Synopsis of Talk

Clinical Utilization of Nutraceuticals for Inflammation Control as Tools for Fighting Metabolic Syndrome and Diabetes

Chris Meletis, N.D.

A review of the latest scientific literature relative to the application of natural therapeutics to control systemic inflammation in clinical practice. A special focus will be given to the therapeutic effects of novel approaches to healthy blood glucose levels and

70 million individuals in the United States suffer from the afflictions of the disease accelerants associated with Metabolic Syndrome. The relationship between inflammation and the “Catch 22 of Altered Cellular Homeostasis” places this category of patient at high risk of becoming stuck in the vicious cycle of obesity, elevated glucose, hypertension, fatigue and cardiac dysfunction.

Integration of clinical management of body mass, prediabetes, diabetes and the resultant inflammatory dysfunction will interwoven throughout this discussion.

Bottomline: This dynamic discussion will provide simple and clear clinical interventions to liberation patients from stuck in the biochemical spin cycle of dysglycemia and hyper-glycation.

Chris D. Meletis, ND1

Abstract

Iodine levels in the United States have dropped precipitously over the past few decades, whereas antagonists such as bromine,
perchlorate, and fluoride have become more ubiquitous. These changes have placed a nutritional burden on the human body and
increased the potential for pathophysiological change at the cellular level. This review examines the clinical and peer-reviewed
literature and provides perspective related to health-compromising trends that warrant close scrutiny in clinical practice and
future research mandates.

Keywords

iodine, fluoride, chlorine, bromine, thyroid, breast, prostate, cognition
Iodine is a trace element required in the diet to support various
physiological functions. It is found primarily in plants grown in
iodine-sufficient soil and in seafood, particularly kelp and saltwater
fish. The World Health Organization (WHO) reports that
despite efforts at salt iodization, 2 billion people (approximately
29%) worldwide are iodine deficient.1 Health effects
of iodine deficiency are substantial, and deficiency is currently
the leading cause of brain damage.2 In addition, hypothyroidism,
goiter, cretinism, cognitive and neurological disorders,
gastric cancer, and breast disease have been associated with
iodine deficiency. The recommended daily allowance for
iodine in adults is 150 mg (0.15 mg) per day, and it is 220 mg
per day in pregnant women and 290 mg daily in lactating
women. Although recent reports suggest that the United States
population is iodine sufficient, other data indicate that subclinical
deficiency could exist.

Read More…

This video is a preview of a lecture given at the 18th international A4M conference in Orlando. The full video with slides is available for purchase at DigiVisionMedia.com/A4M Item #A4M101WD1. To learn more about the A4M Visit WorldHealth.net. The A4M is dedicated to the advancement of technology to detect, prevent, and treat aging related disease. The A4M is also dedicated to educating physicians, scientists, and members of the public on biomedical sciences, breaking technologies, and anti-aging issues.

Pictured are Dr. David Schleich, President of NCNM and Dr. Chris Meletis.

In a ceremony at the National College of Natural Medicine in Portland, Oregon, Chris Meletis, ND was recognized for his support of the expansion of the NCNM’s Community Clinics. The award gratefully acknowledges Dr. Meletis “for paving the way for the practice of natural medicine within Portland’s Community Clinics”. Dr. Meletis originally founded NCNM’s first Community Clinics during his tenure as Dean and Chief Medical Officer at NCNM.

Dr. Chris Meletis is one of the most respected natural physicians in the world. We believe there is no one more qualified or experienced in the field of natural medicine.

Dr. Meletis was recently recognized as the Naturopathic Physician of the Year. He was the Dean of Naturopathic Medicine and Chief Medical Officer at the National College of Naturopathic Medicine. He has authored 16 health and wellness books, and has had numerous health articles published in both consumer and peer-review health journals.

Last month, I began a three-part series about how stress affects the human body with the introductory article focusing on the effect that stress has on cognition and memory. In part two of this series I will explain how stress can impair proper digestion leading to constipation, diarrhea, irritable bowel syndrome and other digestive disorders.

Like all systems of the human body, the gastrointestinal tract does not operate independently. Its proper functioning depends upon other aspects of the human body. Because gastrointestinal function is controlled and coordinated by the central nervous system to ensure effective motility, secretion, absorption and mucosal immunity,1 it’s logical that emotional stress can have a huge impact on colon health—especially considering the highest amount of serotonin, the neurotransmitter most commonly associated with happiness, resides in our GI tract. Furthermore, during the holidays, a time when we already are exposed to additional amounts of GI-impairing emotional stress, we are further burdening our digestive tracts by consuming large amounts of sugary treats and refined carbohydrates. In this article I will offer some suggestions on how one can strengthen digestive health at this time of year and beyond.

The connection between the gut and emotional health is evidenced by the fact that improving the health of the gut can also improve emotional well being. The absence of probiotic bacteria in the gut has been shown to not only impair colonic health but also to affect the functioning of the hypothalamic-pituitary-adrenal axis and monoaminergic activity, features that have been implicated in the origins of depression. In one study, researchers evaluated the potential antidepressant properties of probiotics, by giving rats the probiotic Bifidobacteria infantis then exposing the animals to a forced swim test in order to stress the animals. The study authors also assessed the effects of the probiotic on immune, neuroendocrine and central monoaminergic activity. After being treated for 14 days with B. infantis, the rats’ swim behaviors did not change. However, the probiotic significantly reduced pro-inflammatory immune responses including IFN-gamma, TNF-alpha and IL-6 cytokines. Furthermore, there was a marked increase in plasma concentrations of tryptophan (an amino acid and serotonin precursor known for its relaxation properties) in the bifidobacteria-treated rats when compared to controls.2 The researchers concluded that the preliminary findings provide “encouraging evidence in support of the proposition that this probiotic may possess antidepressant properties.”

The worsening of irritable bowel syndrome also has been linked to stress. In a study of 105 subjects with mild IBS (68 of the diarrhea-predominant type and 37 of the constipation-predominant type), subjects were followed for three years. During this time, there was a worsening of IBS in 37 subjects. The researchers linked seven factors as being predictive of the onset of full-blown IBS including exposure to emotional stressors, two kinds of stress-coping styles, eating habits, sleeping time and psychological abuse.3

Levels of the stress hormone cortisol also have been found to be elevated in irritable bowel syndrome patients4 and a faster resolution of cortisol to basal values corresponds to lower symptom-severity.5 Additionally, psychological distress and GI symptoms are related to the severity of bloating in women with irritable bowel syndrome.6 Stress also appears to damage the gastrointestinal tracts of individuals not suffering from outright bowel diseases. In healthy individuals, disrupted cortisol levels have been linked to the development of diarrhea.7

Recent well-designed studies have confirmed that adverse life events, chronic stress and depression increase the likelihood of relapse in patients with quiescent IBD. This evidence is increasingly supported by studies of experimental stress in animal models of colitis. In animal models of colitis, psychological or environmental stress may increase gastrointestinal permeability, allowing abnormal antigen to be presented to the immune system and leading to the worsening of intestinal inflammation. The increased intestinal permeability under stress is controlled by corticotropin-releasing hormone stimulation through nicotinic, adrenergic and cholinergic receptors, suggesting a complex interplay between sympathetic and parasympathetic nervous systems.8-9

Chronic stress may have a role to play in the inflammation that occurs in Crohn’s disease (CD), a chronic inflammatory condition of the gastrointestinal tract, whose etiology involves genetic, psychological, immune and inflammatory factors. A higher prevalence of psychological disorders has been observed in CD patients and studies show that there may be a relationship between psychological stress and CD, controlled by the hypothalamic-pituitary-adrenal and the hypothalamic-autonomic nervous system axes.10

Protecting the GI Tract from Stress

Protecting the digestive tract during times of psychological stress is important at any time of year. But during the holiday season, when we are under increased stress and consuming an excess of sugary, rich foods, protecting the GI tract is more important than ever. Protecting the health of the colon with GI Cell Support, Lectin Lock™, BioPRO™ and Digestive Enzymes can be an effective approach to improving GI integrity during times of stress.

GI Cell Support

Glutamine, DGL, N-Acetyl-Glucosamine, Marshmallow, Berberine, Cabbage, Slippery Elm, Phosphatidylcholine and Gamma Oryzanol (all found in GI Cell Support) work together to strengthen the health of the GI Tract. Glutamine, the most abundant free amino acid in the body, is critical for maintaining intestinal structure. The GI tract has the largest demand for glutamine in the body.11 Human studies have shown that supplemental glutamine can reduce the chemotherapy-induced increase in intestinal permeability12 and decrease the duration of diarrhea in children.13 In animal studies, supplemental glutamine promoted repair of intestinal mucosa after chronic diarrhea.14

Other important GI-healing substances include:

•Deglycyrrhizinated licorice (DGL), which seems to be similar to carbenoxolone, a semisynthetic derivative of glycyrrhetic acid used outside the US for treating gastric and duodenal ulcer disease.15-16 Clinically, DGL demonstrates great utility in lessening intestinal irritation and related symptoms.
•N-Acetyl-Glucosamine, which has been found to be deficient in inflammatory bowel disease (IBD), reducing the synthesis of the gastric and intestinal mucosa’s protective glycoprotein cover.17
•Marshmallow, which contains mucilage polysaccharides that soothe and protect mucous membranes from local irritation by creating a protective layer.18-19
•Berberine, which helps control inflammation in the GI tract by selectively inhibiting cyclooxygenase (COX)-2 expression and blocking proinflammatory cytokines.20
•Cabbage, which lowers the risk of developing stomach and colorectal cancer21 and raw cabbage juice consumed by 100 peptic ulcer patients dramatically reduced pain, and significantly reduced healing time.22
•Slippery Elm preparations, which trigger gentle stimulation of nerve endings in the GI tract, leading to mucous secretion that coats and protects the delicate lining of the intestines from ulcers, excess acidity, ingested irritants and toxins.23-24
•Phosphatidylcholine, which was shown in a randomized, double-blind, placebo-controlled study of patients with ulcerative colitis to be low in the colonic mucus of these patients. These low phosphatidylcholine levels are a likely contributory factor involved in the development of ulcerative colitis.25
•Gamma oryzanol, which is highly regarded in Japan to promote a healthy gastrointestinal environment. In animal models, it appears to modulate pituitary secretion, and inhibit excess gastric acid secretion and platelet aggregation.26

Blocking Lectins

Lectins are a class of proteins found in common foods, especially grains, seeds, beans, nuts, some fruits and vegetables and seafood. They act as a sort of an immune system for plants by “sticking” themselves to the structural carbohydrates (sugars) of invaders. When we eat foods containing these proteins we risk lectin attachments to the structural carbohydrates (sugars) antigens found in the gut and immune system. Lectin attacks in the gut initiate inflammation that may be expressed in other parts of the body. Lectins from the diet damage the delicate intestinal lining (the microvilli) and negatively influence gut permeability (leaky gut) and protein digestion. Lectins contribute to food sensitivities (or food intolerances) and may provoke the immune system to make antibodies against them. IBS, for example, is a symptom of lectin-related food intolerances.

Genetic individuality determines our recognition of food as friend or foe and it is not based on the nutritional value of a food. For example, tomatoes contain lycopene, an important antioxidant, but tomatoes also contain a panhemagglutinin lectin (Lycopersicon esculentum agglutinin) that is not harmless. It lowers mucin, binds to blood cells, nerve tissue, and interferes with gastrin in the stomach creating problems in susceptible people.27-28 (Consider watermelon, guava and red grapefruit or a supplement to consume adequate amounts of lycopene.) The same is true of many foods. Foods like corn, dairy, chicken, peas, bananas, beans and legumes, soy, potatoes, pomegranate, nuts, cantaloupe, seafood, wheat, millet and many more, although they contain a variety of very healthful nutrients, contain potentially harmful lectins that can cause problems in some people.

Consuming a combination of lectin-blocking ingredients such as N-acetylglucosamine (NAG), bladderwrack, Okra, D-mannose and sodium alginate (all found in Lectin Lock) can protect the colon against the onslaught of lectin-containing foods we are exposed to during holiday gatherings and all year long.29-34

Digestive Enzymes

Each of the five main digestive enzymes has a different role to play. Amylase digests starch. Protease breaks down the peptide bonds that join the amino acids in a protein, ensuring the amino acids are readily available to the body. The enzyme lipase splits apart emulsified fats. Lactase digests milk sugar, while cellulase helps break down plant and vegetable matter. These enzymes are secreted by the pancreas and are often referred to as pancreatic enzymes. Deficiencies of these enzymes can wreak havoc on the digestive tract, causing bloating, flatulence and gastrointestinal discomfort.35-37 Without proper supplies of these enzymes, the body struggles to digest the high-fat or high-starch meals frequently consumed during the holidays.

Complementary Prescriptions™’ Digestive Enzymes is a unique, plant-based formula containing amylase, protease, lactase, lipase and cellulase. The vegetarian enzymes are generally better tolerated than animal-derived enzymes as a source of nourishment for the intestinal tract.

Friendly Flora

As mentioned earlier in this article, probiotic bacteria are linked to both GI health and mental well being. The “good” bacteria Bifidobacteria infantis has been found to have anti-depressant properties in animals under stress.2 Furthermore, strains of Lactobacillus acidophilus and Bifidobacterium longum have been tested in humans experiencing stress-induced gastrointestinal symptoms. In the double-blind, placebo-controlled, randomized study conducted on volunteers with symptoms of stress, subjects received a probiotic-containing Lactobacillus acidophilus and Bifidobacterium longum or a placebo without probiotics for three weeks. The consumption of probiotics significantly reduced 2 stress-induced gastrointestinal symptoms (abdominal pain and nausea/vomiting).38
Bifidobacteria infantis, Lactobacillus acidophilus and Bifidobacterium longum are all found in BioPRO.

Conclusion

The gastrointestinal tract is especially vulnerable to psychological stress, but never more so than during the holidays when it is being subjected to an array of unhealthy foods. Supplementing with nutrients shown to heal the GI tract, lectin-blocking nutrients, digestive enzymes and a good probiotic formula will strengthen the digestive system and provide it with an overall foundation of health during the holidays and throughout the year.

References

1. Verdu EF. Probiotics effects on gastrointestinal function: beyond the gut? Neurogastroenterol Motil. 2009 May;21(5):477-80.
2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.
3. Fujii Y, Nomura S. A prospective study of the psychobehavioral factors responsible for a change from non-patient irritable bowel syndrome to IBS patient status. Biopsychosoc Med. 2008 Sep 25;2:16.
4. Chang L, Sundaresh S, Elliott J, Anton PA, Baldi P, Licudine A, Mayer M, Vuong T, Hirano M, Naliboff BD, Ameen VZ, Mayer EA. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in irritable bowel syndrome. Neurogastroenterol Motil. 2009 Feb;21(2):149-59.
5. Videlock E, Adeyemo M, Licudine A, Hirano M, Ohning G, Mayer M, Mayer E, Chang L. Childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis responsiveness in irritable bowel syndrome. Gastroenterology. 2009 Sep 5. Published online ahead of print.
6. Park HJ, Jarrett M, Cain K, Heitkemper M. Psychological distress and GI symptoms are related to severity of bloating in women with irritable bowel syndrome. Res Nurs Health. 2008 Apr;31(2):98-107.
7. Karling P, Norrback KF, Adolfsson R, Danielsson A. Gastrointestinal symptoms are associated with hypothalamic-pituitary-adrenal axis suppression in healthy individuals. Scand J Gastroenterol. 2007 Nov;42(11):1294-301.
8. Mawdsley JE, Rampton DS. Psychological stress in IBD: new insights into pathogenic and therapeutic implications. Gut. 2005 Oct;54(10):1481-91.
9. Stasi C, Orlandelli E. Role of the brain-gut axis in the pathophysiology of Crohn’s disease. Dig Dis. 2008;26(2):156-66.
10. Stasi C, Orlandelli E. Role of the brain-gut axis in the pathophysiology of Crohn’s disease. Dig Dis. 2008;26(2):156-66.
11. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999;4:239-48.
12. Li Y, Yu Z, Liu F, Tan L, Wu B, Li J. Oral glutamine ameliorates chemotherapy-induced changes of intestinal permeability and does not interfere with the antitumor effect of chemotherapy in patients with breast cancer: a prospective randomized trial. Tumori. 2006 Sep-Oct;92(5):396-401.
13. Yalçin SS, Yurdakök K, Tezcan I, Oner L. Effect of glutamine supplementation on diarrhea, interleukin-8 and secretory immunoglobulin A in children with acute diarrhea. J Pediatr Gastroenterol Nutr. 2004 May;38(5):494-501.
14. Huang ZX, Ye LY, Zheng ZY, Chen XM, Ren RN, Tong GY. [Effect of glutamine on small intestinal repair in weanling rats after chronic diarrhea]. Zhonghua Er Ke Za Zhi. 2005 May;43(5):368-72.
15. van Marle J, Aarsen PN, Lind A, van Weeren-Kramer J. Deglycyrrhizinised liquorice (DGL) and the renewal of rat stomach epithelium. Eur J Pharmacol. 1981;72:219-25.
16. Tewari SN, Wilson AK. Deglycyrrhizinated liquorice in duodenal ulcer. Practitioner. 1973;210:820-3.
17. Burton AF, Anderson FH. Decreased incorporation of 14C-glucosamine relative to 3H-N-acetyl glucosamine in the intestinal mucosa of patients with inflammatory bowel disease. Am J Gastroenterol.1983;78:19-22.
18. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
19. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
20. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.
21. van Poppel G, Verhoeven DT, Verhagen H, Goldbohm RA. Brassica vegetables and cancer prevention. Epidemiology and mechanisms. Adv Exp Med Biol. 1999;472:159-68.
22. Cheney G. “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 1952;77(4): 248-252.
23. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
24. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
25. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.
26. Cicero AFG, Gaddi A. Rice Bran and Gamma-Oryzanol in the treatment of hyperlipoproteinemias and other conditions. Phytotherapy Research. 15(4):277-289.
27. Porter GA, Palade GE, Milici AJ. Differential binding of the lectins Griffonia simplicifolia I and Lycopersicon esculentum to microvascular endothelium: organ-specific localization and partial glycoprotein characterization. Eur J Cell Biol 1990 Feb;51(1):85-95.
28. Lect. Biol. Biochem. Clin. Biochem. 1985;(4):3.
29. Mikkat U, Damm I, Schroder G, Schmidt K, Wirth C, Weber H, Jones L. Effect of the Lectin Wheat Germ Agglutinin (WGA) and Ulex europaeus Agglutinin (UEA-1) on the alpha-amylase secretion of rat pancreas in vitro and in vivo. Pancreas. 1998 May;16(4):529-38.
30. Horvath K, et al. Improved social and language skills after secretin administration in patients with autistic spectrum disorders. Journal of the Association for Academic Minority Physicians. 1998;9(1):9-15.
31. Boren T, Falk P, Roth KA, et al. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science. 1993; 262:1892-189
32. Kimura Y, Watanabe K, Okuda H. Effects of soluble sodium alginate on cholesterol excretion and glucose tolerance in rats. J Ethnopharmacol. 1996;54:47-54.
33. Criado MT, Ferreiros CM. Selective interaction of a Fucus vesiculosus lectin-like mucopolysaccharide with several Candida species. Ann Microbiol (Paris). 1983;134A:149-154.
34. Criado MT, Ferreiros CM. Toxicity of an algal mucopolysaccharide for Escherichia coli and Neisseria meningitides strains. Rev Esp. Fisiol. 1984;40:227-230.
35. Carroccio A, Guarino A, Zuin G, Verghi F, Berni Canani R, Fontana M, Bruzzese E, Montalto G, Notarbartolo A. Efficacy of oral pancreatic enzyme therapy for the treatment of fat malabsorption in HIV-infected patients. Aliment Pharmacol Ther. 2001 Oct;15(10):1619-25.
36. Kushak RI, Drapeau C, Winter HS. Pancreatic and intestinal enzyme activities in rats in response to balanced and unbalanced plant diets. Plant Foods Hum Nutr. 2002 Fall;57(3-4):245-55.
37. Omogbenigun FO, Nyachoti CM, Slominski BA. Dietary supplementation with multienzyme preparations improves nutrient utilization and growth performance in weaned pigs. J Anim Sci. 2004 Apr;82(4):1053-61.
38. Diop L, Guillou S, Durand H. Probiotic food supplement reduces stress-induced gastrointestinal symptoms in volunteers: a double-blind, placebo-controlled, randomized trial. Nutr Res. 2008 Jan;28(1):1-5.

This is the third and final part of a series discussing the various ways stress affects bodily systems. In this installment I will address the ways in which stress damages the heart, causes an increase in blood pressure and reduces longevity.

It is well established that long-term stress can erode optimal health and accelerate the biological clock. In a study of centenarians, researchers found that a common trait among the subjects was their tendency to react with a low anxiety intensity to stressful conditions and that they reacted positively to stress.1

Scientists have tracked the consequences of stress on cellular aging by determining the effect of stress on telomere length. Telomeres are the specialized genetic segments that cap and protect the ends of chromosomes. Telomeres help determine cell longevity and shortening of telomeres is linked to cancer and cardiovascular disease. Balanced levels of telomerase, an enzyme that prevents telomere shortening, are advantageous in protecting cells against aging.

Research shows that psychological stress—both perceived stress and chronic stress—is significantly associated with higher oxidative stress, lower telomerase activity and shorter telomere length in peripheral blood mononuclear cells (PBMC) from healthy premenopausal women. Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low-stress women.2

Furthermore, scientists have shown that caregivers of Alzheimer’s disease patients have significantly shorter telomere lengths in PBMCs than controls. These same caregivers had basal telomerase activity in PBMCs and T cells that was significantly higher than in controls, indicating cells were unsuccessfully attempting to compensate for the excessive loss of telomeres.3

Likewise, children who experienced adversity were later shown as adults to have significantly shorter telomeres compared to those who did not report a childhood history of maltreatment.4

To further cement the relationship between long-term psychological stress and telomere shortening, researchers exposed human T lymphocytes to the stress hormone cortisol and noted a significant reduction in telomerase activity.5

Impaired telomerase activity also has been associated with the major risk factors for cardiovascular disease: smoking, poor lipid profile, high systolic blood pressure, high fasting glucose and greater abdominal adiposity. Telomere length itself was related to elevated stress hormones (catecholamines and cortisol).6

Cardiac Health and Stress

Numerous studies have demonstrated a strong link between chronic stress and heart disease. In 388 Chinese subjects (292 coronary heart disease cases and 96 controls) aged 30 to 70 years who received coronary angiography for suspected or known ischemic heart disease, researchers examined the association between job stress and coronary heart disease (CHD). The job stress before CHD onset was measured by the effort-reward imbalance (ERI) model, where the researchers measured the amount of effort invested compared to the amount of reward received for those efforts. The results indicated that compared with the baseline, high ERI, high extrinsic effort or high over commitment increased the risk of CHD after adjustment for the traditional CHD risk factors, such as age, gender, primary hypertension, hyperlipidemia, smoking and CHD family history. The combination of high ERI and high over commitment led to the highest risk of CHD. However, high reward reduced the risk of CHD. The researchers concluded that job stress evaluated by the ERI model significantly increased CHD risk, and that it may be an important risk factor independent of the traditional risk factors.7
Scientists also have measured the physical effects of stress in subjects shown a 3-minute frightening video. The fear-induced stress resulted in vasoconstriction (blood vessel narrowing) in the forearm and finger.8

After the World Trade Center attack in 2001, the same negative effect of stress on the heart was noted. In one study, researchers in Florida observed 132 patients with implantable cardioverter-defibrillators (ICD) during routine ICD follow-up around the time of the WTC attack. In the 30 days following the WTC attack, a total of 14 patients (11 percent) had ventricular tachyarrhythmias, compared with 5 (3.8 percent) in the preceding 30 days, numbers that represent a 2.8-fold risk increase.9

The study authors concluded, “The frequency of ventricular arrhythmias requiring ICD treatment increased by 68 percent among patients in Florida around the WTC attack. These findings suggest that stress-related arrhythmogenesis due to the WTC tragedy was not restricted to the geographic location of the attack. A major national tragedy may cause widespread increased risk of potentially life-threatening ventricular arrhythmias.”

Stress and Blood Pressure

Excessive stress has been linked to hypertension in a number of studies. An analysis of the medical literature included 6 studies involving a total of 34,556 subjects. After assessing the studies, the scientists found that individuals who had stronger responses to stressor tasks were 21 percent more likely to develop blood pressure increase when compared to those with less strong responses.10
One of the ways in which stress elevates blood pressure is through the renin-angiotensin-aldosterone system, a cascade that regulates and maintains blood pressure.
The angiotensin-converting enzyme (ACE) gene is associated with the vulnerability for stress-related disorders and with altered stress hormone regulation.11-12 Blood pressure drugs known as ACE inhibitors work by blocking this enzyme.
Even acute mental stress can have prolonged negative effects on factors that help regulate blood pressure. One study investigated the effects of a mental arithmetic test on 19 healthy subjects. Aortic stiffness was then measured in the subjects. The results indicated that mental stress induced a sustained increase in aortic stiffness.13

Nutritional Strategies

A nutritional supplement regimen can be designed around protecting the heart from psychological stress and increasing overall longevity. This regimen includes supplements to reduce anxiety and stress and to support heart health and healthy blood pressure.

Increasing Relaxation

A combination of gamma-aminobutyric acid (GABA), L-theanine, ashwaganda, valerian and passion flower (all found in Allay™) can be extremely helpful in inducing a state of calm relaxation.

GABA is the major inhibitory neurotransmitter in the brain (i.e., it regulates brain excitability and nerve transmission). In human studies, GABA supplementation has been shown to induce relaxation and reduce anxiety.14-15

L-Theanine, an amino acid found in green tea, reduces stress-induced physiological responses (changes in heart rate, sympathetic nervous system activation),16 and decreases the brain’s production of excitatory neurotransmitters while increasing inhibitory neurotransmitters such as GABA.17

Withania somnifera, also known as Ashwaganda, is an adaptogen reported to have mood stabilizing, anxiolytic (anxiety-reducing) and antidepressant actions.18-19 It also has been shown to attenuate physiological stress responses and positively influence the endocrine and central nervous systems.20-21

Valerian (Valeriana officinalis) exerts a regulatory effect on the autonomic nervous system and has been demonstrated to bind to benzodiazepine and GABA receptors,22-23 providing a tranquilizing effect, improving sleep quality and decreasing the time it takes to fall asleep.

Passion flower has anxiety-reducing effects and has an important role in reducing tenseness, restlessness and irritability with difficulty in falling asleep.24

Optimizing Heart Health

A combination of CoQ10, taurine, L-arginine, L-carnitine, hawthorn and salvia (as found in CardioCare) can support the health of the heart during stressful times.

Coenzyme Q10 is essential to cellular energy processes and thus assumes importance in cells with high-energy requirements such as the cardiac cells, which are extremely sensitive to CoQ10 deficiency produced by cardiac diseases. CoQ10 is a vasodilator (widens the blood vessels). It inhibits LDL oxidation and thus the progression of atherosclerosis and decreases blood viscosity, which is helpful in patients with heart failure and coronary artery disease. Researchers have noted significant improvement in exercise tolerance in patients with heart failure, hypertension, ischemic heart disease and other cardiac illnesses who were given adjunctive CoQ10 in doses from 60 to 200 mg daily.25

Other nutrients important for cardiac health include taurine and L-arginine. Deficiencies of these nutrients are linked to heart arrhythmias. Case histories of people with very frequent arrhythmias have shown that 10-20 grams of taurine per day reduced premature atrial contractions (PACs) by 50 percent and prevented all premature ventricular contractions (PVCs), but did not prevent pauses. Adding 4-6 grams of L-arginine immediately terminated essentially all remaining pauses and PACs, maintaining normal cardiac rhythm with continued treatment.26
L-arginine also has been found to enhance endurance exercise tolerance in heart failure patients.27

Carnitine is another nutrient important to proper cardiac functioning and has been shown to reduce LDL oxidation, the process by which free radicals damage lipids in the body and play a role in LDL’s heart-damaging effects.28

Hawthorn has proven itself to be equally important to healthy heart function. A review of the medical literature found that hawthorn extract may improve symptoms in patients with mild to moderate heart failure, significantly enhancing exercise tolerance and reducing shortness of breath and fatigue. Hawthorn extract also increased the maximum workload in a small number of studies and patients.29

Salvia miltiorrhiza is another botanical important to cardiovascular health. Salvia protects cardiac cells known as myocytes from damage and has protected animal hearts from injury after oxygen deprivation.30-31

Maintaining Healthy Blood Pressure

Natural products have many different mechanisms to modulate blood pressure. Cordyceps and shark cartilage, as found in PRESSURE-fX™, address both the renin-angiotensin system as well as parathyroid hypertensive factor (PHF), both of which are implicated in high blood pressure. Animal models show that shark cartilage administration decreased blood pressure and modulated intracellular calcium regulation.32 Studies indicate that Cordyceps also lowers blood pressure in animal models, relaxes blood vessels, and elicits a dose-dependent relaxation of extra-cellular calcium-dependent contractions.33 A clinical trial with hypertensive patients showed that adding PRESSURE-fX was more effective at lowering blood pressure than diet, lifestyle modifications and mineral supplementation alone. In fact, 88 percent of subjects had significantly reduced blood pressure, and 75 percent of subjects were able to maintain normal blood pressure without medication.34

In patients whose blood pressure issues are being caused by nitric oxide deficiency, increased ACE activity and arterial calcification, a combination of grape seed extract, a special form of blueberry extract and vitamin K2 (as in DilaVasic BP™) can often be useful. Grape seed extract has been shown to increase platelet-derived nitric oxide production, which induces relaxation of blood vessels.35-36 One clinical trial showed that 300 mg per day of grape seed extract supplemented for 8 weeks decreased systolic blood pressure by an average of 8.3 mmHg and diastolic blood pressure by 5.7 mmHg.37

Research also suggests that blueberry extract acts as a potent ACE inhibitor. In one study, a diet containing 3 percent blueberry extract or a control diet was fed to spontaneously hypertensive stroke-prone rats for 8 weeks. The blood pressure of the spontaneously hypertensive stroke-prone rats was 30 percent lower on the blueberry diet than on control diet at 6 weeks. In addition, the rats on the blueberry diet showed a 48 percent lower glucose/insulin ratio compared to rats on the control diet.38

Vitamin K2 (menaquinone) can also be an important part of a blood-pressure-maintenance formula. Vitamin K2 promotes arterial elasticity by inhibiting calcification of blood vessel walls.39-40

Conclusion

Stress has been shown to damage the cardiovascular system and decrease life span. Clearly, reducing stress levels with Allay, improving the health of the heart with CardioCare plus extra CoQ10, taurine and L-arginine and reducing blood pressure levels with either DilaVasic BP or PRESSURE-fX can help the body recover from lifetime challenges while at the same time restore optimal heart health.

References

1. Tafaro L, Tombolillo MT, Brükner N, Troisi G, Cicconetti P, Motta M, Cardillo E, Bennati E, Marigliano V. Stress in centenarians. Arch Gerontol Geriatr. 2009 May-Jun;48(3):353-5.
2. Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17312-5.
3. Damjanovic AK, Yang Y, Glaser R, Kiecolt-Glaser JK, Nguyen H, Laskowski B, Zou Y, Beversdorf DQ, Weng NP. Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer’s disease patients. J Immunol. 2007 Sep 15;179(6):4249-54.
4. Tyrka AR, Price LH, Kao HT, Porton B, Marsella SA, Carpenter LL. Childhood Maltreatment and Telomere Shortening: Preliminary Support for an Effect of Early Stress on Cellular Aging. Biol Psychiatry. 2009 Oct 13. Published Online Ahead of Print.
5. Choi J, Fauce SR, Effros RB. Reduced telomerase activity in human T lymphocytes exposed to cortisol. Brain Behav Immun. 2008 May;22(4):600-5.
6. Epel ES, Lin J, Wilhelm FH, Wolkowitz OM, Cawthon R, Adler NE, Dolbier C, Mendes WB, Blackburn EH. Cell aging in relation to stress arousal and cardiovascular disease risk factors. Psychoneuroendocrinology. 2006 Apr;31(3):277-87.
7. Xu W, Zhao Y, Guo L, Guo Y, Gao W. Job stress and coronary heart disease: a case-control study using a Chinese population. J Occup Health. 2009;51(2):107-13.
8. Hayashi N, Someya N, Maruyama T, Hirooka Y, Endo MY, Fukuba Y. Vascular responses to fear-induced stress in humans. Physiol Behav. 2009 Oct 19;98(4):441-6.
9. Shedd OL, Sears SF Jr, Harvill JL, Arshad A, Conti JB, Steinberg JS, Curtis AB. The World Trade Center attack: increased frequency of defibrillator shocks for ventricular arrhythmias in patients living remotely from New York City. J Am Coll Cardiol. 2004 Sep 15;44(6):1265-7.
10. Gasperin D, Netuveli G, Dias-da-Costa JS, Pattussi MP. Effect of psychological stress on blood pressure increase: a meta-analysis of cohort studies. Cad Saude Publica. 2009 Apr;25(4):715-26.
11. Ge D, Zhu H, Huang Y, Treiber FA, Harshfield GA, Snieder H, Dong Y. Multilocus analyses of Renin-Angiotensin-aldosterone system gene variants on blood pressure at rest and during behavioral stress in young normotensive subjects. Hypertension. 2007 Jan;49(1):107-12.
12. Heck A, Lieb R, Ellgas A, Pfister H, Lucae S, Erhardt A, Himmerich H, Horstmann S, Kloiber S, Ripke S, Müller-Myhsok B, Bettecken T, Uhr M, Holsboer F, Ising M. Polymorphisms in the angiotensin-converting enzyme gene region predict coping styles in healthy adults and depressed patients. Am J Med Genet B Neuropsychiatr Genet. 2009 Jan 5;150B(1):104-14.
13. Vlachopoulos C, Kosmopoulou F, Alexopoulos N, Ioakeimidis N, Siasos G, Stefanadis C. Acute mental stress has a prolonged unfavorable effect on arterial stiffness and wave reflections. Psychosom Med. 2006 Mar-Apr;68(2):231-7.
14. No authors listed. Gamma-aminobutyric acid (GABA), Monograph. Altern Med Rev. 2007 Sep;12(3):274-9.
15. Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors. 2006;26(3):201-8.
16. Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007 Jan;74(1):39-45.
17. Yamada T, Terashima T, Okubo T, Juneja LR, Yokogoshi H. Effects of theanine, r-glutamylethylamide, on neurotransmitter release and its relationship with glutamic acid neurotransmission. Nutr Neurosci. 2005 Aug;8(4):219-26.
18. Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine. 2000 Dec;7(6):463-9.
19. Gupta GL, Rana AC. Protective effect of Withania somnifera dunal root extract against protracted social isolation induced behavior in rats. Indian J Physiol Pharmacol. 2007 Oct-Dec;51(4):345-53.
20. Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine. 2000 Dec;7(6):463-9.
21. Gupta GL, Rana AC. Protective effect of Withania somnifera dunal root extract against protracted social isolation induced behavior in rats. Indian J Physiol Pharmacol. 2007 Oct-Dec;51(4):345-53.
22. No authors listed. Valeriana officinalis, Monograph. Altern Med Rev. 2004 Dec;9(4):438-41.
23. Benke D, Barberis A, Kopp S, et al. GABA(A) receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts. Neuropharmacology. 2008 Jun 17. Published Online Ahead of Print.
24. Krenn L. Passion Flower (Passiflora incarnata L.)—a reliable herbal sedative. [Article in German]. Wien Med Wochenschr. 2002;152(15-16):404-6.
25. Kumar A, Kaur H, Devi P, Mohan V. Role of coenzyme Q10 (CoQ10) in cardiac disease, hypertension and Meniere-like syndrome. Pharmacol Ther. 2009 Jul 25. [Epub ahead of print]
26. Eby G, Halcomb WW. Elimination of cardiac arrhythmias using oral taurine with l-arginine with case histories: Hypothesis for nitric oxide stabilization of the sinus node. Med Hypotheses. 2006;67(5):1200-4.
27. Doutreleau S, Mettauer B, Piquard F, Rouyer O, Schaefer A, Lonsdorfer J, Geny B. Chronic L-arginine supplementation enhances endurance exercise tolerance in heart failure patients. Int J Sports Med. 2006 Jul;27(7):567-72.
28. Malaguarnera M, Vacante M, Avitabile T, Malaguarnera M, Cammalleri L, Motta M. L-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes. Am J Clin Nutr. 2009 Jan;89(1):71-6.
29. Pittler MH, Guo R, Ernst E. Hawthorn extract for treating chronic heart failure. Cochrane Database of Systematic Reviews 2008, Issue 1.
30. Ling S, Luo R, Dai A, Guo Z, Guo R, Komesaroff PA. A pharmaceutical preparation of Salvia miltiorrhiza protects cardiac myocytes from tumor necrosis factor-induced apoptosis and reduces angiotensin II-stimulated collagen synthesis in fibroblasts. Phytomedicine. 2009 Jan;16(1):56-64.
31. Nie R, Xia R, Zhong X, Xia Z. Salvia miltiorrhiza treatment during early reperfusion reduced postischemic myocardial injury in the rat. Can J Physiol Pharmacol. 2007 Oct;85(10):1012-9.
32. Communication with Peter Pang, Ph.D., professor emeritus, University of Alberta, December 2001.
33. Pang PK, Shan JJ, Chiu KW. The Cardiovascular Effects of Cordyceps Sinensis in Normotensive Rats. Journal of Chinese Medicine. 1996; 7(2):153-167.
34. Malina O, Malina M, Kotsifas G, et al. Treatment of Mild to Moderate Arterial Hypertension with Pressure-FX®. Unpublished research. Instituto de Medicina Ortomolecular, Parana, Brazil.
35. Edirisinghe I, Burton-Freeman B, Tissa Kappagoda C. Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract. Clin Sci (Lond). 2008 Feb;114(4):331-7.
36. Freedman JE, Parker C, Li L, et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001;103:2792-8.
37. Lu B, Robinson M, Kappagoda T. Effect of a Novel Grape Seed Extract on Blood Pressure in Subjects with Prehypertension. Presented at the FASEB Experimental Biology Conference, Washington, DC, April 30, 2007.
38. Sweeney M, Shaughnessy K, Gottschall-Pass K. Blueberry diets delay the onset of hypertension and reduce insulin resistance in spontaneously hypertensive stroke prone rats. FASEB J. 2007;21:847.
39. Schurgers LJ, Cranenburg EC, Vermeer C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost. 2008 Oct;100(4):593-603.
40. Beulens JW, Bots ML, Atsma F, et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2008 Jul 19. Published online ahead of print

The following is my interview with Portland’s own Dr. Chris Meletis. If you haven’t heard of Dr. Meletis, or would like to know more about him, please read on. At 44 years of age his list of accomplishments left me feeling inspired. We met in his Beaverton office about a month ago. It was during this meeting that I learned he has written 18 books, was named as the 2003 AANP Physician of the Year, has opened 16 community clinics in Portland to serve the poor and under-privileged, and is a nationally sought after speaker. His willingness to teach classes through MindGlo speaks to his giving spirit and love for his community. Please read on I promise you will find it thought provoking. And please visit www.MindGlo.com to learn more about our self-enrichment courses.

When did you discover that Naturopathic Medicine is your passion?

I was finishing my 2nd year of conventional MD medical school and I was taking biochemistry and the single class offered in nutrition that semester. All of a sudden the light went on and I realized that without the proper nutrition, the biochemistry in the body would be off, and a person’s cells, all 75 trillion of them would be under fueled. Bottom-line: If our cells are under fueled, and we are a composite of our cells, we are under fueled, thus leading to disease, premature death and a less than optimal existence.

You have a mission to “Change America’s Health One Person at a Time”. What inspired that mission?

In 1996, I had a big choice to stay in private practice, or become the Dean and Chief Medical Officer at the oldest Naturopathic Medical School in North America, located right here in Portland. So, I had to search my mind and heart to figure out why I was a doctor, why I existed as a human being relative to my professional life, and it came to be. I must have a yardstick in which to measure each step of my life. This yardstick guided my decision making when considering the Deanship/CMO calling and even now with the great opportunity to reach out and fulfill my mission within my home town community.

You have such a busy schedule. Why is finding time to teach important to you?

It is with education that we gain perspective and the power to make informed decisions in all aspects of our life. Healthcare and more importantly wellness care should not be limited to only those of privilege or unique access. Natural medicine is the medicine that has sustained humanity over the millennia, the only difference now is we have the scientific validation to prove that it works, even though our ancestors already knew this empirically.

You are a nationally sought after teacher in Naturopathy. Why teach at MindGlo?

I have a love for my home city, I was born and raised in Portland. Went to Benson High School and did my undergraduate studies to earn my Bachelor’s degree at Reed College. To share with my community is a true honor. I have recently lectured in New York, Atlanta, North Carolina, Florida and San Jose to name a few cities. It seems like it’s time to share with Portlanders the secrets of wellness that everyone can implement.

Your list of accomplishments is extensive. Is there one that you are most proud of? If so why?

The most important accomplishment was when I received the nationally awarded 2003 Physician of the Year by AANP (American Association of Naturopathic Physicians), our national naturopathic association. Sure, the recognition and award was nice, but what was really touching is why I got the award. I was honored as Dean and Chief Medical Officer to help create, with the help of lots of talented and heart driven people, 16 community clinics that still to this day serve the poor and under-privileged in the Portland Metro Area. The National College of Natural Medicine still offers extremely discounted services through these clinics to this very day.

If you could do anything else in the world what would you do and why?

I would become the Surgeon General of the United States and I would immediately implement wellness care, shifting the focus from disease management and reactive medicine. We would transition into a health oriented society that provided vitamin D supplements to all Americans that wanted it, we would put iodine back into our bread, and we would caution people about common mistakes that they don’t even know they are making that is risking their health and that of their loved ones.

If you could give one piece of advice to the MindGlo learners, about anything, what would that be?

There is nothing more important than your health. You may have gone to your doctor and gotten a “clean bill of health” yet, it is not enough. The laboratory tests are interpreted way too loosely, the optimal ranges for lab values are generally far too broad and current healthcare is really disease management and/or early detection. Sure it is important to catch a disease early, but could you imagine catching a disease process prior to manifesting it. For instance according to the Centers for Disease Control, there are 60 million pre-diabetics. These folks get a clean bill of health more often than not from their routine annual physicals. So are they well, I think we can all agree the answer is no, not even close. Yet, since they don’t have a diagnosis, they walk through their life with a false sense of security. Just like 50% of people that die of heart disease have normal or even good cholesterol. We can’t afford to play Rip Van Winkle with our health and wake up one morning and realize that we could of, should of, would of….done something different.
This interview reprinted from www.mindglo.com, with permission of the author

Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants in the world. Often, however, individuals taking SSRIs for depression also suffer from one or more painful conditions, such as arthritis, sports injuries, back problems, and headaches. To alleviate pain, a person on an SSRI will commonly reach for a class of analgesic drugs known as NSAIDs (ibuprofen, naproxen, aspirin etc.). Research is beginning to indicate, however, that combining these two classes of drugs could prove to be a lethal mistake as the risk of gastrointestinal bleeding is now thought to be increased in SSRI users who also take NSAIDs. Furthermore, emerging science indicates that the combination of SSRIs and even low-dose aspirin also can elevate the risk of GI bleeding, sobering news for people taking both SSRIs and an aspirin a day to reduce the risk of heart attacks.

Eight analgesic preparations with approved indications for acute pain were among the top 200 drugs prescribed in the United States in 2006. Additionally, an estimated 36 million Americans use over-the-counter analgesics daily. Most people are aware that the over-the-counter analgesics known as NSAIDs can cause gastrointestinal bleeding when taken alone. But it’s less commonly known that when NSAIDs are combined with SSRIs, it increases the SSRI’s tendency to promote bleeding in the gut. Because aspirin is often promoted as a safer alternative to the rest of the NSAIDs family, many people taking SSRIs with aspirin probably don’t realize they are putting themselves at additional risk.

Gastrointestinal Bleeding

Gastrointestinal bleeding can originate in the gastrointestinal tract, anywhere from the mouth to the anus. Bleeding can be microscopic, where the amount of blood is so small that only lab testing can detect it, or it can be acute, massive, and life threatening. Prolonged microscopic bleeding can cause loss of iron and anemia. Acute, massive bleeding can result in diminished blood volume (hypovolemia), shock, and death.
Bleeding in this area in the body is referred to as either upper GI bleeding, which occurs in the upper gastrointestinal tract between the mouth and outflow tract of the stomach, or lower GI bleeding, which occurs in the lower GI tract from the outflow tract of the stomach to the small and large bowels to the anus.

Certain individuals are at higher risk of suffering from gastrointestinal bleeding, including the elderly and people who have hemorrhoids, duodenal and gastric ulcers, ulcerative colitis, Crohn’s disease, esophageal varices, esophagitis, intestinal polyps and tumors, celiac sprue, intestinal vasculitis, cow’s milk allergy, and anal fissures.
Gastrointestinal bleeding is a common clinical presentation increasing in an aging population, frequently requiring hospitalization, with significant morbidity, mortality, and costs.

Symptoms of GI Bleeding

GI bleeding is internal and doesn’t always manifest in an obvious manner, so people who experience GI bleeding can be pain free. Therefore, recognizing the symptoms is important. Depending on whether the source of the bleeding is in the upper or lower digestive tract, the symptoms vary. If the upper GI tract is affected, the symptoms can include vomiting bright red blood, vomiting dark clots or coffee ground-like material, or passing black, tar like stool. When bleeding occurs in the lower GI tract, symptoms can manifest as passing pure blood or bright red or maroon blood mixed in stool.
Microscopic bleeding often does not present with these obvious symptoms and therefore can go unnoticed, slowly eroding away ones foundation of health.

How SSRIs Disrupt the Digestive Tract

Normally, when serotonin from blood platelets is released it augments platelet aggregation, the process where blood cells clump together to prevent bleeding. Evidence suggests that SSRI antidepressants may inhibit uptake and storage of serotonin by platelets. When serotonin uptake is reduced in blood platelets, platelet aggregation also is reduced, which may predispose patients to bleeding.1
Other researchers have proposed that SSRIs may increase gastrointestinal bleeding due to an increase in capillary fragility after taking the drugs.2

SSRIs Plus NSAIDs = Double Disaster

Researchers have obtained mixed results when studying whether SSRIs alone increase the risk of gastrointestinal bleeding. However, compelling and consistent evidence exists to show that when SSRIs are combined with the analgesic pain relievers known as NSAIDs (ibuprofen, Naproxen, etc.) including low-dose aspirin, it substantially increases the risk of GI bleeding. In one of the most comprehensive studies on this subject, published earlier this year, researchers conducted an analysis of the medical literature to determine whether there is an interaction between SSRIs and NSAIDs. Four studies involving 153,000 patients met their criteria for inclusion in the review. After studying the medical literature, they concluded that the risk of developing upper gastrointestinal bleeding increased significantly in SSRI users who also took NSAIDs. In subjects more than 50 years old with no risk factors of upper gastrointestinal bleeding, the subjects needed to take 411 SSRIs per year to experience bleeding, but only 106 SSRIs per year were needed to experience GI bleeding when NSAIDs were used concomitantly with the SSRIs. Analysis of further reports showed that upper gastrointestinal bleeding occurred after a median of 25 weeks on SSRIs and that 67 percent of these patients experiencing bleeding also were on NSAIDs.3

A recent study on SSRIs and bleeding indicates the increased risk of gastrointestinal harm may expand beyond NSAIDs to other classes of drugs such as corticosteroids, which are commonly used by rheumatoid arthritis patients. Researchers studied 1,321 subjects with upper GI bleeding and compared them with 10,000 control patients with no GI bleeding.

The results indicated that 5.3 percent of the subjects who had GI bleeding were taking SSRIs, compared to only 3 percent of the controls, an increased risk of 60 percent. There was an almost fivefold increased risk of GI bleeding among users of SSRIs also using corticosteroids. Among those taking NSAIDs and SSRIs, there was a ninefold increased risk of gastrointestinal bleeding.4

Other studies have found that even low-dose aspirin, when combined with SSRIs, can increase the risk of bleeding, although the risk is slightly less than with other NSAIDs.5

Safe Pain Support

Individuals on SSRIs who want to manage pain without increasing risk of Gl bleeding can engage in a two-step approach that includes both 1) strengthening the gastrointestinal tract to repair the damage already done by antidepressants plus NSAIDs or corticosteroids and 2) using natural substances to alleviate pain.
First, to strengthen GI health, consuming GI Cell Support, which contains glutamine, deglycyrrhizinated licorice (DGL), N-acetyl glucosamine, marshmallow, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol can be critical in nourishing the GI tract.

Glutamine is essential for maintaining intestinal structure and serves as metabolic fuel for enterocytes that line the colon and affect cell proliferation.6-7 DGL licorice is of particular interest to those concerned about GI bleeding since most of the research on DGL has focused on upper GI health, including ulcer healing.8-9 Another nutrient relevant to GI health is N-acetyl glucosamine, important in inflammatory bowel disease (IBD) when N-acetylation of glucosamine is relatively deficient, possibly reducing the synthesis of the gastric and intestinal mucosa’s protective glycoprotein cover.10

Other nutrients that can protect the GI tract include 1) Marshmallow leaf and root, which supports colon health by soothing and protecting mucous membranes from local irritation,11 2) Berberine, which helps control inflammation by selectively inhibiting cyclooxygenase (COX)-2 expression and blocking proinflammatory cytokines,12 3) Cabbage, which has significantly reduced the healing time in peptic ulcer patients,13 4) Slippery elm, which stimulates mucous secretion that coats and protects the delicate lining of the intestines from ulcers and ingested irritants,14 5) Phosphatidylcholine, which has been shown to support the health of ulcerative colitis patients and reduce their dependence on corticosteroids,15 and 6) gamma oryzanol, which inhibits excess gastric acid secretion.16

After using GI Cell Support to strengthen GI health, the next step for SSRI users is to alleviate pain without increasing the risk of GI bleeding. One of the most effective natural approaches involves using a formula called EnFlex™ that contains the amino acid DL-phenylalanine, the botanicals turmeric and Boswellia serrata, and the proteolytic enzyme nattokinase, which work synergistically specifically to inhibit pain.

A number of compounds have been shown to inhibit the break down of enkephalins, which are the body’s natural opioid pain reducers. DL-Phenylalanine, one of these enkephalinase inhibitors, may be effective in a number of human “endorphin deficiency diseases” such as depression and arthritis. It has been used successfully for the management of chronic pain in humans.17-18 DL-Phenylalanine works synergistically with turmeric, a botanical with known anti-inflammatory activity.19 Turmeric has profoundly inhibited joint inflammation and joint destruction in a dose-dependent manner in animal models of rheumatoid arthritis.20

Two other substances used clinically to enhance the effects of DL-P henylalanine and turmeric are Boswellia serrata and nattokinase. Boswellia serrata is a traditional herb with reported anti-inflammatory and analgesic activity. In a randomized, double-blind, placebo-controlled crossover study in 30 patients with osteoarthritis of the knee, Boswellia serrata extract or placebo was given for 8 weeks. All the patients receiving Boswellia supplementation reported a decrease in knee pain and frequency of swelling, and an increase in knee flexion and walking distance.21
Nattokinase is a proteolytic (protein-dissolving) enzyme. Proteolytic enzymes have analgesic effects in addition to anti-inflammatory and anti-edemic properties, indicating they may have a role to play in pain management.22 Nattokinase leads to dissolution of fibrin that build inside vessel walls in response to injuries.23 This proteolytic enzyme is used to digest the fibrin and reduce inflammation, the likely mechanism by which nattokinase may help reduce pain.

Conclusion

Combining SSRIs with NSAIDs, aspirin or corticosteroids is the equivalent of playing a game of gastrointestinal Russian roulette. For anyone taking SSRIs, a combination of natural pain relievers that includes DL-phenylalanine, turmeric, Boswellia serrata, and nattokinase can prove to be a safe alternative. Furthermore, using a supplement that contains glutamine, deglycyrrhizinated licorice (DGL), N-acetyl glucosamine, marshmallow, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol is an effective way to strengthen the GI tract for individuals who continue with SSRI treatment. Individuals planning to stop SSRI treatment should always discuss their plans with their physician before doing so.

References
1. Nelva A, Guy C, Tardy-Poncet B, Beyens MN, Ratrema M, Benedetti C, Ollagnier M. Hemorrhagic syndromes related to selective serotonin reuptake inhibitor (SSRI) antidepressants. Seven case reports and review of the literature. Rev Med Interne. 2000 Feb;21(2):152-60.
2. No authors listed. Do SSRIs cause gastrointestinal bleeding? Drug Ther Bull. 2004 Mar;42(3):17-8.
3. Loke YK, Trivedi AN, Singh S. Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther. 2008 Jan 1;27(1):31-40.
4. de Abajo FJ, García-Rodríguez LA. Risk of Upper Gastrointestinal Tract Bleeding Associated With Selective Serotonin Reuptake Inhibitors and Venlafaxine Therapy. Interaction With Nonsteroidal Anti-inflammatory Drugs and Effect of Acid-Suppressing Agents. Arch Gen Psychiatry. 2008;65(7):795-803.
5. Dalton SO, Johansen C, Mellemkjaer L, Nørgård B, Sørensen HT, Olsen JH. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med. 2003 Jan 13;163(1):59-64.
6. Sacks GS. Glutamine supplementation in catabolic patients. Ann Pharmacother. 1999;33:348-54.
7. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999;4:239-48.
8. van Marle J, Aarsen PN, Lind A, van Weeren-Kramer J. Deglycyrrhizinised liquorice (DGL) and the renewal of rat stomach epithelium. Eur J Pharmacol. 1981;72:219-25.
9. Tewari SN, Wilson AK. Deglycyrrhizinated liquorice in duodenal ulcer. Practitioner. 1973;210:820-3.
10. Burton AF, Anderson FH. Decreased incorporation of 14C-glucosamine relative to 3H-N-acetyl glucosamine in the intestinal mucosa of patients with inflammatory bowel disease. Am J Gastroenterol. 1983;78:19-22.
11. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
12. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.
13. Cheney G. Vitamin U Therapy of Peptic Ulcer. California Medicine. 1952;77(4): 248-252.
14. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
15. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.
16. Cicero AFG, Gaddi A. Rice Bran and Gamma-Oryzanol in the treatment of hyperlipoproteinemias and other conditions. Phytotherapy Research. 15(4):277-289.
17. Ehrenpreis S. Pharmacology of enkephalinase inhibitors: animal and human studies. Acupunct Electrother Res. 1985;10(3):203-208.
18. Walsh NE, Ramamurthy S, Schoenfeld L, et al. Analgesic effectiveness of D-phenylalanine in chronic pain patients. Arch Phys Med Rehabil. 1986 Jul;67(7):436-439.
19. Hsu CH, Cheng AL. Clinical studies with curcumin. Adv Exp Med Biol. 2007;595:471-480.
20. Funk JL, Frye JB, Oyarzo JN, et al. Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis. Arthritis Rheum. 2006 Nov;54(11):3452-3464.
21. Kimmatkar N, Thawani V, Hingorani L, et al. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee–a randomized double blind placebo controlled trial. Phytomedicine. 2003 Jan;10(1):3-7.
22. Klein G, Kullich W. Reducing pain by oral enzyme therapy in rheumatic diseases. Wien Med Wochenschr. 1999;149(21–22):577–580.
23. Suzuki Y, Kondo K, Ichise H, et al. Dietary supplementation with fermented soybeans suppresses intimal thickening. Nutrition. 2003 Mar;19(3):261-264

By Chris D. Meletis, ND

In 1956, a now famous article appeared titled, Aging: a theory based on free radical and radiation chemistry in the Journal of Gerontology written by Denham Harman. In his theory of aging he mentioned that the oxidation of LDL cholesterol was the earliest molecular event that triggers the process of atherosclerosis, or hardening of the arteries.1

At that time, the notion that LDL oxidation was the earliest molecular event leading to atherosclerosis was really just a “medical hypothesis” that needed many years (actually decades) of corroborating scientific data before it was indeed accepted as fact. It is now accepted as fact, although the exact implications of LDL cholesterol oxidation are still being explored in human studies and animal experiments.

Decades of experimentation with atherosclerosis using in vitro models and animal models eventually produced a skeleton outline of how hardening of the arteries begins at the molecular level and finally progresses to bulges in the artery wall, which cause partial or complete blockage of arteries in various critical areas. Eventually, eruptions or bursting of these atherosclerotic pockets can occur and this extremely serious phenomenon is referred medically as “erupting atherotomas” or “unstable erupting atherotomas.”

The subject of vascular disease covers an enormous area of scientific research that will not be reviewed here. In this article, I will present a basic outline of LDL oxidation leading to atherosclerosis in a more narrow sense and explain why antioxidants are a critical component of any regimen designed to support healthy cholesterol levels.

Cholesterol—Not the Bad Guy It’s Made Out to Be?

Cholesterol is an absolutely essential compound in the animal kingdom. Just as plants use cellulose as the building blocks of the structural components of their trunks, stems, leaves and roots, animals use cholesterol as their building blocks for cell membranes and other structural components. Cholesterol is the basic structural building block for hormones and various other molecules essential to animal and human life.

The notion that the cholesterol molecule itself is “bad” is an inaccurate notion. Furthermore, the popular notion that there is “good” cholesterol and “bad” cholesterol also is an oversimplified view of cholesterol transport. This notion of “good” versus “bad” cholesterol originated as a misunderstanding of the fact (the earliest example a 1980 article) that there is a forward and reverse cholesterol transport system from the liver, which produces most of the cholesterol in the body.5 LDL cholesterol particles (often referred to as “bad cholesterol”) carry cholesterol from the liver to the “loading docks,” or receptor sites on the endothelial cells and peripheral cells, where the cholesterol is then transported for cellular construction and repair purposes.

HDL cholesterol particles are the main reverse cholesterol transport system which carry excess cholesterol away from the peripheral and artery cells back to the liver. This is why HDL has been termed “good cholesterol.” The liver then takes in the excess returned cholesterol where it is excreted it into the bile as free cholesterol destined for the colon, or converted by the liver into cholesterol bile acids.6

There are three pathways that deliver cholesterol to arterial vessels and other peripheral cells—the lipid absorption pathway, the exogenous pathway (from the food intake of cholesterol) and the endogenous pathway where cholesterol is produced directly by the liver. All three pathways can result in an over accumulation of cholesterol in the peripheral cells and especially an over accumulation in the artery cells which leads to atherosclerosis.7

The Real Culprit—LDL Oxidation

LDL cholesterol delivery from the liver thorough the bloodstream is the weakest link in the delivery system. Free radicals in the bloodstream attack and oxidize the LDL cholesterol, and chemically modify it enough so that the receptor sites or the “loading docks” on the artery cell walls (the endothelial cells) no longer recognize it and reject it. However, the immune system scavenger cells, the macrophages, do have receptor sites that immediately recognize the oxidized LDL cholesterol at the endothelial artery lining. The source of these free radicals in the blood are mostly copper and iron, which act as catalysts taking ordinary hydrogen peroxide and converting it into the more powerful hydroxyl radical.8-10
This is the beginning of chaos at the molecular and cellular level. Macrophages “read” the oxidized cholesterol molecule (OXY-LDL) as a foreign invader, just like bacteria or other non-self proteins, because their receptor sites recognize it as a foreign protein. Through a process called phagocytosis, the macrophages engulf the oxidized cholesterol particle at the endothelial “loading dock” and eventually transport it back deeper into the arterial wall to the intimal cells or simply stay at the surface where the fusion product appears as fatty streaks on the artery wall. Eventually other immune responses take place and the whole particle becomes a foam cell.11-12
Small amounts of oxidized LDL that are engulfed by macrophages can be absorbed, broken down, and disposed of in the artery. But what if there is so much oxidized LDL/macrophage product that the disposal mechanism in the artery is saturated or oversaturated? This leads to foam cell buildup in the artery wall resulting in calcification and cellular debris accumulation where a bulge occurs in the artery wall. Sufficiently large artery bulges can block off or slow blood circulation in critical arteries such as coronary arteries, and carotid or vertebral arteries leading to the brain. Artery plaque formation and its clearance by resorption are a dynamic balance between plaque formation and plaque removal.12-13

A 2008 human trial measuring oxidized LDL (OXY-LDL, or Ox-LDL-C) as a key factor in initiating and accelerating atherosclerosis was conducted in patients with a diagnosis of coronary artery disease. The researchers used the ratio of OXY-LDL to albumin in patient blood as one of their primary measures. The diseased groups included patients with acute myocardial infarction, unstable angina pectoris, stable angina pectoris, and dyslpidemia (high cholesterol and high blood lipids). In all diseased groups, OXY-LDL was higher than levels seen in normal control patients. In groups complicated with hypertension or diabetes, the oxidized LDL ratio was seven times higher than the normal control group.14
The researchers concluded that with a 95.7 to 97.5 percent prediction rate, the blood level of OXY-LDL was a better biomarker than total cholesterol (TC), triglycerides (TG), HDL-C (HDL cholesterol) or LDL-C (low density lipoprotein cholesterol) in diagnosing people with coronary artery disease.14
Earlier research had shown in patient studies that oxidized LDL cholesterol can be formed in two ways, membrane damage (lipid peroxidation) of LDL fatty acids by metal ions, mainly iron in the blood, or by enzymatic damage independent of metal ions. The difference is academic, however, because the end result is the same—the release of aldehydes, which in both cases causes the LDL particle damage. The researchers concluded that there are two forms of oxidized LDL cholesterol. The one form of OXY-LDL is a marker for coronary atherosclerosis in general whereas the other form, MDA-modified LDL, is a good marker of artery plaque instability.15-16
A 1996 study revealed that patients at high risk for atherosclerosis, including those patients with renal failure, diabetes, hypercholesteremia and hypertension, had LDL with an increased susceptibility to oxidation in comparison to LDL from healthy patients. The authors mentioned that supplementation with nutritional antioxidants to humans, gene susceptible mice, or hypercholesteremic patients, have been shown in various studies to reduce the susceptibility of LDL to oxidation. “This effect could be associated with a reduction in the size of the atherosclerotic lesion and may thus contribute to attenuation of the atherosclerotic process,” the researchers stated.17

Antioxidants and Lipid Oxidation

The ultimate healthy goal of cholesterol transport through the blood is to make sure that the reducing antioxidant potency of the blood is sufficient to “quench” free radicals before they attack the fatty acid portions of the LDL particle. This means that the antioxidant levels in the blood are sufficiently high to avoid or minimize this problem. At the same time, the fat-soluble antioxidant content of the LDL particle should be sufficiently high to prevent the oxidation of the fatty acids, the phospholipids in the LDL particle. Therefore, fat-soluble and water-soluble antioxidants play key roles in preventing oxidized cholesterol in both the blood and in the LDL particles themselves.18-20
In studies, antioxidants have an excellent record of preventing atherosclerosis, especially in European and foreign human clinical trials of longer duration. However, in “intervention” studies where there is fully advanced atherosclerosis in patients and antioxidant therapy is used to intervene in a well established disease state, the results range from mixed to disappointing. Most of this data means that antioxidants prevent cholesterol oxidation and atherosclerosis in the first place, but do not reverse it once it is expressed as fully developed atherosclerosis.21-22
Vitamins A, C and E are some of the best-known antioxidants. These powerful antioxidants can work synergistically with other antioxidants to help reduce the extent of lipid oxidation occurring in the body. N-acetyl cysteine, bilberry, rosemary, turmeric, green tea, grape seed, and lutein are some of the most powerful and well-researched antioxidants. Consuming a formula that combines these synergistic antioxidants (such as Extension Antioxidant) is one of the most important steps to reduce the damaging effects of lipid oxidation.
N-acetyl cysteine helps increase levels of glutathione, the body’s “master antioxidant,” which minimizes the lipid peroxidation of cellular membranes known to occur with oxidative stress.23 Bilberry anthocyanosides are extremely powerful antioxidants that can protect against DNA damage and LDL oxidation.24 Research into another free-radical quencher—rosemary—has found it to be a potent antioxidant.25 Other botanicals used to fight free radicals include turmeric, which contains curcumin, a potent inhibitor of LDL oxidation.26 Green tea extract also has demonstrated antioxidant abilities both in vitro and in vivo.27 Grape seed and lutein are two other antioxidants that should be included in any regimen designed to quench free radicals and reduce lipid oxidation.28-29

Conclusion

The oxidation of LDL in the blood and on the artery wall plays a key role in the formation of atherosclerosis. LDL particles carry cholesterol from the liver to the peripheral cells, including the cells that line the arteries, and this is called the forward cholesterol transport system. Low antioxidant status of the blood and LDL particles, and other sources of oxidative stress, cause oxidative modifications to LDL by free radicals. Immune system cells, the macrophages, recognize the modified LDL cholesterol particles and engulf them. Eventually, further modifications convert this fused particle into a foam cell. Foam cell buildup in the arteries and the microcirculatory system cause bulges and streaks in the artery wall that we call atherosclerosis, or hardening of the arteries. Supplementation with a key group of antioxidants can help stop LDL oxidation from occurring and are therefore a critical component of any heart health regimen.

References
1. Harman, D., Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956 Jul; 11(3):298-300.
2. Tsimikas, S. Oxidative biomarkers in the diagnosis and prognosis of cardiovascular disease. Am J Cardiol. 2006 Dec 4; 98(11A):9P-17P.
3. Siqueira AF, Abdalla DS, Ferreira SR. LDL: from metabolic syndrome to instability of the atherosclerotic plaque. Arq Bras Endocrinol Metabol. 2006 Apr; 50(2):334-43.
4. Matsuura E, Kobayashi K, Tabuchi M, Lopez LR. Oxidative modification of low-density lipoprotein and immune regulation of atherosclerosis. Prog Lipid Res. 2006 Nov; 45(6):466-86.
5. Ask the doctors. (Editorial column) You often write about “good” and “bad” cholesterol, but most people I know believe that all cholesterol—or a high total cholesterol number—is bad. Is it? Heart Advis. 2006 Feb; 9(2):8.
6. Good and bad cholesterol. S Afr Med J. 1980 Apr 5; 57(14):517-8.
7. Groen, B., The Ins and Outs of Reverse Cholesterol Transport, AMC Liver center, Academic Medical Center, publishers, Amsterdam, 2007.
8. Huang H, Mai W, Liu D, Hao Y, Tao J, Dong Y.The oxidation ratio of LDL: A predictor for coronary artery disease. Dis Markers. 2008; 24(6):341-9.
9. Holvoet P. Relations between metabolic syndrome, oxidative stress and inflammation and cardiovascular disease.Verh K Acad Geneeskd Belg. 2008;70(3):193-219.
10. Rietzschel ER, Langlois M, De Buyzere ML, Segers P, De Bacquer D, Bekaert S, Cooman L, Van Oostveldt P, Verdonck P, De Backer GG, Gillebert TC; for the Asklepios Investigators.Oxidized Low-Density Lipoprotein Cholesterol Is Associated With Decreases in Cardiac Function Independent of Vascular Alterations.Hypertension. 2008 Jul 28. [Epub ahead of print].
11. Andican G, Seven A, Uncu M, Cantasdemir M, Numan F, Burcak G.Oxidized LDL and anti-oxLDL antibody levels in peripheral atherosclerotic disease.Scand J Clin Lab Invest. 2008 Feb18:1-7. [Epub ahead of print].
12. Ishigaki Y, Katagiri H, Gao J, Yamada T, Imai J, Uno K, Hasegawa Y, Kaneko K, Ogihara T, Ishihara H, Sato Y, Takikawa K, Nishimichi N, Matsuda H, Sawamura T, Oka Y. Impact of plasma oxidized low-density lipoprotein removal on atherosclerosis. Circulation. 2008 Jul 1;118(1):75-83.
13. Choi SH, Chae A, Miller E, Messig M, Ntanios F, DeMaria AN, Nissen SE, Witztum JL, Tsimikas S. Relationship between biomarkers of oxidized low-density lipoprotein, statin therapy, quantitative coronary angiography, and atheroma: volume observations from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) study.J Am Coll Cardiol. 2008 Jul 1; 52(1):24-32.
14. Huang, H., Mai, W., Liy., D, Hao, Y., Tao, J., Dong, Y. The oxidation ratio of LDL: A predictor for coronary artery disease. Dis. Markers. 2008; 24: 341-9.
15. Aviram, M., Fuhrman, B. LDL oxidation by arterial wall macrophages depends on the oxidative status in the liopoprotein and in the cells: role of proxididants vs. antioxidants. Mol. Cell Biochem. 1998 Nov; 188 (1-2): 149-59.
16. Holvoet, P. Endotelial dysfunction, oxidation of low-density lipoprotein, and cardiovascular disease. Ther. Apher. 1999 Nov; 3(4): 287-93.
17. Aviram, M. Interaction of oxidized low density lipoprotein with macrophages in atherosclerosis, and the antiatherogenicity of antioxidants. Eur. J. Chem. Clin. Biochem. 1996 Aug; 34(8): 599-608.
18. Terao J, Kawai Y, Murota K.Vegetable flavonoids and cardiovascular disease. Asia Pac. J. Clin Nutr. 2008; 17Suppl 1:291-3.
19. Choi JS, Choi YJ, Shin SY, Li J, Kang SW, Bae JY, Kim DS, Ji GE, Kang JS, Kang YH. Dietary flavonoids differentially reduce oxidized LDL-induced apoptosis in human endothelial cells: role of MAPK- and JAK/STAT-signaling. J. Nutr. 2008 Jun;138(6):983-90.
20. Yuen B, Furrer L, Ballmer PE. [Antioxidant vitamin supplementation in the prevention of cardiovascular disease] Ther Umsch. 2005 Sep; 62(9):615-8.
21. Meydani M. Vitamin E modulation of cardiovascular disease. Ann N Y Acad Sci. 2004 Dec; 1031:271- 9.
22. Moats C, Rimm EB. Vitamin intake and risk of coronary disease: observation versus intervention. Curr Atheroscler Rep. 2007 Dec; 9(6):508-14.
23. Kerksick C, Willoughby D. The antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stress. J Int Soc Sports Nutr. 2005 Dec 9;2:38-44.
24. Laplaud PM, Lelubre A, Chapman MJ. Antioxidant action of Vaccinium myrtillus extract on human low density lipoproteins in vitro: initial observations. Fundam Clin Pharmacol. 1997;11:35-40.
25. Ho, C-T., et al. Phytochemicals in tea and rosemary and their cancer-preventive properties. In Ho, C-T., et al., eds., Food Phytochemicals for Cancer Prevention, II: 2-19. Washington, DC: American Chemical Society, 1994.
26. Chen WF, Deng SL, Zhou B, Yang L, Liu ZL. Curcumin and its analogues as potent inhibitors of low density lipoprotein oxidation: H-atom abstraction from the phenolic groups and possible involvement of the 4-hydroxy-3-methoxyphenyl groups. Free Radic Biol Med. 2006 Feb 1;40(3):526-35.
27. Ouyang P, Peng WL, Lai WY, Xu AL. [Green tea polyphenols inhibit low-density lipoprotein-induced proliferation of rat vascular smooth muscle cells] [Article in Chinese]. Di Yi Jun Yi Da Xue Xue Bao, 2004 Sep;24(9):975-9.
28. Shafiee M, Carbonneau MA, Urban N, Descomps B, Leger CL. Grape and grape seed extract capacities at protecting LDL against oxidation generated by Cu2+, AAPH or SIN-1 and at decreasing superoxide THP-1 cell production. A comparison to other extracts or compounds. Free Radic Res. 2003 May;37(5):573-84.
29. Dwyer JH, Navab M, Dwyer KM, Hassan K, Sun P, Shircore A, Hama-Levy S, Hough G, Wang X, Drake T, Merz CN, Fogelman AM. Oxygenated carotenoid lutein and progression of early atherosclerosis: the Los Angeles atherosclerosis study. Circulation. 2001 Jun 19;103(24):2922-7.

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