Revisiting Supplements, The Case Of Vitamin E

I've been reading about Dr. Bruce Ames. The gentleman has a distinguished career. He's currently Professor of Biochemistry at the University of California, Berkeley, and Senior Scientist at Children's Hospital Oakland Research Institute. He has published over 500 peer-reviewed articles (one of the most-cited scientists on record), is the recipient of numerous awards (In 1998, President Clinton awarded him the National Medal of Science for his "creativity, resolve, and a restless spirit of innovation to ensure continued US leadership across the frontiers of scientific knowledge."¹), and at 82 he's is still publishing.²

Dr. Ames' research focuses on aging, in particular, mitochondrial decay and degenerative diseases, e.g. cancer. Here's something he said about dietary supplements:

"Suboptimal consumption of micronutrients often accompanies caloric excess and may be the norm among the obese and contribute to the pathologies associated with obesity."
...
"Micronutrient inadequacies are widespread in the population, and a multivitamin-mineral (MVM) supplement is inexpensive. A solution is to encourage MVM supplementation, particularly in those groups with widespread deficiencies such as the poor, teenagers, the obese, African Americans, and the elderly, in addition to urging people to eat a more balanced diet."
- Low Micronutrient Intake May Accelerate The Degenerative Diseases Of Aging Through Allocation Of Scarce Micronutrients By Triage, Proceedings Of the National Academy of Sciences, 2006

I really like this triage theory of his. He has some other ideas, concerning pesticides for example or public health vs. personal responsility, that I'm not as enthusiastic about. Anyway...

Dr. Ames's research is prompting me to revisit my stance on supplementation. I've been thinking that for the majority of Americans most dietary supplements aren't necessary and may at times be harmful, that it's better to fix the food environment than to suggest a pill. Maybe that's idealistic. There are groups of people, in certain stages of life, with certain disabilities, that may do well to take a supplement. Given the state of food these days, those groups may make up a sizable portion of the population.


The Case Of Vitamin E

The rest of this post concerns one area of Dr. Ames' interest and research - vitamin E.

"Vitamin E" is actually a bucket term. There are at least 8 forms, 4 tocopherols (alpha, beta, gamma, and delta) and 4 tocotrienols (alpha, beta, gamma, and delta). Dr. Ames makes a convincing case that one of those forms, gamma-tocopherol (γT), is as important as, and in some cases more important than, the widely studied alpha-tocopherol (αT):

"γ-Tocopherol, the main form of vitamin E in the U.S. diet, unlike α-tocopherol, the main form of vitamin E in supplements, is an effective inhibitor of three different inflammatory pathways cyclooxygenase (COX), LTB4, and TNFα at physiological concentrations, both in human cells in culture and in rats.³ Previous work on γT had shown it is an effective nucleophile, unlike αT, and can inactivate lipid-soluble electrophilic mutagens such as nitrogen oxides. Epidemiological evidence supporting the importance of dietary γT has been reviewed.⁴ γT also is effective in inhibiting prostate and lung tumor cells by interrupting sphingolipid synthesis.⁵"

That forth reference was fairly comprehensive. It describes how gamma-tocopherol or its metabolite γ-CEHC, but not alpha-tocopherol:

• Has natriuretic activity (helps remove excess sodium from the body).
  
• Inhibits cyclooxygenase activity (acts as an antiinflammatory, like an NSAID).

Also, the gamma version has been linked to:

• Lower incidence of cataracts
  
• Lower risk of death from cardiovascular disease ("In a 7-y follow-up study of 34,486 postmenopausal women, Kushi et al concluded that the intake of dietary vitamin E (mainly γ-tocopherol), but not of supplemental vitamin E (mainly α-tocopherol), was significantly inversely associated with increased risk of death by CVD.")
  
• Lower risk of certain cancers, e.g. digestive tract, lung, and prostate ("The most striking finding was that men in the highest quintile of plasma γ-tocopherol concentrations had a 5-fold reduction in the risk of prostate cancer compared with those in the lowest quintile.")

Most supplements contain alpha-tocopherol, not gamma tocopherol. That's unfortunate because "high doses of alpha-tocopherol deplete plasma and tissue gamma-tocopherol."

Vitamin E is an essential nutrient. That means we need it, our bodies don't make it, we have to eat it. It's made only by plants, and because it's a fat-soluble nutrient, it's found in higher quantities in plant oils.

The gamma form of tocopherol (γT) is the dominant form in plants; the alpha form (αT) is thought to be the dominant form in most animal/human tissue (including blood plasma) - which is why αT has been more rigorously studied than γT. However, research is discovering that we have a lot of γT in skin, muscle, vein, and fat tissue. (αT may dominate in human tissue, even though we eat more γT, and even though they're absorbed and transported almost identically, because γT is degraded in the liver more readily. However, the water-soluble compound that's produced from γT, γ-CEHC, has its own biological activity, as Ames' research describes.)

So, if your supplement says "alpha-tocopherol" under vitamin E, it may not be as healthful as something that says "mixed tocopherols." If it's mixed, it may not reveal how much of the blend is alphaT and gammaT. And then, how much of each is best to take? Knowing that the alpha depletes the gamma?

You could always go the food route:⁴

"Vegetable oils such as corn, soybean, and sesame, and nuts such as walnuts, pecans, and peanuts are rich sources of γ-tocopherol."

From NutritionData:

• Walnuts, 1 ounce, 8.0 mg gamma-tocopherol, 0.5 alpha-tocopherol
  
• Pecans, 1 ounce, 6.8 mg gamma-tocopherol, 0.4 alpha-tocopherol
  
• Peanut Butter, 2 tablespoons, 2.7 mg gamma-tocopherol, 1.9 alpha-tocopherol
  
• Almonds, 1 ounce, 0.2 mg gamma-tocopherol, 7.3 alpha-tocopherol

So, almonds are a poor source for gamma-tocopherol, relative to alpha-tocopherol. How about that.
________¹ Cellular Nutrition / The Hunt To Fix Hidden Hunger / Biochemist Bruce Ames Thinks A Simple Multivitamin May Fight Obesity, San Francisco Chronicle, 2006
² Adaptive Dysfunction Of Selenoproteins From The Perspective Of The Triage Theory: Why Modest Selenium Deficiency May Increase Risk Of Diseases Of Aging, FASEB Journal, 2011
³ γ-Tocopherol, But Not α-tocopherol, Decreases Proinflammatory Eicosanoids And Inflammation Damage In Rats, FASEB Journal, 2003
⁴ γ-Tocopherol, The Major Form Of Vitamin E In The Us Diet, Deserves More Attention, The American Journal of Clinical Nutrition, 2001
⁵ γ-Tocopherol Or Combinations Of Vitamin E Forms Induce Cell Death In Human Prostate Cancer Cells By Interrupting Sphingolipid Synthesis, PNAS, 2004