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Effects of vitamin E on patients with mild cognitive impairment

Form Rides With Function

A single study proves nothing, no matter how well designed and executed it may be. But a single study with a key element missing manages to prove less than nothing.

You may have heard the news last week (it was widely reported by the TV networks) that a Johns Hopkins study in the New England Journal of Medicine found vitamin E to have no effect on patients with mild cognitive impairment. Given the scope of the study, this is a significant finding. Over three years, nearly 770 subjects received daily doses of 10mg of donepezil (a drug for cognitive impairment), or 2,000 IU of vitamin E, or a placebo.

Pretty conclusive, right? Three years – 2,000 IU of vitamin E daily (a particularly high dose) – and no effect on mild cognitive impairment. But there was one element missing in this study. And it’s a glaring omission that calls the validity of the research into question.

What’s wrong with this picture?

Any time you see a placebo-controlled study about vitamin E, this question MUST be answered: What form of the vitamin was used? I read the Hopkins study. Again and again vitamin E is referred to without ever stating the form. This is significant because some studies have used the synthetic dl-alpha tocopherol form of vitamin E with poor results. Here’s how HSI Panelist Allan Spreen, M.D., describes this form: “This is a molecule shape that the body is not designed to handle, whereas the ‘d’ form alone is the one the body is able to use. It is important to use the ‘dl’ form only topically.”

But the form question doesn’t end there because vitamin E also comes in beta, delta and gamma forms. When these forms are combined with d-alpha you have mixed tocopherols. The d-alpha form is often used alone, and that’s fine, but in a study when you’re putting the reputation of vitamin E to the test – at 2,000 IUs per day for three years, no less! – you’ve got to use the mixed tocopherols. Got to.

In the end, the validity of the Hopkins study rests on whether or not a mix of tocopherols was used, or if dl-alpha was used, or if d-alpha was used alone. But we simply don’t know. If I was the editor of the New England Journal of Medicine, I’d hand this study back to the researchers and say, “Come on, guys, this is bush league. You need to fill in all the details before I consider it for publication.”

Sum of the parts

To get a better idea of the effect that vitamin E might have on cognitive impairment, let’s look at two previous Johns Hopkins studies. Note that the first study concerns dietary intake – no supplements – and the second concerns interviews about supplement intake. In other words, unlike the new study, neither of these were placebo-controlled.

In study number one (reported in 2002), nearly 580 subjects, aged 60 or older, were followed for more than seven years. After adjusting for gender, education, and age (all factors that come into play with AD risk), a diet high in vitamin E was strongly associated with a significant reduction of Alzheimer’s risk. Intake of dietary vitamin C was somewhat useful in reducing AD risk, but not nearly as effective as vitamin E.

Nearly two years later, another Johns Hopkins team interviewed more than 4,700 subjects (aged 65 or older) in Cache County, Utah. Supplement intake was assessed, as well as the prevalence of dementia and Alzheimer’s disease, from 1995 to 1997, and again from 1998 to 2000. The collected data showed that in the first phase, those who took supplements of vitamins C and E combined had a 78 percent lower risk of AD. In the second phase, the percentage dropped to 64, but still indicated a significant level of protection.

In addition, subjects who took a vitamin E supplement along with a multivitamin that contained vitamin C, had a lower AD risk. But researchers found no evidence of protection among subjects who took vitamin C or E supplements alone (with no multivitamins), or among subjects who took multivitamins alone, or multivitamins with B-complex supplements (with no additional C or E).

What’s significant here is the recognition that multivitamins are useful, but key vitamins such as C and E may deserve additional supplementation.

Come and get it

Good dietary sources of vitamin E include spinach, eggs, nuts and seeds, avocados, tomatoes, peaches, and blackberries.

As for supplements, in the e-Alert “C-ing Double” (6/12/03), HSI Panelist Allan Spreen, M.D., recommended 400 IU of vitamin E daily (ideally, as d-alpha or mixed tocopherols, of course), as well as 200 mcg of selenium for general antioxidant protection. And while it is possible to get too much selenium, a range of 200-400 mcg daily is considered quite safe.

“Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment” The New England Journal of Medicine, published online 4/13/05, scheduled for publication in the June 9, 2005, issue of NEJM,
“Reduced Risk of Alzheimer Disease in Users of Antioxidant Vitamin Supplements: The Cache County Study” Archives of Neurology, Vol. 61, No. 1, January 2004,
“Study: High Doses of Vitamins Ward Off Alzheimer’s” Reuters Health, 1/19/04,