Supplements For Cardiac Protection
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Supplements For Cardiac Protection By CJ Lau 15 July 2009
What are dietary supplements?
a product (other than tobacco) that is intended to supplement the diet which contains one or more of the following dietary ingredients: a vitamin, a mineral, a herb or other botanical, an amino acid, a dietary substance for use by man to supplement the diet. It is intended for ingestion in pill, capsule, tablet or liquid form, and should not be used to replace a meal or diet. In UK, the definition includes substances such as garlic, ginseng, psyllium, enzymes, fish oil and other ingredients.
Cardiac Protection Supplements Outline Coenzyme Q10 Fish Oil L- Carnitine Antioxidant Folic acid
Coenzyme Q10 (Ubiquinone)
Is a naturally occurring enzyme cofactor found in the mitochondria of the body cells. It is involved in electron transport and supports the synthesis of adenosine triphosphate (ATP) in the mitochondrial membrane It is a fat-soluble antioxidant that helps to stabilise cell membranes, preserving cellular integrity and function It may be obtained from the diet or a food supplement, but it is also produced endogenously
Coenzyme Q10
Meat and fatty fish products are the most concentrated sources smaller quantities are found in wholegrain cereals, soya beans, nuts and vegetables, particularly spinach and broccoli no Dietary Reference Values or RDAs have been established as it is not an essential nutrient Deficiency has been linked to chronic heart failure, ischemic heart disease, cardiomyopathy and hypertension
Coenzyme Q10
Coenzyme Q10 is sold in capsules and tablets in strengths of 10–150 mg. Doses used in studies investigating CVD have ranged from 100 to 150 mg daily. Higher doses have been used in angina (150–600 mg daily). Safety in pregnancy has not been established. Coenzyme Q10 seems to be safe and relatively well tolerated in doses of up to 10–200 mg daily. There are occasional reports of gastrointestinal discomfort, dizziness and skin rash, but these tend to occur with doses > 200 mg daily.
Drug Interaction
Simvastatin, pravastatin and lovastatin reduce endogenous synthesis of coenzyme Q10 Case reports suggest that coenzyme Q10 may decrease international normalised ratio (INR) in patients previously stabilized on anticoagulant. In patients on warfarin, high doses of coenzyme Q10 should be used with caution.
Clinical efficacy
Coenzyme Q10 inhibits superoxide dismutase and may have a role in antioxidant. A meta-analysis of eight clinical trials (1997) of coenzyme Q10 in patients with CHF found that supplemental treatment of CHF was significant, with significant improvement in stroke volume, ejection fraction, cardiac output, cardiac index and diastolic volume index. However, not all clinical trials show positive results. A recent randomized ,double blind studies of patients with New York Heart Association class III and IV heart failure did not show significant improvement in ejection fraction after receiving 200mg coenzyme Q10.
Clinical efficacy
In another RCT, 55 patients with CHF were randomly assigned to receive 200 mg coenzyme Q10 or a placebo daily for 6 months. Patients receiving the supplement had higher serum concentrations of coenzyme Q10, but there were no differences in cardiac performance, peak oxygen consumption and exercise duration between the treated group and the placebo group. As for angina, in one RCT, 144 patients with acute myocardial infarction were given 120 mg coenzyme Q10 or a placebo daily for 28 days, starting within 3 days of the heart attack. There was a significant improvement in angina pectoris, total arrhythmias and poor left ventricular function in the intervention. However, further studies are needed to support these findings.
Clinical efficacy
Studies in hypertension are inconclusive although there are two studies suggesting a reduction in systolic and diastolic blood pressure with coenzyme treatment.
Overall
Results from preliminary studies with coenzyme Q10 suggest that it may help improve symptoms of CHF, and may help to protect against myocardial infarction At present, coenzyme Q10 lacks definitive data for recommendation in patients with coronary artery disease or heart failure. Prospective examination is certainly needed with possibly longer duration of therapy before any conclusion is possible. All patients with cardiovascular conditions should take medical advice before taking coenzyme Q10.
Fish Oil
Fish liver oil is generally derived from the liver of the cod or shark Fish body oil usually derived from sardine or anchovy Fish liver oil is a rich source of vitamins A and D as compared to fish body oil. Both fish liver oil and fish body oil are sources of polyunsaturated fatty acids (PUFAs) of the omega-3 series [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. WHO suggests 2 portions of fish intake/week, which is equivalent to 250-500mg/daily EPA + DHA.
Fish Oil 1. 2. 3. 1.
2.
Fish oil are thought to have several effects: reduces plasma triglycerides level Inhibition of atherosclerosis Prevention of thrombosis Fish oil appears to act by modulation of pro-inflammatory and prothrombotic eicosanoid (prostaglandin, thromboxane and leukotriene) production reduction in interleukin-1 and other cytokines
Fish Oil
US systemic review (2004) found that the strongest and most consistent effect of omega-3 fatty acids is on lowering triglycerides. In general, LDL cholesterol and HDL cholesterol were found to rise to a small extent. A meta-analysis (2002) of 11 RCTs that compared dietary or non-dietary intake of n-3 fatty acids with placebo in patients with CHD found that intake of n-3 fatty acids reduces mortality due to myocardial infarction and sudden death in patients with CHD. A large Japanese trial (2007) in 18 645 patients with a total cholesterol of 6.5 mmol/l or greater, randomised patients to receive either EPA 1.8 g daily with a statin or a statin control with a 5-year follow-up. There was a 19% relative reduction in major coronary events in the EPA group compared to the statin control group. The benefits were in addition to statin treatment.
Fish Oil Dose – not established, but doses of 1-2g/daily (combined EPA/DHA) may be adequate Use in pregnancy should be supervised because of the potential for vitamin A toxicity with excessive intake of fish oil Adverse effects - safety concern includes the potential to increase bleeding time. Intake of <3g/daily of EPA/DHA should not be a problem. Patients taking anticoagulant medications should inform their doctors if they are taking fish oil. Interactions – anticoagulants, gingko biloba and ginseng. May increase the risk of bleeding, use of fish oil should be medically supervised.
L-Carnitine
Carnitine is an amino acid derivative, L-carnitine is the naturally occurring carnitine Carnitine may be beneficial in patients with ischaemic heart disease, but only those who have low serum carnitine levels Orally administered L-carnitine (2 g daily) has been shown to improve symptoms of angina, and to reduce anginal attacks and glyceryl trinitrate consumption (1980). Carnitine supplementation (4 g daily) has also been reported to improve heart rate, arterial pressures, angina and lipid patterns in a controlled study of patients who had experienced a recent myocardial infarction (1992).
Overall
Preliminary studies (1979) have shown that l-carnitine may reduce blood cholesterol levels. Oral administration of lcarnitine (3–4 g daily) significantly reduced serum levels of total cholesterol or triglyceride or both, and increased those of high-density lipoprotein (HDL) cholesterol. No sufficient evidence to guarantee the safety of carnitine in pregnancy use Dose- not established, but doses of 1-6g have been used in studies Nausea, vomiting and diarrhea may occur in high doses Anticonvulsants, pivampicillin may increase excretion of carnitine
Antioxidants
Antioxidants offer protection against free radicals and prevent damage to vital biological structures such as lipid membranes, proteins and DNA. vitamin A (usually as beta-carotene), vitamins C and E are marketed as supplements having antioxidant activity. beta-carotene are found in most dark green, red or yellow fruits and vegetables. Epidemiological evidence suggests that low plasma levels of antioxidant nutrients and low dietary intakes are related to an increased risk of coronary heart disease (CHD).
Clinical efficacy
One systematic review assessed whether antioxidants in food or supplements can offer primary prevention against myocardial infarction or stroke. Eight RCTs were included, six of which tested supplements of beta-carotene and two on ascorbic acid. None of the RCTs showed any benefit of antioxidant supplementation on CVD. A large trial (2002) involving 20 536 UK adults aged 40–80 with coronary disease, other occlusive arterial disease or diabetes, randomly allocated participants to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene daily) or matching placebo over 5 years. There were no significant differences in all-cause mortality, or in deaths due to vascular or non-vascular causes. In 2004, the American Heart Association Council on Nutrition, Physical Activity and Metabolism concluded that antioxidant supplements have little or no proven value for preventing or treating CVD.
Folic Acid
Folic acid is a water-soluble vitamin Marginal folate status is also associated with elevated plasma homocysteine levels, a known risk factor for CVD mortality. Current studies support a link between homocysteine and atherosclerosis. However, there has not been a definite link between reduction of homocysteine level ands and prevention or resolution of coronary artery disease. Dose- as a dietary supplement, oral, 100– 500 μg daily
Role of Pharmacists
able to assess an individual’s risk of nutrient deficiency and need for further referral must not give the impression that any dietary supplement is efficacious when there is no evidence for such efficacy There is a need to be aware of the potential for adverse effects with supplements and drugs interactions Help patient in making informed decision
References
Goodnight SH Jr, Harris WS, Connor WE, Illingworth DR. Polyunsaturated fatty acids, hyperlipidaemia and thrombosis. Arteriosclerosis 1982; 2: 87–113. Bucher HC, Hengstler P, Schindler C, et al. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med 2002; 112: 298–304 Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised openlabel, blinded endpoint analysis. Lancet 2007 369: 1090–1098 Food and Drug Administration Final Rule. Substances affirmed as generally recognized as safe: menhaden oil. Fed Reg 1997; 62: 30750–30757 Kamikawa T, Suzuki Y, Kobayashi A, et al. Effects of l-carnitine on exercise tolerance in patients with stable angina pectoris. Jpn Heart J 1984; 25: 587–597
References
Davini P, Bigalli A, Lamanna F, et al. Controlled study on l-carnitine therapeutic efficacy in post-infarction. Drugs Exp Clin Res 1992 Kris-Etherton PM, Lichtenstein AH, Howard BV, et al. Antioxidant vitamin supplements and cardiovascular disease. Circulation 2004; 110: 637–641. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 23–33. Gaytan RJ, Michael PL. Oral nutritional supplements and heart disease: a review. American Journal of Therapeutics 8, 255-274. Wald DS, Wald NJ, Morris JK, Law M. Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. BMJ 2006; 333: 1114–1117 Dietary supplements database, medicines complete.
What are dietary supplements?
a product (other than tobacco) that is intended to supplement the diet which contains one or more of the following dietary ingredients: a vitamin, a mineral, a herb or other botanical, an amino acid, a dietary substance for use by man to supplement the diet. It is intended for ingestion in pill, capsule, tablet or liquid form, and should not be used to replace a meal or diet. In UK, the definition includes substances such as garlic, ginseng, psyllium, enzymes, fish oil and other ingredients.
Cardiac Protection Supplements Outline Coenzyme Q10 Fish Oil L- Carnitine Antioxidant Folic acid
Coenzyme Q10 (Ubiquinone)
Is a naturally occurring enzyme cofactor found in the mitochondria of the body cells. It is involved in electron transport and supports the synthesis of adenosine triphosphate (ATP) in the mitochondrial membrane It is a fat-soluble antioxidant that helps to stabilise cell membranes, preserving cellular integrity and function It may be obtained from the diet or a food supplement, but it is also produced endogenously
Coenzyme Q10
Meat and fatty fish products are the most concentrated sources smaller quantities are found in wholegrain cereals, soya beans, nuts and vegetables, particularly spinach and broccoli no Dietary Reference Values or RDAs have been established as it is not an essential nutrient Deficiency has been linked to chronic heart failure, ischemic heart disease, cardiomyopathy and hypertension
Coenzyme Q10
Coenzyme Q10 is sold in capsules and tablets in strengths of 10–150 mg. Doses used in studies investigating CVD have ranged from 100 to 150 mg daily. Higher doses have been used in angina (150–600 mg daily). Safety in pregnancy has not been established. Coenzyme Q10 seems to be safe and relatively well tolerated in doses of up to 10–200 mg daily. There are occasional reports of gastrointestinal discomfort, dizziness and skin rash, but these tend to occur with doses > 200 mg daily.
Drug Interaction
Simvastatin, pravastatin and lovastatin reduce endogenous synthesis of coenzyme Q10 Case reports suggest that coenzyme Q10 may decrease international normalised ratio (INR) in patients previously stabilized on anticoagulant. In patients on warfarin, high doses of coenzyme Q10 should be used with caution.
Clinical efficacy
Coenzyme Q10 inhibits superoxide dismutase and may have a role in antioxidant. A meta-analysis of eight clinical trials (1997) of coenzyme Q10 in patients with CHF found that supplemental treatment of CHF was significant, with significant improvement in stroke volume, ejection fraction, cardiac output, cardiac index and diastolic volume index. However, not all clinical trials show positive results. A recent randomized ,double blind studies of patients with New York Heart Association class III and IV heart failure did not show significant improvement in ejection fraction after receiving 200mg coenzyme Q10.
Clinical efficacy
In another RCT, 55 patients with CHF were randomly assigned to receive 200 mg coenzyme Q10 or a placebo daily for 6 months. Patients receiving the supplement had higher serum concentrations of coenzyme Q10, but there were no differences in cardiac performance, peak oxygen consumption and exercise duration between the treated group and the placebo group. As for angina, in one RCT, 144 patients with acute myocardial infarction were given 120 mg coenzyme Q10 or a placebo daily for 28 days, starting within 3 days of the heart attack. There was a significant improvement in angina pectoris, total arrhythmias and poor left ventricular function in the intervention. However, further studies are needed to support these findings.
Clinical efficacy
Studies in hypertension are inconclusive although there are two studies suggesting a reduction in systolic and diastolic blood pressure with coenzyme treatment.
Overall
Results from preliminary studies with coenzyme Q10 suggest that it may help improve symptoms of CHF, and may help to protect against myocardial infarction At present, coenzyme Q10 lacks definitive data for recommendation in patients with coronary artery disease or heart failure. Prospective examination is certainly needed with possibly longer duration of therapy before any conclusion is possible. All patients with cardiovascular conditions should take medical advice before taking coenzyme Q10.
Fish Oil
Fish liver oil is generally derived from the liver of the cod or shark Fish body oil usually derived from sardine or anchovy Fish liver oil is a rich source of vitamins A and D as compared to fish body oil. Both fish liver oil and fish body oil are sources of polyunsaturated fatty acids (PUFAs) of the omega-3 series [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. WHO suggests 2 portions of fish intake/week, which is equivalent to 250-500mg/daily EPA + DHA.
Fish Oil 1. 2. 3. 1.
2.
Fish oil are thought to have several effects: reduces plasma triglycerides level Inhibition of atherosclerosis Prevention of thrombosis Fish oil appears to act by modulation of pro-inflammatory and prothrombotic eicosanoid (prostaglandin, thromboxane and leukotriene) production reduction in interleukin-1 and other cytokines
Fish Oil
US systemic review (2004) found that the strongest and most consistent effect of omega-3 fatty acids is on lowering triglycerides. In general, LDL cholesterol and HDL cholesterol were found to rise to a small extent. A meta-analysis (2002) of 11 RCTs that compared dietary or non-dietary intake of n-3 fatty acids with placebo in patients with CHD found that intake of n-3 fatty acids reduces mortality due to myocardial infarction and sudden death in patients with CHD. A large Japanese trial (2007) in 18 645 patients with a total cholesterol of 6.5 mmol/l or greater, randomised patients to receive either EPA 1.8 g daily with a statin or a statin control with a 5-year follow-up. There was a 19% relative reduction in major coronary events in the EPA group compared to the statin control group. The benefits were in addition to statin treatment.
Fish Oil Dose – not established, but doses of 1-2g/daily (combined EPA/DHA) may be adequate Use in pregnancy should be supervised because of the potential for vitamin A toxicity with excessive intake of fish oil Adverse effects - safety concern includes the potential to increase bleeding time. Intake of <3g/daily of EPA/DHA should not be a problem. Patients taking anticoagulant medications should inform their doctors if they are taking fish oil. Interactions – anticoagulants, gingko biloba and ginseng. May increase the risk of bleeding, use of fish oil should be medically supervised.
L-Carnitine
Carnitine is an amino acid derivative, L-carnitine is the naturally occurring carnitine Carnitine may be beneficial in patients with ischaemic heart disease, but only those who have low serum carnitine levels Orally administered L-carnitine (2 g daily) has been shown to improve symptoms of angina, and to reduce anginal attacks and glyceryl trinitrate consumption (1980). Carnitine supplementation (4 g daily) has also been reported to improve heart rate, arterial pressures, angina and lipid patterns in a controlled study of patients who had experienced a recent myocardial infarction (1992).
Overall
Preliminary studies (1979) have shown that l-carnitine may reduce blood cholesterol levels. Oral administration of lcarnitine (3–4 g daily) significantly reduced serum levels of total cholesterol or triglyceride or both, and increased those of high-density lipoprotein (HDL) cholesterol. No sufficient evidence to guarantee the safety of carnitine in pregnancy use Dose- not established, but doses of 1-6g have been used in studies Nausea, vomiting and diarrhea may occur in high doses Anticonvulsants, pivampicillin may increase excretion of carnitine
Antioxidants
Antioxidants offer protection against free radicals and prevent damage to vital biological structures such as lipid membranes, proteins and DNA. vitamin A (usually as beta-carotene), vitamins C and E are marketed as supplements having antioxidant activity. beta-carotene are found in most dark green, red or yellow fruits and vegetables. Epidemiological evidence suggests that low plasma levels of antioxidant nutrients and low dietary intakes are related to an increased risk of coronary heart disease (CHD).
Clinical efficacy
One systematic review assessed whether antioxidants in food or supplements can offer primary prevention against myocardial infarction or stroke. Eight RCTs were included, six of which tested supplements of beta-carotene and two on ascorbic acid. None of the RCTs showed any benefit of antioxidant supplementation on CVD. A large trial (2002) involving 20 536 UK adults aged 40–80 with coronary disease, other occlusive arterial disease or diabetes, randomly allocated participants to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene daily) or matching placebo over 5 years. There were no significant differences in all-cause mortality, or in deaths due to vascular or non-vascular causes. In 2004, the American Heart Association Council on Nutrition, Physical Activity and Metabolism concluded that antioxidant supplements have little or no proven value for preventing or treating CVD.
Folic Acid
Folic acid is a water-soluble vitamin Marginal folate status is also associated with elevated plasma homocysteine levels, a known risk factor for CVD mortality. Current studies support a link between homocysteine and atherosclerosis. However, there has not been a definite link between reduction of homocysteine level ands and prevention or resolution of coronary artery disease. Dose- as a dietary supplement, oral, 100– 500 μg daily
Role of Pharmacists
able to assess an individual’s risk of nutrient deficiency and need for further referral must not give the impression that any dietary supplement is efficacious when there is no evidence for such efficacy There is a need to be aware of the potential for adverse effects with supplements and drugs interactions Help patient in making informed decision
References
Goodnight SH Jr, Harris WS, Connor WE, Illingworth DR. Polyunsaturated fatty acids, hyperlipidaemia and thrombosis. Arteriosclerosis 1982; 2: 87–113. Bucher HC, Hengstler P, Schindler C, et al. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med 2002; 112: 298–304 Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised openlabel, blinded endpoint analysis. Lancet 2007 369: 1090–1098 Food and Drug Administration Final Rule. Substances affirmed as generally recognized as safe: menhaden oil. Fed Reg 1997; 62: 30750–30757 Kamikawa T, Suzuki Y, Kobayashi A, et al. Effects of l-carnitine on exercise tolerance in patients with stable angina pectoris. Jpn Heart J 1984; 25: 587–597
References
Davini P, Bigalli A, Lamanna F, et al. Controlled study on l-carnitine therapeutic efficacy in post-infarction. Drugs Exp Clin Res 1992 Kris-Etherton PM, Lichtenstein AH, Howard BV, et al. Antioxidant vitamin supplements and cardiovascular disease. Circulation 2004; 110: 637–641. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 23–33. Gaytan RJ, Michael PL. Oral nutritional supplements and heart disease: a review. American Journal of Therapeutics 8, 255-274. Wald DS, Wald NJ, Morris JK, Law M. Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. BMJ 2006; 333: 1114–1117 Dietary supplements database, medicines complete.
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