Rob Winwood of Winwood BioScience writes a guest blog for James Hutton Limited. 

Vitamin E was discovered nearly 100 years ago because it was found to be required to prevent fetal resorption in pregnant, vitamin E-deficient rats that had been fed high fat diets that were easily oxidisable (Niki & Traber 2012).

Vitamin E is the generic term for molecules that possess the biological effects of α-tocopherol. It consists of four tocopherols (α,β,γ and δ) and four tocotrienols  (α,β,γ and δ) . All of which occur naturally with α and γ tocopherol being the main vitamers found in Western diets. The word Tocopherol is derived from Greek words tocos (childbirth) and pherein (to bring forth). The α, β and δ forms of tocopherol differ in the methyl groups on the ring structure (Rs), tocopherol and tocotrienols differ in the side chain. Importantly, they all possess antioxidant activity.

In humans, only alpha – tocopherol is specially selected and enriched by the liver and is therefore the most abundant in the human body. The other vitamin E forms are much more rapidly metabolised and thus present at much lower concentrations. For example, RRR α-tocopherol has a half life in the human body of 48 hours, whereas tocotrienols only have a half life of around 4 hours.

By far the most common form of tocopherol found in plants is RRR-alpha – tocopherol (also referred to as natural or d-alpha – tocopherol). However, the vitamin E form mainly used in fortified foods and dietary supplements is all-rac-alpha-tocopherol (synthetic or dl-alpha – tocopherol).

Chiral carbon-centres are located at α tocopherol positions 2, 4' and 8' in the side chain. In naturally occurring a-tocopherol, these carbons are in the R-conformation, but can be in either the R- or the S-conformation when produced by chemical synthesis. Chemical a–tocopherol synthesis produces an equal mixture of eight different stereoisomers (RRR, RSR, RRS, RSS, SRR, SSR, SRS, SSS). Only those beginning with an R are considered nutritionally relevant, therefore when using synthetic form you need twice as much as the natural form. The stereoisomers beginning with an S possess low affinity for α-TTP (a specialist protein that maintains α tocopherol level in human tissues) and are rapidly metabolised in the liver.

DL-α-tocopherol is prepared synthetically by condensation of tri-methylhydroquinone and isophytol.

α-Tocopherol is often esterified to the acetate, succinate or nicotinate form to improve its stability, but this does reduce its potency. (A factor of 0.67 is typically used for these esters to calculate the contribution to total α-Tocopherol content of a sample). Tocopherol mixtures are widely used as an anti-oxidant in food systems with high lipid contents. They have the advantage of being regarded as a “clean-label” ingredient. Such mixtures are usually supplied commercially in a liquid form, but powdered or beadlet forms are also available. Once tocopherols are oxidised, they can be regenerated in-situ by Vitamin C.

The largest market for tocopherols is animal health. The human health market is considerably smaller with sales into the cosmetic sector, smaller still.

The key role of tocopherols in the human body is to prevent cells from oxidative stress, and indeed there is an EU article 13.1 health claim to that effect. In a wider role, they are able to protect and repair cell membranes. Specifically, they protect nutritionally critical long chain polyunsaturated fatty acids (PUFAs) from oxidation including omega 3 fatty acids. Tocopherols are widely accepted as having an important role in reproductive and maternal health.

Tocopherols are absorbed in the small intestine and from there transferred to most tissues in the human body with higher concentrations building up in the liver, muscles and adipose tissue. However, such tocopherol absorption requires the presence of fat. The NDA expert panel of the EU EFSA in 2015 considered that the average α tocopherol absorption from a typical European diet is around 75 %.

Vitamin E deficiency does not manifest itself as prominently as for most other vitamins. However, rare inherited disorders that result in vitamin E deficiency have been described. These disorders can lead to nerve damage, muscle weakness, loss of ability to walk or blindness if not treated with supplemental Vitamin E.

Medical science is continuing to understand the benefits of tocopherols in an emerging range of conditions including cardiovascular health, liver health, dementia and possible protection against the effects of air pollution. The underlying protective mechanism is that of the anti-oxidant property of Vitamin E. Particularly protecting important lipid-based components in the cell membrane from oxidation.

Medical science is continuing to understand the benefits of tocopherols in an emerging range of conditions including cardiovascular health, liver health, dementia and possible protection against the effects of air pollution.

The RDA for α-Tocopherol is 15 mg/day, which is easily achieved in a typical western diet. Indeed, in the US National Health and Nutrition Examination Survey (1999–2000) of US adults, only 0.5% had deficient plasma α-Tocopherol concentrations of less than µmol/L (Traber & Head 2021). Where clinical α-Tocopherol deficiency has been reported, it has been attributed to severe malnutrition or heavy consumption of peroxidised oil and/or ultra-processed foods.

The 2000 US Dietary Reference Intakes for α-Tocopherol of 2000 estimated the upper level (UL) to be 1000 mg/d due to an increased tendency to bleed.  Miller et al. (2005) published a meta-analysis that came to the conclusion that consumption of α-Tocopherol supplements in excess of 400 IU/day or more increased all-cause mortality, but his has been refuted by several studies since. Indeed, interventions with α-Tocopherol in a number of clinical trials has appeared to have benefits in ameliorating some degenerative illness, particularly those attributed to ageing.  However, the daily dose of α-Tocopherol used in these studies was below the UL.

The α-Tocopherol content of food samples and human tissues can be analysed using High Performance Liquid Chromatography (HPLC). In the case of foodstuffs, it is important that such analysis is carried out to verify the on-pack nutritional labelling. The specialist laboratories at Mylnefield Lipid Analysis in Scotland are well-equipped to carry out such analysis.

References:

1. Borel P et al; 2013, “Bioavailability of vitamin E in humans: an update” Nutrition Reviews Vol. 71(6):319–331
2. EFSA Journal 2015; “Scientific Opinion on Dietary Reference Values for vitamin E as α-tocopherol”; 13(7):4149.
3. Miller ER et al. 2005; “Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality”; Annals of Internal Medicine; 142:37-46.
4. Niki E & Traber MG; “A history of Vitamin E”; Ann Nutr Metab 2012;61(3):207-12.
5. Traber MG & Head B, “Vitamin E: How much is enough, too much and why!” October 2021, Free Radical Biology and Medicine 177(Pt 2); 212-225.
6. Traber M, “Vitamin E : metabolism and requirements”: January 2022; DOI:10.1016/B978-0-12-821848-8.00077-9 In book: Reference Module in Food Science.