By Benjamin V. Treadwell, Ph.D.

Vitamin E can positively affect cellular health. But do your diet and/or multi-vitamin supply enough of it? Or should we say enough of "them"?

A Family Affair
Vitamin E is actually a group of eight structurally different compounds. As with most vitamins, these essential micronutrients must be obtained through diet because the body cannot synthesize them. But there's a lot more to the story of the vitamin E family's relationship to cellular health.

Vitamin E, the Early Days

For the most part, vitamin E was first thought to be important to cellular health as an antioxidant. In the early 1900s, studies focused largely on demonstrating vitamin E’s effectiveness in protecting those areas of the cell rich in lipids, such as the numerous membranes separating various cellular compartments (nucleus, cytoplasm, mitochondria etc.). A fatty substance itself, vitamin E readily enters and resides in these lipid structures and protects them from toxic oxidants and free radicals.
The early research examined only one form of the vitamin, alpha tocopherol. It was considered the biologically important form for various reasons, some of them outlined below. Over the years, research has continued to focus on this member of the vitamin E family, almost exclusively, even with indications that it may not be the form with the most health potential.

The Other Vitamin Es
Vitamin E exists in nature as eight distinct compounds (for more details on structure and function go to The Eight Faces of Vitamin E). Four of these are referred to as tocopherols. Depending on the number and position of a specific chemical group (methyl group), they are designated as alpha, beta, gamma or delta. The remaining four, the tocotrienols, are similar in structure but contain three unsaturated bonds on what is known as the phytyl side chain. These unsaturated bonds not only distinguish the tocotrienols from the tocopherols but also, as discussed below, have profound effects on the potential health benefits of the tocotrienols.

The Alpha Tocopherol Attraction
So why has alpha tocopherol been the chosen one in terms of scientific interest? The cells of the body, particularly liver cells, manufacture specific proteins designed to transport vitamin E as well as protect it from being metabolized and excreted. Research shows that these chaperone-like proteins have a much higher affinity for alpha tocopherol than the other seven forms of vitamin E. Consequently, the other Es, especially the tocotrienols, are more rapidly metabolized and excreted from the body and, hence, are poorly represented in the plasma and cells.
The fact that a number of proteins appear to favor alpha tocopherol and promote its retention in the tissues prompted researchers to believe this was the biologically important form of the vitamin. It certainly was logical, but perhaps a smokescreen, as it is now known that other forms of vitamin E have potent biological effects not exhibited by alpha tocopherol. The tocotrienols, specifically, are active at very low plasma levels relative to the more prevalent alpha tocopherol.
Actually, it appears that the relative affinities of a cell’s vitamin E retention proteins for the various forms of E may be a reflection of how much of each is needed for biological activity. In other words, just because alpha tocopherol, the extrovert of the E’s, is copious does not necessarily indicate it is either more important or more beneficial than its less visible relatives.

The Research Pendulum
Nevertheless, the vast majority of research on vitamin E has been alpha tocopherol-related. That the tocotrienols have been virtually left out is evident from the lopsided publication record: almost 24,000 research papers relate to the tocopherols (mostly alpha tocopherol) compared to 200 tocotrienol-associated publications. Even though these studies are limited, they seem to be shining the spotlight on the other forms of vitamin E.

Tocotrienols vs. Tocopherols
Can tocotrienols do things tocopherols can't? Both have similar capacities to protect cellular membrane components from oxidative damage and attack by free radicals. Actually, the tocotrienols, due to their unsaturated bonds, more readily enter the cellular lipid membranes and, thus, are probably more effective antioxidants than their saturated bond counterparts.
But recent research has demonstrated other exciting potential tocotrienol benefits, unrelated to their capacity to function as antioxidants. In cell culture and animal studies, some of the tocotrienols have inhibited cancer growth, lowered cholesterol, and protected cells of the nervous system from toxic damage.

Pathways, Prevention and Protection
Gamma and delta tocotrienols, for example, have been shown to activate a cellular pathway (ubiquitin-proteasome pathway) that leads to the partial removal of a rate-limiting enzyme involved in cholesterol synthesis. The net result is a decrease in cholesterol and, more importantly, the bad cholesterol, LDLc.
Additional positive effects of gamma tocotrienol have been attributed to its activity in preventing the over-activation of NF-kB, a factor involved in turning on genes that promote inflammation. Over-production of NF-kB has been implicated in cancer growth, cardiovascular disease, and a number of age-associated neurodegenerative diseases, including Alzheimer’s and Parkinson’s.
Tocopherols, on the other hand, demonstrated virtually no effect on this inflammatory switch when tested in cell culture. Recent clinical trials also showed little, if any, positive effect of alpha tocopherol on cardiovascular health. Should those clinical studies be revisited with gamma and/or delta tocotrienol?
Speaking of cardiovascular health studies, hypertensive rats susceptible to stroke (vascular hemorrhage) and treated with alpha tocotrienol showed significantly reduced damage to the neurons in the affected areas of the brain. The alpha tocotrienol appears to afford this neuroprotection by preventing the stroke-induced activation of an enzyme involved in production of inflammatory molecules, the leukotrienes. The extrovert, alpha tocopherol, provided no protective effect to the central nervous system.

Eight is Greater
This introduction to the eight members of the vitamin E family and their roles in protecting cellular health leads us back to our original question. Does your diet and/or multi-vitamin supply enough of them?
The food sources for tocopherols and tocotrienols are different. Tocopherols are largely present in nuts and oils such as canola, soybean, wheat germ and sunflower. These vegetable oils are common to the Western diet so a deficiency in the tocopherols is less likely to occur. The tocotrienols are more concentrated in oats, barley, rice bran and rye, with the greatest concentration in palm oil. A diet rich in non-refined cereal grains will provide a good source of the tocotrienols.
For those who feel their diet may be deficient, there are supplements available which contain both E family branches. It's important to select the natural form, the D isomer, and not the synthetic product, the DL form. In other words, don't forget to read the label.

In an article published in Life Sciences in 2006, three researchers - Chandan K. Sen, Savita Khanna and Sashwati Roy of the Laboratory of Molecular Medicine, Department of Surgery, Davis Heart and Lung Research Institute, Ohio State Medical Center – call for a change in vitamin E research strategy. They suggest shifting the emphasis for a better balance in basic and clinical research between the tocopherol and lesser-known tocotrienol forms of vitamin E.

By way of background, the authors begin with a brief history of vitamin research, including tocopherol-focused vitamin E research. They offer an overview/comparison of the chemical make-up of the tocopherols and tocotrienols, touching on relative bioavailability, antioxidant capacity and other curative properties. (In animal and laboratory studies, tocotrienols demonstrated neuroprotective, antioxidant, anti-cancer and cholesterol-lowering properties.)

Sen, Khanna and Roy note, "current developments in vitamin E research clearly indicate that members of the vitamin E family are not redundant with respect to their biological functions." They recommend caution against empirical claims while stressing the significance of filling the research void.

To read the abstract, click here.
"Tocotrienols: Vitamin E beyond tocopherols."
Life Sci. 2006 Mar 27;78(18):2088-98. Epub 2006 Feb 3.

This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

QUESTION: I am 37, 5'1+" and about 107 lbs. I eat vegetarian foods, stay away from caffeine, and I exercise. I like the boost of energy and mentally focused feeling I have when I take Juvenon™ Cellular Health Supplement, but it does feel a bit like the effects of caffeine on my body. The other thing I notice is a withdrawal-type feeling of irritability. What would cause this? I only take one pill and I take it early in the day. Should I cut the pill in half?
K

ANSWER: Yes, I do recommend you cut the Juvenon tablet in half if you are currently taking one tablet per day. Your gene profile, along with your weight, metabolism, diet, activity level and over-all health, play a significant part in how you metabolize compounds and, specifically, how you respond to Juvenon.

I think you notice a more intense effect because your vegetarian diet contains very little of one of Juvenon's components. Also, you are on the low end of the scale for recommended weight (a healthy thing!). So, it's possible the cells of your body are not metabolizing and excreting the compound as rapidly.

In other words, the compound has a much longer half-life in your body. Consequently you need less than most people for optimum effect, and too much can cause the effects you describe.

Send your questions to AskBen@juvenon.com.
For more questions and answers, go to juvenon.com/product/qa.htm.

Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon's Scientific Advisory Board.