Industry experts say too narrow and too many variables

The August 20, 2008 edition of the Journal of the American Medical Association reported that B vitamins did not work effectively to prevent death or cardiovascular events in patients with coronary artery disease or aortic valve stenosis. In the wake of this report, industry experts say the study is not credible, as it failed to acknowledge elements that could have altered the conclusions.

The study, conducted from 1999-2006, on 3,096 patients in two Norwegian hospitals, was headed by Marta Ebbing, MD, at Haukeland University Hospital. The study ended prematurely due to concerns about increased cancer risk.

The study divided participants into one of four groups: daily oral treatment of folic acid plus vitamin B12 and vitamin B6; folic acid plus vitamin B12; vitamin B6 alone; or a placebo. The doses included 0.8mg of folic acid, 0.4mg of B12 and 40mg of B6. One of many questions that arose afterward was whether beta blockers, statins and anti-platelets were used for the duration. The participants began the study while in their mid-60s, and more than 75 per cent had already used the above-mentioned drugs for existing heart disease.

Another issue: Norway does not add folic acid to its wheat, as does the US. This, in turn, meant that any folic acid, B6 or B12 through supplementation or foods was not factored into the study. Analysts also believe the study involved too narrow a section of the population, and could not provide answers to what B vitamins do for healthy people, or from a preventive standpoint.

With so many variables unaccounted for in the study, one might wonder how it still went on for years without intellectual intervention. Hindsight, though, is 20/20, and the missing factors are quite evident in retrospective analysis.

Dr Andrew Shao, of the Council for Responsible Nutrition (CRN), in an interview with NPIcenter, explained that groups like the CRN "try to caution against over-interpretation of results and broad sweeping conclusions that you hear from some people." Shao added, "B vitamins may not work for people who already have heart disease, but these studies don't answer the question of whether the healthy population, if they take B vitamins on a regular basis over the course of decades, may be at a lower risk for heart disease."

Industry frequently complains, in cases like this, about study design.

Shao observed, "The study was actually pretty well designed. Every study has limitations. No matter what, you're always going to have limitations to a study, and it's important to identify those limitations; if you're overly critical, that is a really difficult position to take because no one is ever going to conduct the absolute perfect study that answers every question anyone would possibly want to ask in the world."

Despite what seem like flaws in the study, it is important to remember that a be-all, end-all cure was not the final goal for Dr Ebbing and colleagues. The study was to see if the use of B vitamins would lower homocysteine levels and help those with existing heart disease, not simply if B vitamins prevent heart disease, and it seems to have done that.

"You have a tool box of prevention, and there are all kinds of tools in there that you can use to try and keep yourself healthy and avoid disease," Shao said. "Using supplements is just one of these tools, among a whole bunch. It is not 'the' tool, it is 'a' tool. You have other components such as diet, stress, exercise [and] genetics, which is a tool you can't do anything with but you've still got it. Supplements are just one of those tools. If that's your outlook and you understand it… that's where the benefit will be seen."