Vitamins, Minerals, and Supplements

 for Heart Disease Prevention & Treatment

Folic acid, vitamin D, vitamin K, and magnesium look good, but vitamins C and E don't seem that helpful.  Vitamin A supplements are a very bad idea in view of a 30% increase in the death rate in seven recent, large studies.  I like melatonin and taurine, but the research is primarily animal research to date.  Carnitine, coenxyme Q10, and arginine are covered under treatment, but carnitine and CoQ10, both mitochondrial factors, probably have preventive value.  Policosanol is probably the single most useful supplement for preventing heart disease, but it has it's own page under cholesterol.  Of course, fish oil or fish and a good diet are very important and have their own pages.

Multivitamin-Mineral, and Vitamins C and E No Health Value Heart or Stroke: In a U.S. study of 83,639 physicians with 5.5 years of follow-up, there was no difference linked to self-medication: Vitamin E had a RR 0.90, vitamin C RR 0.86, and multivitamins RR 1.04. Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality. Muntwyler J, Hennekens CH, et al. Arch Intern Med 2002 Jul 8;162(13):1472-6

L-Arginine Might Help Heart Attacks a Little: L-arginine is a substrate for nitric oxide synthesis in vascular endothelial cells, NO bioavailability is decreased during myocardial infarction (MI). In a 30-day DB PC study of 792 patients with heart attacks within 24 hours, oral L-arginine (3.0 g t.i.d for 30 days) had a composite of 30 day cardiovascular death, reinfarction, successful resuscitation, shock/pulmonary edema or recurrent myocardial ischemia in 24% patients treated with L-arginine and 27% with placebo (OR 0.63, p=0.06). The end point was observed less frequently in 226 patients with hyperlipidemia (19 vs 31, p<0.05). No serious adverse effects were observed during L-arginine supplementation. Efficacy and safety of oral l-arginine in acute myocardial infarction. Results of multicenter, randomized, double-blind, placebo-controlled ARAMI pilot trial. Bednarz B, Jaxa-Chamiec T, et al. Grochowski Hospital, Warsaw. Kardiol Pol. 2005 May;62(5):421-427.

Anti-Oxidant Vitamins Not Good with Simvastin-Niacin: 160 cardiac patients in a DB PC study with 4 cells found simvastin-niacin had a decrease in LDL of 47%, an increased HDL of 26% and a 3% regression in vascular defects. Anti-oxidants had no effect on LDL-HDL and caused only slightly less progression than placebo and may have interfered with simvastin-niacin. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. Brown BG, Zhao XQ, et al. N Engl J Med 2001 Nov 29;345(22):1583-92

Beta-Carotene Lower Heart Attack Risk in Elderly: Vitamin E is commonly found helpful in studies with middle aged. The Rotterdam study of 4802 adults ages 55-95 found no association with Vitamin C or B but those in the highest third of beta-carotene had a relative risk of heart attack of RR .55 vs. lowest third. Klipstein-Grobusch, Am J Clin Nutr 69:261-6, 2/99. Ed: Unfortunately, other research suggests slightly higher rates of death from beta-carotene supplements.  Carotenes in the diet are much better than from supplements.

Carotenoids and Tocopherols Didn’t Help: Harvard’s physician study with 13 years of follow-up studied 534 who had suffered heart attacks and compared them to matched controls. Blood levels of 5 major carotenoids (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene), retinol, and alpha- and gamma-tocopherol were not protective. Plasma carotenoids and tocopherols and risk of myocardial infarction in a low-risk population of US male physicians. Hak AE, Stampfer MJ, Campos H, Sesso HD, Gaziano JM, Willett W, Ma J. Circulation. 2003 Aug 19;108(7):802-7. 

B-1 Thiamine Helped Congestive Heart Failure: In a DB PC 1 week study of CHF patients on furosemide diuretic, thiamine 200 mg IM decreased erythrocyte thiamine pyrophosphate effect and increased left ventricular ejection fraction. In another 6 weeks of open treated of all 30 patients, the LVEF increased 22% with increased diuresis and sodium excretion. Israel. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Shimon I, Almog S, et al.  Am J Med. 1995 May;98(5):485-90 

Folic acid & B-6 Help: ’98 279:359-64 

Folic & B-6 Help in DB: 250 mg B-6 and 5 mg folate per day in 158 patients in DB placebo 2 yr study found lower homocysteine levels and EKG abnormalities. E G J Vermeulen Lancet 2000 Feb. 12; 355: 517-22

Folate and B-12, Not B-6 Reduced Homocysteine: In a 1-year DB PC study of 185 elderly with ischemic vascular disease, 3 active treatments: folic acid (2.5 mg) plus vitamin B-12 (500 mug), vitamin B-6 (25 mg), and riboflavin (25 mg) were tried. Plasma homocysteine was reduced by the folic acid plus vitamin B-12 but was not associated with statistically significant beneficial effects on cognitive function over the short or medium term. Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease. Stott DJ et al. Am  Clin Nutr 2005 Dec;82(6):1320-1326.

B-6, B-12, Folate Not Help Stroke, Heart: In a 2 year DB PC study of 3068 stroke victims given high dose (25 mg, 0.4 mg, 2.5 mg respectively) or low dose (0.2 mg, 0.006 mg, 0.02 mg), there was no difference what so ever in strokes, heart attacks, or death during follow-up although there was a moderate decrease (2 micromol/L) in homocysteine. The study did find a more major decrease (3 micromol/L) in homocysteine was linked to decrease health risks. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. Toole JF, Malinow MR, et al. JAMA. 2004 Feb 4;291(5):565-75

B6 Helps: In a study of 769 adults ages 45-64, B6 intake was associated with a 70% lower risk of heart disease. Circ 3:204-10;’98 Circ 2/10/98 European study low B6 doubled heart disease and stroke in individuals with normal homocysteine; JAMA 2/4/98 reported that at least 360 micrograms of folate and 3.2 mg B6/day in the diet had the lowest risks heart disease in the Nurses Health Study of 80,000 nurses in 14 year follow-up. Ed: This doesn't mean that B6 supplements are a good idea.  Indeed, one study found worse results with high dose supplements.

Folate & B-12 Levels Not Related to CHD or CVD: 29 yr f/u of 2950 men and women found no relation. Busselton, Australia study. only 3.1% of the population having a reduced folate and 0.4% having a reduced B-12 concentration based on the normal reference intervals for red cell folate (115-600 µg/l) and serum B-12 (160-850 ng/l). Folate and vitamin B-12 and risk of fatal cardiovascular disease: cohort study from Busselton, Western Australia Joseph Hung, John P Beilby, Matthew W Knuiman, Mark Divitin, BMJ 2003;326:131 ( 18 January )

Folate Dietary Intake Linked to Lower Heart Disease: US Nurses' health study and the Kuopio ischaemic heart disease risk factor study of Finnish men found a significant inverse association between dietary folate intake and coronary heart disease events over 14 and 10 years respectively. However, these results need to be interpreted with caution as a high folate intake from food and vitamin supplements may also be related to other dietary factors or unmeasured risk behaviors that are independently associated with coronary heart disease. Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 1998; 279: 359-364; Voutilainen S, Rissanen TH, Virtanen J, Lakka TA, Salonen JT, Kuopio Ischemic Heart Disease Risk Factor Study Group. Low dietary folate intake is associated with an excess incidence of acute coronary events. Circulation 2001; 103: 2674-2680

Folic, B-6, & B-12 Combo Lowers Homocysteine: 126 men with mild increase homocysteine DB Fol-6-12 or added anti-ox vitamins or anti-ox alone or PC. Only Fol-6-12 lowered homocysteine and especially in men with 5,10-tetrahydrofolate reductase gene type. Woodside, U Belfast, Am J Clin Nutr 5/98;67:858

Melatonin: Heart Attack Victims Lower Nighttime Melatonin and Higher Interleukin-6: Atherosclerosis involves inflammatory cells, inflammatory proteins, and inflammatory responses from vascular cells. Cytokine activities are under neuroendocrine control, in part exerted by the pineal gland through the circadian secretion of its main product melatonin. In a study of 60 heart attack victims and 60 health adults, IL-6 was higher in the acute myocardial infarction group (101.26 vs. 52.67 pg/ml at 02:00 h,  and 41.93 vs. 22.98 pg/ml at 09:00 h, p < 0.05). Nighttime melatonin levels were high in the healthy adults (48.19 at 02:00 h, 14.51 at 09:00 h, pg/ml) vs. (25.97 at 02:00 h, 12.29 at 09:00 h, pg/ml) (p < 0.05). Melatonin seems to have an anti-inflammatory effect. Light/dark patterns of interleukin-6 in relation to the pineal hormone melatonin in patients with acute myocardial infarction. Dominguez-Rodriguez A, Abreu-Gonzalez P, et al. Hospital Universitario de Canarias, Spain. Cytokine. 2004 Apr 21;26(2):89-93; Similar melatonin findings were reported in an earlier study. Yaprak M, Altun A, et al. Int J Cardiol. 2003 May;89(1):103-7.

Melatonin: Heart Failure Victims Low in Melatonin: Urinary 6-sulfatoxymelatonin was much lower in 33 hospitalized patients with CHF than in 146 healthy volunteers (2.6 vs. 6.0 mcg; p<.0001). There were no significant differences in urinary 6-sulfatoxymelatonin levels between chronic and acute CHF patients. Such a decrease may precede aggravation of heart failure. Low urinary 6-sulfatoxymelatonin levels in patients with severe congestive heart failure. Girotti L, Lago M, et al. Buenos Aires, Argentina. Endocrine. 2003 Dec;22(3):245-8

Melatonin: Protected Heart Against Cancer Drugs' Damage: Effect of melatonin on the cardiotoxicity of doxorubicin. Balli E, et al. Histol Histopathol. 2004 Oct;19(4):1101-8. Melatonin protects the heart against ischaemia-reperfusion injury and also against cardiotoxic effects of adriamycin and alloxan. Lack of melatonin was repeatedly reported in patients with coronary heart disease. Intake of this hormone leads to decrease of blood pressure in normotensive and hypertensive subjects, while pinealectomy induces hypertension. Vazan R, Beder I, Styk J. Cesk Fysiol. 2004;53(1):29-33; Similar, earlier report on adriamycin by Kocak, et al. Turkey. Can J Cardiol. 2003 Apr;19(5):535-41.

Melatonin Prolongs Cardiac Transplant Survival in Rats: Jung FJ, et al. University Hospital Zurich, Zurich, Switzerland J Pineal Res. 2004 Aug;37(1):36-41

Melatonin: Protects Mice Against Myocardial Infarction. Either pretreatment or at time of induced heart attack. Chen Z, et al. East Tennessee State University. Am J Physiol Heart Circ Physiol. 2003 May;284(5):H1618-24.

Melatonin Reverses Urinary System and Aorta Damage in the rat due to Chronic Nicotine administration. Sener G, et al. Marmara University, Istanbul, Turkey. J Pharm Pharmacol. 2004 Mar;56(3):359-66

Melatonin Better than Lipoic Acid, Vitamins C and E, and Fish Oil for MDA and Homocysteine: Malondialdehyde (MDA) levels decreased in melatonin (p <0.01), lipoic acid (p <0.01), and vitamin E (p <0.05) groups but not significantly with vitamin C and VC6OP (p >0.05) and fish oil supplementation caused an insignificant increase in rats. Plasma lipid levels in animals treated with melatonin, vitamin E, vitamin C, lipoic acid, and fish oil were significantly lower than  controls; melatonin and fish oil significantly lowered homocysteine levels. Firat Univ. Turkey. Arch Med Res. 2002 Nov-Dec;33(6):515-9.

Melatonin: Protects Against Myocardial Injury of Isoproterenol in Rats: Acikel M, et al. Ataturk University. J Pineal Res. 2003 Sep;35(2):75-9

Taurine Inversely Associated with Coronary Heart Death: Taurine supplementation reduced the risk of hypertension and stroke in stroke-prone spontaneously hypertensive rats (SHRSP). The WHO-CARDIAC (Cardiovascular Diseases Alimentary Comparison) study found wide differences in 24-h urinary taurine excretion, which were inversely associated with age-adjusted mortality rates of coronary heart diseases (CHD). Hypercholesterolemia as well as arterial fat deposition related to the cause of CHD was attenuated by dietary taurine supplementation in SHRSP on high-fat cholesterol diet. Taurine affected the gene expression of 7alpha-hydroxylase and thus regulated serum cholesterol level through the control of the rate limiting step of cholesterol excretion into bile acids. Taurine attenuated atherogenesis due to the control of oxidative stress through the inhibition of the production of oxidative LDL and to its scavenger effect on hypochlorous acid (HOCl) from leucocytes and macrophages. FISH and LIFESTYLE-RELATED DISEASE PREVENTION: EXPERIMENTAL AND EPIDEMIOLOGICAL EVIDENCE FOR ANTI-ATHEROGENIC POTENTIAL OF TAURINE. Yamori Y, Murakami S, et al. Mukogawa Women's University, Nishinomiya, Japan. Clin Exp Pharmacol Physiol. 2004 Dec;31 Suppl 2:S20-3

Taurine Protects Rat Aorta From High Cholesterol-Fat Diet: Taurine reduced aortic lesions in rats fed high fat diets. Rats depend on taurine for conjugation of bile acids. Sethupathy S, et al, Annamalai University, India. Indian J Exp Biol. 2002 Oct;40(10):1169-72

Taurine Improved Cardiovascular Function in Iron-Overload Mice: Iron overload increases oxidative stress and cardiovascular death rates. Taurine accounts for 25% to 50% of the amino acid pool in myocardium, possesses antioxidant properties, and can inhibit L-type Ca2+ channels. Oudit GY, et al, University of Toronto. Circulation. 2004 Apr 20;109(15):1877-85.

Te:Dog Taurine Deficiency Causing Heart Disease: 12 dogs are reported suffering from dilated cardiomyopathy. All had low taurine blood levels and all were on lamb and rice diets. They were treated successfully with taurine. Fascetti AJ et al. UC Davis. J Am Vet Med Assoc. 2003 Oct 15;223(8):1137-41

Taurine Protects Rat Heart From Hyperhomocysteinemia Damage:  Myocardial mitochondria dysfunction in the rats with hyperhomocysteinemia induced by diet methionine loading, Taurine antagonized the oxidative stress injury in the myocardial mitochondria induced by the hyperhomocysteinemia. Chang L, et al, Beijing University, Beijing, China. Amino Acids. 2004 Aug;27(1):37-48 

Taurine Protects Rabbits from High Cholesterol Diet: The extent of atherosclerotic lesions in the aorta was less in the taurine-treated regressed group than in the non-treated regressed group. Balkan J, et al, Istanbul University, Turkey. Biosci Biotechnol Biochem. 2004 May;68(5):1035-9. 

Taurine Protects Against Enlargement by Blocking Antiotensin II Effects: Taurine has anti-angiotensin II and osmoregulatory activity. When the intracellular content of taurine is dramatically reduced, the heart develops contractile defects and undergoes an eccentric form of hypertrophy. Excessive heart enlargement is due to angiotensin II, whose growth properties are antagonized by taurine Schaffer S, et al. University of South Alabama. J Cardiovasc Pharmacol. 2003 May;41(5):751-

Taurine Protects Animal Heart Against Isoproterenol-induced Injury: Shi YR, et al. Acta Pharmacol Sin. 2002 Oct;23(10):910-8

Vitamin C Might Help: Brit Med J ’97, 314:634-8

Vitamin D: Heart Deaths Lowered in Elderly Women by Vitamin D Supplements: The University of California at San Francisco studied 9,704 women aged 65 and older. Of these, 4,272 were taking vitamin D supplements. Over a period of nearly 11 years, 420 of the women died of coronary heart disease (CHD). Women who used vitamin D supplements had a 31% lower risk of heart disease death. Women with osteoporosis, a disease caused by loss of calcium from the bones, are more likely to die of CHD. BBC News 4/29/02

Vitamin D: Heart Failure Patients Had Lower Vitamin D Levels: Comparing 54 patients with chronic heart failure with 34 healthy people, researchers found that vitamin D levels were up to 50% lower in the blood of CHF patients. BBC News 2/18/03 and Journal of the American College of Cardiology. U Bonn

Vitamins D Plus K Appeared Better Than D Alone: In a DB PC 181-patient study, those on a mineral plus D plus vitamin K did best. Univ. Maastricht, Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study. Thromb Haemost. 2004 Feb;91(2):373-80 

Vitamin E Didn't Help Cancer or Heart in Huge 7-Year Study: In the very large DB PC HOPE study of 9541 adults over age 54 with vascular disease or diabetes, 3994 agreed to continue in HOPE-TOO for a total of 7 years taking vitamin E 400 IU/d or placebo. There were no significant differences for cancer (vitamin E 11.6% vs. placebo 12.3%), cancer deaths (156 vs. 176), or major cardiovascular events, 1022 (21.5%) vs 985 (20.6%). Patients in the vitamin E group had a slightly higher risk of heart failure (RR, 1.13; P = .03). Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. Lonn E, Bosch J, et al. McMaster University, Hamilton, Ontario. JAMA. 2005 Mar 16;293(11):1338-47.

Vitamin E May Help: Although 400 units per day in DB Canadian study of 9500 showed no benefit, report that 1200 units per day reduces C-reactive protein, a marker for inflammation, caused researchers to urge higher dose for those at risk, e.g. diabetics. May also help other inflammatory diseases such as rheumatoid arthritis, and ulcerative colitis. Oct/00 Free Radical Biology & Medicine.

Vitamin E Works in CHAOS Study: Although the initial report found only a decrease in non-fatal MIs in patients on Vit E, after careful follow-up it was found that the large majority of heart attacks in the Vit E group occurred to those non-compliance with their meds. Lancet 1/30/99 

Vitamin K Associated with Fewer Heart Deaths: Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. In 4807 adults with no history of heart attacks followed for 10 years, after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors, the relative risk (RR) of coronary heart disease mortality was reduced in the mid and upper thirds of dietary vitamin K-2 compared to the lower third [RR = 0.73 and 0.43]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 and 0.74] and severe aortic calcification [odds ratio of 0.71 and 0.48]. Phylloquinone intake was not related to any of the outcomes. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the rotterdam study. Geleijnse JM, Vermeer C, et al., Erasmus Medical Center Rotterdam, The Netherlands; J Nutr. 2004 Nov;134(11):3100-5. Ed: K(1) intake is small as is K(2). A 500 mcg K(1) supplement is 6 times with normal K(1) intake and, by biological conversion, will increase K(2). It is very likely that increase will place the individual in the upper third. 

Minerals

Calcium & Magnesium in Hard Water Protects: Swedish study women in 16 towns dying ‘82-93 between 50-69yo. Higher levels of magnesium and calcium consumed by women at lower risk. Several similar earlier studies. Epidemiol, 1998.

Magnesium: Coronary Heart Disease Decreased in Health Professionals by Magnesium: In the Harvard 39,000 male health professional study during 12 years of follow-up, there were 1,021 non-fatal heart attacks, and 428 fatal ones. The age-adjusted relative risk (RR) of developing CHD in the highest quintile (median intake = 457 mg/day) compared with the lowest quintile (intake = 269 mg/day) was 0.73 (p <0.0001). After controlling for standard CHD risk factors and dietary factors, the RR was 0.82 (p = 0.08). For supplemental magnesium intake, the RR comparing the highest quintile to non-supplement users was 0.77. Magnesium intake and risk of coronary heart disease among men. Al-Delaimy WK, Rimm EB, Willett WC, Stampfer MJ, Hu FB. J Am Coll Nutr. 2004 Feb;23(1):63-70 

Zinc Deficiency Linked to DM, Heart Disease: 3575 in India. Those consuming less than 7 mg/d increased risk. Zn involved with insulin synthesis and secretion. Zinc is found in whole grains and meats, fish, and eggs. J Am Coll Nutr, 1998.