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Life Extension Magazine

Do Your Antioxidants Suppress Enough Free Radicals?

February 2005

By Jim English

Scientists have unanimously concluded that free radicals damage cells and contribute to the common diseases associated with aging. Health-conscious people today consume antioxidant supplements to help neutralize these toxic free radicals.

As people age, however, they generate more free radicals that inflict greater damage to cellular DNA, mitochondria, and cell membranes. The result is illness and premature death, even in those who take conventional antioxidant supplements.

Back in 1980, the Life Extension Foundation first recommended antioxidants to reduce the risk of disease. While our pioneering work has been validated in tens of thousands of published studies, extraordinary efforts are required to counteract the increased levels of free radicals to which aging people are exposed.

The encouraging news is that researchers have discovered more potent antioxidants that significantly boost our defenses against destructive free radical attack. For instance, new forms of lipoic acid called R-lipoic acid and R-dihydro-lipoic acid provide much greater protection against free radical reactions inside the cell. (These new forms of lipoic acid are discussed in the article that follows the one you are about to read.)

What has us most excited is that sesame lignans can amplify the antioxidant efficacy of vitamin E, including critically important gamma tocopherol.

Vitamin E is an essential, fat-soluble antioxidant that inhibits fatty acid oxidative damage in cell and mitochondrial membranes. The problem until now has been that the amount of gamma tocopherol and other vitamin E compounds that could be delivered to the tissues was limited. Adding standardized sesame lignans to dietary supplements, however, enhances the ability of these compounds to quench free radicals and thus provide greater protection against destructive free radical attack.

This article discusses some remarkable findings about sesame lignans and why they have become so important to those seeking to derive optimal benefits from their dietary supplement program.

Sesame (Sesamum indicum), one of the world’s oldest cultivated foods, has been valued throughout history for its contributions to diet, medicine, and household uses. Modern research reveals that this long-prized plant offers a wealth of health benefits.

Sesame and its lignans boost antioxidant levels, reduce inflammation, normalize blood pressure, improve lipid levels, and promote fat burning. They act synergistically with other nutrients such as gamma tocopherol, fish oil, and conjugated linoleic acid, thereby enhancing the bioavailability and effectiveness of those nutrients. Through its many biochemical actions, sesame may help in managing some of today’s most pressing health concerns, including heart disease, high blood pressure, obesity, and inflammatory disorders.

Sesame arrived in the Middle East from Africa some 5,000 years ago. It was especially well suited to the region due to its high resistance to oxidation and rancidity in warm climates. Sesame was incorporated in traditional folk remedies throughout Asia and the Middle East, where it was used to treat conditions ranging from colds and flu to asthma and jaundice. Today, sesame seeds play an important role in Ayurveda, the ancient healing tradition of India, and sesame products are consumed in Japan and China as health foods to prevent aging.1,2

Modern research has found that sesame seeds offer a broad range of health benefits. Sesame may be especially well suited to helping reduce the risk of heart disease, the leading killer of men and women in America today. Numerous biochemical processes can contribute to the pathogenesis of heart disease, including unfavorable lipid profiles, oxidative stress, elevated blood pressure, and reduced levels of protective antioxidants.

Sesame and its lignans—fibrous compounds that may act as antioxidants and influence hormone metabolism—may be valuable therapeutic tools in modulating cardiovascular risk through their numerous actions in the body. Sesame lignans have been found to enhance the anti-inflammatory effects of essential fatty acids, lower total cholesterol and low-density lipoprotein (LDL), block oxidative damage implicated in atherosclerosis, and reduce blood pressure. Sesame lignans can dramatically increase tissue and serum levels of the vitamin E fractions alpha tocopherol and gamma tocopherol, thereby enhancing their protective properties.3 Studies have shown that sesame can also reduce inflammatory processes known to promote cancer, senescence, and aging.

Unique Benefits of Gamma Tocopherol

Early research on vitamin E focused on alpha tocopherol, the form most commonly found in supplements. When scientists started examining other vitamin E fractions, one in particular—gamma tocopherol—was found to possess several unique properties. Although not as powerful an antioxidant as alpha tocopherol, gamma tocopherol was found to be the only vitamin E fraction capable of quenching reactive nitrogen oxide species such as peroxynitrite and nitrogen dioxide. Generated by inflammation, these dangerous free radicals are implicated in a host of degenerative diseases, including atherosclerosis, AIDS dementia complex, amyotrophic lateral sclerosis, Alzheimer’s disease, Huntington’s disease, multiple sclerosis, and Parkinson’s disease.4,5 Re-searchers also discovered that gamma tocopherol and its water-soluble metabolite, gamma-CEHC, reduce inflammation by inhibiting prostaglandin E2 (PGE-2).6

In addition to inhibiting chronic inflammation, gamma tocopherol exerts additional non-antioxidant effects to prevent cancer.7 Gamma tocopherol is believed to prevent colon cancer by inhibiting the formation of mutagens produced by oxidized fecal fats, while decreasing oxidative damage to the epithelial cells of the colon.8 Gamma tocopherol may act as a chemopreventive agent to prevent prostate and colorectal cancers by influencing biological mechanisms involved in cell death, cell cycle, and gene transcription.9 High serum levels of gamma tocopherol have been correlated with a lowered incidence and reduced risk of death from cardiovascular disease. In one study involving 34,486 postmenopausal women, increased intake of dietary vitamin E, primarily gamma tocopherol, was associated with a reduced risk of death from coronary heart disease.10 This association was not observed in women who took vitamin E supplements of alpha tocopherol.

Sesame Lignans Boost Gamma Tocopherol

As the health benefits of gamma tocopherol became more apparent, researchers were puzzled to find that although gamma tocopherol is the primary form of vitamin E in the diet, blood serum levels of alpha tocopherol are four to ten times higher than those of gamma tocopherol.11 Researchers were further intrigued to discover that supplementing the diet with alpha tocopherol results in significantly lower gamma tocopherol levels, both in the blood and in tissues.12,13

Several factors contribute to the problem of raising gamma tocopherol levels in humans. First, although gamma tocopherol and alpha tocopherol are absorbed equally in the intestines, the carrier protein that transports vitamin E from the liver to the tissues is highly selective for alpha tocopherol, transporting the alpha fraction in a 20:1 ratio compared to the other tocopherols. As a result, relatively little gamma tocopherol ends up in cell membranes.14

Additionally, the liver’s P-450 enzyme responsible for breaking down vitamin E tocopherol—omega-hydroxylase—exhibits a markedly higher catalytic activity for gamma tocopherol than for alpha tocopherol, which is why taking alpha tocopherol by itself ends up suppressing serum and tissue levels of gamma tocopherol.15

Increasing one’s intake of alpha tocopherol actually depresses gamma tocopherol levels, whereas adding gamma tocopherol to the diet increases serum and tissues levels of both gamma tocopherol and alpha tocopherol.16 This finding may explain why vitamin E from dietary sources has been found to be more effective than alpha tocopherol supplements in reducing deaths from cardiovascular disease.

Sesame’s Effects on Tocopherol Metabolism

In a series of experiments, researchers discovered that serum levels of alpha tocopherol actually increased when rats deprived of alpha tocopherol were supplemented with sesame. In one of the experiments, rats were fed one of five different diets: a control diet free of vitamin E; a diet low in alpha tocopherol; or one of three diets low in alpha tocopherol but supplemented with 5%, 10%, or 15% sesame seed content, respectively. The researchers examined changes in lipid peroxides in the liver, red blood cell hemolysis, and pyruvate kinase activity, as indices of vitamin E deficiency. These indices were high in the diet that was low in alpha tocopherol, whereas supplementation with even 5% sesame seed suppressed these indices completely and caused a significant increase in alpha tocopherol in the plasma and liver. These experiments revealed that sesame seed lignans significantly enhance vitamin E activity and increase alpha tocopherol concentrations in the blood and tissue of rats fed a diet containing alpha tocopherol and sesame seed or its lignans.17

In a related study, researchers examined liver, brain, kidney, and serum levels of gamma tocopherol in rats fed either gamma tocopherol alone or gamma tocopherol in combination with sesame. Rats receiving only gamma tocopherol exhibited small increases of gamma tocopherol in their tissues and serum. By contrast, rats fed a mixture of sesame and gamma tocopherol had significant increases— ranging from 833% to 1,000%—in gamma tocopherol levels in both their serum and tissues. The researchers also noted that urinary excretion of gamma-CEHC, the water-soluble metabolite of gamma tocopherol, declined by 50% in the sesame-supplemented rats.14

Japanese researchers recently examined the effects of sesame and sesame lignans on tocopherol metabolism to clarify the mechanism responsible for raising gamma tocopherol levels. They found that urinary levels of gamma-CEHC in rats fed sesamin or the sesame lignan sesaminol were markedly lower than in rats fed gamma tocopherol alone. The researchers concluded that sesame seed and sesame lignans elevate gamma tocopherol concentration by inhibiting an enzyme involved in breaking down tocopherols and tocotrienols.14