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Nutritional and Vitamin Supplements: Do They Prevent Coronary Artery Disease?

By Craig William Raphael, MS5 & Darcy Green Conaway, MD

Abstract

This article will review background information and data supporting the use of fish oil, folic acid, coenzyme Q, and vitamins C, D, and E in the prevention and/or treatment of coronary artery disease.

Introduction

Numerous nutritional or vitamin supplements have been proposed as having beneficial effects on reducing coronary artery disease. This article will review background information and data supporting the use of fish oil, folic acid, coenzyme Q, and vitamins C, D, and E in the prevention and/or treatment of coronary artery disease (CAD).

Fish Oil

In 1969, it was observed that the Greenland Inuit and Okinawa Islanders had low risks of death from coronary artery disease (CAD) and it was postulated that their lowered risk was related to the abundant fish in their diet.^1,2 This finding stimulated research into whether fish oils could be used to prevent CAD.

Fish oils are rich sources of long chain fatty acids called “essential” fatty acids that can only be obtained through diet or supplementation. Fish oils are interchangeably referred to as omega-3 fatty acids or n-3 polyunsaturated fatty acids (n-3 PUFAs). Three important n-3 PUFAs include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha linoleic acid (ALA).³ EPA and DHA are synthesized by fresh water algae. Fish consume the algae, and man subsequently consumes fish as part of the food chain.^3,4 ALA is not obtained from fish, but is found in flaxseed, walnuts, and other tree nuts.⁴ Humans convert ingested ALA to EPA and DHA, but the enzymatic pathways cannot produce enough EPA and DHA to sustain good health.²

When taken as supplements, EPA and DHA may reduce heart failure, whereas evidence regarding ALA is substantially weaker.⁴ It is proposed that low dose of n-3PUFAs ( 0.5-1g/day) decreases  the incidence of sudden cardiac death.⁴  At higher doses (3-4g/day), n-3PUFAs can reduce triglyceride synthesis in the liver.^3,4  Fish oils possess antiatherosclerotic, antiarrhythmic, and antithrombotic effects.^1,4 The n-3 PUFAs incorporate within atherosclerotic plaques and stabilize plaque morphology, manifested histologically by reduced macrophages and foam cells. The n-3 PUFAs competitively inhibit arachidonic acid, decreasing synthesis of classical pro-inflammatory eicosanoids. They also suppress the pro-inflammatory cytokines IL-6, IL-1b, and TNFa.^1,3,4,5 In addition, n-3 PUFAs stimulate synthesis of other eicosanoids called E-series and D-series resolvins that suppress pro-inflammatory effects of activated neutrophils, macrophages, dendritic cells and T cells.^1,4,5 These anti-inflammatory effects may collectively suppress the development of CAD.

The sudden cardiac death that follows a myocardial infarction (MI) or heart surgery may involve generation of ventricular arrhythmias. The n-3 PUFAs exert several antiarrhythmic properties, including profound inhibition of sodium channels, and modulation of potassium channels, L-type calcium channels, sodium calcium exchanger proteins, and calcium handling proteins.¹ The net effect is a shift in electrical potential across cell membranes, reducing the generation of action potentials.¹ With acute injury, cardiomyocytes partially depolarize and lower this threshold for generating action potentials and arrhythmias. By producing a voltage dependent shift towards membrane hyperpolarization, fish oils inhibit the generation of arrhythmogenic action potentials.²  In a study of patients undergoing coronary artery surgery, post operative atrial fibrillation occurred in 33.3% of placebo-treated patients, but in only 15.2% of patients pre-treated with EPA and DHA.⁴ However, Kowey et al. treated 663 patients with paroxysmal atrial fibrillation or persistent atrial fibrillation with high dose (4g/day) EPA/DHA for six months and found no reduction in the subsequent development of symptomatic atrial fibrillation.⁶

In terms of anti-thrombotic effect, n-3 PUFAs reduce synthesis of thromboxane A2, decreasing the ability of platelets to aggregate and form blood clots.¹ In addition, n-3 PUFAs produce a modest reduction in blood pressure through increased synthesis of the vasodilator nitric oxide.¹  Several randomized clinical trials have demonstrated benefits of fish oil on CAD. The Diet and Reinfarction Trial (DART) in 1989 examined the cardiovascular (CV) benefit of supplementing the diet with fish twice a week in post-MI patients. Adding fish to the diet resulted in a 29% reduction in CV-related mortality.^1,3,4 The GISSI-Prevenzione trial in 1999 monitored CV events (MI, unstable angina, sudden cardiac death, cardiac intervention, and/or stroke) in patients treated with 1 g/day of n-3PUFAs. After 3.5 years, there was a 45% reduction in sudden death and a 20% reduction in all-cause mortality.³ In another large study, the Japan EPA Lipid Intervention Study (JELIS), patients with hypercholesterolemia with or without pre-existing CAD decreased their risk of major CV events by 18% after taking 1.8 g of EPA daily.^1,4 In contrast, Rauch et al. in 2010 treated 3551 post-MI patients with 1g/day of n-3 PUFAs plus state-of-the-art post-MI medical therapy for one year. Fish oil supplementation added no benefit regarding sudden cardiac death compared to standard post-MI treatment alone.⁷ In a similar trial of 4,837 post-MI patients treated with low dose fish oil for 40 months, Kromhout et al. found no benefit from adding fish oil to standard post-MI treatment.⁸ 

Although results from clinical trials on fish oil supplementation have been controversial regarding prevention of CAD, the American Heart Association recommends  consuming 1 serving of fatty fish or 1g of EPA/DHA-containing supplements twice a week for good cardiovascular health. For hypertriglyceridemia, 4g/day is currently recommended.³

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