ATHEROSCLEROSIS

 ASTAXANTHIN

1. Daily doses of astaxanthin (1.8, 3.6,14.4 and 21.6 mg /day) for 14 days slowed LDL oxidation and therefore may be effective in preventing atherosclerosis.

J Atheroscler Thromb. 2000;7(4):216-22. 
Inhibition of low-density lipoprotein oxidation by astaxanthin.
Iwamoto T, Hosoda K, Hirano R, Kurata H, Matsumoto A, Miki W, Kamiyama M,Itakura H, Yamamoto S, Kondo K.

BORON

2. This study suggests that supplementing the diet with boron (10 mg/day) may help prevent atherosclerosis.

Biol Trace Elem Res. 1997 Mar;56(3):273-86. 
The effect of boron supplementation on its urinary excretion and selected cardiovascular risk factors in healthy male subjects.
Naghii MR, Samman S.
PMID: 9197924

COPPER
Animal Study

3. Rabbits were fed a low copper, high cholesterol diet and given copper (either 0, 1, 3 or 20 mg/day). Rabbits receiving 1 or 3 mg copper/day had fewer aortic lesions and therefore lower risk of developing atherosclerosis.

Int J Exp Pathol. 2001 Oct;82(5):287-94. 
Biphasic modulation of atherosclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit.
Lamb DJ, Avades TY, Ferns GA.
PMID: 11703538

Animal Study
4. A diet containing either dose of copper (12 and 0.3 mg per 100 grams/diet) fed to high cholesterol rabbits resulted in fewer aortic lesions and therefore a reduced risk for developing atherosclerosis.

Atherosclerosis. 2002 Oct;164(2):229-36. 
Effect of dietary copper supplementation on cell composition and apoptosis in atherosclerotic lesions of cholesterol-fed rabbits.
Lamb DJ, Avades TY, Allen MD, Anwar K, Kass GE, Ferns GA.
PMID: 12204792

FOLIC ACID

5. Compared to placebo, supplementation with folic acid (5 mg/day) and vitamin B6 (250 mg/day) for 2 years resulted in fewer abnormal results on electrocardiogram testing and thus a lower risk for atherosclerosis in adults.

Lancet. 2000 Feb 12;355(9203):517-22. 
Comment in:
    Lancet. 2000 Feb 12;355(9203):511-2.
    Lancet. 2000 Jun 24;355(9222):2249; discussion 2250.
Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial.
Vermeulen EG, Stehouwer CD, Twisk JW, van den Berg M, de Jong SC, Mackaay AJ, van Campen CM, Visser FC, Jakobs CA, Bulterjis EJ, Rauwerda JA.
PMID: 10683000

6. Compared to placebo, supplementation with folic acid (5 mg/day) for 4 weeks improved endothelium-dependent vasodilation, reducing the risk of atherosclerosis in patients with high cholesterol.

Circulation. 1999 Jul 27;100(4):335-8. 
Comment in:
    Circulation. 2000 Sep 12;102(11):E92.
Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. A randomized placebo-controlled trial.
Verhaar MC, Wever RM, Kastelein JJ, van Loon D, Milstien S, Koomans HA, Rabelink TJ.
PMID: 10421591

GREEN TEA
(1 gram = 1000 milligrams)

Animal Study

7. Administration of green tea extract (0.8 grams per liter) for 14 weeks reduced lipid peroxide levels in mice being fed an atherosclerosis-inducing diet, suggesting that the green tea helps to prevent the development of atherosclerosis.

J Nutr 2001 Jan;131(1):27-32
Tea catechins Prevent the Development of Atherosclerosis in Apoprotein E-Deficient Mice.
Miura Y, Chiba T, Tomita I, Koizumi H, Miura S, Umegaki K, Hara Y, Ikeda M,

LYCOPENE

8. Daily intake of tomato juice (160 grams of tomato juice = 14 mg lycopene), or (480 grams of tomato juice = 45 mg lycopene) during 1 menstrual cycle decreased LDL, and increased in beta carotene thus lowering risk of atherosclerosis in Japanese women.

J Nutr Sci Vitaminol (Tokyo). 2001 Jun;47(3):213-21. 
Effects of tomato juice consumption on plasma and lipoprotein carotenoid concentrations and the susceptibility of low density lipoprotein to oxidative modification.
Maruyama C, Imamura K, Oshima S, Suzukawa M, Egami S, Tonomoto M, Baba N, Harada M, Ayaori M, Inakuma T, Ishikawa T.

MAGNESIUM
(1 micromolecule = one-thousandth of a gram-molecule)

9. Compared to placebo, daily supplementation with magnesium (15 micromole/day) decreased triglyceride and LDL levels while HDL cholesterol levels increased in patients with ischemic heart disease thus concluding that magnesium deficiency may lead to ischemic heart disease and atherosclerosis.

Arch Intern Med. 1989 May;149(5):1050-3. 
Influence of magnesium substitution therapy on blood lipid composition in patients with ischemic heart disease. A double-blind, placebo controlled study.
Rasmussen HS, Aurup P, Goldstein K, McNair P, Mortensen PB, Larsen OG, Lawaetz H.
PMID: 2719498

MILK THISTLE/SILIBININ

Cell Study

10. Application of silibinin (50-200 micromoles per liter) to smooth muscle cells delayed the progress of LDL autooxidation, which may have implications in the treatment and prevention of atherosclerosis.

Arzneimittelforschung. 1998 Mar;48(3):236-9. 
Inhibitory action of silibinin on low density lipoprotein oxidation.
Locher R, Suter PM, Weyhenmeyer R, Vetter W.

NARINGIN

Animal Study

11. Diets supplemented with naringin (0.1% of their diet) or naringenin (0.05% of their diet) for 8 weeks lowered liver cholesterol levels and the number of areas in the aorta with fatty streaks in high cholesterol rabbits.

Biochem Biophys Res Commun. 2001 Jun 15;284(3):681-8. 
Anti-atherogenic effect of citrus flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP-1 in high cholesterol-fed rabbits.
Lee CH, Jeong TS, Choi YK, Hyun BH, Oh GT, Kim EH, Kim JR, Han JI, Bok SH.

trimethylglycine (TMG) BETAINE
(1 gram = 1000 milligrams)

Animal Study

12. Rats were given TMG betaine (1.5 grams per kilogram body weight) which effectively transformed cholesterol into bile for excretion. This action may be effective against atherosclerosis.

Biull Eksp Biol Med. 1987 Jul;104(7):30-2.  

[Cholagogic effect of trimethylglycine in normal animals of different ages and in experimental atherosclerosis]

[Article in Russian]

Zapadniuk VI, Panteleimonova TN.

Animal Study

13. Rabbits with atherosclerosis were given TMG betaine (1.5 grams per kilogram body weight) for 30 days, which prevented a decrease of nicotinamide coenzymes and adenine nucleotides in the heart and liver. This action may be effective against atherosclerosis.

Farmakol Toksikol. 1986 Jul-Aug;49(4):71-3.  

[Corrective effect of trimethylglycine on the nicotinamide coenzyme and adenine nucleotide content of the tissues in experimental atherosclerosis]

[Article in Russian]

Zapadniuk VI, Chekman IS, Panteleimonova TN, Tumanov VA.

Animal Study

14. Rabbits with atherosclerosis were given TMG betaine (0.5 grams per kilogram body weight), which reduced elevated cholesterol, lipids and total liver cholesterol and triglycerides.

Farmakol Toksikol. 1983 Jul-Aug;46(4):83-5. 

[Effect of trimethylglycine on lipid metabolism in experimental atherosclerosis in rabbits]

[Article in Russian]

Panteleimonova TN, Zapadniuk VI.

VITAMIN B6/PYRIDOXINE

Animal Study

15. Doses of pyridoxine (8 mg per kilogram body weight) caused total fat and lipid levels to return to normal in rats that were exposed to carbon disulfide for 90 days. Thus, pyridoxine could prevent atherosclerotic lesions in carbon disulfide poisoning.

Vopr Pitan. 1985 Sep-Oct;(5):43-5. 
[Action of pyridoxine   on lipid metabolism in carbon disulfide-poisoned rats]
[Article in Russian]
Petrova S.
PMID: 4082520

Animal Study

16. Compared to placebo, doses of pyridoxine (3.2 mg per kilogram body weight) inhibited the development of atherosclerosis in rabbits.

Vopr Pitan. 1979 Jan-Feb;(1):26-32. 
[Action of biotin-pyridoxine   complex on the development of experimental atherosclerosis]
[Article in Russian]
Borets VM, Kishkovich VP, Lis MA, Butkevich ND, Mironchik VV.
PMID: 419724

VITAMIN B12/COBALAMIN

17. Compared to placebo, daily doses of folic acid (5 mg), vitamin B6 (50 mg), and vitamin B12 (0.4 mg), for 6 months reduced homocysteine levels in patients with hyperhomocysteinemia and improved the measures for predicting atherosclerosis.

Transplantation. 2003 May 15;75(9):1551-5. 
Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients.
Marcucci R, Zanazzi M, Bertoni E, Rosati A, Fedi S, Lenti M, Prisco D, Castellani S, Abbate R, Salvadori M.
PMID: 12792513

VITAMIN C

18. Compared to placebo, daily doses of vitamin C (500 mg) and vitamin E, (400 IU) more effectively impeded the early development of atherosclerosis in heart transplant patients.

Lancet. 2002 Mar 30;359(9312):1108-13.
Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial.
Fang JC, Kinlay S, Beltrame J, Hikiti H, Wainstein M, Behrendt D, Suh J, Frei B, Mudge GH, Selwyn AP, Ganz P.

19. Compared to placebo, daily doses of slow release vitamin C (250 mg) and vitamin E, (136 IU) for 3 years more effectively slowed the development of atherosclerosis in men.

J Intern Med. 2000 Nov;248(5):377-86.
Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis.
Salonen JT, Nyyssonen K, Salonen R, Lakka HM, Kaikkonen J, Porkkala-Sarataho E, Voutilainen S, Lakka TA, Rissanen T, Leskinen L, Tuomainen TP, Valkonen VP, Ristonmaa U, Poulsen HE.

20. Oxidative stress has been shown to damage endothelial function and contribute to atherosclerosis. Patients were given a single dose of vitamin C (2000 mg) which improved flow mediated dilation of the artery. Patients given a long-term dose of vitamin C (500 mg/day) also showed improvement in endothelial function. Thus, long-term vitamin C supplementation may be beneficial to coronary artery disease patients.

Circulation. 1999 Jun 29;99(25):3234-40
Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease.
Gokce N, Keaney JF Jr, Frei B, Holbrook M, Olesiak M, Zachariah BJ, Leeuwenburgh C, Heinecke JW, Vita JA

21. A dose of ascorbic acid (1000 mg) increased fibrinolytic activity (dissolving fibrin and removing blood clots) in patients with cardiovascular disease. When patients were given ascorbic acid with 100 g of fat, there was a 64% increase in fibrinolytic activity.

Atherosclerosis. 1978 Aug;30(4):351-4.
Acute effect of ascorbic acid on fibrinolytic activity.
Bordia A, Paliwal DK, Jain K, Kothari LK.

VITAMIN E/TOCOTRIENOL

Animal Study

22. Daily feeding of vitamin E (60 mg per kilogram body weight) for 10 weeks improved lipid levels and reduced lipid peroxidation in rabbits fed a high cholesterol diet.

Int J Food Sci Nutr. 2000;51 Suppl:S79-94. 
Vitamin E and factors affecting atherosclerosis in rabbits fed a cholesterol-rich diet.
Ismail NM, Abdul Ghafar N, Jaarin K, Khine JH, Top GM.
PMID: 11271860

23. Daily doses of vitamin E (600 IU) f or 6 weeks improved inflammatory responses of immune cells and may therefore be of benefit in the prevention of atherosclerosis in patients with high triglyceride levels.

Am J Clin Nutr.  2000 Feb;71(2):458-64. 
alpha-tocopherol supplementation decreases production of superoxide and cytokines by leukocytes ex vivo in both normolipidemic and hypertriglyceridemic individuals.
van Tits LJ, Demacker PN, de Graaf J, Hak-Lemmers HL, Stalenhoef AF.
PMID: 10648258

24. Platelet aggregation was optimal when subjects took 75 IU/day of vitamin E.

Atherosclerosis.  1999 Nov 1;147(1):177-85. 
Moderate supplementation with natural alpha-tocopherol decreases platelet aggregation and low-density lipoprotein oxidation.
Mabile L, Bruckdorfer KR, Rice-Evans C.
PMID: 10525139

Animal Study

25. Rabbits were fed a high cholesterol diet and some rabbits’ diets were supplemented with a combination of vitamin E (146 IU/day), vitamin C (791 mg/day) and selenium, (22 micrograms/day )or the drug probucol (406 mg/day). The results indicated that vitamin E and selenium were as effective as the drug probucol in inhibiting atherosclerosis.

Circ Res.  1998 Aug 24;83(4):366-77. 
Vitamin E combined with selenium inhibits atherosclerosis in hypercholesterolemic rabbits independently of effects on plasma cholesterol concentrations.
Schwenke DC, Behr SR.
PMID: 9721693

26. Daily doses of vitamin E (400 IU/day) reduces risk of coronary heart disease as it increases the lag time before LDL oxidation and therefore decreases the risk of atherosclerosis.

Biofactors.  1998;7(1-2):51-4. 
Effect of supplementation with vitamin E on LDL oxidizability and prevention of atherosclerosis.
Suzukawa M, Ayaori M, Shige H, Hisada T, Ishikawa T, Nakamura H.
PMID: 9523028

27. The development of coronary artery disease can be impaired with a minimum dose of 100 IU/day vitamin E.

J Am Diet Assoc.  1997 Jul;97(7 Suppl):S31-41. 
The effect of dietary fat, antioxidants, and pro-oxidants on blood lipids, lipoproteins, and atherosclerosis.
Kwiterovich PO Jr.
PMID: 9216565

28. Doses of vitamin E, (500 IU, 1000 IU or 1500 IU/day) all slowed the LDL oxidation rate. Doses of 500 IU and 1500 IU had the highest lag time before LDL oxidation with 500 IU/day being sufficient to reduce LDL oxidation

Aust N Z J Med.  1996 Aug;26(4):496-503. 
What dose of vitamin E is required to reduce susceptibility of LDL to oxidation?
Simons LA, Von Konigsmark M, Balasubramaniam S.
PMID: 8873932

29. Compared to placebo, daily doses of vitamin E (either 400 IU or 800 IU) significantly reduced risk of cardiovascular death and myocardial infarction in patients with atherosclerosis after one year of supplementation.

Lancet.  1996 Mar 23;347(9004):781-6. 
Comment in:
    ACP J Club. 1996 Jul-Aug;125(1):15.
    Lancet. 1996 Mar 23;347(9004):775.
    Lancet. 1996 Mar 23;347(9004):776-7.
    Lancet. 1997 Aug 30;350(9078):667-8.
    Lancet. 1999 Oct 30;354(9189):1554; author reply 1556-7.
    Lancet. 1999 Oct 30;354(9189):1555; author reply 1556-7.
Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS)
Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ.
PMID: 8622332

30. Atherosclerosis can be a complication related to diabetes. Doses of vitamin E (200 IU/day) can inhibit platelet adhesion.

Z Ernahrungswiss.  1993 Dec;32(4):243-61. 
Prevention of platelet dysfunction by vitamin E in diabetic atherosclerosis.
Gerster H.
PMID: 8128746

GREEN TEA
(1 microgram = 0.001 milligrams)

31. Administration of green tea polyphenols (40 – 50 micrograms per milliliter) slowed growth of atherosclerotic lesions, inhibiting atherosclerosis.

FASEB J. 2003 Apr;17(6):702-4. Epub 2003 Feb 05.
Green tea polyphenol epigallocatechin-3 gallate induces apoptosis of proliferating vascular smooth muscle cells via activation of p53.
Hofmann CS, Sonenshein GE.