chronic inflammation

  • Macronutrients Part 2 - Carbohydrates and Fiber

    Carbohydrates are the most abundant biomolecules on our planet and in our food supply. They exhibit some of the largest differences in their metabolism by different members of the animal kingdom. At one extreme, herbivores can almost completely break down dietary plant material with the help of beneficial bacteria that dwell within their gastrointestinal tract; at the other extreme, true carnivores can’t process most dietary carbohydrates. Humans fall somewhere in between; we derive a great deal of nutrition out of some dietary carbohydrates, but are unable to process others.

    In our diets, digestible carbohydrates consist of sugars and starches, while the indigestible carbohydrates are the fibers and resistant starches1. Dietary sugars are predominantly monosaccharides (sugars consisting of a single unit, such as glucose and fructose) or disaccharides (sugars consisting of two monosaccharides linked together, such as sucrose and lactose). Starches are long chains (polymers) of many linked monosaccharide molecules, usually glucose.

    Monosaccharides are the preferred form by which sugars are absorbed from the intestines, therefore, starches and disaccharide sugars (sucrose, lactose) must be broken down by digestive enzymes before assimilation. Starches are fairly easily digested by the action of pancreatic enzymes, while disaccharide sugars are degraded by enzymes that dwell on the surface of the small intestines. The familiar lactose maldigestion (“lactose intolerance”) experienced by many individuals actually results from the lack of one of these intestinal enzymes (lactase, the enzyme that breaks down lactose into glucose and galactose).

    Fibers and resistant starches are carbohydrates as well. Like starches, fiber is composed of polymers of linked monosaccharide sugars. Unlike starches, however, fibers and resistant starches are not used as a source of calories; humans lack the necessary enzymes to break down resistant starches and fibers, therefore, they are not absorbed. Some soluble fiber and resistant starch is broken down by intestinal bacteria, the rest passes through the gastrointestinal tract intact.

    The majority of dietary carbohydrates are obtained from plant sources (fruits, vegetables, grains). In contrast to animal tissues, which are held together by mostly proteins, plants cells are held together by cellulose and lignin, two types of dietary fiber. The edible portions of plants are usually those that contain large amounts of storage carbohydrates, such as the kernels of grains (which store starches) or fruits (which store sugars). Smaller amounts of carbohydrates are found in animal products; carbohydrates constitute only about one percent of the mammalian body2.

    ROLES OF DIETARY CARBOHYDRATES AND FIBER IN NORMAL METABOLISM
    Although they do not have the diversity in human metabolism as do proteins, dietary carbohydrates and fibers still have a number of fates:
    Fuel Source and Fuel Storage.

    As versatile as humans are in obtaining energy from a variety of macronutrients, the preferred energy source in our metabolism is the carbohydrate glucose. Under normal conditions, the brain uses glucose as an energy source almost exclusively, and most other tissues rely heavily on it. To accommodate the body’s need for glucose, most sugars and starches can be converted into glucose as they are absorbed and distributed amongst various tissue following a meal. Additionally, some amino acids from digested protein can also be converted into glucose (in true carnivores like cats, this is where most glucose comes from).

    Unlike other cellular energy sources (amino acids and fatty acids), glucose can be converted into energy in the absence of oxygen (anaerobic glycolysis). This makes glucose a critical source of quick energy during times when oxygen is scarce, such as during intense exercise.

    Glucose can also be stored for later usage, in the form of glycogen (“animal starch”). Glycogen is abundant in the liver, which stores about a day’s worth of glucose in order to provide enough energy to fuel the brain during periods between meals. Glycogen is also used to store glucose for use in muscles, which rely on it for quickly generating energy. If the dietary intake of carbohydrates exceeds what is needed for immediate energy and glycogen reserves, then the excess is converted to fat for long-term storage.

    Precursors to other biomolecules. Carbohydrates are used to make other important biomolecules. These include: glycosaminoglycans (such as chondroitin, keratin, and hyaluronic acid), important constituents of joints and connective tissues; nucleic acids (DNA and RNA are partially constructed from the sugar ribose); as well as other amino acids and fatty acids for making new cellular proteins and cell membranes.

    Stimulation of digestion. Fiber, despite its non-nutritive value, still has evolved important roles in human physiology. The bulk of insoluble fibers helps digested food to move more easily through the intestines and be readily eliminated from the body. Soluble fibers and resistant starches can provide a source of energy for intestinal bacteria, which themselves provide a number of health benefits, including the stimulation of immunity, protection from pathogenic bacteria, and enhanced absorption of minerals from the diet. Prebiotics, a subset of soluble fiber, have gained attention in recent years in their ability to be selectively fermented by gut flora for a diversity of potential health-promoting benefits3.

    SPECIFIC HEALTH BENEFITS OF CARBOHYDRATES AND FIBER
    Many of the health benefits realized by modifying carbohydrate intake involve altering patterns of consumption: reducing intake of sugars, and increasing intake of fiber. For example, recent emphasis on increased intake of whole grains (which contain significantly more fiber, phytonutrients, and protein than do refined cereal flours) has resulted from several studies which suggest that its consumption may reduce the risk of certain cancers, diabetes, and cardiovascular disease4. Fiber intake, in particular, has been the subject of thousands of studies in humans and animals, in part for its ability to successfully reduce the risk of several diseases by different mechanisms:

    Reducing Chronic Low-level Inflammation. In contrast to the conspicuous inflammation that is characteristic of an injury or infection, chronic low-level inflammation can progress unnoticed. This potentially silent affliction has been associated with the progression of several diseases, including cancer, diabetes, cardiovascular, and kidney diseases. In an analysis of 7 studies on the relationship between weight loss and inflammation, increased fiber consumption correlated with significantly greater reductions in C-reactive protein (CRP), one indicator of low-level inflammation5. In these studies, daily fiber intakes ranging from 3.3 to 7.8 g/MJ (equivalent to about 27 to 64 g/day for a standard 2000 kcal diet) reduced CRP from 25–54 percent in a dose-dependent fashion. The Women’s Health Initiative Study also found significant inverse relationships with dietary soluble and insoluble fiber (over 24 g/day) and certain markers of chronic inflammation6.

    Promoting Healthy Blood Pressure. It is not clear how dietary fiber reduces blood pressure, but many studies have observed this trend. Fiber, when taken with a meal, may by reducing the glycemic index of foods and lowering the response of insulin following a meal (insulin may play a role in blood pressure regulation). Soluble fibers may also increase mineral absorption (such as calcium, magnesium, and potassium; all important for healthy blood pressure) by feeding intestinal flora, which lowers intestinal pH and establish a favorable acidic environment for mineral absorption7. Whatever the cause, at least thirty randomized, controlled clinical trials examined the effects of fiber in both hypertensive and normotensive patients. Across all participants, increased fiber intake demonstrated modest average reductions in systolic (1.13–1.15 mm Hg), and diastolic (1.26–1.65 mm Hg) blood pressure89. Amongst hypertensive patients, the average blood pressure reductions were much larger: A significant average reduction in both systolic (-5.95 mm Hg) and diastolic (-4.20 mm Hg) blood pressure was observed over 8 weeks in trials where hypertensive participants increased their daily fiber intake9.

    Promoting Healthy Levels of Blood Lipids. High-fiber diets have been associated with lower prevalence of cardiovascular disease (10). When included as part of a low-saturated fat/low cholesterol diet, dietary fiber can lower low-density lipoprotein cholesterol (LDL-C) by 5–10 percent in persons with high cholesterol, and may reduce LDL-C in healthy individuals as well10. Dozens of controlled clinical trials have shown the cholesterol-lowering potential of dietary fibers including soluble oat fiber, psyllium, pectin, guar gum, b-glucans from barley, and chitosan3,12,13.

    Soluble fibers lower cholesterol by several potential mechanisms (3). They may directly bind cholesterol in the gut, preventing its absorption. The high viscosity of soluble fiber and its ability to slow intestinal motility may help to limit cholesterol and fat uptake as well. Fiber can also increase satiety, which can limit overall energy intake14,15. Lowering Uric Acid. Elevated blood uric acid (hyperuricemia) is a risk factor for kidney disease, cardiovascular diseases, and diabetes; it is also a primary cause for gout16. Fiber intake may lower blood uric acid levels. A significant inverse relationship between fiber intake and hyperuricemia risk was established by analyzing dietary fiber intake data from over 9000 otherwise healthy adults participating in the National Health and Nutrition Examination Survey (NHANES) from 1999–2004. Based on these data, participants with high fiber diets (over about 19 grams fiber/day for the average 2000 kcal diet) had a 55 percent reduction in hyperuricemia risk compared to those on lower fiber diets (<9.2 g fiber/day)17. While these mechanisms for this reduction is unknown, dietary fiber may reduce the absorption of purines from the diet, one of the inciting factors for hyperuricemia.

    HOW MUCH CARBOHYDRATES AND FIBER SHOULD I BE GETTING?
    The amount and composition of carbohydrates in the “ideal” diet is amongst the most heavily debated topics in nutrition. There are scientifically-substantiated merits to both the “low-carb” and “low-fat, high-carb” diets in terms of reducing disease risk and maintaining a healthy body mass index (these will be discussed in greater detail in a future article). The common ground between the two schools of thought is that the average Western diet probably contains too little fiber, and too much refined grains and added sugar. A low-fiber/high-sugar diet, when coupled with excessive caloric intake, has been associated with significant increases in the risk for a number of ailments, including obesity, insulin resistance/type II diabetes, and cardiovascular disease.

    As mentioned previously, the benefits of dietary fiber are numerous. The average daily fiber intake in the American diet, based on data from 2007–2008 NHANEs survey, is about half of the 28 grams/day recommendation by the Institute of Medicine (IOM). Significant numbers of people consume even less than the national average. The highest intakes of dietary fiber are associated with the lowest disease risks; for several observational studies, the greatest risk reductions required intakes exceeding the IOM recommendations.

    In contrast, the American diet contains no shortage of refined grains or sugars. The U.S. Department of Agriculture estimates average grain consumption at about 33 percent more than 6 oz./day recommended in its Dietary Guidelines for Americans. Most of this grain is refined; the same group estimates Americans consume only one-third of the recommended 3 oz./day of whole grains18,19.

    Analysis of data from the last NHANEs survey (2007–2008) determined that Americans consume an average of 120 grams/day of total sugars (about 30 teaspoons), most of which are added sugars. This amounts to approximately 480 kilocalories of energy per day. Most of these sugars come from sweetened carbonated beverages (~37 percent); other top sources include desserts and fruit drinks (fruitades and fruit punches). While arguments can be made that it is the added fructose or corn syrup are particularly dangerous to health (there is evidence that supports and refutes this hypothesis), or that sugar is additive and contributes to overeating (animal models may support this claim), added sugar clearly contributes a significant amount of calories to the average diet, and in many cases displaces essential nutrients20,21.

    To read the series on Macronutrients:

    References:

    1. Fardet A. New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? Nutr Res Rev 2010 Jun.;23(1):65–134.
    2. Engelking L. Textbook of Veterinary Physiological Chemistry. Updated 2nd ed. Burlington, MA: Academic Press; 2011.
    3. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr 1999 Jan.;69(1):30–42.
    4. Higgins JA. Whole grains, legumes, and the subsequent meal effect: implications for blood glucose control and the role of fermentation. J Nutr Metab 2012;2012:829238.
    5. North CJ, Venter CS, Jerling JC. The effects of dietary fibre on C-reactive protein, an inflammation marker predicting cardiovascular disease. Eur J Clin Nutr 2009 Aug.;63(8):921–33.
    6. Ma Y, Hébert J, Li W, Bertone-Johnson E. Association between dietary fiber and markers of systemic inflammation in the Women’s Health Initiative Observational Study. Nutrition 2008;
    7. Greger J. Nondigestible carbohydrates and mineral bioavailability. J Nutr 1999.
    8. Streppel MT, Arends LR, van t Veer P, Grobbee DE, Geleijnse JM. Dietary fiber and blood pressure: a meta-analysis of randomized placebo-controlled trials. Arch Intern Med 2005 Jan.;165(2):150–6.
    9. Whelton SP, Hyre AD, Pedersen B, Yi Y, Whelton PK, He J. Effect of dietary fiber intake on blood pressure: a meta-analysis of randomized, controlled clinical trials. J. Hypertens 2005 Mar.;23(3):475–81.
    10. Badimon L, Vilahur G, Padro T. Nutraceuticals and atherosclerosis: human trials. Cardiovasc Ther 2010 Aug.;28(4):202–15.
    11. Anderson J, Randles K. Carbohydrate and fiber recommendations for individuals with diabetes: a quantitative assessment and meta-analysis of the evidence. J Am Coll Nutr 2004.
    12. AbuMweis SS, Jew S, Ames NP. -glucan from barley and its lipid-lowering capacity: a meta-analysis of randomized, controlled trials. Eur J Clin Nutr 2010 Dec.;64(12):1472–80.
    13. Baker WL, Tercius A, Anglade M, White CM, Coleman CI. A meta-analysis evaluating the impact of chitosan on serum lipids in hypercholesterolemic patients. Ann Nutr Metab 2009;55(4):368–74.
    14. Brighenti F, Casiraghi M, Canzi E. Effect of consumption of a ready-to-eat breakfast cereal containing inulin on the intestinal milieu and blood lipids in healthy male volunteers. Eur J Clin Nutr 1999; Pages 726–33.
    15. Li S, Guerin-Deremaux L, Pochat M, Wils D, Reifer C, Miller LE. NUTRIOSE dietary fiber supplementation improves insulin resistance and determinants of metabolic syndrome in overweight men: a double-blind, randomized, placebo-controlled study. Appl Physiol Nutr Metab 2010 Dec.;35(6):773–82.
    16. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: The National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum 2011 Oct.;63(10):3136–41.
    17. Sun SZ, Flickinger BD, Williamson-Hughes PS, Empie MW. Lack of association between dietary fructose and hyperuricemia risk in adults. Nutr Metab 2010;7(1):16.
    18. Grotto D, Zied E. The Standard American Diet and its relationship to the health status of Americans. Nutr Clin Pract 2010 Dec.;25(6):603–12.
    19. U. S. Department of Agricuture USDOHAHS. Dietary Guidelines for Americans 2010. 2011 Jan.;:1–112.
    20. Avena NM, Rada P, Hoebel BG. Sugar and fat bingeing have notable differences in addictive-like behavior. Journal of Nutrition 2009 Mar.;139(3):623–8.
    21. Berner LA, Avena NM, Hoebel BG. Bingeing, self-restriction, and increased body weight in rats with limited access to a sweet-fat diet. Obesity (Silver Spring) 2008 Sep.;16(9):1998–2002.

  • Nutraceutical Relief for Inflammation

    Inflammation is a useful natural reaction that the body has in response to injury and certain other conditions. Chronic inflammation, however, can be more destructive than beneficial. Indeed, when we hear the word inflammation, we tend to associate with conditions like arthritis and other more serious issues. Nevertheless, there are many common causes of inflammation that are not associated with disease states. These include eating diets high in certain inflammation-promoting foods (e.g., polyunsaturated fats, simple carbohydrates— especially refined sugars1, common allergens like casein and gluten2), being in colder temperatures3, experiencing menopause (with hormone fluctuations)4, experiencing psychological stress5 and exposure to environmental toxins.6

    Ramifications Of Inflammation
    That being said, there can still be ramifications associated with common, non-disease types of inflammation, even low-grade systemic inflammation. Examples include but are not limited to everyday aches and pains, alterations in digestion and absorption7, behavioral changes8, minor disruption in microcirculation and blood flow over the course of the aging process9, and a minor negative impact on immune health.10 In addition, obesity is associated with inflammation.

    Specifically, overweight and obese children and adults have elevated serum levels of C-Reactive Protein and other known markers of inflammation. This is not to say that inflammation causes obesity, but rather the reverse: obesity causes low-grade systemic inflammation. While obesity is commonly thought of as adipose tissue, it is also associated with fat storage in other tissues—including the liver and skeletal muscle. This may lead to insulin resistance and may also stimulate inflammation. Obesity also changes the type of chemicals that our fat cells secrete, which may include the secretion of several pro-inflammatory mediators.11 Since chronic inflammation is closely associated with cardiovascular risk factors, including cardiovascular and non-cardiovascular causes of death, this may help explain the increased risk of diabetes, heart disease, and many other chronic diseases in the obese.12

    Anti-Inflammatory Nutraceuticals
    One of the strategies to help decrease inflammation is the use of anti-inflammatory nutraceuticals—and there are many from which to choose. Following is a discussion of some of my favorite anti-inflammatory nutraceuticals, which includes resveratrol, grape seed extract, calcium fructoborate, turmeric (curcumin) and ginger.

    Resveratrol
    Resveratrol (RSV), a natural substance found in grapes, peanuts and Japanese Knotweed (Polygonum cuspidatum), made a big splash when it was introduced into the dietary supplement market because it was considered to contribute to the “French paradox,” the unexpectedly low rate of death from cardiovascular disease in the Mediterranean population, despite a diet that is relatively high in saturated fat. Since then research has demonstrated other benefits for RSV, among them its effectiveness as an anti-inflammatory agent. This was seen in a randomized, placebo-controlled study13 investigating the effectiveness of 40 mg RSV or placebo daily (for six weeks) on oxidative and inflammatory stress in normal subjects. The results were that RSV significantly reduced oxidative stress (P < 0.05) and also significantly suppressed levels of several inflammatory markers, including TNF-alpha, IL-6, and C-Reactive Protein (P <). There was no change in these indices in the control group given placebo.

    Grape Seed Extract And Resveratrol
    Grape seed extract contains phenolic compounds known as oligomeric proanthocyanidins (OPC). These OPC have significant antioxidant properties.14 In addition, they also appear to have significant anti-inflammatory properties—at least when combined with RSV. In a triple-blind, randomized, placebo-controlled, one-year follow-up, 3-arm pilot clinical trial15, 75 stable–coronary artery disease (CAD) patients received a combination of grape seed phenolics (i.e. OPC) and RSV, grape seed extract alone, or a placebo. The daily doses of the combination were as follows: 139 mg of grape seed OPC for the first six months, and then doubled for the following six months, which would require about 293 mg (a grape seed extract providing 95 percent OPC, 146.32 mg is required to yield 139 mg OPC); RSV was eight mg and 16 mg for the first six months and the remaining six months, respectively. The daily dose of grape seed OPC alone was 151 mg during six months, and then doubled for the following six months. The results showed that after one year, in contrast to the placebo and grape seed extract only groups, the combination group showed an increase of the antiinflammatory serum adiponectin (9.6 percent, p = 0.01).

    In addition, in the combination group six key inflammation factors were significantly improved (p < 0.05) without any adverse effects.

    Using the same dosage strategy and group types as in the last study, a randomized placebo-controlled, triple-blind, dose–response, 1-year follow-up study16 with three parallel arms was conducted in 35 in hypertensive male patients with type 2 diabetes mellitus (T2DM). Results showed that after 12 months there was a significant reduction in levels of the inflammatory markers ALP (p = 0.02) and IL-6 (p = 0.00) in the combination group. In addition, the production of proinflammatory cytokines was also reduced significantly.

    Calcium Fructoborate
    Calcium fructoborate (CF) is a form of the mineral boron, known for its role in bone health—but it is also good for joints and inflammation. A double-blind, placebo-controlled study17 examined the effect of 108 mg CF twice a day in patients with knee osteoarthritis (OA). Results showed that in the CF group, pain scores at Day seven dropped to 82 percent of the Day one value (from 74.0 to 59.9, p<0.05). By Day 14, the pain score reduced to 71 percent of the baseline (from 74.4 to 52.2, p<0.01). In contrast, there was no significant reduction in pain scores in the placebo group on either Day seven or Day 14. Other measures of pain were also significantly reduced (p< 0.05) on Day seven and Day 14 (p< 0.01). In addition, blood level of C-Reactive Protein were reduced up to 37 percent compared to Day one baseline levels in 79 percent of subjects. Interestingly, the study also showed that blood level of vitamin D was increased more than 19 percent compared to baseline, but not in the placebo group. The CF was well tolerated by all study subjects with no reports of adverse effect.

    Calcium Fructoborate And Resveratrol
    A 60-day, randomized, double-blinded, active-controlled, parallel clinical trial18 was conducted in three groups of subjects to evaluate the effects of oral supplementation with CF (112 mg/day), RSV (20 mg/day), and their combination (RSV – 20 mg/day + CF – 112 mg/day) for 60 days on the clinical and biological statuses of patients with stable angina pectoris. Of the total number of subjects included in study (n = 166), 87 completed the test treatment study period and 29 followed in parallel their usual medical care and treatment. Results showed that there was a significant decrease of high-sensitivity C-Reactive Protein in all groups at the 30-day and 60-day visits. At 60 days, this decrease was greater for CF (39.7 percent), followed by RSV + CF (30.3 percent). Markers for congestive heart failure were significantly lowered by RSV (59.7 percent) and by CF (52.6 percent). However, their combination induced a decrease of 65.5 percent. The improvement in the quality of life was best observed for subjects who received the RSV + CF mixture.

    Turmeric (Curcumin)
    Turmeric, a member of the ginger family, has been used as a traditional remedy in Chinese and Ayurvedic medicine as well as for condiment and flavoring purposes for over 2,000 years, based on records dating back to 600 BCE.19 Its primary active constituent is the flavonoid curcumin (diferuloylmethane), which is responsible for the plant’s yellow color and the compound providing most of its medicinal qualities.20,21 Certainly, research has demonstrated that the curcumin molecules inhibit 5-lipoxygenase (LOX) and cyclooxygenase (COX), resulting in a well-established anti-inflammatory action.22,23,24 This ability to help relieve common, everyday inflammation has been demonstrated in a significant number of published human clinical studies on curcumin.25,26,27,28,29,30,31,32,33,34,35

    Ginger
    Although it’s probably more known for its anti-nausea properties (i.e., treatment of motion sickness and morning sickness), Ginger is also an effective anti-inflammatory herb that has historically been used for arthritis and rheumatism. In a study of patients with rheumatoid arthritis, osteoarthritis and muscular discomfort, the majority experienced (to varying degrees) relief of pain and swelling. None of the patients reported adverse effects during the period of ginger consumption, which ranged from three months to 2.5 years.36

    Another double-blind trial found ginger extract to be more effective than placebo at relieving pain in people with OA of the hip or knee.37 Likewise, in another doubleblind study ginger was significantly more effective than a placebo in pain relief and overall improvement.38 Ginger is considered to exert its anti-inflammatory activity by inhibiting COX-2 and lipoxygenase pathways.39

    Conclusion
    Inflammation may be present in disease or non-disease states. In either case, resveratrol, grape seed extract, calcium fructoborate, turmeric (curcumin) and ginger may be helpful in reducing markers of inflammation, reducing pain, and improving other parameters of health.

    References:

    1. Lopez-Garcia E, Schulze MB, Fung TT, Meigs JB, Rifai N, Manson JE, Hu FB. Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr 2004;80(4):1029–35.
    2. Caputo I, Lepretti M, Martucciello S, Esposito C. Enzymatic strategies to detoxify gluten: implications for celiac disease. Enzyme Res 2010 Oct 7;2010:174354.
    3. Halonen JI, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Associations between outdoor temperature and markers of inflammation: a cohort study. Environmental Health 2010;9:42.
    4. Abu-Taha M, Rius C, Hermenegildo C, Noguera I, Cerda-Nicolas JM, Issekutz AC, Jose PJ, Cortijo J, Morcillo EJ, Sanz MJ. Menopause and ovariectomy cause a low grade of systemic inflammation that may be prevented by chronic treatment with low doses of estrogen or losartan. J Immunol. 2009 Jul 15;183(2):1393– 402. Epub 2009 Jun 24.
    5. Black PH, Garbutt LD. Stress, inflammation and cardiovascular disease. J Psychosom Res 2002;52(1):1–23.
    6. Watkins BA, Hannon K, Ferruzzi M, Li Y. Dietary PUFA and flavonoids as deterrents for environmental pollutants. J Nutr Biochem 2007;18(3):196 –205.
    7. Peuhkuri K, Vapaatalo H, Korpela R. Even low-grade inflammation impacts on small intestinal function. World J Gastroenterol 2010;16(9):1057– 62.
    8. Teeling JL, Felton LM, Deacon RMJ, Cunningham C, Rawlins JNP, Perry VH. Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines. Brain, Behavior, and Immunity 2007;21(6):836–850.
    9. Payne GW. Effect of Inflammation on the Aging Microcirculation: Impact on Skeletal Muscle Blood Flow Control. Microcirculation 2006;13(4):343–52.
    10. Ader R. Psychoneuroimmunology, Volume 1, 4th Ed. Elsevier Science & Technology Books; 2006:438.
    11. Stienstra R, Duval C, Müller M, Kersten S. PPARs, Obesity, and Inflammation. PPAR Res. 2007;2007:95974.
    12. Das UN. Is obesity an inflammatory condition? Nutrition. 2001 Nov-Dec;17(11-12):953–66.
    13. Ghanim H, Sia CL, Abuaysheh S, Korzeniewski K, Patnaik P, Marumganti A, Chaudhuri A, Dandona P. An anti-inflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J Clin Endocrinol Metab. 2010 Sep;95(9):E1–8.
    14. Feringa HH, Laskey DA, Dickson JE, Coleman CI. The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials. J Am Diet Assoc. 2011 Aug;111(8):1173–81.
    15. Tomé-Carneiro J, Gonzálvez M, Larrosa M, Yáñez-Gascón MJ, García-Almagro FJ, Ruiz-Ros JA, Tomás-Barberán FA, García-Conesa MT, Espín JC. Grape resveratrol increases serum adiponectin and down regulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc Drugs Ther. 2013 Feb;27(1):37–48.
    16. Tomé-Carneiro J, Larrosa M, Yáñez-Gascón MJ, Dávalos A, Gil-Zamorano J, Gonzálvez M, García-Almagro FJ, Ruiz Ros JA, Tomás-Barberán FA, Espín JC, García-Conesa MT. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013 Jun;72:69–82.
    17. Reyes-Izquierdo T, et al. Short-term Intake of Calcium Fructoborate Improves WOMAC and McGill Scores and Beneficially Modulates Biomarkers Associated with Knee Osteoarthritis: A Pilot Clinical Double-blinded Placebocontrolled Study. Am J Biomed Sci. 2012; doi: 10.5099.
    18. Militaru C, Donoiu I, Craciun A, Scorei ID, Bulearca AM, Scorei RI. Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life. Nutrition. 2013 Jan;29(1):178–83.
    19. Curcuma longa (turmeric). Monograph. Altern Med Rev 2001;6 Suppl:S62–6.
    20. Chattopadhyay I, Biswas K, Bandyopadhyay U, Banerjee RK. Turmeric and curcumin: Biological actions and medicinal applications. Current Science. 2004;87(1):44–53.
    21. Curcuma longa (turmeric). Monograph. Altern Med Rev 2001;6 Suppl:S62-6.
    22. Chandra D, Gupta S. Anti-inflammatory and anti-arthritic activity of volatile oil of Curcuma longa (Haldi). Ind J Med Res 1972; 60:138–42.
    23. Arora R, Basu N, Kapoor V, et al. Anti-inflammatory studies on Curcuma longa (turmeric). Ind J Med Res 1971;59:1289–95.
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    28. Lal B, Kapoor AK, Asthana OP, et al. Efficacy of curcumin in the management of chronic anterior uveitis. Phytother Res 1999;13:318–22.
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    36. Srivastava KC, Mustafa T. Ginger (Zingiber officinale) inrheumatism and musculoskeletal disorders. Med Hypotheses 1992; 39:342–8.
    37. Bliddal H, Rosetzsky A, Schlichting P, et al. A randomized, placebo-controlled crossover study of ginger extracts and buprofen in osteoarthritis. Osteoarthritis Cartilage 2000;8:9–12.
    38. Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum 2001; 44:2531– 8.
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  • Sierrasil, A Joint Pain Product That Works, Naturally

    Results from a clinical trial published in the international Journal of Inflammation demonstrate that SierraSil®, a powerful, uniquely balanced blend of numerous naturally occurring macro and trace minerals, is safe and effective for significantly decreasing pain and inflammation in patients with osteoarthritis.*

    Mark Miller, Ph.D., and Professor of Cardiovascular Sciences and Pediatrics at Albany Medical College (NY), supervised the study and was instrumental in the in-depth analysis of its data. “SierraSil,” said Miller, “may offer exciting new approaches to limiting the joint destruction and lack of mobility associated with arthritis.”

    The SierraSil product for this study was provided by Sierra Mountain Minerals, Inc. Michael Bentley, the company’s Executive Vice President and Chief Operating Officer, is more than pleased with this latest testament to the effectiveness of SierraSil.

    “We know from past trials, patient testimonials and reports from physicians that SierraSil improves joint mobility and flexibility,”* said Bentley. “Now, we see how important it can be as a support to those suffering from the pain of osteoarthritis.”*

    An emerging supplement in the battle against inflammation, SierraSil is found only in the high Sierra Mountains.

    The human body can make many vitamins, amino acids, fatty acids and their derivative molecules, but it cannot make a single mineral. Due to mineral depletion in soil, some doctors say people cannot rely on getting all of these necessary nutrients from food. Also, when minerals are not consumed in adequate amounts, the body will resort to stealing minerals from its fluids, soft tissues and bones.

    That’s why many health professionals advise people to use supplements rich in macro and trace minerals. SierraSil is considered an excellent mineral supplement because it is comprised of numerous naturally occurring macro- and trace minerals including calcium, potassium, magnesium, copper, iron, zinc, phosphorus, manganese, selenium, vanadium, chromium, boron and molybdenum in a form that possesses unusual health-promoting properties.

    SierraSil helped pro golfer Ken Venturi. A former US Open Champion and 1964 Sports Illustrated Sportsman of the Year, Venturi gave up playing golf due to hand injuries. Finally, after a distinguished 35-year career of broadcasting as CBS Golf Analyst, Ken is playing golf again—thanks to SierraSil. Venturi says, “I believe in this product so very much that I’m willing to endorse it. It can help you, because it helped me. And what it’s done for me most of all, it’s given me back the game of golf, which I love so much. Without it I wouldn’t be able to hit golf balls.”

    Is Ken alone in his discovery? Absolutely not! Al Stonehouse, Senior Men’s Captain at Kelowna Golf and Country Club read about Ken’s success with SierraSil and gave it a try. “I have achieved remarkable success with SierraSil,” Stonehouse said. “Normally I am very reluctant to try any form of drug or supplement but after reading about the success achieved by Ken Venturi, I decided to give it a try. Within days I noticed improved flexibility with my golf swing, increased driving distance and reduced carpal-tunnel pain in my hands. It’s great to be able to play three to four rounds a week and not have to go through the pain and suffering that I had been accustomed to for the past few years. I’m hitting the ball further than ever! I have had no hesitation in recommending SierraSil to my golfing friends. Thanks for making golf the pleasurable experience it should be.”

    SierraSil is completely natural and vegetarian. It contains no glucosamine or chondroitin and exhibits beneficial properties even in small amounts. Only two to three grams a day are needed. Unlike other well-known joint support supplements, like glucosamine and chondroitin, which reportedly take up to three months to work, many SierraSil users are reporting noticeable benefits in less than two weeks.*

    The past Vioxx recall led a number of health care professionals and consumers to take a closer look at natural approaches to joint health. Even the Arthritis Foundation, which only twelve years ago discouraged the use of supplements, is now encouraging its members to explore exercise, a healthy diet and dietary supplements. “Dietary supplements present a safe and effective long-term option, and consumers have a wide range of options when deciding which approach is right for them,” said James LaValle, R.Ph., N.D., an expert on naturopathic medicine. “The Vioxx recall should serve as a wake-up call. The truth of the matter is that in some cases there are serious side effects with prescription drugs,” Dr. LaValle said. “The good news is that there are safe and effective dietary supplements that are a better first choice for improving joint health.”

    For more information please visit www.SierraSil.com.

    The complete clinical trial report is available at the Journal of Inflammation's website:
    www.journal-inflammation.com/content/2/1/11/abstract.

  • SierraSil: A New Joint Pain Solution

    Some diseases, or health conditions, seem to be women’s issues. Arthritis and osteoporosis are in that category. Although men also struggle with joint inflammation and bone loss, the literature focuses on women. Are women at greater risk? According to the research, they are. Over 50 percent of women will suffer an osteoporotic bone break, while just one in eight men will experience an episode of fracture due to bone loss. Arthritis statistics are similar. While younger men are more likely to experience arthritis, due to accidents and injuries, the disease is three times more prevalent in women after the age of 45.


    The bones and joints are not the only parts of the body affected by inflammation. Research now correlates chronic inflammation with obesity, hypothyroidism, heart disease (yes, heart disease is a woman’s issue), diabetes, and Alzheimer’s disease. It is clear, then, that if women are to thrive through their senior years, they must develop a strategy for dealing with “the body on fire.”

    Fortunately, minerals from the rocky reaches of the Sierra Nevada mountains provide an excellent way to dampen the fires of inflammation, wherever they occur in the body. SierraSil® is a blend of over 65 naturally-occurring minerals that have been shown, in both in vitro and human studies, to “shut off the genetic switch to inflammation.”

    What Is It About Minerals?
    When we discuss chronic inflammation, we seldom mention minerals, but these essential nutrients play a vital role in bone and joint integrity, and they confer powerful anti-inflammatory benefits. The research community is just now delving into the world of minerals and beginning to understand their diverse and complex roles in the human body. They participate in the structural integrity of the body and catalyze enzymatic reactions. They help regulate the pH of the body.

    One of the most important tasks of minerals, particularly the unique blend of minerals in SierraSil, is that they help regulate the genetic expression of inflammation. To understand how this works, Sierra Mountain Minerals embarked on a series of human studies to assess both the safety and efficacy of SierraSil. One hundred twenty study participants were asked to answer the following question: Is SierraSil safe, and is SierraSil effective in reducing osteoarthritis symptoms?

    The treatment protocol lasted for eight weeks, and at the conclusion of the trial, researchers and patients found that every marker of arthritis (pain, stiffness and function) was greatly improved. Equally important, SierraSil was completely safe.

    SierraSil has been used clinically to relieve the pain of injury, fibromyalgia, colitis, and many other sources of pain. Benefits generally appear within seven to ten days, and without side effects. The recommended dose is three capsules each morning on an empty stomach.

    One medical doctor in Canada is testing C-reactive protein levels (a marker for inflammation) in his pain patients who have been using SierraSil for several years, and finds that their inflammatory markers are low, a sign that the inflammation, wherever it has lodged in the body, is abating.

    What else can women (and men) do to improve joint and bone health? Remove inflammatory foods like red meat, sugar, alcohol, and grains from the diet. Red meat contains a fatty acid called arachidonic acid, a precursor to pro-inflammatory hormones called eicosanoids. Grains, sugar and alcohol are highly acidic foods; low pH levels are associated with inflammation. Grains, particularly wheat and corn, are problematic in terms of allergies, an inflammatory process.

    An anti-inflammatory diet provides seven to eight servings of fresh vegetables per day, plenty of oils like fish, flax and olive oil, and good sources of protein like organic poultry, wild-raised seafood and lamb (preferably organic).

    Lifestyle factors can be either pro- or anti-inflammatory as well. Get plenty of sleep; it is during the dark hours of the night that the body repairs itself and the bones are built. Stress can heighten inflammation. Women often juggle two full-time jobs: employment outside the home and the care of the home and family. Since they seldom take time to rest and recover, the continual stress can cause pain.

    Restoring the integrity of the bones and resolving joint inflammation starts with diet and lifestyle, but well-chosen supplements are a vital part of the diet. Since both osteoporosis and arthritis share a common link in inflammation, as well as the other “illnesses of inflammation,” it makes sense to supplement with an anti-inflammatory mineral blend like SierraSil.