Posts

Don’t Jump To Occlusions

legcrampPeripheral artery disease (PAD) is among the most underdiagnosed, untreated and potentially deadly conditions people can face, raising the risk of heart attack and stroke. An aging population and an increase in obesity and diabetes are causing a wave of non-cardiac vascular disease, affecting as many as eight million people. Canadian cardiologists learned that five percent of the adults over fifty who were screened for PAD had it, but an astounding 80% were unaware of it. Those pains and cramps you feel in your legs when you climb the stairs or simply walk down the driveway to get the mail might be more than you think.

Only about a fourth of the over-fifty group is aware of PAD. That’s the group most likely to be affected by it. PAD can be identified by comparing blood pressure in the arm to the blood pressure in the leg. Those who have already suffered a heart attack or stroke are at the highest risk, and need to be screened at least once a year. Dr. Ross Tsuyuki, of Canada’s U. of Alberta, adds that, “The second highest priority would be people middle-aged and beyond who are at risk for heart disease and stroke, such as people with high blood pressure, diabetes and high cholesterol.”  Besides leg pain, other PAD symptoms include leg sores that are slow to heal, toe pain in the evening, and a sensation of coldness or numbness in one or both legs. Dr. Peter Hibberd contributed that, “The secret to treatment is first-line prevention by avoiding…cigarettes and reducing risk factors for vascular disease (such as lipid disorders) as much as possible as early as possible.”  (Scaglione. Newsmax Health. 2011)  (Makowsky. 2011)

Rapidly evolving vascular technologies have introduced non-invasive, cutting-edge procedures for treating PAD. Interest in screening for non-cardiac vascular disease has also grown since preventive approaches to medicine are on the upswing. One of the latest treatments, although somewhat invasive, is the use of the patient’s own stem cells to make new blood vessels to replace or to augment those choked off by plaque buildup. (Society for Interventional Radiology. 2010)

A person at risk for PAD might consider dietary interventions to help manage contributing factors. Increasing fruits and vegetables, and decreasing empty calories can help to attenuate the accumulation of arterial fat deposits. Of course, drug treatments abound. Cholesterol drugs, blood pressure drugs, blood sugar drugs, anti-blood clot drugs, and symptom-relief drugs are at your doctor’s fingertips…or pen point. On the other hand, there is a body of research to support alternative measures to address PAD, as you’ll see in a minute.

Mortality in patients with recognized coronary artery disease (CAD) and PAD is unsurprisingly high, but therapy can mitigate that. Maintenance of normal weight is an important step, and keeping the body mass index lower than 25.0 is vital, even for those who have never smoked. (Ix. 2011)  Research has shown that a greater BMI will intensify PAD symptoms as evidenced by a decline in walking velocity and performance. (McDermott. 2006)  In cases such as this, supervised exercise training and education provide significant benefits in quality of life and reduced risk for cardiovascular episodes. (Casillas. 2011)

European medicine is supportive of complementary and alternative approaches to the healing arts, so it comes as no surprise that a considerable level of research starts there. German studies have used ginkgo biloba in PAD trials that date back to the late 90’s, finding that efficacy of the herb is dose-dependent, with 240 mg a day superior to the standard dose of half that. (Schweizer. 1999)  (Li. 1998) The British agree that ginkgo is better than placebo in treating the intermittent claudication that accompanies PAD. (Pittler. 2000)    Besides ginkgo, L-arginine, the amino acid that tells blood vessels to relax via the manufacture of nitric oxide, has shown benefits in handling intermittent claudication of PAD (Boger. 1998)  Nitric oxide inhibits contractions of vascular smooth muscle and keeps the blood flowing while helping to sustain blood pressure. There is some evidence that arginine improves the management of multiple CVD indications. (Cheng. 2001)

It might be comforting to know that alternatives to drugs for PAD exist, but it is prudent to look at diet, exercise, and lifestyle before heading to the supplement aisle.

References

Donna V. Scaglione
Peripheral Artery Disease: More Than Just an Ache
www.newsmaxhealth.com/headline_health/Peripheral_Artery_Disease/2011/09/15/407320.html
Thursday, September 15, 2011 1:08 PM

Makowsky M, McMurtry MS, Elton T, Rosenthal M, Gunther M, Percy M, Wong K, Fok J, Sebastianski M, Tsuyuki R.
Prevalence and treatment patterns of lower extremity peripheral arterial disease among patients at risk in ambulatory health settings.
Can J Cardiol. 2011 May-Jun;27(3):389.e11-8.

Society for Interventional Radiology. 16 March 2010
Stem cells build new blood vessels to treat peripheral arterial disease
http://www.sirweb.org/news/newsPDF/92_stem_cells_final.pdf

Ix JH, Biggs ML, Kizer JR, Mukamal KJ, Djousse L, Zieman SJ, de Boer IH, Nelson TL, Newman AB, Criqui MH, Siscovick DS.
Association of Body Mass Index With Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.
Am J Epidemiol. 2011 Sep 13. [Epub ahead of print]

McDermott MM, Criqui MH, Ferrucci L, Guralnik JM, Tian L, Liu K, Greenland P, Tan J, Schneider JR, Clark E, Pearce WH.
Obesity, weight change, and functional decline in peripheral arterial disease.
J Vasc Surg. 2006 Jun;43(6):1198-204.

Casillas JM, Troisgros O, Hannequin A, Gremeaux V, Ader P, Rapin A, Laurent Y.
Rehabilitation in patients with peripheral arterial disease.
Ann Phys Rehabil Med. 2011 Aug 5.

Schweizer J, Hautmann C.
Comparison of two dosages of ginkgo biloba extract EGb 761 in patients with peripheral arterial occlusive disease Fontaine’s stage IIb. A randomised, double-blind, multicentric clinical trial.
Arzneimittelforschung. 1999 Nov;49(11):900-4.

Li AL, Shi YD, Landsmann B, Schanowski-Bouvier P, Dikta G, Bauer U, Artmann GM.
Hemorheology and walking of peripheral arterial occlusive diseases patients during treatment with Ginkgo biloba extract.
Zhongguo Yao Li Xue Bao. 1998 Sep;19(5):417-21.

Pittler MH, Ernst E.
Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials.
Am J Med. 2000 Mar;108(4):276-81.

Böger RH, Bode-Böger SM, Thiele W, Creutzig A, Alexander K, Frölich JC.
Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease.
J Am Coll Cardiol. 1998 Nov;32(5):1336-44.

Cheng JW, Baldwin SN.
L-arginine in the management of cardiovascular diseases
Ann Pharmacother. 2001 Jun;35(6):755-64.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Allergy and Inflammation

allergiesIf you’re among the susceptible, the first whack in the face by a giant pollen ball is enough to set you back.  You get the runny nose, the watery eyes, the headaches and all the accessories.  If they were temporary symptoms, you wouldn’t pay much attention.  A handful of tissues and a couple of antihistamines, and you’re on your way.  Few of us understand, though, that seasonal allergies incite an inflammatory response, which is a protective attempt by the body to remove the enemy and clean up the place where it was.  Inflammation is not infection, but may be caused by it.  It’s considered part of the innate immune system, which activates as a function of your natural biological makeup.

Allergic disorders, which include hay fever, eczema and asthma, afflict almost a quarter of the population in the developed world (Holgate, 1999) (Galli, 2008).  Persistent exposure to allergens, basically innocuous substances in the environment, results in chronic allergic inflammation.  This can cause the affected organ(s) to go through substantial changes in function.  In fact, some people can develop a potentially fatal systemic reaction, called anaphylaxis, within seconds of exposure to an allergen (Simons, 2011).  Certain foods, as well as other non-infectious substances, may be involved.  In allergic responses, allergen-specific immunoglobulin E (IgE) and T helper cells (Th2) are switched on.

An acute response to an allergen that happens after a single exposure is called an early-phase reaction, or a Type-1 immediate hypersensitivity reaction.  Histamine is released here during mast cell degranulation. These molecules hook up with IgE and eventually cause itching, mucus production, swelling of blood vessels (vasodilation), edema and the airway constriction seen in allergic asthma (Hansen, 2004)  (Katelaris, 2003).  Chronic inflammation may be characterized by a continuum of tissue destruction and healing that may lead to loss of function, but this is not often seen with seasonal allergies, called allergic rhinitis. Allergic rhinitis is linked to decreased learning, poor performance at work and school, and of course, reduced quality of life.  The course of action taken by a doctor offers several pharmacologic options (Sadeq, 2004), many of which are shunned by patients in favor of natural alternatives.  Allergen-specific immunotherapy is designed to suppress the mechanism that responds to allergen attack.  This entails the use of chemical agents to regulate body function (Fujita, 2012), and this engenders a jaundiced eye among the holistic crowd.

Within the domain of complementary and alternative medicine is a plant whose use predates medieval times—stinging nettle, scientifically known as Urtica dioica.   For hundreds of years it’s been used to treat gout, painful joints, arthritis, eczema and anemia.  In modern times, nettle has been used to treat urinary problems during the early stages of benign prostate hyperplasia, and to treat urinary infections and hay fever.  It’s also been used in compresses to address joint pains, sprains and strains, tendinitis and insect bites.  Freeze-dried preparations were matched against placebo in a double-blinded randomized allergic rhinitis study performed at the National College of Naturopathic Medicine, and were found to be more effective than placebo at relieving symptoms (Mittman, 1990).  Cytokines are regulatory proteins that are released by cells of the immune system, where they act as mediators in the generation of an immune response, and may be assayed by the measurement of Th1 and Th2 cells, as well as by other markers of immune activation.  Extracts of stinging nettle, registered in Germany for therapy of rheumatic disease, were found to inhibit the inflammatory cascade identified by these artifacts (Klingelhoefer, 1999).

Quercetin is a bioflavonoid derived from red wine, citrus, onions, parsley, apples and tea, demonstrating several noble qualities, anti-inflammation and anti-oxidation among them.  The anti-inflammatory property arises from its inhibition of the production and activity of leukotrienes and pro-inflammatory prostaglandins, and inhibition of histamine release by basophils and mast cells.  Additionally, quercitin represses expression of the COX2 enzyme that is responsible for the manufacture of pro-inflammatory substances, and it stems the interleukins that characterize inflammation (Nieman, 2007).  Studies at Northwestern University agree that quercitin has its place as a primary therapy or as an adjunct in the treatment of allergic rhinitis (Thornhill, 2000).  Ocular symptoms of allergy are uncomfortable and often more bothersome than nasal symptoms.  Japanese scientists found that quercitin, in a double-blind placebo-controlled study, was substantially more effective than placebo at ameliorating the ocular symptoms that can plague sufferers of allergic rhinitis.  Ocular scores that rated tearing, itching and ocular congestion were low, while nasal scores differed little from the control group (Hirano, 2009).

Complementary medicine is not without allies in the allopathic medical community, especially when a supplement has proven efficacy against a traditional modality.  In the conventional medical sector, where raised eyebrows are the norm after the mention of complementary approaches, bromelain, the proteolytic enzyme from pineapple that digests proteins and tenderizes meat, has found favor in the treatment of otolaryngology disorders that include allergic rhinitis.  In a multicenter trial composed of 116 children, bromelain monotherapy (used by itself) effected faster recovery from sinusitis compared with standard therapy (Karkos, 2007).  As adjunctive to traditional therapy, bromelain exhibited supportive strength against acute rhinosinusitis (Guo, 2006).  Although marketed as a digestive aid, bromelain appears to have systemic anti-inflammatory activity (Hale, 2005) (Kumakura, 1988) (Onken, 2008).

In recent announcements, oral vitamin D added to regular intranasal corticosteroid dosing improves symptoms beyond that seen with corticosteroids alone, leading researchers to conclude that vitamin D affords benefit to patients with allergies (Baroody, 2012).  Treating inflammation may be nearer at hand than previously thought, and that just might eliminate, or at least reduce, the misery of seasonal allergy.

References

Ahmadiafshar A, Taghiloo D, Esmailzadeh A, Falakaflaki B.
Nasal eosinophilia as a marker for allergic rhinitis: A controlled study of 50 patients.
Ear Nose Throat J. 2012 Mar;91(3):122-4.

F. M. Baroody, J. Lane, S. Watanabe, M. DeTineo, J. Pinto, R. M. Naclerio;
The Addition of Vitamin D (VitD) to an Intranasal Steroid (INS) Improves Control of Symptoms in Seasonal Allergic Rhinitis (SAR)
J ALLERGY CLIN IMMUNOL.  FEBRUARY 2012;  abstract 510

G. Walter Canonica, MD
Treating Asthma as an Inflammatory Disease
CHEST July 2006 vol. 130 no. 1 suppl 21S-28S

Fujita H, Meyer N, Akdis M, Akdis CA.
Mechanisms of immune tolerance to allergens.
Chem Immunol Allergy. 2012;96:30-8.

Fujita H, Soyka MB, Akdis M, Akdis CA.
Mechanisms of allergen-specific immunotherapy.
Clin Transl Allergy. 2012 Jan 5;2(1):2

Stephen J. Galli, Mindy Tsai & Adrian M. Piliponsky
The development of allergic inflammation
Nature 454, 445-454 (24 July 2008)

Granado-Serrano AB, Martín MA, Bravo L, Goya L, Ramos S.
Quercetin Attenuates TNF-Induced Inflammation in Hepatic Cells by Inhibiting the NF-κB Pathway.
Nutr Cancer. 2012 Mar 27.

Guo R, Canter PH, Ernst E.
Herbal medicines for the treatment of rhinosinusitis: a systematic review.
Otolaryngol Head Neck Surg. 2006 Oct;135(4):496-506.

Hale LP, Greer PK, Trinh CT, Gottfried MR.
Treatment with oral bromelain decreases colonic inflammation in the IL-10-deficient murine model of inflammatory bowel disease.
Clin Immunol. 2005 Aug;116(2):135-42.

Hansen I, Klimek L, Mösges R, Hörmann K.
Mediators of inflammation in the early and the late phase of allergic rhinitis.
Curr Opin Allergy Clin Immunol. 2004 Jun;4(3):159-63.

Hirano T, Kawai M, Arimitsu J, Ogawa M, Kuwahara Y, Hagihara K, Shima Y, Narazaki M, Ogata A, Koyanagi M, Kai T, Shimizu R, Moriwaki M, Suzuki Y, Ogino S, Kawase I, Tanaka T.
Preventative effect of a flavonoid, enzymatically modified isoquercitrin on ocular symptoms of Japanese cedar pollinosis.
Allergol Int. 2009 Sep;58(3):373-82. Epub 2009 May 25.

Holgate ST.
The epidemic of allergy and asthma.
Nature. 1999 Nov 25;402(6760 Suppl):B2-4.

Jaber R.
Respiratory and allergic diseases: from upper respiratory tract infections to asthma.
Prim Care. 2002 Jun;29(2):231-61.

Jutel M, Akdis CA.
T-cell regulatory mechanisms in specific immunotherapy.
Chem Immunol Allergy. 2008;94:158-77.

Karkos PD, Leong SC, Arya AK, Papouliakos SM, Apostolidou MT, Issing WJ.
‘Complementary ENT’: a systematic review of commonly used supplements.
J Laryngol Otol. 2007 Aug;121(8):779-82. Epub 2006 Nov 24.

Katelaris CH.
Ocular allergy: implications for the clinical immunologist.
Ann Allergy Asthma Immunol. 2003 Jun;90(6 Suppl 3):23-7.

Klingelhoefer S, Obertreis B, Quast S, Behnke B.
Antirheumatic effect of IDS 23, a stinging nettle leaf extract, on in vitro expression of T helper cytokines.
J Rheumatol. 1999 Dec;26(12):2517-22.

Kostyuk VA, Potapovich AI, Suhan TO, de Luca C, Korkina LG.
Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation.
Eur J Pharmacol. 2011 May 11;658(2-3):248-56.

Kumakura S, Yamashita M, Tsurufuji S.
Effect of bromelain on kaolin-induced inflammation in rats.
Eur J Pharmacol. 1988 Jun 10;150(3):295-301.

Mittman P.
Randomized, double-blind study of freeze-dried Urtica dioica in the treatment of allergic rhinitis.
Planta Med. 1990 Feb;56(1):44-7.

Nieman DC, Henson DA, Davis JM, Angela Murphy E, Jenkins DP, Gross SJ, Carmichael MD, Quindry JC, Dumke CL, Utter AC, McAnulty SR, McAnulty LS, Triplett NT, Mayer EP.
Quercetin’s influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA.
J Appl Physiol. 2007 Nov;103(5):1728-35. Epub 2007 Aug 23.

Obertreis B, Giller K, Teucher T, Behnke B, Schmitz H.
Anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic acid.
Arzneimittelforschung. 1996 Jan;46(1):52-6.

Jane E Onken, Paula K Greer, Brian Calingaert, Laura P Hale
Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro.
Clin Immunol. Volume 126, Issue 3, March 2008, Pages 345–352

Overman A, Chuang CC, McIntosh M.
Quercetin attenuates inflammation in human macrophages and adipocytes exposed to macrophage-conditioned media.
Int J Obes (Lond). 2011 Sep;35(9):1165-72.

Sadeq A. Quraishi, MHA;  Michael J. Davies, MD;  Timothy J. Craig, DO
Inflammatory Responses in Allergic Rhinitis: Traditional Approaches and Novel Treatment Strategies
J Am Osteopath Assoc May 1, 2004 vol. 104 no. 5 suppl 7S-15S

Simons FE.
Anaphylaxis pathogenesis and treatment.
Allergy. 2011 Jul;66 Suppl 95:31-4.

Skiepko R, Zietkowski Z, Tomasiak-Lozowska MM, Tomasiak M, Bodzenta-Lukaszyk A.
Bronchial hyperresponsiveness and airway inflammation in patients with seasonal allergic rhinitis.
J Investig Allergol Clin Immunol. 2011;21(7):532-9.

Thornhill SM, Kelly AM.
Natural treatment of perennial allergic rhinitis.
Altern Med Rev. 2000 Oct;5(5):448-54.

tYoon JS, Lee HJ, Choi SH, Chang EJ, Lee SY, Lee EJ.
Quercetin inhibits IL-1β-induced inflammation, hyaluronan production and adipogenesis in orbital fibroblasts from Graves’ orbitopathy.
PLoS One. 2011;6(10):e26261.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Reduce Inflammation through Weight Loss

acute-pain-in-a-woman-kneeSome of us know inflammation too well. When getting out of bed in the morning becomes an auditory event in your joints that rivals a flamenco dancer’s castanets, you know inflammation. What you may not know, or at least not realize, is that your weight has something to do with it. For many of us, the seeds of inflammation were planted years ago. Our genes, body weight, diet, lifestyle and fitness determine our states of wellness and non-wellness, some of which we cannot sense. Silent inflammation is probably worse than that we can feel from getting cut or hit by a baseball. If it hurts or is uncomfortable, we’ll take care of it right away. If it’s not noticeable, it can smolder for years, eventually exploding into a chronic illness.

Inflammation is the response of tissue to injury or insult, occasionally caused by an invading pathogen. Characteristics, which you can sense, include increased blood flow to the injured area, elevated temperature, redness, swelling and pain. Inflammatory responses to what should have been a harmless agent include allergies and autoimmune diseases, states where the response is either out of proportion to the threat it faces or is directed against an inappropriate target, such as self. In these cases, the response is worse than anything the agent itself could have generated, and is often insensate. The cascade of cellular and molecular signals that accompany inflammation can perpetuate it and make it chronic, in which case monocytes and macrophages take over the management. This may sound cool, but the chemicals they create inside the tissues wreak havoc. Macrophages begin to swallow everything that appears derelict, including senescent cells and whatever is deemed a pathogen, whether it truly is or not.

At some point in this chronology, chemical mediators are released, including things like Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-a) and prostaglandins that keep the ball rolling…on and on. When the body tries to control all this nefarious activity it replaces damaged tissue with replacement cells of the same type, but occasionally fails and results in diseased states, such as asthma, rheumatoid arthritis, tendonitis, celiac and inflammatory bowel diseases.

Inflammation is recognized as causal to several chronic diseases and all-cause mortality, and is prevalent among those who have a body mass index above 30.0.  Biomarkers of inflammation are used to examine the relationship of inflammation to chronicity, with C-reactive protein (CRP), IL-6, TNF-a, and IL-8 as indicators. CRP probably is the first one your doctor will interpret, since it’s a prime marker of inflammation. It just doesn’t pinpoint the location. CRP is a native protein made by the liver in response to factors released by fat cells. In acute inflammation, such as from an infection, levels can rise in less than six hours and be hundreds of times higher than normal, which is lower than 10 mg per liter. With a severe bacterial infection, it can reach 200 or more. The absolutely perfect reading is 1.0. Levels above 2.4 are supposed to be associated with increased risk of cardiovascular events, but that’s debatable because the studies were done with people who had unstable angina (Pepys, 2003).

Human adipose tissue expresses and releases the pro-inflammatory artifacts, inducing low-grade systemic inflammation in people with too much body fat. Pediatricians in the Netherlands looked at overweight children in their country and saw higher levels of CRP than in normal-weight children (Visser, 2001), accompanied by higher white cell counts. In 2007, the Archives of Internal Medicine published an analysis of more than thirty separate studies, concluding that weight loss is a major factor in the reduction of CRP, adding that a loss of one kilogram (2.2 lbs) equates to a 0.13 mg/L drop in CRP (Selvin, 2007).

Many parents think that their kids will outgrow the chubby stage. Sometimes, yes; often, no. We now see 400-pound 20-year-olds who were obese at age eight, whose parents ignored admonitions to address the foreboded tragedy at the early age. That collection of fat that hangs over the belt, sometimes reaching the thighs, is called a panniculus, and is more than just a dormant spare tire. It secretes adipokines, or chemical signals, to other parts of the body, increasing risk of serious disease through disrupted homeostasis (Rosenow, 2010). If this describes someone you know, eventually you’ll likely see diabetes, heart disease, and maybe even some form of cancer (Ibid).

There are plenty of overweight seniors, some of whom achieve that senior designation at age 40, others above 70. Just by virtue of their age, they’re more likely to report joint pain, but obesity at any age is a predictor of low-grade chronic inflammatory state.  Whether by diet or exercise, or both, weight loss is extremely vital to maintaining one’s health. In comparisons, the low-carb folks lost more weight than the low-fat. Think about this.  The knee pain in the 50-year-old guy is so bad he can’t walk behind his lawnmower. The problem is that he’s carrying 375 pounds on a frame designed to carry 150-180, and his femur is squeezing the cushions at the tibia. Yes, it’s distinctly possible that thyroid issues are causative of the extra weight. There may be other factors that include lack of sleep, too much stress, certain medications, uncontrolled cortisol (kinda rare), and menopause in women. Some of these can be managed and can be worked out with the family physician and maybe a visit to a dietitian. However, looking more closely at his eating habits, we see carbohydrates as the main source of gustatory input, with beneficial fats and lean protein given the back seat. Self-inflicted obesity has no excuse. Inflammatory biomarkers can be attenuated with even a small reduction in weight (Miller, 2008) (You, 2006).  Now, get this. The physical movement required to mow the lawn might be just enough to reduce inflammation, despite the immediate discomfort, which will eventually taper off. (Ford, 2002) (Miller, 2008).

Obesity is a problem of epidemic proportions. Certain people are perceived as anathema, bête noir, pariah, and may pay for self-destructive behavior. If cigarette cessation clears the lungs, could weight reduction clear the blood? Yep. Dietary interventions will help both, but sticking a finger into the dike doesn’t quite do it.

References

Clément K, Viguerie N, Poitou C, Carette C, Pelloux V, Curat CA, Sicard A, Rome S, Benis A, Zucker JD, Vidal H, Laville M, Barsh GS, Basdevant A, Stich V, Cancello R, Langin D.
Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects.
FASEB J. 2004 Nov;18(14):1657-69.

Mary Elizabeth Dallas
Losing Weight May Lower Cardiac Risks
Study finds both low-carb and low-fat diets help overweight people reduce inflammation
NIH, 5 Nov, 2012
MedlinePlus Trusted Health Information for You A service of the U.S. National Library of Medicine
From the National Institutes of HealthNational Institutes of Health
http://www.nlm.nih.gov/medlineplus/news/fullstory_131011.html

Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D.
Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial.
JAMA. 2003 Apr 9;289(14):1799-804.

Ford, Earl S.
Does Exercise Reduce Inflammation? Physical Activity and C-Reactive Protein Among U.S. Adults
Epidemiology:. September 2002 – Volume 13 – Issue 5 – pp 561-568

Gilbert CA, Slingerland JM.
Cytokines, Obesity, and Cancer: New Insights on Mechanisms Linking Obesity to Cancer Risk and Progression.
Annu Rev Med. 2012 Oct 26. [Epub ahead of print]

Kawasaki N, Asada R, Saito A, Kanemoto S, Imaizumi K.
Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue.
Sci Rep. 2012;2:799. Epub 2012 Nov 12.

Stephen P Messier, Claudine Legault, Shannon Mihalko, Gary D Miller, Richard F Loeser, Paul DeVita, Mary Lyles, Felix Eckstein, David J Hunter, Jeff D Williamson and Barbara J Nicklas
The Intensive Diet and Exercise for Arthritis (IDEA) trial: design and rationale
BMC Musculoskeletal Disorders 2009, 10:93

Miller GD, Nicklas BJ, Loeser RF.
Inflammatory biomarkers and physical function in older, obese adults with knee pain and self-reported osteoarthritis after intensive weight-loss therapy.
J Am Geriatr Soc. 2008 Apr;56(4):644-51. Epub 2008 Feb 28.

Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW.
Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo.
J Clin Endocrinol Metab. 1997 Dec;82(12):4196-200.
Navarro SL, Brasky TM, Schwarz Y, Song X, Wang CY, Kristal AR, Kratz M, White E, Lampe JW.
Reliability of serum biomarkers of inflammation from repeated measures in healthy individuals.
Cancer Epidemiol Biomarkers Prev. 2012 Jul;21(7):1167-70. Epub 2012 May 7.

Nicklas BJ, Ambrosius W, Messier SP, Miller GD, Penninx BW, Loeser RF, Palla S, Bleecker E, Pahor M.
Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial.
Am J Clin Nutr. 2004 Apr;79(4):544-51.

Pepys MB, Hirschfield GM.
C-reactive protein: a critical update.
J Clin Invest. 2003 Jun;111(12):1805-12.

Anja Rosenow, Tabiwang N. Arrey, Freek G. Bouwman, Jean-Paul Noben, Martin Wabitsch, Edwin C.M. Mariman, Michael Karas, and Johan Renes
Identification of Novel Human Adipocyte Secreted Proteins by Using SGBS Cells
J. Proteome Res., 2010, 9 (10), pp 5389–5401

Roth CL, Kratz M, Ralston MM, Reinehr T.
Changes in adipose-derived inflammatory cytokines and chemokines after successful lifestyle intervention in obese children.
Metabolism. 2011 Apr;60(4):445-52. Epub 2010 May 24.

Elizabeth Selvin, PhD, MPH; Nina P. Paynter, MHS; Thomas P. Erlinger, MD, MPH
The Effect of Weight Loss on C-Reactive ProteinA Systematic Review
Arch Intern Med. 2007;167(1):31-39

Tam CS, Clément K, Baur LA, Tordjman J.
Obesity and low-grade inflammation: a paediatric perspective.
Obes Rev. 2010 Feb;11(2):118-26. Epub 2009 Oct 21.

André Tchernof, PhD; Amy Nolan, RD; Cynthia K. Sites, MD; Philip A. Ades, MD; Eric T. Poehlman, PhD
Weight Loss Reduces C-Reactive Protein Levels in Obese Postmenopausal Women
Circulation. 2002; 105: 564-569

You T, Nicklas BJ
Chronic inflammation: role of adipose tissue and modulation by weight loss.
Current Diabetes Reviews [2006, 2(1):29-37]

Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB.
Elevated C-reactive protein levels in overweight and obese adults.
JAMA. 1999 Dec 8;282(22):2131-5.

Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB.
Low-grade systemic inflammation in overweight children.
Pediatrics. 2001 Jan;107(1):E13.

Viviane Zorzanelli Rocha, M.D., Eduardo J. Folco, PhD, Galina Sukhova, PhD, Koichi Shimizu, M.D., Israel Gotsman, M.D., Ashley H. Vernon, M.D., and Peter Libby, M.D.
Interferon-gamma, a Th1 Cytokine, Regulates Fat Inflammation A Role for Adaptive Immunity in Obesity
Circ Res. 2008 August 29; 103(5): 467–476.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Arthritis and Common Chemicals

arthritisMerely because something is hereditary doesn’t mean it has to be inherited unless it’s a defined, overt physical characteristic, such as eye color or hairline. Disease or propensity for disease does not have to telegraph itself through gene expression. In the belief that genetic activity can be turned on and off, more than a handful of scientists are convinced that arthritis, in this case, does not have to pass from seed to seed along the family tree. Arthritis, the osteo- kind, can be spawned from unseen environmental assaults, namely perfluorinated chemicals, which are fluorocarbon derivatives. You remember fluorocarbons. They’re part of the chlorofluorocarbons (CFC’s) once used as propellants in spray cans and in refrigerant fluids. Although they aren’t used for aerosol sprays any more, they’re still in the marketplace. When released into the atmosphere, CFC’s affect stratospheric ozone, the depletion of which is implicated in the rise of skin diseases and climate change, not to mention depressed growth in plants and interrupted photosynthesis. Photosynthesis is important only to those of us who need to eat. Fluorocarbons are bioaccumulative—they are stored in the body.

Of special concern are perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). (Aren’t abbreviations great?) What in the world are these things used for? If what you own resists stains and water, it probably contains one of these. Ever hear of Scotchgard? How about stone or tile sealers? Got your new sofa treated against kids’ spillage? Fast food wrappers don’t leak grease, do they? Gunk doesn’t stick to dental floss, does it? Ever do any plumbing and use Teflon tape to help seal a joint? Oh, yeah, got Teflon? The oxygen atoms on these chemicals help them to bind proteins to fatty acids or hormone substrates such as albumin, and to nuclear receptors that regulate genes, such as PPAR’s (Anitole, 2007) (Cheng, 2008). Their half-life is about three years. Production of these nifty chemicals has declined for safety reasons, ahem, but exposure remains widespread.

PFOA, especially, is associated with infertility (Fei, 2009) (Joensen, 2009) and ADD/ADHD in young adolescents (Hoffman, 2010). But its association with osteoarthritis concerns us at this time. Fluorine (chemical symbol F) is a corrosive gas that reacts with practically everything else in the periodic table except the noble gases, which happen to be so noble that they don’t mix with anything. If fluorine mixes with something else, it’s now a fluoride. On teeth, from the outside, fluoride is O.K. From inside the body, it’s not. That’s why the toothpaste label says not to swallow it. Fluoride usually enters the body either by inhalation or ingestion. (Did you know that tea contains fluoride? We’ll get to that in a minute.)

F reacts with hydrochloric acid in the stomach to form hydrofluoric acid (HF), which just so happens to be the precursor to Prozac. This acid passes to the liver, but evades phase 1 detoxification, where the liver uses O2 and enzymes to oxidize toxins to make them water-soluble. This short circuit occurs because fluorine is the strongest oxidizer currently known. At this point, hydrofluoric acid passes into the bloodstream and is distributed to all body parts, including bones. Now, bones are made from calcium compounds, particularly carbonated hydroxyapatite. When an acid and a base combine, they form a salt. Hydrofluoric acid mixes with the calcium (alkaline) to form CaF2, an insoluble salt. That increases density of bone, but lowers strength. The bone is less elastic and more prone to fractures. As bone thickens, it restricts mobility. To compound matters, factors that acidify the urine increase the retention of fluoride. However, happily, the opposite is also true. Absorption of fluoride is reduced by calcium (Whitford, 1994).

Tea may pose problems for heavy tea drinkers. Being labeled a heavy tea drinker is not common in the United States unless you earn membership in the gallon-a-day club. Tea plants readily absorb fluoride—and aluminum—from soil. Therefore, the beverage will contain various levels of fluoride, depending on soil levels. Brewed black tea in the States contains about 3 to 4 parts per million (which is practically identical to milligrams per liter); commercial iced tea has between 1 and 4 (Whyte, 2006) (Whitford, 1994) (Izuora, 2011). The number of skeletal fluorosis reports has grown in recent years, but that has been seen mostly in people who consumed 20 milligrams of fluoride a day for decades. In the mean time, 5 milligrams a day (That would be about a quart a day.) can present preclinical stages of fluorosis, so what has been diagnosed as arthritis may actually be skeletal fluorosis. Though this problem is more extensive in the tea cultures of Asia, it’s still a good idea to drink tea in moderation.

Getting back to PFOA and PFOS, levels in humans vary widely. Certain occupations can increase exposure thousands of times, especially for those working in chemical, metal refining and power plants. Drinking water contaminated with these chemicals contributes to human misery as much as direct exposure. Some American states have ground water that contains either naturally occurring fluoride compounds or the wastes from industrial sources. Ohio and West Virginia are two. In areas such as these, osteoarthritis prevalence exceeds that in other regions. Though a terrible affliction for anyone, women seem to be affected more than men. Cartilage damage and inflammatory responses are part of the spectrum (Uhl, 2013).

If you start to feel aches and pains that are new to you, take a look at what you’re been wearing, where you’ve been, and what you ate and drank. Stain resistant trousers and shirts, high intake of black and green teas, and the wrappers from the fast-food joint might be the cause. (See http://www.bodybio.com/content.aspx?page=Enhancing-the-worst)  Global production of these substances has been on the wane, but leftovers still occupy the environment. Substitute compounds are no doubt in the future, but now we have to be concerned about their long-term effects. Although research is sketchy, iodine, calcium, magnesium and boron are being studied as antidotes to fluoride toxicity (Kao, 2004) (Heard, 2001).

References

Cao J, Bai X, Zhao Y, Liu J, Zhou D, Fang S, Jia M, Wu J.
The relationship of fluorosis and brick tea drinking in Chinese Tibetans.
Environ Health Perspect. 1996 Dec;104(12):1340-3.

Cao J, Zhao Y, Liu J, Xirao R.
[Brick-tea type adult bone fluorosis].
Wei Sheng Yan Jiu. 2003 Mar;32(2):141-3.

Cao J, Zhao Y, Liu J, Xirao R, Danzeng S, Daji D, Yan Y.
Brick tea fluoride as a main source of adult fluorosis.
Food Chem Toxicol. 2003 Apr;41(4):535-42.

Cheng X, Klaassen CD.
Perfluorocarboxylic acids induce cytochrome P450 enzymes in mouse liver through activation of PPAR-alpha and CAR transcription factors.
Toxicol Sci. 2008 Nov;106(1):29-36.

Czerwinski E, Nowak J, Dabrowska D, Skolarczyk A, Kita B, Ksiezyk M.
Bone and joint pathology in fluoride-exposed workers.
Arch Environ Health. 1988 Sep-Oct;43(5):340-3.

Fei C, McLaughlin JK, Lipworth L, Olsen J.
Maternal levels of perfluorinated chemicals and subfecundity
Hum Reprod. 2009 May;24(5):1200-5.

Grandjean P, Thomsen G.
Reversibility of skeletal fluorosis.
Br J Ind Med. 1983 Nov;40(4):456-61.

Hayacibara MF, Queiroz CS, Tabchoury CP, Cury JA.
Fluoride and aluminum in teas and tea-based beverages.
Rev Saude Publica. 2004 Feb;38(1):100-5.

Heard K, Hill RE, Cairns CB, Dart RC.
Calcium neutralizes fluoride bioavailability in a lethal model of fluoride poisoning.
J Toxicol Clin Toxicol. 2001;39(4):349-53.

Hoffman K, Webster TF, Weisskopf MG, Weinberg J, Vieira VM.
Exposure to polyfluoroalkyl chemicals and attention deficit/hyperactivity disorder in U.S. children 12-15 years of age
Environ Health Perspect. 2010 Dec;118(12):1762-7.

Izuora K, Twombly JG, Whitford GM, Demertzis J, Pacifici R, Whyte MP.
Skeletal fluorosis from brewed tea.
J Clin Endocrinol Metab. 2011 Aug;96(8):2318-24.

Joensen UN, Bossi R, Leffers H, Jensen AA, Skakkebaek NE, Jørgensen N.
Do perfluoroalkyl compounds impair human semen quality?
Environ Health Perspect. 2009 Jun;117(6):923-7.

Kao WF, Deng JF, Chiang SC, Heard K, Yen DH, Lu MC, Kuo BI, Kuo CC, Liu TY, Lee CH.
A simple, safe, and efficient way to treat severe fluoride poisoning–oral calcium or magnesium.
J Toxicol Clin Toxicol. 2004;42(1):33-40.

Kavanagh D, Renehan J.
Fluoride in tea–its dental significance: a review.
J Ir Dent Assoc. 1998;44(4):100-5.

Kurland ES, Schulman RC, Zerwekh JE, Reinus WR, Dempster DW, Whyte MP.
Recovery from skeletal fluorosis (an enigmatic, American case).
J Bone Miner Res. 2007 Jan;22(1):163-70.

Lau C, Anitole K, Hodes C, Lai D, Pfahles-Hutchens A, Seed J.
Perfluoroalkyl acids: a review of monitoring and toxicological findings.
Toxicol Sci. 2007 Oct;99(2):366-94.

Luo Rui, Liu Ri-guang1, Ye Chuan, Yu Yan-ni, Guan Zhi-zhong
Total knee arthroplasty for the treatment of knee osteoarthritis caused by endemic skeletal fluorosis
Chinese Journal of Tissue Engineering Research. Feb 26, 2012; 16 (9): 1555-1558

Petrone P, Giordano M, Giustino S, Guarino FM.
Enduring fluoride health hazard for the Vesuvius area population: the case of AD 79 Herculaneum.
PLoS One. 2011;6(6):e21085.

Savas S, Cetin M, Akdoğan M, Heybeli N.
Endemic fluorosis in Turkish patients: relationship with knee osteoarthritis.
Rheumatol Int. 2001 Sep;21(1):30-5.

Howard Thomas
Some Non-essential Aerosol Propellant Uses Finally Banned
Federal Regulations:  43 F. R. 11301 (1978)
http://lawlibrary.unm.edu/nrj/19/1/16_thomas_some.pdf

Sarah A. Uhl, Tamarra James-Todd, and Michelle L. Bell
Association of Osteoarthritis with Perfluorooctanoate and Perfluorooctane Sulfonate in NHANES 2003–2008
Environ Health Perspect. February 14, 2013

Whitford GM.
Intake and metabolism of fluoride.
Adv Dent Res. 1994 Jun;8(1):5-14.

Whitford GM.
Fluoride metabolism and excretion in children.
J Public Health Dent. 1999 Fall;59(4):224-8.

Whyte MP.
Fluoride levels in bottled teas.
Am J Med. 2006 Feb;119(2):189-90.

Wong MH, Fung KF, Carr HP.
Aluminium and fluoride contents of tea, with emphasis on brick tea and their health implications.
Toxicol Lett. 2003 Jan 31;137(1-2):111-20.

Xiangjin Ge, Yuting Jiang, Guohua Tang, Meilie Zhang, Yurong Zhao
Investigations on the Occurrence of Osteoarthritis in Middle-aged and Elderly Persons in Fluorosis Afflicted Regions of Gaomi City with High Fluoride Concentration in Drinking Water
Preventive Medicine Tribune. Volume 12, No. 1;  January 2006:  pp. 57-58 ·57·

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

The Rumors on Rheumatoid Arthritis

hands-jarAunt Martha’s mother was the kindest, gentlest soul you’d ever meet. She went out of her way to make you feel at home. Food and drink were hallmarks of her cordial greeting. But she couldn’t open a package, twist open a jar or cut a cake. Her fingers were so badly gnarled that no two pointed in the same direction. Some of the joints formed the letter “Z.” Yet, despite the pain she must have borne, her loving smile prevailed. She was victimized by rheumatoid arthritis (RA) in an era when research was in its infancy, barely crawling.

This nefarious disease causes pain, swelling, stiffness and loss of function in joints— mostly hands and fingers, though it can strike any. It hits women more often than men, starting between ages twenty-five and fifty-five, though some statisticians start at forty. Unlike osteoarthritis, RA is an autoimmune condition that can affect body parts besides joints, such as the eyes, mouth and lungs. Nobody knows the cause. It could be genes, maybe the environment, or maybe hormones that direct the immune system to attack the body’s own tissues. Whatever it is, RA afflicts more than a million Americans, a sizeable fraction being kids.

The inflammation of RA can reach to the tendons, ligaments and muscles in some patients. Its chronic nature causes degradation of cartilage, bone and the ligaments that bind bones, causing deformity. Active disease presents with fatigue, appetite loss, low-grade fever, muscle and joint aches, and stiffness, the last being most notable in the morning or following periods of inactivity. Because RA is a systemic ordeal, its malevolence can inflame the glands around the eyes and mouth, causing Sjögren’s syndrome. RA-induced pleuritis is the inflammation of lung lining that causes pain with a deep breath. Because the number of red blood cells is reduced, anemia occurs, while a drop in white cells can be associated with an enlarged spleen and increased risk of infection.

Following examination of inflammatory blood markers and other criteria, the doctor can make a proper diagnosis, at which time medications probably will be prescribed. Cortisone and aspirin have been first-line drugs for decades because they act quickly. The slower ones are called disease-modifying anti-rheumatic drugs—DMARD’s—and include some heavy duty chemistry, not all of which is anti-inflammatory, but most of which has truly nasty side effects, many you have learned from television ads. What may not be realized is that some drugs destroy the substances your body needs to work the right way. The package insert that comes with the drug doesn’t tell you this, so you’ll think the absence of pain has all the bases covered. This is sufficient reason to visit an integrative dietitian or holistic-minded physician, the rare one who knows about nutrition.

Keeping your physician in the loop, you may opt to explore integrative measures to deal with RA. The good news is that there are recognized mediators of inflammation-induced bone damage (Nanjundaiah, 2013). Because of space constraints, we’ll address those with a pretty reliable track record, starting with gamma linolenic acid (GLA), an omega-6 fatty acid found in borage and evening primrose oils. While it is true that borage contains almost twice the levels of GLA as evening primrose, it is also true that borage contains pyrrolizidine alkaloids that can tax the liver. Though possibly in non-toxic amounts, these alkaloids are nonetheless there.  For that reason, EPO is often a preferred source of GLA. On the other hand, borage oil is used in clinical and observational studies because of its higher GLA values, thus requiring a smaller dosage (that may influence subject participation) and reducing cost. A University of PA study done in the early 90’s found that patients who took borage oil capsules for three months experienced reductions in pro-inflammatory prostaglandins and leukotrienes, leading to noticeable clinical improvement in RA symptoms (Pullman-Mooar, 1990).

Supplementing GLA at 3.0 and 6.0 grams a day enhances its conversion to the anti-inflammatory dihommo-gamma-linolenic-acid (DGLA), causing neutrophils to synthesize less pro-inflammatory leukotriene and platelet-activating factor (PAF—a major trigger of thrombosis), thereby attenuating discomfort (Johnson, 1997).  Compared to placebo in a six-month trial in Philadelphia, GLA was found to reduce the number of tender joints by more than a third and swollen joint count by more than a fourth, in a study from which no one withdrew (Leventhal, 1993).

Not to be outdone by its omega-6 counterpart, omega-3 fish oil flexed its anti-inflammatory muscle in trials that included non-steroidal anti-inflammatory drugs (NSAIDS) as part of the treatment. Swelling index and duration of early morning stiffness were used as markers for RA severity, and were found to have improved in subjective assessment by virtue of a decrease in pro-inflammatory leukotrienes (van der Tempel, 1990). Patients who received fish oil in combination with naproxen fared better in similar assessments than those without the fish oil or with placebo oil in studies carried out in Norway (Kjeldsen-Kragh, 1992) and New York (Kremer, 2000). A Canadian meta-analysis of seventeen n-3 studies concluded that morning stiffness and number of tender joints were reduced in those who used n-3 PUFA’s (Goldberg, 2007). Those who supplemented their OTC medications with omega-3’s from cod liver oil were able to reduce their dependence on NSAIDS (Galarraga, 2008).

In early reports, Danish scientists found that RA patients were deficient in the only mineral with anti-oxidant properties—selenium. They noted that those with the most active disease had the lowest values, and that there is significant correlation of selenium status with the number of affected joints (Tarp, 1985). Almost a decade later, the same researchers confirmed their initial findings, but also found that some subjects lack the physiological wherewithal to convert selenium to functional anti-oxidant enzymes, a state that can be overcome by supplemental mineral (Tarp, 1994).

From frankincense through ginger, to the resveratrol of grapes, science is takinga deliberate look at additions to the arsenal of RA treatments.

References

Astorga G, Cubillos A, Masson L, Silva JJ.
Active rheumatoid arthritis: effect of dietary supplementation with omega-3 oils. A controlled double-blind trial.
Rev Med Chil. 1991 Mar;119(3):267-72.

Galarraga B, Ho M, Youssef HM, Hill A, McMahon H, Hall C, Ogston S, Nuki G, Belch JJ.
Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis.
Rheumatology (Oxford). 2008 May;47(5):665-9.

Goel, F. J. Ahmad, R. M. Singh, and G. N. Singh
3-Acetyl-11-keto-β-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity
Journal of Pharmacy and Pharmacology, vol. 62, no. 2, pp. 273–278, 2010.

Goldberg RJ, Katz J.
A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain.
Pain. 2007 May;129(1-2):210-23.

Johnson MM, Swan DD, Surette ME, Stegner J, Chilton T, Fonteh AN, Chilton FH.
Dietary supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy humans.
J Nutr. 1997 Aug;127(8):1435-44.

Kjeldsen-Kragh J, Lund JA, Riise T, Finnanger B, Haaland K, Finstad R, Mikkelsen K, Førre O.
Dietary omega-3 fatty acid supplementation and naproxen treatment in patients with rheumatoid arthritis.
J Rheumatol. 1992 Oct;19(10):1531-6.

Knekt P, Heliövaara M, Aho K, Alfthan G, Marniemi J, Aromaa A.
Serum selenium, serum alpha-tocopherol, and the risk of rheumatoid arthritis.
Epidemiology. 2000 Jul;11(4):402-5.

Kremer JM.
n-3 fatty acid supplements in rheumatoid arthritis.
Am J Clin Nutr. 2000 Jan;71(1 Suppl):349S-51S.

Lau CS, Morley KD, Belch JJ.
Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis–a double-blind placebo controlled study.
Br J Rheumatol. 1993 Nov;32(11):982-9.

J. H. Lee, H. Jin, H. E. Shim, H. N. Kim, H. Ha, and Z. H. Lee
Epigallocatechin-3-gallate inhibits osteoclastogenesis by down-regulating c-Fos expression and suppressing the nuclear factor-κB signal
Molecular Pharmacology, vol. 77, no. 1, pp. 17–25, 2010.

M. Lei, S. Q. Liu, and Y. L. Liu
Resveratrol protects bone marrow mesenchymal stem cell derived chondrocytes cultured on chitosan-gelatin scaffolds from the inhibitory effect of interleukin-1β
Acta Pharmacologica Sinica, vol. 29, no. 11, pp. 1350–1356, 2008.

Leventhal LJ, Boyce EG, Zurier RB.
Treatment of rheumatoid arthritis with gammalinolenic acid.
Ann Intern Med. 1993 Nov 1;119(9):867-73.

S. A. Levy, O. Simon, J. Shelly, and M. Gardener
6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund’s adjuvant
BMC Pharmacology, vol. 6, article 12, 2006.

D. O. Moon, M. O. Kim, Y. H. Choi, Y. M. Park, and G. Y. Kim
Curcumin attenuates inflammatory response in IL-1β-induced human synovial fibroblasts and collagen-induced arthritis in mouse model
International Immunopharmacology, vol. 10, no. 5, pp. 605–610, 2010.

Morinobu, W. Biao, S. Tanaka et al.,
 (-)-Epigallocatechin-3-gallate suppresses osteoclast differentiation and ameliorates experimental arthritis in mice
Arthritis and Rheumatism, vol. 58, no. 7, pp. 2012–2018, 2008.

Nanjundaiah SM, Astry B, Moudgil KD.
Mediators of inflammation-induced bone damage in arthritis and their control by herbal products.
Evid Based Complement Alternat Med. 2013;2013:518094.

Pullman-Mooar S, Laposata M, Lem D, Holman RT, Leventhal LJ, DeMarco D, Zurier RB.
Alteration of the cellular fatty acid profile and the production of eicosanoids in human monocytes by gamma-linolenic acid.
Arthritis Rheum. 1990 Oct;33(10):1526-33.

M. L. Sharma, S. Bani, and G. B. Singh
Anti-arthritic activity of boswellic acids in bovine serum albumin (BSA)-induced arthritis
International Journal of Immunopharmacology, vol. 11, no. 6, pp. 647–652, 1989.

Tarp U, Overvad K, Hansen JC, Thorling EB.
Low selenium level in severe rheumatoid arthritis.
Scand J Rheumatol. 1985;14(2):97-101.
Tarp U.
Selenium and the selenium-dependent glutathione peroxidase in rheumatoid arthritis.
Dan Med Bull. 1994 Jun;41(3):264-74.

van der Tempel H, Tulleken JE, Limburg PC, Muskiet FA, van Rijswijk MH.
Effects of fish oil supplementation in rheumatoid arthritis.
Ann Rheum Dis. 1990 Feb;49(2):76-80.

G. Xuzhu, M. Komai-Koma, B. P. Leung, et al.
Resveratrol modulates murine collagen-induced arthritis by inhibiting Th17 and B-cell function
Annals of the Rheumatic Diseases, vol. 71, no. 1, pp. 129–135, 2012.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

What Gets YOU Inflamed?

knee-inflammationAre you an adult? Would you prefer the pound(s) of cure to the ounce of prevention? One of the sad commentaries about adulthood is that we don’t take care of ourselves until something hurts, the detection of which relies on the nervous system. The nervous system is plastic, meaning that it exhibits a wide range of responses according to different conditions. The perception of pain depends on more than one factor, the environment included. With inflammation, however, there exists a hypersensitivity state that makes us aware of what’s going on. This realization is called nociception, involving a network that identifies a noxious condition that evokes responses ranging from mild to severe. Once the pain message is recognized by the nervous system it registers as an “ouch.” The greater the intensity of the stimulus, the greater is the perception of pain. In some cases, no external trigger is needed, such as one would experience with arthritis pain.

Inflammation is the body’s attempt at self-protection, the intention of which is to remove the harmful stimuli, including damaged cells, irritants or pathogens. If the stimulus comes from outside, it can be removed, although pain may linger. If it comes from inside, the body is left to its own devices. In either instance, tissue repair is the ultimate goal. To our dismay, inflammation may beget further inflammation in a self-perpetuating cascade. This occurs because of cellular alterations that cause mediator chemicals to be released and certain white cells, called macrophages, to become activated. The job of the macrophage is to swallow (-phage) the debris that comes from, or causes, tissue damage. Without inflammation, infections and wounds would never heal. In fact, too much anti-inflammatory medication, such as cortisone, slows wound healing (Goforth, 1980). The innate immunity with which we were born is always at the ready to start the inflammatory cascade and to bring healing.

Signs of overt inflammation include pain, redness, immobility (as in loss of function), swelling, and heat (more blood to the area makes it feel warm). Covert inflammation, occurring with internal organs, does not necessarily present with all these signs. Pain arises when swelling pushes on nerves, but sometimes the brain gets used to it and ignores the stimulus. The risk for inflammatory conditions rises with weight gain, as determined by an increase in white blood cells. Regardless of body mass index, C-reactive protein and homocysteine are markers for the presence of inflammatory state, which is at the center of many disorders, from arthritis, through Crohn’s disease, to various allergies and vitamin deficiencies.

Treatment for inflammation abounds in the world of allopathic medicine. Most of us know about NSAIDS, non-steroidal anti-inflammatory drugs, among which Tylenol is not, but aspirin, naproxen and ibuprofen are. Then, there are the corticosteroids—or just plain steroids—that are naturally made by the body in the adrenal glands. But these guys, given as drugs, prevent phospholipid release, and that undermines the activity of eosinophils, which are designed to fight back against allergy, for example, by releasing histamine.

Of the alternative modalities to address inflammation, ginger has accrued quite a following. For hundreds of years it’s been used to treat gastric distress, including dyspepsia and constipation. Recent research points to ginger’s role as an anti-inflammatory agent in the prevention of colon cancer, where inflammation has been identified as a precursor to the disease (Zick, 2011), the markers of which are pro-inflammatory prostaglandins—primarily PGE2—produced by cyclooxygenase (COX) as an early event in the course of the condition (Jiang, 2012).

In a British examination of pain studies, those suffering from osteoarthritis, dysmenorrhea, and acute muscle pain had been administered ginger as the sole treatment. Though additional rigorous trials are anticipated, these subjects reported a reduction in pain, as cited on subjective assessment tools (Terry, 2011). Even before interest in alternative medicine was accelerated to its present status, scientists scrutinized ginger’s reputation in the Ayurvedic community among people treated with the herb for rheumatic concerns, finding efficacy that paralleled traditional interventions (Srivastava, 1989). Applying oral powdered ginger to generalized musculoskeletal discomfort, Danish physicians realized that the safety factor of ginger far exceeded that of any known drugs, while presenting significant efficacy in the relief of pain and swelling via the inhibition of pro-inflammatory prostaglandins (Srivastava, 1992).

By sequestering these incendiary prostaglandins (PG’s), ginger proves itself to be on a par with NSAIDS, minus the concerns of adverse side effects. Similar to prostaglandins in promoting physical aberrations are leukotrienes, products of an enzyme called lipoxygenase (LOX), like COX an offspring of arachidonic acid metabolism. Leukotrienes generally work within the immune system, while PG’s almost always play a role in pure inflammation and pain. (There are beneficent PG’s, by the way.)  Leukotrienes are signaling molecules that call immune cells to the site of infiltration, as from airborne allergens. Bluntly, ginger suppresses the synthesis of leukotrienes (Grzanna, 2005), a property that separates it from NSAIDS. Other of ginger’s attributes point to an anti-oxidant character in the interruption of free radical generation (Ali, 2008), which is helpful in the fight against allergens and pain.

Nitric Oxide (NO) is one of the few signaling gases in the body. The smooth muscle that lines blood vessels is told by NO to relax, thus dilating the vessels and lowering blood pressure. In excessive concentrations, though, NO becomes a pro-oxidant as a naturally unstable free radical, especially when made by white cells (monocytes and macrophages)  during their battle against an infective agent. One logistician that maintains regulation of NO is ginger, where it was shown to control white cell activation as part of its job as an anti-inflammatory vehicle (Shimoda, 2010). Modulating inflammation is what ginger does, and not so gingerly, at that.

References

Ali BH, Blunden G, Tanira MO, Nemmar A.
Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research.
Food Chem Toxicol. 2008 Feb;46(2):409-20. Epub 2007 Sep 18.

ltman RD, Marcussen KC.
Effects of a ginger extract on knee pain in patients with osteoarthritis.
A Arthritis Rheum. 2001 Nov;44(11):2531-8.

Drozdov VN, Kim VA, Tkachenko EV, Varvanina GG.
Influence of a specific ginger combination on gastropathy conditions in patients with osteoarthritis of the knee or hip.
J Altern Complement Med. 2012 Jun;18(6):583-8. doi: 10.1089/acm.2011.0202.

Frondoza CG, Sohrabi A, Polotsky A, Phan PV, Hungerford DS, Lindmark L.
An in vitro screening assay for inhibitors of proinflammatory mediators in herbal extracts using human synoviocyte cultures.
In Vitro Cell Dev Biol Anim. 2004 Mar-Apr;40(3-4):95-101.

Goforth P, Gudas CJ.
Effects of steroids on wound healing: a review of the literature.
J Foot Surg. 1980 Spring;19(1):22-8.

Grzanna R, Lindmark L, Frondoza CG
Ginger–an herbal medicinal product with broad anti-inflammatory actions.
J Med Food. 2005 Summer;8(2):125-32.

Jiang Y, Turgeon DK, Wright BD, Sidahmed E, Ruffin MT, Brenner DE, Sen A, Zick SM.
Effect of ginger root on cyclooxygenase-1 and 15-hydroxyprostaglandin dehydrogenase expression in colonic mucosa of humans at normal and increased risk for colorectal cancer.
Eur J Cancer Prev. 2012 Dec 6.

Levy AS, Simon O, Shelly J, Gardener M.
6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund’s adjuvant.
BMC Pharmacol. 2006 Oct 1;6:12.

Lu H, Huang D, Saederup N, Charo IF, Ransohoff RM, Zhou L.
Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury.
FASEB J. 2011 Jan;25(1):358-69.

Ramji, Divya; ho, chi; Huang, Qingron; Rafi, Mohamed; Huang, Mou
Isolation of gingerols and shogaols from ginger and evaluation of their chemopreventive activity on prostate cancer cells and anti-inflammatory effect on 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear inflammation
RUcore – Rutgers University Community Repository. 2007
http://mss3.libraries.rutgers.edu/dlr/showfed.php?pid=rutgers-lib:21328

Shen CL, Hong KJ, Kim SW.
Effects of ginger (Zingiber officinale Rosc.) on decreasing the production of inflammatory mediators in sow osteoarthrotic cartilage explants.
J Med Food. 2003 Winter;6(4):323-8.

Sehwan Shima, Sokho Kima, Dea-Seung Choia, Young-Bae Kwonb, Jungkee Kwona
Anti-inflammatory effects of [6]-shogaol: Potential roles of HDAC inhibition and HSP70 induction
Food and Chemical Toxicology. Volume 49, Issue 11, November 2011, Pages 2734–2740

Shimoda H, Shan SJ, Tanaka J, Seki A, Seo JW, Kasajima N, Tamura S, Ke Y, Murakami N.
Anti-inflammatory properties of red ginger (Zingiber officinale var. Rubra) extract and suppression of nitric oxide production by its constituents.
J Med Food. 2010 Feb;13(1):156-62.

Srivastava KC, Mustafa T.
Ginger (Zingiber officinale) and rheumatic disorders.
Med Hypotheses. 1989 May;29(1):25-8.

Srivastava KC, Mustafa T.
Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders.
Med Hypotheses. 1992 Dec;39(4):342-8.

Terry R, Posadzki P, Watson LK, Ernst E.
The use of ginger (Zingiber officinale) for the treatment of pain: a systematic review of clinical trials.
Pain Med. 2011 Dec;12(12):1808-18.

Tripathi S, Maier KG, Bruch D, Kittur DS.
Effect of 6-gingerol on pro-inflammatory cytokine production and costimulatory molecule expression in murine peritoneal macrophages.
J Surg Res. 2007 Apr;138(2):209-13. Epub 2007 Feb 8.

Tripathi S, Bruch D, Kittur DS.
Ginger extract inhibits LPS induced macrophage activation and function.
BMC Complement Altern Med. 2008 Jan 3;8:1. doi: 10.1186/1472-6882-8-1.

Zick SM, Turgeon DK, Vareed SK, Ruffin MT, Litzinger AJ, Wright BD, Alrawi S, Normolle DP, Djuric Z, Brenner DE.
Phase II study of the effects of ginger root extract on eicosanoids in colon mucosa in people at normal risk for colorectal cancer.
Cancer Prev Res (Phila). 2011 Nov;4(11):1929-37.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Electromagnetic Headaches

emf-headachesWhen it blows in the wind, we try to find out where it’s coming from. Once in a while, though, there’s so much stench we can’t identify the source. Such is the case with electromagnetic fields—EMF’s— and related wavy things. There’s so much hullabaloo about the good and the bad that we can’t decide if EMF’s are, well, good or bad. They’ve been around forever, so exposure to them is nothing new. Man-made EMF’s, from the generation of electricity, household appliances, industrial equipment and, of course, telecommunications and broadcasting, add to the apparent physiological burden already begun by the simplicity of human metabolism and Earth’s magnetic properties. Is it really a big deal?

Tiny electric currents exist in the body because of the chemistry that allows it to work, even in the absence of external electrical fields. Nerves, for example, send signals by transmitting electrical impulses. All our biochemical reactions follow the rearrangement of charged particles. Your heart responds to an electrocardiogram, right? The concern is that low-frequency electrical fields affect the human body just as they affect anything else made from charged particles. These exogenous fields, if large enough, can cause changes inside the body by stimulating nerves or muscles…or organs. Lucky for us, most exogenous currents are too small to have any ill effect, even directly beneath a high voltage transmission line. On the other hand, the biological effect of radiofrequency fields is heating, and this is the reason for scientific intervention in the placement of sources, such as phone towers.

Biological effects are measurable responses to a stimulus or to a change in the environment. Most of these are harmless, like listening to music or exercising. Changes that are irreversible or that persist for a long time might not be harmless. Electromagnetic fields above a certain level present a concern. That is understandable, and measures are taken to limit exposure, even internationally. Lower levels, over the long term, are suspected of causing unwanted biological responses, including headaches, to which some people are more or less sensitive. Cases of hypersensitivity to EMF’s have been reported for a few decades. Some researchers group them with the condition known as multiple chemical sensitivity illness. Oddly, a plethora of those reporting such sensitivity seem to fall into categories that defy characterization (Levallois, 2002). In polls and surveys, people will express a concern about the ill effects of EMF’s in the absence of personal symptoms, worrying that their cell phones may eventually cause sleep disturbances and headaches (Schreier, 2006) (Hillert, 2002).

Cell phones emit waves as long as they’re turned on and are looking for a signal from the tower. Wi-Fi, not necessarily related to wireless fidelity, contains that technology which connects electronic devices to each other and to the internet using radio waves. Some investigators claim that both can interfere with a child’s ability to learn and remember, while others feel that autistic spectrum conditions are likewise related (Herbert, 2013, parts 1 and 2). If the pharmaceutical powers control a considerable part of the economy, they deserve credit for telling us in their TV spiels that the side effects of their products are worse than the diseases they purport to treat. Powerful industrial entities have an interest in leading the unsuspecting public to believe their EMF’s are completely harmless, since they cannot be perceived by the senses, including pain receptors. If, as suspected, DNA damage actually results from EMF-induced oxidative stress, physiologic consequences can be expected and headaches to be the presentation (Wolf, 2005). Children are exposed to EMF’s at home, on the school bus, in the classroom, at the doctor’s office, and probably everywhere else, with few exceptions, if any. Cell phone standards, by the way, were established years ago and have not been revisited. We are unsure of their effects on developing brains, but, by looking at students’ academic orientation, we can guess. Most European nations forbid the sale of cell phones to those under eighteen.

Cause-effect situations are more definitive than associations or relations. Pathologies that may be associated with EMF’s are not definitely caused by them. Therefore, compared to other disease vectors, little is being done to address possibilities of EMF involvement. Some reports indicate the blood-brain barrier to become more permeable after exposure to EMF’s (Leszczynski, 2002), even from fellow riders in a public conveyance (Kato, 2012). That we are constantly bombarded with radiation is a concern of WHO and the children’s health expert panel (WHO, 2011) (ICNIRP, 2009), (IEEE, 2005). But that concern is magnified because mobile phones work close to the head, causing the distribution of energy to be direct. This raises the question of relationships/associations to glioma and neuroma (Hours, 2007) (Schüz, 2006) naturally requiring closer inspection. Because of subjectivity, no determination is possible (Cardis, 2010), although hints are numerous (Cardis, 2011).

Cancer aside, the headache issue is a global topic. In many countries, about a fourth of cell phone users polled associate headache with EMF (Thamire, 2004) (Meg, 2005) (Al-Khlaiwi, 2004) (Genius, 2012) (Kato, 2012) (Schreier, 2006). Yet, until asked, none relates the two. Talking on a mobile phone for one hour a day incurs the cumulative effect that upsets homeostasis, allowing for exposure to ten thousand watts of accrued radiation. A microwave oven emits only 2 milliwatts at two inches distance; a hundredth of that at twenty inches (FDA, 2011).

We all know that lifestyle can’t be dictated. Smokers smoke and drinkers drink.Second-hand smoke is a health matter. There is no such thing as second-hand drinkingexcept to a fetus. But there is such a thing as second-hand radiation. We seemto prefer first-hand.

References

Al-Khlaiwi T, Meo SA.
Association of mobile phone radiation with fatigue, headache, dizziness, tension and sleep disturbance in Saudi population.
Saudi Med J. 2004 Jun;25(6):732-6.

Augner C, Hacker GW.
Are people living next to mobile phone base stations more strained? Relationship of health concerns, self-estimated distance to base station, and psychological parameters.
Indian J Occup Environ Med. 2009 Dec;13(3):141-5.

Belyaev IY, Hillert L, Protopopova M, Tamm C, Malmgren LO, Persson BR, Selivanova G, Harms-Ringdahl M.
915 MHz microwaves and 50 Hz magnetic field affect chromatin conformation and 53BP1 foci in human lymphocytes from hypersensitive and healthy persons.
Bioelectromagnetics. 26(3):173-184, 2005.

Belyaev IY, Markovà E, Hillert L, Malmgren LO, Persson BR.
Microwaves from UMTS/GSM mobile phones induce long-lasting inhibition of 53BP1/gamma-H2AX DNA repair foci in human lymphocytes.
Bioelectromagnetics. 2008 Oct 6. [Epub ahead of print]

Cardis E, Deltour I, Vrijheid M, Combalot E, Moissonnier M, Tardy H, Armstrong B, et al
INTERPHONE Study Group.
Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case-control study.
Int J Epidemiol. 2010 Jun;39(3):675-94.

Cardis E, Armstrong BK, Bowman JD, Giles GG, Hours M, Krewski D, McBride M, Parent ME, et al
Risk of brain tumours in relation to estimated RF dose from mobile phones: results from five Interphone countries.
Occup Environ Med. 2011 Sep;68(9):631-40.

Dahmen N, Ghezel-Ahmadi D, Engel A.
Blood laboratory findings in patients suffering from self-perceived electromagnetic hypersensitivity (EHS). Bioelectromagnetics. 30(4):299-306, 2009.

Eltiti S, Wallace D, Ridgewell A, Zougkou K, Russo R, Sepulveda F, Mirshekar-Syahkal D, Rasor P, Deeble R, Fox E.
Does short-term exposure to mobile phone base station signals increase symptoms in individuals who report sensitivity to electromagnetic fields? A double-blind randomized provocation study.
Environ Health Perspect. 2007 Nov;115(11):1603-8.

FDA. 2011
Microwave Oven Radiation
http://www.fda.gov/radiation-emittingproducts/resourcesforyouradiationemittingproducts/ucm252762.htm

Furubayashi T, Ushiyama A, Terao Y, Mizuno Y, Shirasawa K, Pongpaibool P, Simba AY, et al.
Effects of short-term W-CDMA mobile phone base station exposure on women with or without mobile phone related symptoms.
Bioelectromagnetics. 30(2):100-113, 2009.

Genuis SJ, Lipp CT.
Electromagnetic hypersensitivity: fact or fiction?
Sci Total Environ. 2012 Jan 1;414:103-12.

Herbert MR, Sage C.
Autism and EMF? Plausibility of a pathophysiological link – Part I.
Pathophysiology. 2013 Jun;20(3):191-209.

Herbert MR, Sage C
Autism and EMF? Plausibility of a pathophysiological link part II.
Pathophysiology. 2013 Jun;20(3):211-34.

Hietanen M, Hämäläinen A-M, Husman T.
Hypersensitivity symptoms associated with exposure to cellular telephones: No causal link. Bioelectromagnetics 23:264-270, 2002.

Hillert L, Berglind N, Arnetz BB, Bellander T.
Prevalence of self-reported hypersensitivity to electric or magnetic fields in a population-based questionnaire survey.
Scand J Work Environ Health. 2002 Feb;28(1):33-41.

Hours M, Bernard M, Montestrucq L, Arslan M, Bergeret A, Deltour I, Cardis E.
Cell Phones and Risk of brain and acoustic nerve tumours: the French INTERPHONE case-control study.
Rev Epidemiol Sante Publique. 2007 Oct;55(5):321-32.

Institute of Electrical and Electronics Engineers (IEEE).
IEEE standard for safety levels with respect to human exposure to radio frequency electromagnetic fields, 3 kHz to 300 GHz, IEEE Std C95.1, 2005.

International Commission on Non-Ionizing Radiation Protection (ICNIRP).
Statement on the “Guidelines for limiting exposure to time-varying electric, magnetic and electromagetic fields (up to 300 GHz)”, 2009.

Johansson A, Nordin S, Heiden M, Sandström M.
Symptoms, personality traits, and stress in people with mobile phone-related symptoms and electromagnetic hypersensitivity.
J Psychosom Res. 68(1):37-45, 2010.

Kato Y, Johansson O.
Reported functional impairments of electrohypersensitive Japanese: A questionnaire survey.
Pathophysiology. 2012 Apr;19(2):95-100.

Kim DW, Lee JH, Ji HC, Kim SC, Nam KC, Cha EJ.
Physiological effects of RF exposure on hypersensitive people by a cell phone.
Conf Proc IEEE Eng Med Biol Soc. 2008;1:2322-2325.

Landgrebe M, Hauser S, Langguth B, Frick U, Hajak G, Eichhammer P.
Altered cortical excitability in subjectively electrosensitive patients: results of a pilot study.
J Psychosom Res. 62(3):283-288, 2007.

Landgrebe M, Frick U, Hauser S, Langguth B, Rosner R, Hajak G, Eichhammer P.
Cognitive and neurobiological alterations in electromagnetic hypersensitive patients: results of a case-control study.
Psychol Med. 38(12):1781-1791, 2008.

Dariusz Leszczynski
EFFECT OF GSM MOBILE PHONE RADIATION ON BLOOD-BRAIN BARRIER (2002)
http://www.ursi.org/Proceedings/ProcGA02/papers/p1043.pdf

Levallois P, Neutra R, Lee G, Hristova L.
Study of self-reported hypersensitivity to electromagnetic fields in California.
Environ Health Perspect. 2002 Aug;110 Suppl 4:619-23.

Markova E, Hillert L, Malmgren L, Persson BR, Belyaev IY.
Microwaves from GSM Mobile Telephones Affect 53BP1 and gamma-H2AX Foci in Human Lymphocytes from Hypersensitive and Healthy Persons.
Environ Health Perspect. 113(9):1172-1177, 2005.

McCarty DE, Carrubba S, Chesson AL, Frilot C, Gonzalez-Toledo E, Marino AA.
Electromagnetic hypersensitivity: evidence for a novel neurological syndrome.
Int J Neurosci. 2011 Dec;121(12):670-6.

Meo SA, Al-Drees AM.
Mobile phone related-hazards and subjective hearing and vision symptoms in the Saudi population.
Int J Occup Med Environ Health. 2005;18(1):53-7.

Nieto-Hernandez R, Rubin GJ, Cleare AJ, Weinman JA, Wessely S.
Can evidence change belief? Reported mobile phone sensitivity following individual feedback of an inability to discriminate active from sham signals.
J Psychosom Res. 65(5):453-460, 2008.

Schreier N, Huss A, Röösli M.
The prevalence of symptoms attributed to electromagnetic field exposure: a cross-sectional representative survey in Switzerland.
Soz Praventivmed. 2006;51(4):202-9.

Schuz J, Böhler E, Berg G, Schlehofer B, Hettinger I, Schlaefer K, Wahrendorf J, Kunna-Grass K, Blettner M.
Cellular phones, cordless phones, and the risks of glioma and meningioma (Interphone Study Group, Germany).
Am J Epidemiol. 2006 Mar 15;163(6):512-20.

Simkó M, Mattsson MO.
Extremely low frequency electromagnetic fields as effectors of cellular responses in vitro: possible immune cell activation.
J Cell Biochem. 2004 Sep 1;93(1):83-92.

Thamire  Al-Khlaiwit,  Sultane A Meoos
Association of mobile phone radiation with fatigue, headache, dizziness, tension and sleep disturbance in Saudi population
Saudi Medical Journal 2004; Vol. (6): 732-736

WHO
Electromagnetic fields and public health: mobile phones
Fact sheet N°193. June 2011
http://www.who.int/mediacentre/factsheets/fs193/en/

Wolf FI, Torsello A, Tedesco B, Fasanella S, Boninsegna A, D’Ascenzo M, Grassi C, Azzena GB, Cittadini A.
50-Hz extremely low frequency electromagnetic fields enhance cell proliferation and DNA damage: possible involvement of a redox mechanism.
Biochim Biophys Acta. 2005 Mar 22;1743(1-2):120-9.

Yokus B, Cakir DU, Akdag MZ, Sert C, Mete N.
Oxidative DNA damage in rats exposed to extremely low frequency electro magnetic fields.
Free Radic Res. 2005 Mar;39(3):317-23.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.