Nutritional Ingredients to Prevent, Recover from Heart Attack, Stroke (Escaping from Ischemia)

In 2004, the Journal of Nutrition published the Proceedings of the Symposium on Arginine, which was supported in part by a grant from Ajinomoto USA Inc. “Arginine Metabolism: Enzymology, Nutrition and Clinical Significance” (134(10S)) covers the basics of arginine metabolism and its pathophysiology. A review out of the Boston University School of Medicine on L-arginine and atherothrombosis noted the amino acid has several mechanisms by which it improves endothelial function, preventing the earliest pathologic process of atherothrombosis and related infarction.¹⁵ These mechanisms include increased intracellular transport and levels of NO, an antioxidant effect, competitive antagonism of asymmetric dimethylarginine (an inhibitor of NO), and altered intracellular signaling. Additional insights from a review out of Brigham & Women’s Hospital included L-arginine’s ability to help treat coronary artery disease and peripheral artery disease, and regulation of vascular tone.¹⁶

Animal trials have shown L-arginine protects the heart in models of MI, helping balance energy demands,¹⁷ and preventing myocardial and endothelial dysfunction.¹⁸ In a human study out of Grochowski Hospital, Warsaw, Poland, 792 men with MI, admitted within 24 hours after onset of symptoms, received oral L-arginine or placebo for 30 days.¹⁹ Supplementation was well tolerated and a non-significant beneficial trend toward reduction of major clinical events such as reinfarction or CVD death was seen. Similarly, Turkish researchers found adding L-arginine to a cardioplegia solution for MI patients increased NO levels and attenuated free-radical-mediated myocardial injury.²⁰

Two more important amino acids in this arena are L-taurine and L-carnitine. L-taurine comprises more than 50 percent of the total free amino acids in the heart; it has been shown to strengthen the heart muscle and may lower blood pressure. Japanese researchers recently reported administering taurine before or after inducing ischemia in rat hearts could prevent infarction and reduce myocardial injury; given after reperfusion, it significantly enhanced functional recovery.²¹

L-carnitine transports fatty acids into the mitochondria, supporting energy production; the heart is particularly rich in mitochondria and has very high energy demands. Researchers who provided L-carnitine or exogenous NO to rats subjected to ischemia-reperfusion found both interventions worked to protect the heart from myocardial damage.²² The acetylated form, acetyl-L-carnitine (ALC), is of particular interest in the stroke arena. Studies have shown ALC may have the ability to reduce neuronal damage, possibly due in part to activating the choline uptake system.²³ It also appears to restore mitochondrial function in aged rats, which can protect against ischemic damage.²⁴

Combination formulas may be particularly beneficial. A study out of St. Michael’s Hospital, Toronto, evaluated the impact of a combination of L-carnitine, L-taurine and coenzyme Q10 (CoQ10) vs. carnitine alone or placebo on survival, infarct size and cardiac function in a rat MI model.²⁵ The combination supplement significantly improved survival (60 percent vs. 34 percent of control animals) and cardiac function, and reduced infarct size (30 percent vs. 42 percent of control). Carnitine improved survival in a similar manner to the combination, but did not reduce infarct size. On its own, CoQ10 administered prior to²⁶ or during MI²⁷ can improve the survival of myocardial cells and limit postinfarct myocardial remodeling. A review out of Duke University, Durham, N.C., further noted CoQ10’s antioxidant activity may make it a neuroprotectant in stroke cases.²⁸

Antioxidants may work to prevent free radical damage that can result during MI or stroke. Vitamin E, on its own or in combination, has been studied for its ability to decrease oxidative damage. In particular, the tocotrienol isomers appear to have efficacy preventing neuronal and cardiovascular damage induced by ischemia. Researchers from the University of Connecticut School of Medicine, Farmington, used natural palm tocotrienol complex and individual tocotrienol isomers (as Tocomin®, from Carotech Inc.) to study the effects and mechanisms of tocotrienol’s cardioprotective function.²⁹ Results showed all forms of tocotrienols could improve postischemic ventricular function, reduce myocardial infarct size, reduce the percentage of apoptotic cardiomyocytes and partially protect the proteasome during ischemia. Gamma-tocotrienol had the highest cardioprotective activity, followed by alpha-tocotrienol and, with the lowest level, delta-tocotrienol.

Carotech has supported research efforts at the Ohio State University Medical Center, Columbus, since 2000 looking at the effect of Tocomin and Tocomin SupraBio™ in reducing stroke-induced neurodegeneration. The researchers have reported alpha-tocotrienol from Tocomin is significantly more potent than alpha-tocopherol in protecting neurons from glutamate-induced toxicity,³⁰ and has the ability to cross the blood-brain barrier to protect neurons from glutamate-induced neurodegeneration as seen in stroke.³¹ When Tocomin was given to spontaneously hypertensive rats (SHR), the levels of tocotrienols in the brain increased significantly, and exerted protection against stroke-induced brain injury.³²

Combining vitamin E with vitamin C may work to improve recovery from MI, reducing oxidative damage and supporting ventricular remodeling.³³ A randomized pilot trial out of Warsaw, Poland, involving 800 patients with acute MI found providing 1,000 mg of vitamin C for a 12 hour infusion plus 1,200 mg/24 hours orally with 600 mg/24 hours of vitamin E reduced non-fatal new MI and cardiac mortality.³⁴ Similarly, when a team at the University of Sheffield, England, started acute ischemic stroke patients on 800 IU/d vitamin E, 500 mg/d vitamin C and B vitamins (5 mg folic acid, 5 mg B2, 50 mg B6 and 0.⁴ mg B12) within 12 hours of symptom onset, oral supplementation was found to increase plasma antioxidant concentrations, mitigate oxidative damage and reduce inflammatory markers.³⁵

Another fat-soluble antioxidant, the carotenoid astaxanthin, may also play a role in preventing stroke-induced damage. Researchers at the International Research Center for Traditional Medicine, Toyama, Japan, investigated whether long-term administration of astaxanthin could protect against hypertension and stroke.³⁶ Their study compared stroke-prone SHR, given 50 mg/kg of astaxanthin (as AstaReal®, from Fuji Chemical Industry), and normotensive rats. Two weeks of supplementation significantly reduced blood pressure in SHR; the researchers also found astaxanthin exerted neuroprotective effects in ischemic mice. A review from the same research team noted astaxanthin has been shown to exert anti-inflammatory and antioxidant activity.³⁷ Interestingly, pharmaceutical-grade astaxanthin is now being commercialized as a drug, Cardax™, from Cardax Pharmaceuticals. In vitro and animal trials have shown treatment with Cardax prior to ischemia induction can reduce infarct size and support myocardial salvage.^38,39

The plant kingdom also offers a range of antioxidants, often attributed to their flavonoid components. Data from the Kuopio Ischemic Heart Disease Risk Factor Study illustrated the association between intake of different classes of flavonoids and CVD, with men in the highest quartile of flavonol and flavan-3-ol intakes reducing the risk of ischemic stroke by 45 and 41 percent, respectively, compared to the lowest quartiles.⁴⁰ Italian researchers conducted an eight-year study among older adults and found those in the highest quintile of anthocyanidins had a 55 percent reduction in acute MI risk; the highest quintile of intake of flavonols dropped the risk by 35 percent.⁴¹ And a Japanese study linked higher intake of isoflavones by women—particularly postmenopausal women—to a reduced risk of cerebral and myocardial infarctions.⁴²