivated with Allium sativum extract. Arch Physiol Biochem.2015 Feb;121(1):19-25.
4. Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Biol Pharm Bull. 2008 Sep;31(9):1727-32.
5. Lee DH, Kim HW. Innate immunity induced by fungal ?-glucans via dectin-1 signaling pathway. Int J Med Mushrooms. 2014;16(1):1-16.
6. Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis E Effects of beta-glucans on the immune system. Medicina (Kaunas).2007;43(8):597-606.
7. Lai PL, Naidu M,Sabaratnam V,Wong K, DaviP, Kuppusamy UR, Abdullah N, Malek SN. Neurotrophic properties of the Lion’s mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms.2013;15(6):539-54.
8. Phan CW, David P, Naidu M, Wong KH, Sabaratnam V. Therapeutic potential of culinary-medicinal mushrooms for the management of neurodegenerative diseases: diversity, metabolite, and mechanism. Crit Rev Biotechnol.2015;35(3):355-68.
9. Scientifica (Cairo).2016;2016:3109254.
10. Berry antioxidants: small fruits providing large benefits. J Sci Food Agric.2014 Mar 30;94(5):825-33
11. Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia. Recent Pat Food Nutr Ag. 2013 Aug;5(2):128-43.
12. The impact of fruit flavonoids on memory and cognition. Br J Nutr.2010 Oct;104 Suppl 3:S40-7. d
13. Grape juice, berries, and walnuts affect brain aging and behavior. J Nutr. 2009 Sep;139(9):1813S-7S.
14. Fruit polyphenolics and brain aging: nutritional interventions targeting age-related neuronal and behavioral deficits. Ann N Y Acad Sci.2002 Apr;959:128-32.
15. Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr.2005 Jan;81(1 Suppl):313S-316S.
16. Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, Joseph JA. Blueberry supplementation improves memory in older adults. J Agric Food Chem.2010 Apr 14;58(7):3996-4000.
17. Funding for the studies was provided by the US Highbush Blueberry Council, the National Institute on Aging, and Wild Blueberries of North America. Dr. Krikorian has disclosed no relevant financial relationships.
18. Lobo GP Amengual J, Baus D, Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX. J Biol Chem.2013 Mar 29;288(13):9017-27
?-carotene Is Not Retinol (Vitamin A)
?-Carotene is converted to vitamin A in the intestine by the enzyme ?-carotene-15,15′- monoxygenase (BCMO1) to support vision, reproduction, immune function, and cell differentiation.
Considerable variability in BCMO1 exists and can effect individual vitamin A status
Nutritional Adequacy (%RDA) US Diet Vs. Study Diet
Multimodal Intervention Improves Quality Of Life
Mood & Cognition
In the setting of progressive MS Improved thinking ability and reduced anxiety and reduced depression
Average daily servings of the study diet recommended (vegetables/fruits) and excluded (gluten/dairy/eggs) foods p < 0.01 difference from baseline to 12 months
Average Scores On The Mood Measures At Each Study Visit
Average Scores On The DKEFS & WAIS Sub-Scales At Each Study Visit.
Relapsing Remitting MS
Reduce Fatigue
?Mental & Physical QoL 16% (> 5 points)
Improved Motor Function
A Simplified Model Of FMD?Mediated Effects On Glucocorticoid, Immune Suppression & Oligodendrocyte Regeneration & Differentiation In MS
N=60 6 Month Human Clinical Trial
FMD 100 ml broth, 1 T flax oil tid, 200 � 350 Kcal, Plus enema as needed 7 days Mediterranean diet
Ketogenic(KD) 160gmfatm<100gPro,<50g CHO
Usual diet
Change at 3 month of (k) overall quality of life, (l) change in health, (m) physical health composite, and (n) mental health composite. The dotted line represents a threshold that is thought to be clinically important
The Two Routes By Which Diet Can Influence Our Health:
(A) the metabolism of our cells and
(B) the population of our gut microbiota.
Paolo Riccio, and Rocco Rossano ASN Neuro
2015;7:1759091414568185
Copyright � by SAGE Publications Inc, or the American Society for Neurochemistry, unless otherwise
noted. Manuscript content on this site is licensed under Creative Commons Licenses.
Gut Brain Immune Axis
Gut microbiota influence the brain and immune system balance
Diet influences the microbiome strongly
Exercise, sleep, stress level also important
Changes in the colon mucosa every early in the disease process
The composition of gut microbiota is influenced by multiple factors, such as diet and host genotype. Within the gut, ecological processes such as selection and evolution take place. The use of antibiotics reduces the numbers and diversity of gut microbiota.
Higher quality diet (food), stress reduction, movement � are relatively safe with large favorable benefits for all cause mortality
3 month trial of a grain free, dairy free, sugar free vegetable rich (or gluten free vegetarian) diet is relatively safe with potential for many favorable benefits
Autoimmunity is the reaction of cells (lymphocytes) or antibodies�of the immune system along with the body�s own tissues leading to certain pathology. Autoimmunity can produce various conditions, which depend upon the target of the attack.�While intrinsic factors, which include age, sex, and genetics contribute to autoimmunity, it is believed that extrinsic factors such as drugs, chemicals, microbes, and/or the environment can trigger the initiation of autoimmune responses.
Autoimmune Disease & Environmental Toxicants
Educational Objectives
Review air pollution, cigarette smoking, and citrullination as models for the genesis of autoimmune disease
Explore the role of general cell stressors in autoimmune disease
Discuss the impact of lung and gut barrier disruption by environmental toxins and food additives in autoimmune disease
Utilize the Functional Medicine ATM model to illustrate the various mechanisms by which toxicants could contribute to the pathophysiology of autoimmune disease.
�Mild forms of the autoimmune response probably occur naturally in most people. But, for people with a predisposition to autoimmunity, environmental factors, such as toxic chemicals, drugs, bacteria or viruses, may trigger a full?fledged response.�
�NOVEL CRYSTAL BALL: One day Y?shaped molecules called autoantibodies in a patient�s blood may tell doctors whether a patient is �brewing� certain diseases and may even indicate roughly how soon the individual will begin to feel symptoms.�
Autoimmune Disease: �Delayed Gratification�
Scientific American, March, 2007
Many autoimmune diseases do not develop spontaneously, but instead evolve through an extended germination period before they become clinically evident…
Well over 10 million people test positive for ANA, years before they have any symptoms.
This implies the presence of additional environmental factors that dampen or amplify the process over time.
Arbuckle MR, et al, N Engl J Med. 2003 Oct 16;349(16):1526?33.
Elevated Levels Of Antibodies Against Xenobiotics In A Subgroup Of Healthy Subjects
Vojdani, A, Kharrazian, D, Mukherjee, PS
Some environmental chemicals, acting as haptens, can bind to a high? molecular?weight carrier protein such as human serum albumin (HSA), causing the immune system to misidentify self?tissue as an invader and launch an immune response against it, leading to autoimmunity
The levels of specific antibodies against 12 different chemicals bound to HSA were measured by ELISA in serum from 400 blood donors.
10% (IgG) and 17% (IgM) of tested individuals showed significant antibody elevation against aflatoxin?HSA adduct.
The percentage of elevation against the other 11 chemicals ranged from 8% to 22% (IgG) and 13% to 18% (IgM).
Detection of antibodies against various protein adducts may indicate chronic exposure to these chemical haptens in about 20% of the tested individuals
J Appl Toxicol. 2015 Apr; 35(4): 383�397.
Could Environmental Toxins Be A Key Missing Link That Pushes The Immune System Over The Brink To Permanently Lose Control Of Its Tolerance To Self?Antigens?
(A Corollary Question: Does The Persistent Presence Of Autoantibodies Or Autoreactive T Cells Imply An Inevitable Progression To Full?Blown Autoimmune Disease?)
Rheumatoid Arthritis: Swan neck deformity from chronic synovitis
Anti?Cyclic Citrullinated Peptide Antibody
Current method is 96% specific for RA
Elevated titers detected >10 years before onset of clinical disease
Sensitivity (likelihood of positive test) increases from 50% at Dx to >75% over course of disease
Likely involved in pathogenesis
Citrullinated Ags are highly expressed in inflamed joints
Citrulline is formed by posttranslational modification of arginine residues by peptidyl arginine deiminases (PADs)
PADs are upregulated by inflammation, injury, and toxicants
Inflammation and injury thus increases citrullination of multiple synovial proteins
Multiple HLA?DR variants (shared epitope) associated with RA preferentially display citrullinated Ags on MHCII � activating citrulline?specific autoreactive T cells
Smoking increases risk of +anti?CCP when coupled with HLR?DR shared epitope
Floris van Gaalen et al. J Immunol 2005;175:5575-5580
Autoimmunity To Specific Citrullinated Proteins Gives The First Clues To The Etiology Of Rheumatoid Arthritis
Four citrullinated whole protein antigens, fibrinogen, vimentin, collagen type II, and alpha?enolase, are now well established, with others awaiting further characterization All four proteins are expressed in the joint, and there is evidence that antibodies to citrullinated fibrinogen and collagen type II mediate inflammation by the formation of immune complexes Antibodies to citrullinated proteins are associated with HLA ‘shared epitope’ alleles
Porphyromonas gingivalis, pathogenic bacteria that is a major cause of periodontal disease, expresses endogenous citrullinated proteins
Thus, both smoking and Porphyromonas gingivalis are attractive etiological agents for further investigation into the gene/environment/autoimmunity triad of RA.
Wegner N, Lundberg K, Kinloch A, et al, Immunol Rev. 2010 Jan;233(1):34?54
�More than 20,000 physicians, after Luckies had been furnished them for tests, basing their opinions on their smoking experience, stated that Luckies are less irritating than other cigarettes.�
Mad Men?
Holy Smokes!!
Cigarette Smoking Has Been Strongly Linked To Numerous Autoimmune Diseases
Cigarette Smoking & Autoimmune Disease: What Can We Learn From Epidemiology?
Rheumatoid arthritis and cigarette smoking:
Risk is highest in men: OR up to 4.4 X
Smoking increases risk of seropositive RA 2.4X in women
Smoking intensity and duration both greatly increase risk
Smoking increases severity of symptoms
Increased risk remains for 20 yrs after cessation
�Cigarette smoking is the most conclusively established environmental risk factor for RA�
Smoking & Air Pollution As Pro?Inflammatory Triggers For The Development Of Rheumatoid Arthritis.
Smoking initiates chronic inflammatory events in the lungs.
These, in turn, promote the release of the enzymes, peptidylarginine deiminases 2 and 4 from smoke?activated, resident and infiltrating pulmonary phagocytes.
Peptidylarginine deiminases mediate conversion of various endogenous proteins to putative citrullinated autoantigens.
In genetically susceptible individuals, these autoantigens trigger the production of autoantibodies to anti?citrullinated peptide, an event which precedes the development of RA.
Anderson R, Meyer PW, Ally MM, Tikly M, Nicotine Tob Res. 2016 Jul;18(7):1556?65
Floris van Gaalen et al. J Immunol 2005;175:5575-5580
Cigarette Smoking & Autoimmune Disease: What Can We Learn From Epidemiology?
Systemic lupus erythematosis
Highest risk in current smokers
Current smokers have higher levels of anti?dsDNA Ab
Multiple sclerosis
Increased risk of MS in both current & past smokers
Risk increases with intensity of smoking (more cigarettes per day)
Increased severity of MS in current smokers
Cirtrullination of myelin?basic protein ?? antigenic
Graves� hyperthyroidism
Smoking is esp. strong risk factor for opthalmopathy
Industrial Air Emissions & Proximity To Major Industrial Emitters, Are Associated With Anti?Citrullinated Protein Antibodies.
Randomly sampled 1586 subjects out of 20,000 population from Quebec, Canada
After adjusting for age, sex, smoking, and ethnicity, found
Positive association between anti?CCPA and annual industrial PM 2.5 and sulfur dioxide emissions (i.e. living closer to emitters increases anti?CCPA)
Negative association between anti?CCPA and to a major industrial emitter of both PM 2.5 and SO2 (living further away from emitters decreases anti?CCPA)
�These analyses suggest that exposure to industrial emissions of air pollutants is related to ACCPA positivity.�
Bernatsky S, Smargiassi A, Joseph L, et al, Environ Res. 2017 Aug;157:60?63
Air Pollution As A Determinant of Rheumatoid Arthritis
The induction by air pollution of an inflammatory environment with high citrullination levels in the lung may induce iBALT formation, thereby causing a transition toward a more specific immune response via the production of anti?citrullinated peptide antibodies.
Air pollution not only triggers innate immune responses at the molecular level, increasing the levels of proinflammatory cytokines and reactive oxygen species, but is also involved in adaptive immune responses.
Thus, via the aryl hydrocarbon receptor (AHR), diesel exhaust particles can trigger a T?cell switch to the Th17 profile.
Sigaux J, et al Joint Bone Spine. 2018 Mar 7. pii: S1297?319X(18)30043?5
The Aryl Hydrocarbon Receptor Links TH17?Cell? Mediated Autoimmunity To Environmental Toxins
The aryl hydrocarbon receptor (AhR) is a ligand?dependent transcription factor that mediates a range of critical cellular events in response to halogenated aromatic hydrocarbons and non?halogenated polycyclic aromatic hydrocarbons such as dioxin (TCDD)
In a murine model of multiple sclerosis, which is mediated by Th17 cells, activation of cells using the AhR exacerbated disease, whereas mice deficient in the AhR had attenuated autoimmune disease.
This paper thus links activation of Th17 cells with environmental toxins, suggesting a plausible hypothesis for the increase in such diseases with industrialization.
Veldhoen, M., Hirota, K., Westendorf, A.M, et al Nature. 2008 May 1;453(7191):106?9
J Inflamm (Lond). 2015; 12: 48.
Does Rheumatoid Arthritis (& Other Autoimmune Diseases) Start In The Gut, Or In The Lungs?
Gomez?Mejiba SE, Zhai Z, Akram H, et al. Inhalation of Environmental Stressors & Chronic Inflammation: Autoimmunity and Neurodegeneration.
Mutation research. 2009;674(1?2):62?72.
Citrullination & Autoimmunity
Environmental exposure to cigarette smoke and nanomaterials of air pollution may be able to induce citrullination in lung cells prior to any detectable onset of inflammatory responses, suggesting that protein citrullination could be considered as a sign of early cellular damage
Citrullination has been reported to be a process present in a wide range of inflammatory tissues. Indeed, citrullinated proteins have been detected also in other inflammatory arthritides and in inflammatory conditions other than arthritides (multiple sclerosis, polymyositis, inflammatory bowel disease and chronic tonsillitis)
Histone hypercitrullination can activate neutrophil extracellular traps (NETS)� high inflammatory
These data support the hypothesis that rather than being a disease?dependent process, citrullination is an inflammatory?dependent condition that plays a central role in autoimmune diseases.
Valesini G, Shoenfeld Y, et al Autoimmun Rev. 2015 Jun;14(6):490?7 Wang S,
Wang Y.Biochim Biophys Acta. 2013 Oct;1829(10):1126?35
Air Pollution In Autoimmune Rheumatic Diseases: A Review
Environmental factors contribute to the onset of autoimmune diseases, especially smoking and occupational exposure to silica dust in rheumatoid arthritis and systemic lupus erythematosus
Scleroderma may be triggered by the inhalation of chemical solvents, herbicides and silica dust.
Primary vasculitis associated with anti?neutrophil cytoplasmic antibody (ANCA) may be triggered by silica exposure
Air pollution is one of the environmental factors involved in systemic inflammation and autoimmunity
Farhat SC, et al, Autoimmun Rev. 2011 Nov;11(1):14?21
Silica, Silicosis & Autoimmunity
Exposure to respirable crystalline silica (<10 ?m in size) occurs most often in occupational settings � the �dusty� trades
Epidemiological studies link occupational exposure to crystalline silica dust with systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis
Findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production (NLRP3 inflammasome), pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, and autoantibodies and tissue damage
Pollard KM, Front Immunol. 2016; 7: 97.
Asbestos = Magnesium Silicate
Assessment Of Autoimmune Responses Associated With Asbestos Exposure In Libby, Montana, USA
The population in Libby, Montana, provides a unique opportunity for study because of both occupational and environmental exposures that have occurred as a result of the mining of asbestos?contaminated vermiculite near the community
Libby serum samples showed significantly higher frequency of positive ANA and ENA tests, increased mean fluorescence intensity and titers of the ANAs, and higher serum IgA, compared with Missoula serum samples
The results support the hypothesis that asbestos exposure is associated with autoimmune responses and suggests that a relationship exists between those responses and asbestos?related disease processes.
Pfau JC, et al Environ Health Perspect, 2005, Vol 113: 25-30
Air Pollution, Oxidative Stress & Exacerbation Of Autoimmune Diseases
Particulate matter present in air pollution can induce oxidative stress and cell death, both by apoptosis and necrosis of human cells leading to aggravation of chronic inflammation, i.e. the tissue damaging reaction observed in autoimmune diseases.
Therefore, identification of strong inducers of oxidative stress among components of PM seems to be crucial for their neutralization and elimination from the ambient environment.
It seems likely that PM 2.5 may exacerbate the onset of the SLE because they were attributed to a significant increase of the level of anti?dsDNA antibodies, and the presence of the renal casts in SLE patients
Exposure to ozone, sulphates, and other pollutants present in the air has been associated with type 1 diabetes in children
MS occurrence and hospitalization was associated with exposure to air pollutants such as PM10, SO2, NO2, and NOx
In addition to tobacco smoke and silica, pollution emissions from road traffic may be an environmental factor responsible for exacerbation of RA
Gawda, A, et al, Central European Journal of Immunology 2017; 42(3)
What Do Environmental Pollutants, Toxins, Infections & Unhealthy Diets Have In Common?
Increase inflammation and additional free radical production,
Which damages tissues (bystander effect), disrupts barriers, and/or modifies DNA…
Creating �foreign?like� tissues that break immune tolerance (eg anti?nuclear antibodies)
Cell Stressors
Macario, A. J.L. et al. N Engl J Med 2005;353:1489-1501
Damage Associated Molecular Patterns
Molecular structures that activate immunologic receptors
Released with cellular injury and/or necrosis after exposure to cellular stressors
DNA fragments
Mitochondria
Misfolded proteins
Advanced glycation end products have similar biological effects
Initiate and perpetuate inflammatory response (esp NLRP3 inflammasome)
Ojcius D, Sai?d?Sadier N. Alarmins, inflammasomes and immunity. Biomedical Journal. 2012;35(6):437.
Vakrakou AG, Boiu S, Ziakas PD, et al, Systemic activation of NLRP3 inflammasome in patients with severe primary Sjo?gren’s syndrome fueled by inflammagenic DNA accumulations.
J Autoimmun. 2018 Mar 15. pii: S0896?8411(17)30789?8.
Environmental Xenobiotic Exposure & Autoimmunity
We argue that localized tissue damage and chronic inflammation elicited by xenobiotic exposure leads to the release of self?antigens and damage?associated molecular patterns …
As well as the appearance of ectopic lymphoid structures and secondary lymphoid hypertrophy,
Which provide a milieu for the production of auto-reactive B and T cells that contribute to the development and persistence of autoimmunity in predisposed individuals.
Pollard KM, Christy JM, Cauvi DM, Kono DH, Current Opinion in Toxicology, Volume 10, August 2018, Pages 15?22
The Functional Medicine Paradigm (Slightly Modified)
Immune disruption = increased susceptibility to triggers
Overload in hepatic detoxification pathways
Effect on triggers:
Synergistic action (immunotoxicant)
Adjuvant: chemical modification of self?antigen to make it appear foreign or immunogenic (neoantigens)
Enhanced apoptosis: danger/damage signals (DAMPs)
Effect on mediators:
Amplified inflammatory pathways
Increased oxidative stress
Disruption of pro?resolution counter?regulatory mechanisms
Functional Toxicology
Changes In Intestinal Tight Junction Permeability Associated With Industrial Food Additives Explain The Rising Incidence Of Autoimmune Disease
The incidence of autoimmune diseases and food additive consumption are both increasing in parallel
Dysfunction of intestinal tight junctions is common in multiple autoimmune diseases
Commonly used industrial food additives including glucose, salt, solvents, emulsifiers, gluten, microbial transglutaminase, and nanoparticles increase intestinal tight junction leakage.
Intestinal entry of foreign antigen activates the autoimmune cascade
Lerner A, Matthias T. Autoimmunity Reviews 14 (2015) 479�489
Autoimmunity Reviews 14 (2015) 479�489
Autoimmune Disease: �Two?Hit� Signal Theory
Barrier disruption allows immune system to be repeatedly exposed to a combination of an autoantigen & an �adjuvant� [Adjuvants can be toxicants, microbes, foods]
This triggers a genetically predisposed immune system to react to the autoantigen as a non?self �stranger�
�Danger� signals released at the site of clearance of dead cells amplify the process; shaping the features & severity of the resulting autoimmune disease
Persistent �Stranger + Danger� = loss of tolerance
Based on this model, strategies aimed at preventing the accumulation of dying cells lowering the adjuvant (toxic) load may be beneficial for the prevention & treatment of autoimmune disease
Anaya JM, Ramirez?Santana C, Alzate MA, Molano?Gonzalez N, Rojas?Villarraga A, The Autoimmune Ecology., Front Immunol. 2016 Apr 26;7:139
Oxidatively Modified Autoantigens In Autoimmune Diseases
Oxidative modification of proteins has been shown to elicit antibodies in a variety of diseases, including SLE, diabetes mellitus & RA.
Oxidatively modified DNA & LDL occur in SLE, a disease in which premature atherosclerosis is a serious problem. AGE pentosidine & AGE?modified IgG have been shown to correlate with RA disease activity.
In the face of overwhelming evidence for the involvement of oxidative damage in autoimmunity, the administration of antioxidants is a viable untried alternative for preventing or ameliorating autoimmune disease…�
Kurien BT, Hensley K, Bachmann M, Scofield RH., Free Rad Biol & Med, 2006, Vol 41: 549-556
Oxidative Stress In The Pathology & Treatment Of Systemic Lupus Erythematosus.
Oxidative stress is increased in SLE, and it contributes to immune system dysregulation, abnormal activation and processing of cell? death signals, autoantibody production and fatal comorbidities.
Oxidative modification of self antigens triggers autoimmunity, and the degree of such modification of serum proteins shows striking correlation with disease activity and organ damage in SLE.
Reactive oxygen intermediates (ROI) mostly originate from mitochondria, and T cells from patients with SLE exhibit mitochondrial dysfunction
In T cells from patients with SLE and animal models of the disease, glutathione, the main intracellular antioxidant, is depleted and serine/threonine?protein kinase mTOR undergoes redox?dependent activation.
In turn, reversal of glutathione depletion by application of its amino acid precursor, N?acetylcysteine, improves disease activity in lupus? prone mice; pilot studies in patients with SLE have yielded positive results that warrant further research.
Antioxidant therapy might also be useful in ameliorating damage caused by other treatments.
Oxidative stress (OS) plays an important role in the pathogenesis of a variety of autoimmune diseases (ADs) and many environmental agents participate in this process.
Environmental agents, including trichloroethylene (TCE), silica, pristane (TMPD in mineral oil), mercury, and smoke, are known to induce an autoimmune response, potentially through OS?mediated mechanisms.
Antioxidants can attenuate SLE disease activity by down regulating NLRP3 inflammasome activation and activating Nrf2 signaling.
Khan MF, Wang G. Curr Opin Toxicol. 2018 Feb;7:22?27.
Metals & Minerals Associated With Autoimmune Diseases
Heavy metals
Mercury
Cadmium
Lead
Gold
Minerals & Metalloids
Silica (crystalline silicon dioxide)
Asbestos (chrysotile = magnesium silicate)
Arsenic
Lithium
Iodine
Bigazzi PE., Metals and kidney autoimmunity. Environ Health Perspect. 1999 Oct;107 Suppl 5:753?65
Biologic Markers in Immunotoxicology National Research Council (US) Subcommittee on Immunotoxicology. Washington (DC): National Academies Press (US); 1992.
Anaya JM, et al, The Autoimmune Ecology., Front Immunol. 2016 Apr 26;7:139
Messages To Take Home
Autoimmune and autoinflammatory diseases are steadily increasing in our society
The rise in exposure to environmental pollutants and other toxins is increasing the total body burden of xenobiotics
A central theme in the development of autoimmune diseases is the loss of immune tolerance
Immune tolerance can be broken by disruption of barriers (skin, lung, gut, brain) and/or immune dysregulation
Numerous xenobiotics have been shown to disrupt healthy barriers and dysregulate immune responses
Xenobiotics may play a central role in the initiation and perpetuation of autoimmune disease
Explosion Of Autoimmune Diseases: The Mosaic Of Old & Novel Factors
Modern life and exposures to novel chemical and xenobiotic compounds may lead to the development of new complexes of symptoms that do not necessarily belong to one of the well?known autoimmune diseases
As physicians and scientists, we must continue to study novel pathogenic mechanisms and susceptible alleles to help us identify new therapeutic venues.
Agmon?Levin N, Lian Z, Shoenfeld Y. Cell Mol Immunol. 2011 May; 8(3): 189�192.
IFM Annual International Conference Hollywood, Florida May, 2018
Robert Rountree, MD
Robert Rountree, MD is a speaker, consultant, and advisory board member for Thorne and Balchem. He is also a clinical trial board member for Thorne Research.
Allergy Sufferers!�As winter gives way to spring, seasonal allergies can really get you down. Whether you get a few sniffles and some sneezing or you are down for the count with every terrible allergy symptom known to man, it can make spring pretty unbearable.
There is no shortage of allergy medications on the market, but they come with their own issues. The majority of them cause drowsiness and other unpleasant side effects, leaving you barely able to function. Those that are made from a �non drowsy� formula sound great, but if you have certain health conditions, like high blood pressure, you are out of luck � and stuck either taking the ones that make you sleep sucking it up and dealing with your allergies sans medication.
That�s no way to live.
What Are Allergies?
When your immune produces histamines in response to an allergen that you encounter the physiological reaction that you experience is broadly referred to as allergies or hay fever. The allergens may be simple substances that normally do not affect people, but when your body is out of balance, it can cause a variety of problems.
Symptoms of allergies include:
Runny nose
Stuffy nose
Headache
Sneezing
Itchy eyes
Coughing or scratchy throat
Skin Rash or Hives
Swelling
Diarrhea
Nausea
Fatigue
Anaphylaxis, severe, life threatening allergies can include swelling of the airways, tongue, and throat, inability to breathe due to blocked airway, and other dangerous symptoms.
The allergens can be something you come in contact with, like poison ivy, something you breathe in, like mold or dust, or it can be something you ingest, like strawberries or peanuts. Different people will have different allergies, but those who are allergic to the same things may not have the same reaction. Often a doctor or allergist will diagnose your allergies.
Chiropractic Care For Allergy Sufferers
Chiropractic treatments have been found to be very effective for relieving allergy symptoms and even stopping allergies at their source. It reduces the severity of allergy symptoms as well as the frequency of occurrence. It does not work like allergy medications which have an anti-histamine effect and only work as a short term fix for your allergy symptoms.
Chiropractic treatments help your body become more balanced so that it is better equipped for combating allergies at the source. When your spine is not aligned it can impact your nervous system leading to a variety of problems � including allergies. Your immune system can be affected, causing it to malfunction.
A chiropractor can help relieve the stress on your nervous system by aligning your spine. This takes the pressure off of nerves, allowing your immune system to function at a more optimal level. This makes it easier for your body to ward off infections while recognizing allergens as harmless.
When your immune system encounters allergens it doesn�t overreact to them. Instead, the reaction is much more subdued, or even nonexistent. Chiropractic has also been found to help asthma patients breathe easier. Asthma symptoms are diminished.
Chiropractic care is more than just spinal manipulation, though. It promotes whole body wellness. Patients are taught exercise, stress relief, and nutrition so that the entire system is treated. The whole body treatment plan for chiropractic patients will help you be allergy free in a short time.
It is important to follow your chiropractic plan thoroughly and consistently. Get plenty of rest and take time to destress. The more you can relax and take care of yourself, the healthier you will be overall. Chiropractic care can help so many health conditions; it can actually make you healthier. Allergy sufferers or if you are struggling with allergies for the first time, give chiropractic care a try you just might be surprised.
Most people stretch and hardly pay any attention to it. Throughout the day a person may stretch upon waking or after they�ve been sitting in the same position for a while. They might do some stretches before working out or as part of physical therapy. Stretching often makes us feel better but it might be surprising to discover that it is actually beneficial to optimal body function.
As a person ages their muscles begin to tighten. This is a natural part of the aging process. However, it can cause inhibit range of motion and joint stiffness, making normal day to day activities more difficult. After certain injuries stiffness can set in, causing pain and decreased flexibility.
What many chiropractic patients may be surprised to learn is that stretching is a great complement to chiropractic care. When combined with simple stretches and low impact exercises, chiropractic patients often find that their injuries heal faster, their pain is reduced, and they simply feel better and more energetic. If that isn�t enough to convince you to incorporate stretching into your daily wellness routine, maybe these four compelling benefits will.
STRETCHING
Helps Keep The Spine Aligned
When you stretch the muscles in your chest, shoulders, and lower back it will improve your posture by helping to keep your spine in better alignment. When your muscles are not stretched properly they begin to draw up � and it usually isn�t in a uniform or symmetrical manner.
This means that muscles on one side of your spine may draw up more than the muscles on the other side. This can result in your body being pulled to that side, causing your spine to be pulled that way. Stretching prevents this from happening and when combined with consistent chiropractic care it can ensure good spinal health.
Improves Flexibility & Range Of Motion
Most people know, on some level, that stretching improves flexibility and range of motion. However, many do not act on that knowledge and they often wind up at the doctor�s office complaining of back pain. Stretching will make you more flexible which, in turn, will make you less prone to injury.
Your muscles will be able to work as effectively as possible. It is important that you don�t overdo it though. Some people take terrible risks when they stretch, thinking that if they force their bodies into certain positions or if they �bounce� to get a deeper stretch then they will be more flexible. Actually, the reverse is true. Stretching in an unsafe way such as bouncing or forcing your body far beyond its limits will result in injury including pulled muscles and muscle tearing.
Helps Relieve Stress & Detoxify The Body
When you stretch, two very significant things happen. First, your blood flow increases as blood is rushed to the muscles, your organs, and your brain. Secondly, it moves oxygen through these areas. As a result, toxins that have accumulated in your soft tissues are dispelled.
The simple stretching that relieves tension in muscles, combined with the detoxifying effect will help you feel less stressed. Stretching is a great stress management exercise, one you can do just about anywhere. You don�t need any special equipment and you can even do it right at your desk while you are working. A bonus is that you�ll feel the de-stressing effects instantly.
It relies on the body�s natural ability to heal itself by releasing the tension and easing the stiffness of the muscles in that area. The stiffer those muscles are, the more they will hurt when you try to move. By relaxing them through stretching you will find that you move much easier and with less pain.
Stretching has so many great benefits. Talk to your chiropractor about a customized stretching plan that you can do at home. You�ll love what it does for you. If you don�t have a chiropractor, give us a call at (915)850-0900. We�re here to help!
Chronic fatigue syndrome (CFS) is a condition that is not as straightforward as other illnesses. The symptoms can often mimic other states, including some that are pretty serious, so they must all be ruled out before a diagnosis of CFS can be determined.
This is usually not a quick process, so the patient is left dealing with troubling and often debilitating symptoms and no real answers for months or even years. By the time a patient receives a diagnosis of CFS, they are usually physically and emotionally exhausted.
Overview Of Chronic Fatigue Syndrome
According to the Centers for Disease Control (CDC), more than one million people in the United States have CFS. It is more prevalent in the U.S. than lupus, multiple sclerosis, and many types of cancer.
It is found more often in women than men; women are four times more likely to get it. While anyone of any age can get CFS, it seems to be most common in people in their 40s and 50s. Researchers have found no evidence to suggest that CFS is contagious, but they believe there may be a genetic or familial link.
Complications that can come from CFS include depression, increased absence from work, lifestyle restrictions, and inability to carry out normal daily activities like caring for children, housekeeping, or wedding functions. It can cause significant social isolation and loneliness.
Chiropractic For Chronic Fatigue Syndrome
Many people have found that chiropractic for CFS helps reduce the pain that accompanies the condition and increases injury in some patients. The chiropractor uses spinal manipulation to treat the CFS patient, allowing many symptoms associated with the disease without invasive treatments or medication.
Many CFS patients report more energy, less pain or no pain, greater flexibility, increased mobility, and reduced inflammation of joints after just a few chiropractic adjustments. Often, the patient will be recommended to attend several sessions a week for spinal adjustments and counseling on supplements and diet. All these treatments work together to relieve the symptoms, strengthen the immune system, and help the patient feel more in control of their body and condition.
Whole Patient Treatment
One of the benefits of chiropractic treatment for CFS is that it treats the whole patient, not just the symptoms. A doctor of chiropractic may recommend various chiropractic services such as spinal adjustments. Still, they will also sit with the patient and discuss that patient’s diet, daily routine, and any medications or supplements they are taking.
The chiropractor will then make dietary recommendations, including supplements that help CFS, such as:
Omega 3 fatty acids
Eiscosapentaenoic acid (EPA)
Docosahexaenoic acid (DHA)
Magnesium
Malic Acid
Linoleic Acid
Depending on the patient, they may also recommend a liver detox program and a more structured diet and exercise program.
Hope For Patients With CFS
Chiropractic care can give much-needed hope to patients with CFS. The whole patient care they receive helps not only the physical and emotional suffering as well.
The changes in diet, recommended supplements, and chiropractic treatments help the patient’s physical symptoms but also address the emotional ones, particularly depression and frustration. It is essential that patients with CFS know that there is someone who hears them, understands their difficulties, and wants to help them on every level, not just symptom control. Chiropractic care addresses all of these for optimal whole patient care.
Clinic News – Dr. Jimenez Takes A Look At Stress Management
Manual therapy migraine treatment, or manipulative therapy, is a physical treatment approach which utilizes several specific hands-on techniques to treat a variety of injuries and/or conditions. Manual therapy is commonly used by chiropractors, physical therapists and massage therapists, among other qualified and experienced healthcare professionals, to diagnose and treat soft tissue and joint pain. Many healthcare specialists recommend manual therapy, or manipulative therapy as a treatment for migraine headache pain. The purpose of the following article is to educate patients on the effects of manual therapies for migraine treatment.
Manual Therapies for Migraine: a Systematic Review
Abstract
Migraine occurs in about 15% of the general population. Migraine is usually managed by medication, but some patients do not tolerate migraine medication due to side effects or prefer to avoid medication for other reasons. Non-pharmacological management is an alternative treatment option. We systematically reviewed randomized clinical trials (RCTs) on manual therapies for migraine. The RCTs suggest that massage therapy, physiotherapy, relaxation and chiropractic spinal manipulative therapy might be equally effective as propranolol and topiramate in the prophylactic management of migraine. However, the evaluated RCTs had many methodological shortcomings. Therefore, any firm conclusion will require future, well-conducted RCTs on manual therapies for migraine.
Migraine is usually managed by medication, but some patients do not tolerate acute and/or prophylactic medicine due to side effects, or contraindications due to co-morbidity of myocardial disorders or asthma among others. Some patients wish to avoid medication for other reasons. Thus, non-pharmacological management such as massage, physiotherapy and chiropractic may be an alternative treatment option. Massage therapy in Western cultures uses classic massage, trigger points, myofascial release and other passive muscle stretching among other treatment techniques which are applied to abnormal muscle tissue. Modern physiotherapy focuses on rehabilitation and exercise, while manual treatment emphasis postural corrections, soft tissue work, stretching, active and passive mobilization and manipulation techniques. Mobilization is commonly defined as movement of joints within the physiological range of motion [1]. The two most common chiropractic techniques are the diversified and Gonstead, which are used by 91 and 59% of chiropractors [2]. Chiropractic spinal manipulation (SM) is a passive-controlled maneuver which uses a directional high-velocity, low-amplitude thrusts directed at a specific joint past the physiological range of motion, without exceeding the anatomical limit [1]. The application and duration of the different manual treatments varies among those who perform it. Thus, manual treatment is not necessarily as uniform as, for instance, specific treatment with a drug in a certain dose.
This paper systematically review randomized controlled trials (RCTs) assessing the efficacy of manual therapies on migraine, i.e., massage, physiotherapy and chiropractic.
Method
The literature search was done on CINAHL, Cochrane, Medline, Ovid and PubMed. Search words were migraine and chiropractic, manipulative therapy, massage therapy, osteopathic treatment, physiotherapy or spinal mobilization. All RCTs written in English using manual therapy on migraine were evaluated. Migraine was preferentially classified according to the criteria of the International Headache Societies from 1988 or its revision from 2004, although it was not an absolute requirement [3, 4]. The studies had to evaluate at least one migraine outcome measure such as pain intensity, frequency, or duration. The methodological quality of the included RCT studies was assessed independently by the authors. The evaluation covered study population, intervention, measurement of effect, data presentation and analysis (Table 1). The maximum score is 100 points and ?50 points considered to be methodology of good quality [5�7].
Results
The literature search identified seven RCT on migraine that met our inclusion criteria, i.e., two massage therapy studies [8, 9], one physiotherapy study [10] and four chiropractic spinal manipulative therapy studies (CSMT) [11�14], while we found no RCTs studies on spinal mobilization or osteopathic as a intervention for migraine.
Methodological Quality of the RCTs
Table 2 shows the authors average methodological score of the included RCT studies [8�14]. The average score varied from 39 to 59 points. Four RCTs were considered to have a good quality methodology score (?50), and three RCTs had a low score.
Randomized Controlled Trials
Table 3 shows details and the main results of the different RCT studies [8�14].
Massage Therapy
An American study included 26 participants with chronic migraine diagnosed by questionnaire [8]. Massage therapy had a statistically significant effect on pain intensity as compared with controls. Pain intensity was reduced 71% in the massage group and unchanged in the control group. Interpretation of the data is otherwise difficult and results on migraine frequency and duration are missing.
A New Zealand study included 48 migraineurs diagnosed by questionnaire [9]. The mean duration of a migraine attack was 47 h, and 51% of the participants had more than one attack per month. The study included a 3 week follow-up period. The migraine frequency was significantly reduced in the massage group as compared with the control group, while the intensity of attacks was unchanged. Results on migraine duration are missing. Medication use was unchanged, while sleep quality was significantly improved in the massage group (p < 0.01), but not in the control group.
Physical Therapy
An American physical therapy study included female migraineurs with frequent attacks diagnosed by a neurologist according to the criteria of the International Headache Society [3, 10]. Clinical effect was defined as >50% improvement in headache severity. Clinical effect was observed in 13% of the physical therapy group and 51% of the relaxation group (p < 0.001). The mean reduction in headache severity was 16 and 41% from baseline to post-treatment in the physical therapy and relaxation groups. The effect was maintained at 1 year follow-up in both groups. A second part of the study offered persons without clinical effect in the first part of the study, the other treatment option. Interestingly, clinical effect was observed in 55% of those whom received physical therapy in the second round who had no clinical effect from relaxation, while 47% had clinical effect from relaxation in the second round. The mean reduction in headache severity was 30 and 38% in the physical therapy and relaxation groups. Unfortunately, the study did not include a control group.
Chiropractic Spinal Manipulative Treatment
An Australian study included migraineurs with frequent attacks diagnosed by a neurologist [11]. The participants were divided into three study groups; cervical manipulation by chiropractor, cervical manipulation by physiotherapist or physician, and cervical mobilization by physiotherapist or physician. The mean migraine attack duration was skewed in the three groups, as it was much longer in cervical manipulation by chiropractor (30.5 h) than cervical manipulations by physiotherapist or physician (12.2 h) and cervical mobilization groups (14.9 h). The study had several investigators and the treatment within each group was beside the mandatory requirements free for the therapists. No statistically significant differences were found between the three groups. Improvement was observed in all three groups post-treatment (Table 3). Prior to the trial, chiropractors were confident and enthusiastic about the efficacy of cervical manipulation, while physiotherapists and physicians were doubtful about the relevance. The study did not include a control group although cervical mobilization is mentioned as the control group in the paper. A follow-up 20 months after the trial showed further improvement in the all three groups (Table 3) [12].
An American study included 218 migraineurs diagnosed according to the criteria of the International Headache Society by chiropractors [13]. The study had three treatment groups, but no control group. The headache intensity on days with headaches was unchanged in all three groups. The mean frequency was reduced equally in the three groups (Table 3). Over the counter (OTC) medication was reduced from baseline to 4 weeks post-treatment with 55% in the CSMT group, 28% in the amitriptyline group and 15% in the combined CSMT and amitriptyline group.
The second Australian study was based on questionnaire diagnoses on migraine [14]. The participants had migraine for mean 18.1 years. The effect of CSMT was significant better than the control group (Table 3). The mean reduction of migraine frequency, intensity and duration from baseline to follow-up were 42, 13, and 36% in CSMT group, and 17, 5, and 21% in the control group (data calculated by the reviewers based on figures from the paper).
Discussion
Methodological Considerations
The prevalence of migraine was similar based on a questionnaire and a direct physician conducted interview, but it was due to equal positive and negative misclassification by the questionnaire [15]. A precise headache diagnosis requires an interview by a physicians or other health professional experienced in headache diagnostics. Three of the seven RCTs ascertained participants by a questionnaire, with the diagnostic uncertainty introduced by this (Table 3).
The second American study included participants with at least four headache days per months [13]. The mean headache severity on days with headache at baseline varied from 4.4 to 5.0 on a 0�10 box scale in the three treatment groups. This implies that the participants had co-occurrence of tension-type headache, since tension-type headache intensity usually vary between 1 and 6 (mild or moderate), while migraine intensity can vary between 4 and 9 (moderate or severe), but usually it is a severe pain between 7 and 9 [16, 17]. The headache severity on days with headache was unchanged between baseline and at follow-up, indicating that the effect observed was not exclusively due to an effect on migraine, but also an effect on tension-type headache.
RCTs that include a control group are advantageous to RCTs that compare two active treatments, since the effect in the placebo group rarely is zero and often varies. An example is RCTs on acute treatment of migraine comparing the efficacy of subcutaneous sumatriptan and placebo showed placebo responses between 10 and 37%, while the therapeutic effect, i.e., the efficacy of sumatriptan minus the efficacy of placebo was similar [18, 19]. Another example is a RCT on prophylactic treatment of migraine, comparing topiramate and placebo [20]. The attack reduction increased along with increasing dose of topiramate 50, 100 and 200 mg/day. The mean migraine attack frequency was reduced from 1.4 to 2.5 attacks per month in the topiramate groups and 1.1 attacks per month in the placebo group from baseline, with mean attack frequencies varying from 5.1 to 5.8 attacks per month in the four groups.
Thus, interpretation of the efficacy in the four RCTs without a control group is not straight forward [9�12]. The methodological quality of all seven RCTs had room for improvement as the maximum score 100 was far from expectation, especially a precise migraine diagnosis is important.
Several of the studies relatively include a few participants, which might cause type 2 errors. Thus, power calculation prior to the study is important in the future studies. Furthermore, the clinical guidelines from the International Headache Society should be followed, i.e., frequency is a primary end point, while duration and intensity can be secondary end points [21, 22].
Dr. Alex Jimenez’s Insight
Manual therapies, such as massage therapy, physical therapy and chiropractic spinal manipulative treatment are several well-known migraine treatment approaches recommended by healthcare professionals to help improve as well as manage the painful symptoms associated with the condition. Patients who are unable to use drugs and/or medications, including those who may prefer to avoid using these, can benefit from manual therapies for migraine treatment, according to the following article. Evidence-based research studies have determined that manual therapies might be equally as effective for migraine treatment as drugs and/or medications. However, the systematic review determined that future, well-conducted randomized clinical trials on the use of manual therapies for migraine headache pain are required to conclude the findings.
Results
The two RCTs on massage therapy included relatively a few participants, along with shortcomings mentioned in Table 3 [8, 9]. Both studies showed that massage therapy was significantly better than the control group, by reducing migraine intensity and frequency, respectively. The 27�28% (34�7% and 30�2%) therapeutic gain in migraine frequency reduction by massage therapy is comparable with the 6, 16 and 29% therapeutic gain in migraine frequency reduction by prophylactic treatment with topiramate 50, 100 and 200 mg/day [20].
The single study on physiotherapy is large, but do not include a control group [10]. The study defined responders to have 50% or more reduction in migraine intensity. The responder rate to physical therapy was only 13% in the first part of the study, while it was 55% in the group that did not benefit from relaxation, while the responder rate to relaxation was 51% in the first part of the study and 47% in the group that did not benefit from physical therapy. A reduction in migraine intensity often correlates with reduced migraine frequency. For comparison, the responder rate was 39, 49, 47 and 23% among those who received topiramate 50, 100 and 200 mg/day and placebo as defined by 50% or more reduction in migraine frequency [20]. A meta-analysis of 53 studies on prophylactic treatment with propranolol showed a mean 44% reduction in migraine activity [23]. Thus, it seems that physical therapy and relaxation has equally good effect as topiramate and propranolol.
Only one of the four RCTs on chiropractic spinal manipulative therapy (CSMT) included a control group, while the other studies compared with other active treatment [11�14]. The first Australian study showed that the migraine frequency was reduced in all three groups when baseline was compared with 20 months post trail [11, 12]. The chiropractors were highly motivated to CSMT treatment, while physicians and physiotherapist were more sceptical, which might have influenced on the result. An American study showed that CSMT, amitriptyline and CSMT + amitriptyline reduced the migraine frequency 33, 22 and 22% from baseline to post-treatment (Table 3). The second Australian study found that migraine frequency was reduced 35% in the CSMT group, while it was reduced 17% in the control group. Thus, the therapeutic gain is equivalent to that of topiramate 100 mg/day and the efficacy is equivalent to that of propranolol [20, 23].
Three case reports raise concerns about chiropractic cervical SMT, but a recent systematic review found no robust data concerning the incidence or the prevalence of adverse reactions following chiropractic cervical SMT [24�27]. When to refer migraine patients to manual therapies? Patients not responding or tolerating prophylactic medication or who wish to avoid medication for other reasons, can be referred to massage therapy, physical therapy or chiropractic spinal manipulative therapy, as these treatments are safe with a few adverse reactions [27�29].
Conclusion
Current RCTs suggest that massage therapy, physiotherapy, relaxation and chiropractic spinal manipulative therapy might be equally efficient as propranolol and topiramate in the prophylactic management of migraine. However, a firm conclusion requires, in future, well-conducted RCTs without the many methodological shortcomings of the evaluated RCTs on manual therapies. Such studies should follow clinical trial guidelines from the International Headache Society [21, 22].
Conflict of Interest
None declared.
Open Access: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.
In conclusion,�chiropractors, physical therapists and massage therapists, among other qualified and experienced healthcare professionals, recommend manual therapies as a treatment for migraine headache pain. The purpose of the article was to�educate patients on the effects of manual therapies for migraine treatment. Furthermore, the systematic review determined that�future, well-conducted randomized clinical trials are required to conclude the findings. 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 .
Curated by Dr. Alex Jimenez
Additional Topics: Neck Pain
Neck pain is a common complaint which can result due to a variety of injuries and/or conditions. According to statistics, automobile accident injuries and whiplash injuries are some of the most prevalent causes for neck pain among the general population. During an auto accident, the sudden impact from the incident can cause the head and neck to jolt abruptly back-and-forth in any direction, damaging the complex structures surrounding the cervical spine. Trauma to the tendons and ligaments, as well as that of other tissues in the neck, can cause neck pain and radiating symptoms throughout the human body.
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14. Tuchin PJ, Pollard H, Bonello R. A randomized controlled trial of chiropractic spinal manipulative therapy for migraine. J Manipulative Physiol Ther. 2000;23:91�95. doi: 10.1016/S0161-4754(00)90073-3. [PubMed][Cross Ref]
15. Rasmussen BK, Jensen R, Olesen J. Questionnaire versus clinical interview in the diagnosis of headache. Headache. 1991;31:290�295. doi: 10.1111/j.1526-4610.1991.hed3105290.x. [PubMed][Cross Ref]
16. Lundquist YC, Benth JS, Grande RB, Aaseth K, Russell MB. A vertical VAS is a valid instrument for monitoring headache pain intensity. Cephalalgia. 2009;29:1034�1041. doi: 10.1111/j.1468-2982.2008.01833.x. [PubMed][Cross Ref]
17. Rasmussen BK, Olesen J. Migraine with aura and migraine without aura: an epidemiological study. Cephalalgia. 1992;12:221�228. doi: 10.1046/j.1468-2982.1992.1204221.x. [PubMed][Cross Ref]
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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: the Subscapularis Muscle
The subscapularis is a large triangular muscle which fills the subscapular fossa and inserts into the lesser tubercle of the humerus and the front of the capsule of the shoulder-joint.
The subscapularis rotates the head of the humerus medially (internal rotation) and adducts it; when the arm is raised, it draws the humerus forward and downward. It is a powerful defense to the front of the shoulder-joint, preventing displacement of the head of the humerus.
Damage or trauma from an injury or an aggravated condition can cause shortness in the subscapularis muscle. The following assessments and treatments can help improve structure and function.
Assessment of Shortness in the Subscapularis Muscle
Subscapularis shortness test (a) Direct palpation of subscapularis is required to define problems in it, since pain patterns in the shoulder, arm, scapula and chest may all derive from subscapularis or from other sources.
The patient is supine and the practitioner grasps the affected side hand and applies traction while the fingers of the other hand palpate over the edge of latissimus dorsi in order to make contact with the ventral surface of the scapula, where subscapularis can be palpated. There may be a marked reaction from the patient when this is touched, indicating acute sensitivity.
Subscapularis shortness test (b) (as seen on Fig. 4.39 below) The patient is supine with the arm abducted to 90�, the elbow flexed to 90�, and the forearm in external rotation, palm upwards. The whole arm is resting at the restriction barrier, with gravity as its counterweight.
If subscapularis is short the forearm will be unable to rest easily parallel with the floor but will be somewhat elevated.
Figure 4.39A, B Assessment and MET self-treatment position for subscapularis. If the upper arm cannot rest parallel to the floor, possible shortness of subscapularis is indicated.
Care is needed to prevent the anterior shoulder becoming elevated in this position (moving towards the ceiling) and so giving a false normal picture.
Assessment of Weakness in the Subscapularis Muscle
The patient is prone with humerus abducted to 90� and elbow flexed to 90�. The humerus should be in internal rotation so that the forearm is parallel with the trunk, palm towards ceiling. The practitioner stabilises the scapula with one hand and with the other applies pressure to the patient�s wrist and forearm as though taking the humerus towards external rotation, while the patient resists.
The relative strength is judged and the method discussed by Norris (1999) should used to increase strength (isotonic eccentric contraction performed slowly).
MET Treatment of the Subscapularis Muscle
The patient is supine with the arm abducted to 90�, the elbow flexed to 90�, and the forearm in external rotation, palm upwards. The whole arm is resting at the restriction barrier, with gravity as its counterweight. (Care is needed to prevent the anterior shoulder becoming elevated in this position (moving towards the ceiling) and so giving a false normal picture.)
The patient raises the forearm slightly, against minimal resistance from the practitioner, for 7�10 seconds and, following relaxation, gravity or slight assistance from the operator takes the arm into greater external rotation, through the barrier, where it is held for not less than 20 seconds.
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
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