Saturday, September 8, 2012

Supplement Use in the Prevention and Treatment of Cardiovascular Disease in the Aging Population


From American Journal of Lifestyle Medicine

Ruth A. Reilly, PhD, RD, LD; Colette Janson-Sand, PhD, RD, LD

Abstract and Introduction

Abstract

As the elderly population grows, so does the incidence of cardiovascular disease and the use of medications. Because of the side effects and cost of prescribed medicine, many aging individuals are seeking out alternative treatment options. Complementary and alternative medicine is gaining popularity, with about a third of people older than 60 years currently using one or more of these therapies. Many individuals are using herbs and nutritional supplements to prevent and treat a variety of cardiovascular diseases and their symptoms. Herbs and nutritional supplements are considered food by the Food and Drug Administration and are exempt from mandatory testing for their safety or efficacy. Also, many individuals consider these products as natural and do not recognize the negative impact that these alternative treatments may have on the efficacy of prescribed medications and overall health. To date, research has reported conflicting evidence as to the beneficial effects of these products; health care providers should exercise caution in recommending their use to avoid drug interactions and side effects.

Introduction

Aging increases the risk for many chronic diseases, including cardiovascular disease (CVD). CVD is the leading cause of death and disability in the industrialized world with nearly 82% of Americans older than 65 years dying from this disease.[1,2] Prevention and treatment of CVD includes lifestyle changes and pharmaceutical interventions. People aged 65 years and older are the largest consumers of both prescription and overthe- counter drugs.[3] Medications, although effective, may cause many unwanted side effects. As a result, many elderly individuals are seeking out complementary and alternative medicine (CAM) to augment or substitute for the medications prescribed by their health care provider. The use of CAM has been growing in popularity in recent years and currently more than 15 million people in the United States use herbal or high-dose vitamins for the prevention and treatment of various diseases.[4] Herbal supplement use is high among individuals who are being treated with prescription medications, particularly the elderly.[5] A recent survey reported that approximately 32% of individuals using CAM are older than 60 years.[6] Many people do not realize that herbs and vitamins are considered food and, unlike prescription medications, are not tested for safety or efficacy. Instead, people regard herbs and nutritional supplements as natural substances and therefore consider them safe. Because CAM may interfere with the absorption and metabolism of prescribed medications, the use of CAM can lead to many health risks. The objective of this article is to identify widely used herbs and nutrient supplements and review their efficacy, potential side effects, and risks for the aging population.

The B Vitamins: Folate, B6, B12, and Niacin

Vitamin B6 performs a wide variety of functions in the body and is involved in more than 100 enzyme reactions, most related to protein metabolism.[7] In the late 1960s, a Boston doctor hypothesized that elevated levels of homocysteine could lead to atherosclerosis.[8]Folate, B6, and BB12 were shown to have the ability to enhance homocysteine conversion to methionine, an amino acid used in building proteins, and consequently decrease homocysteine levels in the blood.[9] Several well-designed research studies showed that B vitamins could lower homocysteine levels but did not show any reductions in CVD.[10–12] A systematic review further confirmed that these supplements do not reduce the risk of developing or dying from CVD.[13] Furthermore, the Norwegian Vitamin Trials (NORVIT) reported that the combination of these 3 B vitamins can have harmful effects in those individuals who have already experienced a myocardial infarction or have coronary stents.[14] Niacin, in the form of nicotinic acid, has long been used as a pharmacologic agent to reduce triglycerides and low-density lipoprotein (LDL) levels and to increase high-density lipoprotein (HDL) in the treatment of atherosclerotic CVD.[9] The European Consensus Panel on HDL considered nicotinic acid to be the most potent agent for increasing HDL as well as being very effective in reducing LDL and lipoprotein (a).[15] When combined with statin therapy, nicotinic acid has been shown to have an even greater lipid-reducing effect.[16,17] However, in 2011, a large, National Institutes of Health clinical trial was stopped 18 months early because there was no sign that high-dose niacin coupled with statins reduced cardiovascular problems in people versus using statins alone. Although niacin raised levels of HDL, this did not translate into fewer fatal and nonfatal heart problems.[18,19] Pharmacologic dosages of niacin can cause flushing of the skin, hyperuricemia, abnormal liver function, and hyperglycemia and therefore should be monitored by a physician.[20]

Coenzyme Q10

Coenzyme Q10, commonly referred to as CoQ10, is also known as ubiquinone. It is a vitamin-like substance produced in the mitochondria of cells; as a component of the electron transport chain, CoQ10 generates ~95% of the human body's energy in the form of adenosine triphosphate (ATP).[21] CoQ10 has demonstrated antioxidant properties and therefore has been studied for its effect on cardiovascular health. A recent study showed that CoQ10 plasma concentrations are an independent predictor of mortality in chronic heart failure, with CoQ10 deficiency being a factor in the long-term prognosis of chronic heart failure.[22] CoQ10 and cholesterol share the same biosynthetic pathway, and the production of mevalonate, an intermediate in this pathway, is inhibited by certain beta blockers[23] and statins.[24] Indeed, statins can reduce serum levels of coenzyme Q10 by up to 40%.[25] Therefore, some research studies recommend supplementing statin use with coenzyme Q10as a routine adjunct. In view of the fact that CoQ10 can lower blood pressure and therefore may not be suitable for certain individuals, people should not begin taking this supplement without first consulting with their physician to insure that there are no contraindications to its use.

Fish Oil Supplements

Most epidemiological studies have found a correlation between fish consumption and a lower risk of coronary artery disease. Fish is a rich source of the essential omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Fish oil supplements have gained popularity in recent years for the prevention and treatment of many diseases, including CVD, largely because of their anti-inflammatory effects.[26] Fish oil supplements reduce serum triglycerides levels by reducing the hepatic production of very low density lipoproteins (VLDL) and accelerating VLDL clearance.[27]However, the role of omega-3 fatty acids in reducing mortality, heart failure, myocardial infarctions, and arrhythmias has not been established.[26] In a recent metaanalysis, 14 randomized, double-blind placebo-controlled trials indicated that fish oil supplements are ineffective in treating individuals with diagnosed CVD.[28] The US Food and Drug Administration has approved only one dietary omega-3 fatty acid supplement: Lovaza (GlaxoSmith Kline). A 1-g capsule contains 375 mg of DHA and 465 mg EPA.[26] Relative safety has been shown in both primary and secondary prevention of heart disease, but caution should be exercised in individuals taking antiplatelet or anticoagulant drugs, vitamin E, or aspirin.[29 (p351)]

Garlic

Garlic (Allium sativan) has been used for more than 5000 years as a medicine and in cooking. Garlic's proposed cardiovascular effects include controlling blood cholesterol and blood pressure, reducing platelet aggregation, improving circulation, and improving the elasticity of blood vessels.[30 (pp172-187)] Epidemiological evidence has shown that garlic consumption may delay the progression of CVD, but more comprehensive studies need to be conducted to confirm this positive effect.[31] In a recent clinical trial, 192 adults with high LDL were randomly assigned into 3 treatment groups and 1 placebo group. The treatment groups were given raw, powdered, or aged garlic supplements for 6 months. There were no significant effects on LDL concentrations in all groups.[32] A recent metaanalysis examined the effect of garlic on blood pressure and reported that 10 of the 25 studies reviewed showed garlic reduced both systolic and diastolic blood pressure in hypertensive individuals when compared with the placebo group.[33] The active component in garlic, ajoene, has been shown to have antiplatelet effects and it is therefore recommended that individuals on anticoagulant or antiplatelet therapies should avoid garlic supplements. It is also advised that individuals planning surgery should discontinue its use 10 days before surgery.[34] Garlic is well tolerated by most individuals with its greatest side effect being undesirable body odor. It is important to note that an average clove of raw garlic contains ~3 g and most of the research on the therapeutic effects of garlic has used ~2 to 5 g of raw garlic, easily consumed in a normal diet.[35 (p293)]

Grape Seed Extract

Grapes (Vitis vinifera) have been used for centuries for eating, and for making juice, wine, and medicines. Grape seed extract, sold commercially in 50- or 100- mg tablets, comes from the seeds of the red grapes and the active ingredient is a subclass of flavonoids called proanthocyanidins.[36,37] Proanthyocyanidins are powerful antioxidants and also improve vascular elasticity.[30] It has been suggested that grape seed extract could be important in the prevention of atherosclerosis and cancer and in wound healing and also in the treatment of hyperlipidemia. In a recent meta-analysis, Feringa et al[38] evaluated the effects of grape seed extract in both animal and human studies. Although animal studies have suggested cardiovascular benefits from grape seed extract, human studies report conflicting results. Grape seed extract administered to humans lowered systolic blood pressure and heart rate but had no significant effect on diastolic blood pressure, C-reactive protein, or lipid levels.[38] There are few reported side effects from grape seed extract except for allergic reactions.[39]

Green Tea

Tea comes from the Camillia sinensis plant and is consumed in various parts of the world as black, oolong, or green tea.[40] Green tea was first exported from India to Japan in the 17th century and is now produced around the world[41] and available as loose tea (caffeinated or decaffeinated) or as a supplement.[30] Green tea has been used to treat a variety of conditions because of its polyphenol (antioxidant) content. Catechins account for 80% to 90% of the polyphenols found in green tea and are thought to confer most of its health benefits.[42] A recent systematic meta-analysis reported on the effect of green tea on lipid concentrations (LDL, HDL, and triglycerides) in humans. Subjects who consumed green tea (doses 145–3000 mg/d) for 3 to 24 weeks had a 5.46 mg/dL reduction in total cholesterol and a 5.30 mg/dL reduction in LDL when compared with controls, with no significant change in HDL.[30,43] Another review of the literature evaluated the health benefits of green tea in the prevention and treatment of metabolic syndrome, hypertension, cancer, and CVD in humans and animals. There is some evidence that green tea may lower blood pressure and thus reduce the risk of stroke and coronary artery disease, but human studies are still limited and more research is needed to confirm these benefits.[40] Side effects of green tea include allergic reactions (rare), gastrointestinal complaints, irregular heartbeat, and sleeplessness.[39] Consumption of green tea has been shown to reduce the effect of warfarin and so should be used with caution by individuals taking anticoagulants. Green tea extract may interfere with iron absorption and caffeinated green tea or supplements should not be used by individuals taking medications that have negative interactions with caffeine such as amphetamines, clozapine, theophylline, and so on.[30]

Hawthorn

Hawthorn is an herb (Crataegus oxyacantha L. and Crataegus monogyna) that is used to treat angina, congestive heart failure (CHF), and cardiac arrhythmias. A review of 14 studies on the effect of hawthorn use in the treatment of congestive heart failure found beneficial effects of this herb as an adjuvant to standard therapy for patients with CHF.[44,45] Exercise tolerance and oxygen consumption improved in patients with CHF who were consuming the hawthorn extract as compared with the placebo. However, the effect of hawthorn on morbidity and mortality has not been studied.[44]Hawthorn's use in the treatment of hypertension and hyperlipidemia has demonstrated positive outcomes in animals, but its use with humans is speculative.[46] In spite of these positive effects from the use of hawthorn, its efficacy and safety have not been elucidated. Hawthorn should be used with caution by patients taking digitalis as it may result in toxicity.[47] Hawthorn can also increase bleeding time and should not be used by patients taking antiplatelet or anticoagulant drugs.[29] The efficacy of hawthorn use in the treatment of patients with CHF is still unclear and caution should be used with patients currently using digoxin and vasodilating drugs (ie, theophylline). Health care providers should use caution and carefully monitor patients who are using this herb. Reported side effects were mild and included nausea, dizziness, increased heart rate, and gastrointestinal complaints.[45]

Policosanol

Policosanol is a mixture of longchain aliphatic alcohols obtained from sugar cane, beeswax, and wheat germ.[48] Policosanol has been marketed for the treatment of a variety of cardiovascular and circulatory disorders such as hypercholesterolemia, atherosclerosis, and intermittent claudication.[49] The appeal of this drug—its promise to lower cholesterol without significant side effects—has made it one of the fastest growing overthe- counter supplements in the United States.[50] Early studies were done by one research facility in Cuba. These studies claimed that 1 to 20 mg/d of policosanol could produce significant reductions in both total cholesterol and LDL cholesterol. These studies also showed that policosanols were potent antioxidants, beneficial to endothelial cell function, and inhibitors of platelet aggregation and thrombosis.[48] Several randomized, double-blind crossover studies in which participants received low to high doses of policosanol derived from sugar cane and either used alone or with statins, were not able to show significant reduction in LDL or total cholesterol levels.[51–54]Although side effects are mild, such as indigestion, skin rash, headache, insomnia, and weight loss, policosanol may increase the effect of medications that interfere with blood clotting or antiplatelet drugs, such as aspirin, warfarin (Coumadin), heparin, clopidogrel (Plavix), ticlopidine (Ticlid), or pentoxifylline (Trental), or supplements such as garlic, ginkgo, or high-dose vitamin E. Policosanol may also increase the efficacy and side effects of levodopa, a medication used for Parkinson's disease.[29,55]

Red Yeast Rice

Red yeast rice is produced by fermenting red rice with the yeastMonascus purpureus. It was marketed for a number of years under the name Cholestin because it contained the drug lovastatin, known to reduce cholesterol levels and cause small to modest increases in HDL levels.[56] A 1999 US district court ruled Cholestin could be sold without a prescription, but in 2000, the 10th US circuit court reversed the ruling.[57,58] As a result, Cholestin was reformulated to contain policosanol instead of lovastatin although red yeast rice formulations containing lovastatin are still available in other countries online.[59]
For most of the over-the-counter red yeast rice products, there is no indication of statin level: different strains of the Monascus fungus can produce different amounts of statin. There are also some accounts of products being spiked with high doses of lovastatin.[60,61] The safety of red yeast rice products has not been established, and some of the supplements samples have been found to contain high levels of a toxin, citrinin.[62] Statin drugs can cause muscle and liver damage. Rhabdomyolysis, associated with statins, can result in kidney damage and possibly lead to renal failure.[63,64] Therefore, anyone taking statins should be monitored by a physician. People choose red yeast rice over pharmaceuticals because they find it to be a more "natural" form of the drug and because it is much less expensive. Red yeast rice can interact with some 188 different medications, of which 40 have major serious effects. Examples of these include all statins, a large number of antibiotics, antifungal and antiviral agents, as well as niacin supplements.[65]

Vitamin E

Vitamin E is a fat-soluble vitamin whose active form, α-tocopherol, functions as an antioxidant. The oxidation process contributes to the development of atherogenesis.[66,67] Oxidized LDL causes endothelial cells to produce inflammatory markers, and has a role in foam cell formation, destruction of endothelial cells, inhibition of the motility of tissue macrophages, and inhibition of nitric oxide–induced vasodilation.[68] Vitamin E has been shown to decrease oxidative stress in vitro and prevent atherosclerotic plaque formation in mouse models.[69] However, reviews of research studies in humans have concluded that vitamin E is of no benefit in the prevention of CVD. In fact, vitamin E supplementation might be linked to an increase in mortality, heart failure, and stroke.[67,70] It has also been shown to decrease HDL, which has a protective effect on the cardiovascular system.[71] The American Heart Association does not support the use of vitamin E supplements to prevent CVD but does recommend the consumption of foods abundant in vitamin E and other antioxidants.[72] This dietary practice has been associated with a lower risk of heart disease in middle-aged and older men and women.[73,74] Doses exceeding 400 IU per day should be avoided when taking anticoagulants and antiplatelet medications.[75]

Conclusion

Since CAM has gained popularity in recent years, health care professionals should be alert to the fact that their patients, especially their older patients, may be taking herbs and other supplements to treat and prevent a variety of illnesses. The combination of many of these substances, especially with traditional medications, can result in serious side effects. Therefore, asking patients whether they are using any herbals or supplements, and educating patients as to the risks their use may present, should be part of every medical assessment.

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