Alternative medical researchers and practitioners from the US, Mexico, Germany, Sweden and Russia gathered recently to explore research on cardiovascular protection, prevention and treatment using dietary supplements. Barbara Anan Kogan, PhD, OD, reports from Washington, DC
Only within the past few years has cardiovascular disease (CVD) gained in recognition as a primary focus of the US Department of Health & Human Services—with a strong emphasis on prevention of this No. 1 killer. More than half of the National Institutes of Health centres have been collaborating with other institutes in the area of complementary and alternative research and public awareness programmes. The US Department of Agriculture has become equally involved in nutritional modalities to reduce and prevent CVD onset and progression. Through such collaborative research, the body's mechanisms are becoming better understood, particularly with genetics and lifestyle effects.
Since a number of legislators, including Vice President Dick Cheney, are afflicted with CVD, their interest has heightened in providing federal funding on research for current and newly diagnosed Americans. We can see the influence of public awareness of this research in retail food stores, schools, print and broadcast media, as well as a number of FDA-authorised health claims that address heart health.
The following report highlights a recent two-day seminar, sponsored by the National Institutes of Health (NIH); National Heart, Lung and Blood Institute (NHLBI); the Office of Dietary Supple-ments (ODS); and the National Center for Complementary and Alternative Medicine (NCCAM).
Garlic: The medicinal properties of garlic (Allium sativum) include its ability to reduce blood viscosity, blood cholesterol and triglyceride levels, to inhibit platelet aggregation and to function as an anti-microbial, anti-fungal and anti-inflammatory agent.
An odourless sulphur compound, allicin, is formed from garlic, and its instability allows decomposition into other sulphur-containing compounds. The sulphur compounds are extremely bio-chemically reactive and, when combined with glutathione, allicin functions both as an antioxidant and protective agent against CVD. Allicin and its related sulphur-containing compounds, known as thiosulfinates, are the principal sources of anti-platelet reduction from garlic juice.
Allicin's ability to rapidly cross cell membranes, including red blood cells, may greatly enhance the intracellular interaction of this herb with sulphur-containing enzymes and microbes and kill them by shutting down their metabolism.
Ajoene, one of the sulphur-containing compounds present when allicin decomposes, is thought to prevent blood clotting by selectively blocking the binding of fibrinogen to platelets. Diallyl polysulfides, another sulphur-containing compound, inhibits formation of thromboxane and affects platelet aggregation.
Other garlic compounds and allicin act on the liver's cholesterol-synthesising enzyme, HMGCoA reductase, to lower cholesterol levels. High allicin intake releases garlic, and garlic supplements have positive hypercholesterolaemia effects. Current clinical trials with animal studies of garlic supplements show that they appear to be able to lower elevated blood pressure with the allicin component. However, dipeptides appear to be more active.
An aqueous garlic extract was studied for its possibilities as a nutraceutical drug to prevent and treat arteriosclerosis and atherosclerosis. Here, the extract markedly slowed the nano-plaque formation and reduced the molecular size by inhibiting Ca 2+ (Ca = calcium), and binding to heparan sulfate proteoglycan (HS-PG). The arteriosclerotic plaque generation from the endothelial cells was greatly blunted.
Ginkgo biloba: The three major components of Ginkgo biloba extracts (EGb), flavonoid glycosides, proanthocyanidins and terpenoids, have shown the ability to reduce platelet activating factors and neutrophil adhesion to cardiovascular endothelial cells. Additionally, these cells can be protected from hypoxia, while improving vasodilation.
Flavonoids and isoflavones: Flavonoids of hawthorn (Crataegus spp) extract of the leaves, flowers and berries are widely used in Western Europe to treat heart failure. Chemical constituents of hawthorn have coronary and peripheral vasodilator, anti-arrhythmic and anti-oxidant activity.
Phyto-oestrogens (isoflavones) bind to oestrogen receptors, and soy phyto-oestrogens have a cardiovascular/brain agonist. This enables SPEs to benefit post-menopausal women against cardiovascular disease. More than 35 clinical trials suggested that consumption of soy protein can reduce LDL cholesterol by up to 14 per cent and triglycerides by up to 10 per cent, while increasing HDL cholesterol by two per cent.
The NIH's ODS released its third issue of the Annual Bibliography of Significant Advances in Dietary Supplement Research in October 2002, covering highlights of research published in 34 international peer-reviewed journals in 2001. Some of the highlights regarding supplements and functional foods with cardio-protective effects are as follows.
B vitamins: Taking 400mcg/day of folic acid lowered homocysteine levels in older adults 62 to 80 years of age by 19.6 per cent, and when taken concomitantly with 1.6mg/day of vitamin B6 (riboflavin), lowered it an additional 7.5 per cent. Ageing is associated with an increase in homocysteine and a decrease in B6, which may increase the risk for CVD.
In another B-vitamin study, researchers evaluated whether the development of vascular dysfunction in monkeys fed a high-fat, high-cholesterol or atherogenic diet could be slowed while preventing hyperhomocysteinaemia.
In a collaborative study on folate located in red blood cells (RBC), researchers found a 24 per cent increase among those also taking B vitamins. This further reduced the homocysteine-associated CVD risk factors.
Vitamin D with calcium: Combining 600mg calcium and 400IU vitamin D3 twice daily was evaluated in women age 70 and older for benefits in the management of elevated blood pressure. The combination D3 was more effective than the calcium alone and decreased systolic blood pressure by 9.3 per cent, blood parathyroid by 17 per cent and heart rates by 5.4 per cent.
Vitamin E: Individuals with type 2 diabetes are predisposed to elevated oxidative stress, which can cause an imbalance in the activity of the cardiac autonomic nervous system. Researchers found that 600mg/day alpha-tocopherol reduced stress. It was also thought that because vitamin E modulates insulin resistance, this may explain the positive effects on the nervous system. In a controlled study on oxidative stress among congestive heart failure patients, those who took 500IU/day vitamin E twice daily for 12 weeks experienced a doubling of vitamin E concentration in the blood during the first six weeks of the trial. However, there was no significant improvement in the long-term management of heart failure.
In another study, 300mg/day vitamin E lowered the incidence of peripheral artery disease.
Dietary soy: In two studies of post-menopausal monkeys evaluating the beneficial effects of therapeutic dietary soy intake on CVD, researchers saw positive results in monkeys that consumed a pre-menopause, moderately atherogenic diet for 26 months. Total cholesterol levels were significantly lowered and HDL cholesterol levels were increased in one of the studies. Soy also lowered systolic/diastolic blood pressures and triglycerides.
L-arginine: Men with stable angina and mild hypercholesterolaemia who took 15g/day L-arginine experienced a 62 per cent increase in the L-arginine/ADMA (L-arginine inhibitor) ratio, a marker of oxidative stress. This is thought to occur from an increase in nitric oxide production.
Dietary absorption: It is well known that sufficient vitamin intake is necessary to enhance the nutritive value and absorption of food for maximum benefits against CVD. To improve absorption, researchers are evaluating the role of amino acids, specifically how parts of peptides fit into the efficacy picture of proteins. Researchers continue to investigate cardio-protective essential fatty acids and minerals, as well as trace minerals such as chromium and selenium.
Phytonutrients: When plants, which are the analogues of neurotransmitters, are eaten, they can have beneficial, but also detrimental, metabolic influences. Scientists now are studying the bioactive allelochemicals in phytonutrients that are thought to promote cardiovascular health. These components include amino acids, glycosides, alkaloids, phenolics and unusual proteins. Formulators are applying their food-medicine continuum knowledge garnered from animal studies to that of the human-plant interaction.
Because researchers believe that lycopene in tomatoes and components of garlic and onions can reduce CVD risks and help manage the disease, the US Department of Agriculture's Maryland Research Service is looking to add phytochemicals to the list of cardio-protective foods.
For more information, visit www.dietary-supplements.info.nih.gov, or e-mail for a copy at [email protected] For more information on the mechanistic studies of cardiovascular effects of botanicals workshop, visit www.nccam.nih.gov. For more on the National Heart Lung Blood Institute's Office of Prevention, Education and Control, visit www.nhlbi.nih.gov.
Barbara Anan Kogan, PhD, OD, has been a clinical researcher in the area of CVD and is a nutritionally oriented optometrist in Washington, DC.