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|Posted: Dec Fri 15, 2006 6:32 pm Post subject: Heart - Cardiovascular Micro-nutrients
|Heart - Cardiovascular Micro-nutrients
This is a rather long article but since it is from a medical website and some members of the forum can't access internet, I thought it worthwhile to reprint the entire article.
Cardiovascular Disease and Micronutrient Therapies
Judith Anderson, ARNP, PhD, Cathy R. Kessenich, ARNP, DSN [Mdscape Nursing 1(2), 2001. © 2001 Medscape, Inc.]
Cardiovascular disease is a problem of epidemic proportions. Its prevalence, morbidity, and mortality have encouraged millions of Americans to seek prevention and treatment by ingesting micronutrients and antioxidants. Patients actively seek information about these complementary therapies in health food stores, via mail order catalogs, and through the Internet. Healthcare providers must acquire knowledge about these substances so they can impart reliable information to their patients. This article reviews the current scientific evidence on the use of garlic, coenzyme Q-10, fish oils, vitamins (B6, B12, C, and E), and folic acid in the treatment and prevention of coronary artery disease.
A great deal of recent biomedical and nursing research has focused on the modification of known cardiovascular risk factors. Despite this attention, coronary artery disease (CAD) continues to be a chief cause of death in the United States. It has been estimated that more than half of the deaths due to cardiovascular disease are related to atherosclerotic pathology. In the last several decades, great strides have been made in the diagnosis and treatment of CAD. New categories of pharmacologic agents have been developed, and intervention strategies to mitigate the progression of CAD have evolved. While these advances are promising, they have not substantially reduced the morbidity and mortality associated with CAD. Improved prevention and treatment strategies for CAD are public health issues of critical importance to all.
Patients and providers are actively seeking alternative methods, such as the use of micronutrients and antioxidants, to prevent and treat CAD. Micronutrients are defined as essential nutrients that are needed for survival, but only in small amounts. The most common micronutrients are vitamins, which are vital organic dietary substances essential in very small amounts for particular metabolic functions or for prevention of disease due to deficiency. In treating CAD, the most important vitamins are C, E, B6, B12, and Folic Acid (the vitamin supplement for folate). Antioxidants are substances that interfere with the oxidation of low-density lipoprotein (LDL) and thus prevent formation of foam cells, which are pathogenic in atherosclerosis development. The antioxidant vitamins are C and E. Other alternative therapies for lowering cholesterol levels include Garlic, Fish Oils, and CoEnzyme Q-10.
The role of many micronutrients and antioxidants is undetermined. Even so, many CAD patients use these substances in large quantities. A study by Eisenberg and colleagues published in 1998 estimated that Americans made 629 million visits annually to practitioners of alternative medicine – a number that exceeds the total number of visits to primary care providers. Primary care providers must be knowledgeable about the scientific evidence that supports or refutes the use of complementary therapies. The purpose of this paper is to review the current evidence on the use of Garlic, Vitamin C, Vitamin E, Coenzyme Q-10, Fish Oils, Vitamin B6, Vitamin B12, and Folate in the treatment/prevention of CAD.
GARLIC – (Allium sativum) has been used since medieval times as a food, a magical substance to cast off evil spirits, and a miracle cure for disease. It may be taken in the form of fresh bulbs, bulk powder, granules, or oils. The proposed action of garlic is to lower blood pressure and lower LDL and triglycerides by several percentage points. Additionally, some reports indicate that garlic contains antiplatelet properties. Many of the proposed beneficial effects of garlic are unsubstantiated. However, there are several meta-analyses that have supported the efficacy of garlic in lowering lipids in the blood and reducing blood pressure. The effect on blood pressure has mixed reviews, with a number of studies demonstrating no effect. Several small studies have found garlic to be effective in reducing atherosclerotic plaques and inhibiting platelet aggregation.
Research shows that garlic might have some effect on the prevention and treatment of CAD. No harmful effects have been discovered, although it is noted that several types of garlic preparations cause malodorous breath and body odor. Therefore, patients who use garlic therapy are probably choosing a safe therapy that complements other lifestyle modifications. The proper use of garlic may deter even the most ardent supporter, however. According to Roberts, the best way to attain the positive effects of garlic is to eat 5-20 raw cloves per day. This therapy may cause gastrointestinal difficulty, including flatulence and esophageal and abdominal pain. To avoid these side effects, manufacturers have developed extracts, powders, and tablets. Unfortunately, many of these preparations contain little or no active garlic ingredient and are no better than placebo for the prevention and treatment of CAD. [Editorial Note: This is the reason NSP does NOT remove anything. The odor is avoided with High Potency Garlic by making it not release until it reaches the intestines and being coated by Chlorophyll]
VITAMIN C – (ascorbic acid) is an essential micronutrient that is required for normal metabolic functioning. Vitamin C must be obtained through the diet [or supplements], because humans are unable to reproduce it via biosynthesis. The vitamin is plentiful in most diets, particularly those with adequate citrus fruits and vegetables. The role of vitamin C as an antioxidant for the prevention of cardiovascular morbidity and mortality has been demonstrated in several large clinical and epidemiologic trials. Data recently published from The Third National Health and Nutrition Examination Survey (NHANES III) study showed that the risk of angina was decreased with higher intakes of vitamin C, particularly among men and women who drank alcohol. Gokce and colleagues recently demonstrated that long-term therapy with vitamin C provided a sustained beneficial effect on endothelial function and ultimately protected patients with CAD. Earlier observational studies have demonstrated a relationship between vitamin C and CAD[11-13] and have suggested that the use of vitamin C may decrease the risk of stroke and death from CAD. The majority of research conducted with vitamin C has investigated daily doses that are much higher than the current recommended levels. These amounts should be safe and effective for most individuals. Historically, there has been some concern about the occurrence of kidney stones in individuals ingesting high doses of vitamin C. According to Goodwin and Tangum, this commonly held perception is based on speculation and is not supported by scientific evidence.
VITAMIN E – (alpha-tocopherol) exists as at least 8 naturally occurring compounds. Alpha-tocopherol is the most active compound. Vegetables, seed oils, eggs, and liver are substantial sources of this nutrient. However, it is postulated that the amount of vitamin E needed for maximal reduction of cardiovascular risk (at least 100 IU per day) cannot be obtained through food intake alone.
The beneficial effects of vitamin E supplementation have been demonstrated in the Nurses' Health Study. This large, prospective study (with up to 8 years' follow-up) demonstrated that women given vitamin E supplements (median dose of 208 IU per day) had a lower risk of CAD. This same observation has been demonstrated in male cohorts. Large, double-blind, placebo-controlled trials such as the Cambridge Heart Antioxidant Study (CHAOS) have also shown that vitamin E supplementation is a safe and economical mechanism for reducing the risk of CAD.
Vitamin E supplements (200 IU per day, 400 IU per day for smokers) appear to be a safe and effective complementary therapy. There has been some concern about the potential of vitamin E supplementation to promote hemorrhage, particularly in patients on warfarin or aspirin therapy. While these issues should be considered in the overall plan of care, the overwhelming majority of patients should benefit from the addition of vitamin E to their preventive regimen.
COENZYME Q-10 -- (ubiquinone) is a nutrient that every cell in the body must have in order to produce energy. It is the coenzyme for at least 3 mitochondrial enzymes of the oxidative phosphorylation pathway which are essential for the production of adenosine triphosphate (ATP). Coenzyme Q-10 also has antioxidant and membrane-stabilizing properties. Because the nutrient is essential to the optimal function of all cell types, it can be beneficial in a wide variety of diseases. Since it was first isolated in 1957, coenzyme Q-10 has demonstrated beneficial uses in the treatment of heart conditions, hypertension, periodontal disease, immune disorders, cancer, and other diseases. As a natural substance, the US Food and Drug Administration does not regulate Coenzyme Q- 10, and it is still not widely prescribed in the United States. Therefore, much of the research has been completed outside the United States. Early studies involving patients with New York Heart Association class III or IV heart failure demonstrated that treatment with coenzyme Q-10 reduced hospitalizations and serious complications such as pulmonary edema and ventricular arrhythmia, improved clinical signs and symptoms, and improved quality of life and exercise capacity.
More recent studies in patients with congestive heart failure have produced mixed results. In one study, treatment for 3 months with coenzyme Q-10 failed to improve resting left ventricular function or quality of life. Conversely, in a smaller study, patients who received coenzyme Q-10 daily for 5 years had an 87% increase in mean ejection fraction after only 6 months. This improvement in left ventricular function was supported in several other studies. Aside from its use in heart failure, coenzyme Q-10 has been used after myocardial infarction and has been found to provide rapid protective effects from arrhythmia and left ventricular dysfunction if administered within 3 days of the onset of symptoms. Additionally, coenzyme Q-10 has been found to decrease lipoprotein (a) in patients with acute coronary disease and to decrease blood pressure in patients with known hypertension, possibly by decreasing oxidative stress.
Epidemiologic evidence suggests that coenzyme Q-10 may make vitamin E an even more efficient antioxidant for LDL. There is evidence that several current therapies for CAD, including lipid-lowering agents such as lovastatin and beta-blockers, lower coenzyme Q-10 levels in tissues, thus increasing the risk for heart disease. It is possible that patients taking lovastatin and beta-blockers should be supplemented with coenzyme Q-10. The dosage reported in experiments ranged from 50-200 mg daily, with no significant adverse effects reported after 6 years of therapy at 100 mg daily. Positive clinical and hemodynamic effects of oral coenzyme Q-10 have been observed in numerous clinical trials, especially in patients with chronic heart failure. Despite its usefulness in the symptomatic treatment of heart failure, it has not been shown to reduce mortality. These clinical findings need further investigation before use of coenzyme Q-10 can be recommended. There have been no studies examining coenzyme Q-10 supplementation for general health, and the effects of prophylactic use are not known.
FISH OILS – Diets high in saturated fat are linked to high blood cholesterol levels, a risk factor for cardiovascular disease. It has been postulated that lowering saturated fat intake by just 3% would prevent about 100,000 new cases of CAD by the year 2005. When dietary saturated fats are decreased, they can be partially replaced with the marine n-3 fatty acids. It is known that native fishing populations have low rates of CAD, possibly associated with their high intake of fatty acids from fish. The fatty acids important in fish oil are eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. The n-3 fatty acids improve endothelial function by promoting the synthesis of nitric oxide. EPA has several antithrombotic actions, particularly in inhibiting the synthesis of thromboxane A2, the prostaglandin that causes platelet aggregation and vasoconstriction. In addition, fish oil retards the growth of atherosclerotic plaque by inhibiting both cellular growth factors and the migration of monocytes. Fish oil may decrease cardiac afterload by an antivasopressor action and by reducing blood viscosity.
Several researchers have examined the effect of fish oil on cholesterol levels. Fish oil supplementation has been shown to significantly decrease triglyceride concentration and very-low-density lipoprotein (VLDL) levels. However, fish oil supplementation alone has had no effect on total plasma cholesterol, and, in fact, has been shown to increase LDL concentrations. [NSP has this in Omega 3 EPA]
Studies have examined the use of fish oil supplementation alone, in combination with a fish diet, and in combination with garlic. Adding garlic to a fish oil regimen reversed the moderate increase in LDL caused by fish oil, and the garlic-fish oil combination significantly decreased both total cholesterol and LDL. Coadministration of garlic with fish oil seems to be well tolerated and appears to have a beneficial effect on lipid and lipoprotein concentration by providing a combined lowering of total cholesterol, LDL, and triglycerides. At the present time, there is not enough evidence to recommend the routine use of fish oil supplementation. However, for the hypercholesterolemic patient, the combination of garlic and fish oil may be of benefit.
FOLATE – is a crucial cofactor in DNA synthesis, contributing a carbon unit to oxidation at various levels of purine synthesis. During purine synthesis the amino acid methionine is produced from homocysteine. Lack of folate leads to impaired DNA synthesis and results in decreased production of methionine and accumulation of homocysteine. Elevated levels of homocysteine may induce endothelial injury, inhibit prostacyclin production, and promote thrombogenesis by increasing production of thromboxane A2. Thromboxane A2 produces platelet aggregation and vasoconstriction, whereas prostacyclin promotes vasodilation. This combination may be a major cause of damage to the endothelium. A common mutation in the gene encoding for the enzyme methylenetetrahydrofolate reductase has been identified as a genetic risk for high levels of homocysteine. Mild hyperhomocystinemia due to gene mutation is estimated to occur in 5% to 10% of the general population.
Homocysteine is an amino acid formed during the metabolism of methionine. Elevated levels may induce endothelial injury, inhibit prostacyclin production, and promote thrombogenesis by increasing production of thromboxane A2. Thromboxane A2 produces platelet aggregation and vasoconstriction, whereas prostacyclin promotes vasodilation. This combination may be a major cause of damage to the endothelium. A common mutation in the gene encoding for the enzyme methylenetetrahydrofolate reductase has been identified as a genetic risk for high levels of homocysteine. Mild hyperhomocystinemia due to gene mutation is estimated to occur in 5% to 10% of the general population.
A plasma homocysteine concentration of more than 15 mcmol/L is referred to as hyperhomocystinemia. Such elevated levels induce pathologic changes in the arterial wall, and the prothrombic environment created in the endothelium accounts for the association between increased plasma homocysteine levels and cardiovascular disease. Elevated levels have been observed among smokers, men, and postmenopausal women. Many cross-sectional and prospective studies have demonstrated the relationship between high levels of total homocysteine and coronary, cerebral, and peripheral artery disease.[38-40] A recent meta-analysis has conclusively established the relationship between hyperhomocystinemia and cardiovascular disease.
Homocysteine levels are inversely related to blood concentrations of folate, and folic acid supplementation, which is the vitamin supplement for folate, can lower homocysteine levels. Studies have demonstrated that daily doses of folic acid at 5-10 mg resulted in higher serum folate levels, lower total plasma homocysteine levels, and improved endothelial function.[37,41,42] Since 1998, folate fortification of foods has been mandated. Even with fortification, however, 76% of the population is below the minimum requirement of folate. Much of the fortification is in whole grains. The Nurses' Health Study demonstrated that whole-grain intake reduces the risk of coronary heart disease in women. Increased consumption of vegetables and citrus fruit, both good sources of folate, has also been associated with the reduction of coronary heart disease. Folate lowers elevated homocysteine levels, but evidence for routine supplemental use does not yet exist. However, it is recommended that all patients suffering from atherosclerosis and elevations of serum homocysteine receive supplementation of folic acid.
Vitamin B6 (pyridoxine) and Vitamin B12 (cobalamin) are water-soluble vitamins that are absorbed in the small intestine, converted to an acid form, and excreted, with very little stored in the body. Both vitamins B6 and B12 are important in the function of protein metabolism reactions, particularly in the conversion of homocysteine. Increased plasma homocysteine concentration is an independent risk factor for premature atherosclerosis. Deficiency of vitamin B6 and vitamin B12, as well as folic acid, leads to mild-to-moderate elevation in homocysteine level. Studies of the association between dietary intake and blood levels of folate, vitamin B6, and vitamin B12 show positive and dose-dependent associations with the risk of cardiovascular disease. Therapy to decrease homocysteine levels includes folic acid taken alone or in combination with vitamins B6 and B12.
Lobo and associates studied a combination of daily low-dose folic acid supplements combined with vitamins B12 and B6 to reduce homocysteine levels in patients with CAD. Patients received 1-5 mg of folic acid, 12.5 mg of vitamin B6, and 500 micrograms of B12. They concluded that a daily does of 4 mg of folic acid combined with vitamins B6 and B12 normalized homocysteine levels in patients with CAD. In addition to deficiencies in folic acid and vitamins B6 and B12, long-term diuretic therapy has been implicated as a cause of elevated homocysteine levels. It has been demonstrated that hypertensive patients receiving long-term diuretic therapy have elevated homocysteine levels. In one study, patients receiving long-term diuretic therapy had significant increases in serum homocysteine concentrations and significant decreases in folate concentration with no change in vitamins B6 and B12.
CONCLUSION AND RECOMMENDATION – The micronutrients described in this article are widely used for the treatment and prevention of cardiac disease. On the whole, these substances do not appear to be harmful, and clinical evidence suggests that they may provide some beneficial effects. Micronutrient therapy may be a useful adjunct to traditional cardiovascular therapies. However, each patient must be considered individually, and a thorough history, physical examination, and laboratory work-up should be conducted prior to the initiation of micronutrient therapy. It is hoped that future research will continue to build a positive case for these economical and generally well-tolerated substances.
If a variety of healthy foods are eaten, the necessary vitamins can possibly be obtained from diet alone. However, supplementation may be required for some patients, particularly those with deficiencies. For supplementation, vitamins should have 50% to 150% of the RDA, and daily treatment should not provide more than 2-10 times the RDA for a specific vitamin. Healthcare providers can safely advise patients that childbearing women need 4 mg of folic acid daily. In addition, vitamins C, E, B6, and B12 may be helpful for the prevention of CAD.
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Judith Anderson, ARNP, PhD, has no significant interests to disclose. Cathy Kessenich, DSN, has no significant interests to disclose.