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

Providing GSE either before or after induced stroke may reduce oxidative and neuronal damage. Researchers out of the University of Debrecen, Hungary, reported rats treated with 50 and 100 mg of grape seed proanthocyanidins/kg had significantly reduced ventricular fibrillation when ischemia was induced; the researchers suggested GSE exerted its effects by direct and indirect antioxidant activity in the myocardium.⁴⁵ Providing GSE to animals after induction of forebrain ischemia appears to have neuroprotective effects by inhibiting DNA damage⁴⁶ and suppressing lipid peroxidation and proapoptotic protein expression.⁴⁷

Another branded standardized GSE (as Leucoselect™, from Indena) has been investigated for its ability to mitigate damage associated with ischemia. Researchers from the University of Milan, Italy, reported Leucoselect could suppress damage to endothelial cells exposed to peroxynitrite generators and also had a vasorelaxant effect.⁴⁸ Work by the same team found perfusing rabbit hearts with Leucoselect (100 or 200 mcg/ml) dose-dependently enhanced postischemic recovery.⁴⁹

One of the major sources of flavonoids in most diets is tea; green tea in particular has been shown to be a potent antioxidant. Green tea catechins’ ability to attenuate oxidative stress and downregulate the inflammatory response may lie at the core of their ability to protect the brain after cerebral ischemia.⁵⁰ Japanese researchers reported providing tea catechins to rats prior to stroke induction could dose-dependently reduce infarct area and volume; plasma concentrations of epigallocatechin gallate (EGCG) were inversely correlated with infarct volume.⁵¹ In their study, catechin ingestion also reduced neurologic deficits.

On the cardiac side, a team from Annamalai University, Tamil Nadu, India, found oral pretreatment of rats with EGCG (10, 20 or 30 mg/kg body weight) had a dose-dependent cardioprotective effect against induced MI.⁵² Also, a specialty green tea extract (Greenselect®, from Indena) specifically appears to protect cardiac myocytes from ischemia-induced apoptotic cell death, while also limiting the extent of infarct size.⁵³ The reduction in cell death was associated with enhance recovery of ventricular function and hemodynamic recovery.

Other dietary compounds have been studied for their role in preventing ischemic damage. Researchers from the National Institute on Drug Abuse, Baltimore, examined whether diets enriched with blueberry, spinach or spirulina could exert neuroprotective effects in focal cerebral ischemia.⁵⁴ Adult rats received equal diets with the different nutrients or a control diet for four weeks, after which the animals’ cerebral artery was ligated and then removed to allow reperfusional injury. The animals that received blueberry-, spinach- or spirulina-enriched diets had significant reductions in volume of infarction and an increase in post-stroke locomotor activity. On their own, blueberries were shown in an animal trial to exert neuroprotective effects in the hippocampus after induced ischemia,⁵⁵ while spirulina’s C-phycocyanin (PC) may attenuate ischemia and reperfusion-induced myocardial injury via antioxidant and anti-apoptotic activity.⁵⁶

The botanical Ginkgo biloba also exerts neuroprotective and cardioprotective effects. Brazilian researchers explored the effects of Ginkgo biloba extract EGb 761 on ischemia-induced memory impairment and hippocampal damage in rats, reporting animals that received the botanical extract had less hippocampal cell loss and related cognitive impairment.⁵⁷ This activity has been linked to its antioxidant properties, which appears to protect against lipoperoxidation.⁵⁸ Additional research, conducted at the University of Leipzig, Germany, examined the impact of EGb 761 on diabetes-induced damage to cardiomyocytes and ischemic injury in spontaneously diabetic rats.⁵⁹ The researchers noted diabetic myocardium is more vulnerable to such damage, but pre-treatment with EGb 761 could significantly improve myocardial recovery.

Complexing Ginkgo biloba extract with phosphatidylcholine (as Ginkgoselect® Phytosome®, from Indena) may enhance its bioavailability and functionality. Researchers at the University of Milan compared antioxidant defense in animals given 300 mg/kg/d of Ginkgo biloba extract or Ginkgoselect, and found the complex had the ability to significantly increase total antioxidant plasma activity.⁶⁰ In addition, animals were subjected to moderate ischemia and reperfusion; recovery was 35 percent of preischemic values in control animals, 50 percent in Gbe animals and 72 percent in rats pre-treated with Ginkgoselect.

Other dietary compounds operate on different parameters than antioxidant protection. For example, studies have shown that lower levels of vitamin B12 and folate increase the risk for cerebral infarction, possibly linked to higher homocysteine levels;⁶¹ and that patients who have suffered ischemic stroke tend to have lower levels of vitamin B6 and higher homocysteine levels.⁶² Additionally, a study out of Cardinal Tien Hospital, Taiwan, assessed circulating levels of homocysteine, folate and B12 in elderly post-stroke patients (n=89) and found folate deficiency and hyperhomocysteinemia were prevalent in the population, and were also strongly, independently associated with the development of brain atrophy.⁶³

Increasing folate intake appears to help reduce the risk of ischemia. Researchers from the German Institute of Human Nutrition Potsdam-Rehbruecke, Germany, using data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, evaluated the association between folate intake and risk of MI in 22,245 healthy adults.⁶⁴ After 4.6 years of follow-up, higher folate intake was associated with a 43 percent reduction in MI risk. And a report out of Stockholm’s Karolinska Instiutet, using data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, found after 13.6 years of follow-up in male smokers, higher folate intake was associated with a statistically significantly lower risk of cerebral infarction.⁶⁵

There has been some controversy surrounding the connection between folate, homocysteine levels and the risk of MI or stroke. A review out of Spedali Civili di Brescia, Italy, noted there is convincing epidemiological evidence on the relation between elevated homocysteine and vascular disease including ischemic stroke; however, the causal relationship has not been proven, and needs further investigation.⁶⁶ For example, nested information from the Nurses Health Study out of Brigham & Women’s Hospital found providing older women (n=5,442) with a combination B vitamin supplement (50 mg B6, 1 mg B12, 2.5 mg folate) lowered homocysteine levels by more than 18 percent, but did not impact the incidence of stroke or MI.⁶⁷ However, folate may well have other mechanisms of action, as Dutch researchers who provided women (n=40) with 10 mg/d of folic acid immediately after acute MI found intervention could improve endothelial function regardless of its impact on homocysteine levels.⁶⁸

Such benefits in recovery are offered by the compound ribose. Ribose is a five-carbon monosaccharide that works to stimulate the metabolic pathway to create purines and pyrimidines, which are essential for producing adenosine triphosphate (ATP)—the “energy currency” of the body. Studies have shown that ribose can help to restore energy and improve function in the heart, particularly in cases of ischemia and heart failure. One study, conducted out of Saddleback Hospital, Laguna Hills, Calif., compared the results of patients with acute myocardial infarction (n=103) given an “off” pump coronary artery bypass (OPCAB) alone, or with oral ribose (as Bioenergy RIBOSE™, from Bioenergy Life Science Inc.), prior to revascularization.⁶⁹ Giving ribose to the patients provided additional functional improvement, compared to OPCAB alone prior to revascularization.

An additional study investigated whether ribose (as Bioenergy Ribose) given to animals in a model of MI could enhance recovery in the animals.⁷⁰ At two and four weeks post-infarction, control animals showed a significant decrease in function of the remote myocardium, which was prevented to a significant degree by ribose infusion. Increasing the myocardial energy levels thereby improved function, which may also delay chronic changes and myocardial remodeling. Similar findings were reported in another animal trial, in which researchers found giving ribose before global MI elevated glycogen stores and reduced injury in normal hearts.⁷¹ In hypertrophied hearts, ribose did not affect ischemic tolerance but it did improve ventricular function.

Another specialty ingredient, aged garlic extract (AGE, as Kyolic®, from Wakunaga) has also been studied for its ability to reduce mortality associated with CVD and stroke. In one trial, S-allyl-L-cysteine (SAC), an active organosulfur compound found in AGE, was found to reduce mortality with lesser incidence of stroke and lower overall stroke-related behavioral score when orally administered to stroke-prone spontaneously hypertensive (SHRSP) rats.⁷² In addition, AGE may help reduce hyperhomocysteinemia and related endothelial dysfunction,⁷³ while it may also increase flow-mediated endothelium-dependent dilation.⁷⁴

In April 2008, Wakunaga presented the results of a recent study from the Los Angeles Biomedical Research Institute of Harbor-UCLA Medical Center, which involved 65 intermediate risk patients who received a placebo or four capsules of 250 mg/d of AGE (as Kyolic), 100 mcg/d of vitamin B12, 300 mcg/d of folic acid, 12.5 mg/d of vitamin B6 and 100 mg/d of L-arginine for one year. The first breakdown of the data showed supplementation with AGE could improve thermal vascular function and reduce coronary artery calcium (CAC) progression in asymptomatic adults with intermediate risk.⁷⁵ The second breakdown of the study showed the ability of AGE, B vitamins, L-arginine and folate to retard progression of CAC and biomarkers of atherosclerosis independent of age, gender and conventional risk factors.⁷⁶

While cholesterol and blood pressure may take center stage in the preventive nutrition arena, awareness of how diet and certain nutritional ingredients can help stave off potentially catastrophic incidents of ischemia can help consumers cover all the bases to increase their years of quality living.

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Editor's Note: References start on the next page.