Alzheimer's Slowed By B Vitamins: Junk Science?

With the accelerating push to control vitamins as drugs, beware junk science claiming benefits from vitamins.

by Heidi Stevenson

11 September 2010

Recent reports hail three of the B vitamins as slowing the progression of Alzheimer's disease. Unfortunately, close examination of the study simply doesn't support the claims. It's a prime example of the manipulation of science for the benefit of Big Pharma. Ultimately, what it does is create yet another excuse for classifying vitamins as drugs, making them available only by prescription and from Big Pharma.

When modern medicine routinely produces junk science that tries to show vitamins as both dangerous and useless, it's heartening to see something that purports to demonstrate their effectiveness. But we need to be cautious before accepting such results. Could the study be a wolf in sheep's clothing? In fact, it is.

The Study

Published by the Public Library of Science One (PLoS One), the study entitled "Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial", concludes:

The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins.

The study presumed that lowering homecysteine would have a beneficial impact on brain atrophy, so lowering homocysteine levels would result in improvements in Alzheimer's symptoms. Three B vitamins, B₆, B₉ (folic acid), and B₁₂, are believed to lower homocysteine levels, so the authors reasoned that large doses of them would improve Alzheimer's outcomes.

Funding

As ever, it's of great value to know who funded a trial and what financial connections the authors have with potential beneficiaries. In this study, it likely explains the results.

The vitamins and placebos were provided by Meda AB's subsidiary, Recip AB, a large Swedish pharmaceutical firm.

Drs. Helga Refsum and AD Smith have been paid by Recip AB as speakers. They also receive funds from Axis-Shield, which makes equipment to assay homocysteine.

The lead author, Dr. AD Smith, is an inventor named on two Oxford University-held patents on the use of folic acid to treat Alzheimer's. Oxford's rules would allow him to benefit financially if the university utilizes the patent.

The study was done under the auspices of OPTIMA, the Oxford Project to Investigate Memory and Ageing. It receives funding from several sources, including Merck & Co, a major pharmaceutical firm. Of course, as a part of Oxford University, which own patents involving folic acid, there is motivation to find a connection between Vitamin B and Alzheimer's.

With connections to Big Pharma and potential financial gains from the results, this study needs to be examined very carefully for bias.

Method

The study used 271 people aged 70 and over who were defined as having "mild cognitive impairment". They were chosen because their rates of brain atrophy were greater than are generally found, so it's presumed they're more likely to develop Alzheimer's.

187 agreed to undergo brain MRIs at the beginning and end of the two-year study. Whether these subjects had different characteristics than those who didn't agree to MRIs was not examined.

Subjects were randomly divided into two groups, a placebo group of 133 people and a vitamin-taking (active) group of 138 people. The vitamin doses given were:

• B₆: 20 mg/day, 80% of the upper limit
• B₉: 800 µg/day, 80% of the upper limit
• B₁₂: 500 µg/day, 2.5% of the upper limit

Please take note of upper limits. The authors of the study claim that the doses used were exceptionally high and potentially dangerous. Yet, not a single one even reaches the level that the European Food Safety Organisation (EFSO) considers to be potentially risky with chronic intake. Note also that the vitamins are not from natural sources. They are simply chemicals produced like drugs by a pharmaceutical company.

Each of these was included in a single pill manufactured by Meda AB/Recip AB as TrioBe Plus^®. It is available in Sweden, but only by prescription.

No explanation is given for the specific doses chosen, though it's obvious that it was predefined by the drug company, which clearly stands to benefit by the results.

23 of the active group and 20 of the placebo group were lost to follow-up. Reasons included withdrawal, development of cancer, miscellaneous reasons, and 2 deaths in the active group only. No discussion of the causes of death was given! In fact, they concluded:

There was no difference in serious adverse events according to treatment category.

Death simply wasn't considered a negative effect. We do not know why they died—and without that information, there's little reason to treat the authors' views of the results as having much meaning.

Analysis Method

The study utilized the intention to treat method of analysis. This means that all subjects who entered the trial were considered equal in terms of their adherence to the methods. Specifically in this trial, it means that whether a subject adhered to taking the prescription was not a consideration in the results. If the subject was still in the study at the end, that subject was counted.

Subjects were not told to refrain from taking B vitamins. Those who took over 300 micrograms of B₉, 3 milligrams of B₆, or 1.5 micrograms of B₁₂ before the study were eliminated from participation. However, those who were accepted were left to take whatever they chose.

Nonetheless, compliance was analyzed—but it wasn't based on knowledge of whether the subjects followed instructions. Compliance was determined by blood analyses of plasma concentrations. In other words, compliance was presumed, based on levels of vitamins in the blood. Also, no consideration was given to the fact that certain drugs, such as Nexium, can interfere with absorption of these vitamins. Whether active subjects classified as noncompliant might have been unable to metabolize the pill ingredients is unknown.

The analyses were quite complex. Age was treated as a confounding factor, and several other factors not defined in the article were adjusted for in the statistical analyses.

Only those people whose MRI scans were considered technically good were considered in the MRI analyses. One must wonder precisely how poor scans were determined. The MRIs were performed under guidance by study authors who are employed by Oxford, not in independent labs.

Conclusions

The authors reported that the rate of brain atrophy was 29.6% lower in the active group.

The authors did not report on the number of subjects whose brains atrophied over the two years, nor did they report on the number whose brains atrophied while their homocysteine levels increased or decreased. This is actually a far more interesting point. Taking the average tells nothing about actual outcomes.

The best way to see this is by looking at a graph the authors supplied:

The rate of atrophy is charted along the y-axis as a percent and the change in homocysteine level is charted along the x-axis. Round blue dots refer to placebo group members and square red docts refer to active group members. What is entirely clear from this chart is that not all brains shrank in either the active or placebo groups. In fact, they often didn't!

It's obvious that there is so much variation among individuals that the statistic of 29.6% shrinkage per year is meaningless when applied to each person. A scatter plot like this is far more revealing than a single statistic, especially one that is based on such a small study with so many weaknesses in design.

Junk Science

The authors of the study stand to gain from the claimed results. Unfortunately, the study was done in a manner that supports the desire of Big Pharma to take over the vitamin industry. Flaws and highly questionable facts include:

• The authors themselves stand to benefit from the results. The group that produced the study is a division of the university that stands to profit from its related patents.
• No thought was given on what potencies of each vitamin should be used. An off-the-shelf prescription-only product sold by a pharmaceutical company was used. That sounds more like a trial to demonstrate the efficacy of a product than to determine whether specific vitamins offer a benefit.
• Two deaths, both from the active group, were deemed to be so insignificant that they weren't counted as adverse effects, and the reasons for their deaths weren't reported.
• Subjects' compliance was not followed. Only a presumption of their compliance, based on blood serum results, was considered. The fact that certain drugs can interfere with absorption of these vitamins wasn't factored in.
• MRIs that weren't considered of high enough quality were not included, but the people who made those determinations (or supervised those who did) were authors of the study.
• A revealing scatter graph clearly documents the most significant flaw of all, an inherent error in the way that modern medicine addresses health. Rather than recognizing that people are individuals, they are thought of as a homogenous group.

The study was done to promote the idea of vitamins as drugs that should be controlled and made available only through prescriptions. It was done to try to prove that folic acid (B₉) raises homocysteine levels, which slows brain shrinkage, which slows the onset of Alzheimer's. The flaws were simply too great for any of those claims to be taken seriously.

A legitimate study might show that taking certain B vitamins, or other nutrients, can slow or prevent Alzheimer's. That, though, wasn't the goal of this one. Its secondary goal was to show that a particular product available only by prescription and supplied by a pharmaceutical corporation can slow the onset of Alzheimer's. It was also intended to give the impression that safe use of vitamins needs to be placed in the hands of doctors.

Close examination demonstrates that the study failed miserably. It doesn't prove what it attempts to prove—but, as in the new modern medical pseudoscience tradition, that didn't stop the authors from claiming that it did. The author made the bold statement:

It's a bigger effect than anyone could have predicted, and it's telling us something biological. These vitamins are doing something to the brain structure—they're protecting it, and that's very important because we need to protect the brain to prevent Alzheimer's.

To be quite frank, when a study's lead author makes such a bold statement about such a limited trial, it's a reasonable assumption that the author has an ulterior motive—and that motive nearly always has dollar signs attached.

What was the study's primary goal? The most significant purpose was to convince the public by producing mass publicity through the news media and charities. In that, it was a rousing success.

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