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February 2013

Topics:

Resveratrol valuable despite research fraud
Omega-3 fatty acids and aging
Mediterranean diet and heart
Vegetarian diet and heart
Vitamin D, DHA, and Alzheimer’s

Resveratrol valuable despite research fraud

Last year it was discovered that a researcher at the University of Connecticut had fabricated results in dozens of studies on resveratrol. This led to the dismissal of the researcher and confusion about the real benefits of supplemental resveratrol. The news headlines suggested that this might mean that resveratrol (and the red wine that is one of its sources) had no value in cardiovascular protection or anti-aging benefits. However, as one researcher pointed out, the falsified research is only a fraction of the over 4000 papers showing benefits from resveratrol.

Recent research in diabetic rats suggests that resveratrol can reduce oxidative damage to white blood cells and reduce oxidative markers in the blood (such as lipid peroxides and oxidized glutathione). The rats were treated for four months with 5mg/kg of resveratrol (for a 60 kg (132 pound) woman this would be equivalent to at least 300 mg, daily). (Soufi FG, et al., Long-term treatment with resveratrol attenuates oxidative stress pro-inflammatory mediators and apoptosis in streptozotocin-nicotinamide-induced diabetic rats. Gen Physiol Biophys. 2012 Dec;31(4):431-8. doi: 10.4149/gpb_2012_039.)

At the end of the four months, oral resveratrol administration significantly reduced high blood sugar levels, in addition to the improvement of oxidative markers. They also found that the resveratrol significantly helped reduce damage to the kidney, heart, retina, and sciatic nerve. Damage to these organs is among the classic features of long-term diabetes, so protecting them with resveratrol is one therapeutic approach to preventing diabetes-related complications.

In a human study on 75 subjects with stable coronary artery disease, they received 350 mg per day of resveratrol-containing grape extract (8 mg of resveratrol plus other grape phenols), a placebo, or a grape extract without the resveratrol. After six months, their dose was doubled. They were followed for a total of one year.

At the end of the study, the researchers found that the resveratrol led to a reduction of six inflammatory markers, an increase of the anti-inflammatory serum adiponectin, and a decrease of the thrombogenic plasminogen activator inhibitor type 1. The resveratrol group also had down-regulation of the genes involved in inflammation and cell migration in the peripheral white blood cells. (Tomé-Carneiro J, et al., Grape resveratrol increases serum adiponectin and downregulates 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. doi: 10.1007/s10557-012-6427-8.)

Omega-3 fatty acids and aging

Telomeres are the end coverings of chromosomes that protect them from DNA losses that are associated with the aging process. As the telomeres degenerate, the chromosome ends become more susceptible to these losses. Shortened telomeres are also associated with cancer risk. (One substance that protects telomere length is resveratrol; while cigarette smoking, on the other hand, shortens telomeres). Recent research shows that omega-3 fatty acids also protect the telomeres.

Telomere length is regulated by the enzyme telomerase, and they are shortened by oxidative stress and inflammation. In a double-blind, four-month trial, researchers evaluated 106 sedentary, overweight adults who were middle-aged or older. They received omega-3 fatty acid supplements at 2.5 grams or 1.25 grams per day, or a placebo that mimicked the fatty acid ratios found in the typical American diet.

Supplementation significantly lowered oxidative stress as reflected by serum F2-isoprostanes, which were 15 percent lower in the supplemented groups than in the placebo group. Telomere length was higher in the subjects with a higher proportion of omega-3 fatty acids compared to omega-6 fatty acids. These data suggest that omega-3 fatty acids can decrease cellular aging. (Kiecolt-Glaser JK, et al., Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial. Brain Behav Immun. 2013 Feb;28:16-24. doi: 10.1016/j.bbi.2012.09.004. Epub 2012 Sep 23.)

Mediterranean diet and heart

The Mediterranean diet has been in the news a lot in recent years. The diet is characterized by large amounts of fruits, vegetables, whole cereal grains, legumes, nuts, and olive oil (which makes it a high fat diet), as well as red wine, a small amount of fish and poultry, and minimal red or processed meats or sweets. In a recent interventional study of the primary prevention of heart disease, researchers enrolled 7447 men and women aged 55 to 80. They analyzed the primary end point of major cardiovascular events (heart attack, stroke, or heart deaths). The trial was stopped after an average follow-up of 4.8 years.

A primary end-point event occurred in 288 participants. After analysis, those on the Mediterranean diet with either additional nuts or olive oil had a 28 to 30 percent lower risk of cardiovascular events than those in the control group. However, there are some problems with drawing conclusions based on this study. The control group was counseled in what was called a low-fat diet. The test diets included additional extra-virgin olive oil and nuts compared to the so-called low-fat diet.

In the “higher” fat Mediterranean diet with added oil or nuts, the calories from fat in the diet were 39.2 and 39.4 percent, respectively, compared to the control diet that had 39.0 percent of calories from fat. This means that all of the diets in question were high fat. (A normal diet, which is by nature low fat) has about 10 to 20 percent of calories from fat, including omega-3 and -6 fats, among others.) (Estruch R, et al., Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013 Feb 25. [Epub ahead of print])

The commentaries published online with the article were very telling. They pointed out that the diet was not effective at reducing heart disease compared to areas of the world where the diet is mainly unprocessed, whole foods, with a fat content of 10 to 20 percent. It is effective if you compare it to the United States, where the average diet is full of processed sugar, processed meats, white flour, highly processed vegetable oils, and a variety of manufactured junk that is not food. The resulting rate of heart disease (and other ailments) is very high, so almost any dietary change would be an improvement.

Vegetarian diet and heart

In the European Prospective Investigation into Cancer and Nutrition (EPIC) study, researchers analyzed data for an association of nutrition to the rate of heart disease leading to hospitalization or death. A total of 44,561 men and women living in England and Scotland were enrolled in the study. Of these subjects, 34 percent were on a vegetarian diet at the start of the study. They were followed for an average of 11.6 years and then compared to the subjects who were not on vegetarian diets.

In addition to the rate of heart disease incidents, they analyzed the body mass index (BMI), non-HDL cholesterol levels, and systolic blood pressures. Overall, there wre 1235 heart disease cases, including 1066 hospital admissions and 169 deaths. (Crowe FL, et al., Risk of hospitalization or death from ischemic heart disease among British vegetarians and nonvegetarians: results from the EPIC-Oxford cohort study. Am J Clin Nutr. 2013 Mar;97(3):597-603.)

Vegetarians had a lower BMI, a lower non-HDL cholesterol concentration, and lower systolic blood pressures. Vegetarians also had a 32 percent lower risk of ischemic heart disease incidents than did the nonvegetarians, and this was independent of sex, age, smoking, BMI, or the presence of other cardiovascular risk factors.

Vitamin D, DHA, and Alzheimer’s

Alzheimer’s disease is a condition in which protein deposits (or plaques) of “amyloid-beta” occur in the brain and lead to the deterioration of neurological tissue and loss of cognitive function. The immune system can help clear amyloid-beta protein if it is functioning properly. Earlier research demonstrated that vitamin D3 and curcumin (a component of turmeric, one of the orange-colored spices in curry) could stimulate the immune system to clear amyloid-beta.

Recent research helps clarify how vitamin D3 might work. Blood cells called macrophages are responsible for removing waste products, including amyloid-beta, from the blood and other tissues. Vitamin D helps the function of two types of macrophages. Curcumin helps with one type of macrophage. They also found that an omega-3 oil called docosahexaenoic acid (DHA, or Resolvin D1 in this study) helped the macrophages clear amyloid-beta, partly by reducing the inflammatory response. The research was done with macrophages from blood samples of Alzheimer’s patients. (Mizwicki MT, et al., 1α,25-Dihydroxyvitamin D3 and Resolvin D1 retune the balance between amyloid-β phagocytosis and inflammation in Alzheimer's disease patients. J Alzheimers Dis. 2013 Jan 1;34(1):155-70. doi: 10.3233/JAD-121735.)

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Information herein is not medical advice or direction. All material in this newsletter is provided for information only. Its contents should not be used to provide medical advice on individual problems. Consult a health care professional for medical or health advice.

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