RELEVATE Nutrients

Alpha- and Gamma-Tocopherol

Key Food Groups: Nuts/Seeds
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Vitamin E: Role in Brain Health

Alpha- and gamma-tocopherols are two natural forms of Vitamin E stored in the brain that work together to protect functional fats essential to the brain (like omega-3’s) from oxidative damage, as well as reducing neuroinflammation.1,2 The two forms are similar in structure and are two of the most common dietary tocopherols. Alpha-tocopherol (the typical vitamin E in most supplements) makes up the majority of the brain’s tocopherols; at the same time, gamma-tocopherol makes up a smaller portion of brain tocopherols, yet it has some antioxidant capabilities that alpha-tocopherol does not, such as being able to efficiently trap certain kinds of free radicals called reactive nitrogen oxide species (RNOS).3,4

When a free radical steals a charge from another molecule, it is oxidized and becomes a free radical itself. Then it steals a charge from another molecule, thus the chain of oxidative damage continues until a “chain-breaking” antioxidant like alpha-tocopherol intervenes by providing its charge and becoming oxidized without becoming a free radical itself.4 As mentioned, gamma-tocopherol is an antioxidant as well, yet it and its metabolites also exhibit anti-inflammatory properties.4

Intake Deficiency and Relevance

Humans do not make their own vitamin E, and so it must be taken in through diet. Despite vitamin E being essential, up to 90% of adults consuming less than the recommended daily allowance. This is why many Americans take a vitamin E supplement, which usually only includes alpha-tocopherol.

However, focusing on a single type of vitamin E may miss the larger picture. A brain healthy diet requires both alpha- and gamma- tocopherols for effective neuroprotection. Both forms may be important because high alpha-tocopherol levels were linked with lower pathologies of age-related brain disease only when gamma-tocopherol levels were also high. The reverse was true when gamma-tocopherol levels were low. This implies that too much alpha-tocopherol may “box-out” the beneficial effects of gamma-tocopherol, unless gamma’s intake is increased to compensate.5

RELEVATE’s Form of Vitamin E

RELEVATE incorporates both alpha- and gamma-tocopherol in a 1:2 (alpha:gamma) ratio to mimic brain healthy dietary intakes and to assure that alpha-tocopherol is balanced by gamma-tocopherol to synergistically improve the impact of both in the brain.6 Unfortunately, most Americans would have to depart significantly from their current dietary practices to include more seeds, nuts, fruits, and vegetables high in vitamin E, without increasing their total fat intake above the recommended levels.7

All forms of vitamin E are fat-soluble, and so it is crucial for vitamin E to be delivered in fats/oils (healthy monounsaturated and poly-unsaturated fats) to enhance its absorption through the digestive system. Thus, the alpha- and gamma-tocopherols provided in the products are derived from and delivered as natural oils and combined with omega-3, the combination of which may improve the absorption efficiency of both tocopherols.2 This way, they are delivered in wet form, rather than most multivitamins that provide it dry.

Concluding Thoughts to Consider

Research demonstrate neuroprotective qualities of vitamin E and its ability to dampen neuroinflammation and decrease of oxidative damage.1,2 Also, human epidemiological studies suggest that as the intake of vitamin E increases, there are corresponding reductions in the risk of Alzheimer’s disease and cognitive decline.6 This led to a number of earlier clinical studies that investigated vitamin E and cognitive health outcomes; however, they only involved alpha-tocopherol, and they resulted in numerous null (and hence disappointing) results.8,9 This has led to a shift in attention toward other forms and combinations of vitamin E (particularly alpha- and gamma-tocopherols), which are delivering promising results.5 This reinforces the concept that brain health (as well as other health areas) is driven best by specific combinations and ratios of various nutrients that mutually assist each other, rather than focusing on single nutrients.

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Cited Research

  1. Luchsinger, J. A., Tang, M.-X., Shea, S. & Mayeux, R. Antioxidant Vitamin Intake and Risk of Alzheimer Disease. JAMA (2003).
  2. Reboul, E. Vitamin E Bioavailability: Mechanisms of Intestinal Absorption in the Spotlight. Antioxidants 6, 95 (2017).
  3. Spector, R. & Johanson, C. E. Vitamin transport and homeostasis in mammalian brain: Focus on vitamins B and E. J. Neurochem. 103, 425–438 (2007).
  4. Jiang, Q., Christen, S., Shigenaga, M. K. & Ames, B. N. γ-Tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am. J. Clin. Nutr. 74, 714–722 (2001).
  5. Morris, M. C. et al. Brain tocopherols related to Alzheimer’s disease neuropathology in humans. Alzheimer’s Dement. 11, 32–39 (2015).
  6. Morris, M. C. et al. Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am. J. Clin. Nutr. 81, 508–514 (2005).
  7. Higdon, J., Drake, V. & Delage, B. Vitamin E. Oregon State University, Linus Pauling Institute, Micronutrient Information Center (2015). Available at: https://lpi.oregonstate.edu/mic/vitamins/vitamin-E.
  8. Petersen, R. C. et al. Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment. N. Engl. J. Med. 352, 2379–2388 (2005).
  9. Kang, J. H., Cook, N., Manson, J., Buring, J. E. & Grodstein, F. A Randomized Trial of Vitamin E Supplementation and Cognitive Function in Women. JAMA Intern. Med. 166, 2462–2468 (2006).