Wednesday, May 2, 2018

Rise and Fall of Vitamin E

Vitamin E was the vitamin D of the 1990s – good for whatever ailed you. Claimed benefits led with cardiovascular disease and cancer, but piled on with macular degeneration, pregnancy, dementia and other significant diseases. With no apparent concerns about safety, there was a race up to mega-dose amounts being widely sold as non-prescription dietary supplements. Vitamin E even ended up in skin care products, with claims for helping hear scars and burns, in shampoos with claims for healthier hair. Things changed.

Worldwide, government organizations are not quite in agreement on how much is recommended and what is the safe upper limit. The U.S. recommends 15 mg/day, and up to 1000 mg/day as safe. Japan recommends 7 mg/day and no more than 900 mg/day (for men, numbers a bit lower for women). The European Union recommends 11 mg/day for women, 13 mg/day for men, and no more than 300 mg/day for both sexes. Actual consumption is less. Worldwide, median dietary intake is 6.2 mg/day for alpha-tocopherol.

Alpha- and gamma-tocopherol are the two most common
forms in plants. Alpha- has three methyl (CH3) groups on
the leftmost ring of carbon atoms while gamma- has two.
The arrows point to the difference. (Internet download).
Click on image to make larger. 
Note that intake number is for alpha-tocopherol. “Vitamin E” is actually a collection of eight chemically related but distinct molecules: alpha-, beta-, delta- and gamma-tocopherol and the same four designations as tocotrienols. Leafy green vegetables are predominately alpha-tocopherol and seed oils gamma-tocopherol (with exceptions). Palm oil is higher in tocotrienols than tocopherols. Although gamma-tocopherol is the highest percentage dietary form, our bodies create a blood transportation protein that preferentially binds only to alpha-tocopherol, making it the majority molecule in blood and organs. It is also by far the most potent antioxidant of the eight. So, “vitamin E” is usually taken to mean alpha-tocopherol, with a minor contribution to alpha-tocopherol equivalents from the other forms.     

The popularity of naturally sourced or synthetic alpha-tocopherol as a dietary supplement began with a juxtaposition of theory and observation. Vitamin E is thought to function as an antioxidant. Oxidation is all about oxygen (duh!). Normal biological processes create oxidating compounds, also referred to as free radicals, that need to be neutralized, else cell damage takes place. One of the theories of aging is that oxidation causes cumulative damage over years and years, leading to what we identify as the diseases of aging. Our bodies create antioxidants and also use vitamin E (and vitamin C, and selenium) as antioxidants. These nutrients, alone and in combination, have been heavily researched for disease prevention. With mixed results.

Observational studies tracked the lifestyle habits and health histories of tens of thousands of nurses and doctors. Results showed that those who on their own either consumed more vitamin E because of food choices, or had chosen to take vitamin E dietary supplements, had a one-third lower risk of heart disease. Publicity from this let to roughly 50% of nurses and doctors to use vitamin E as a dietary supplement. Millions of Americans followed the examples of their health care professionals. Sadly, subsequent clinical trials that enrolled people to either vitamin E or a placebo and tracked them for years were not as consistently positive. Collectively, there appears to be a modest reduced risk for heart attack, no benefit for risk of stroke, and no change in all-cause mortality. With hindsight, in the initial research, health professionals who had decided to consume vitamin E supplements may have made other lifestyle decisions that promoted good health. It is an example of correlation not necessarily reflecting causality.

Research for other diseases has also had mixed results. An antioxidant combination appears to slow progression of age-related macular degeneration, but vitamin E alone has not been evaluated. There has not been enough research for any recommendation on effects on dementia, or on Parkinson’s disease. Vitamin E in combination with vitamin C was not seen as beneficial for pregnancy outcomes. Cancer results are mixed depending on type; also some evidence that while low amounts of a supplement are beneficial, higher amounts actually increase risk (a similar cross-over effect seen for higher amounts and cardiovascular disease).

Despite the widespread belief that topical vitamin E can help with burn and wound healing, rigorous clinical trials belie that conclusion. There is no useful evidence supporting the idea that a vitamin E containing shampoo or conditioner improves hair health.

Cumulatively, doubts about efficacy and concerns for subtle negative effects of higher doses led to a massive decline in the percent of people buying vitamin E.  What to do in the face of all this ambiguity? Eat more fruits and vegetables (always an easy recommendation). Most daily multi-vitamin/mineral products will include 100% of the Daily Value for vitamin E, which can be seen as do-no-harm. Beyond that, the merits for a vitamin E as a supplement are suspect, and this is definitely not a more-is-better situation.

The Wikipedia article on Vitamin E has references for most of this content.

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