The April 28, 2010, issue of The Journal of the American Medical Association (JAMA) published a paper entitled “Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy.” Several news outlets have featured this study in headline stories. In Canada, The Globe and Mail addressed the findings in “B vitamins linked to heart, kidney damage in diabetics: Diabetics with kidney damage who take B vitamins to offset their risk of heart attack and stroke may be doing just the opposite.”
The following information has been prepared by Jamieson Laboratories to offer a science-based summary and interpretation of the study’s key findings and to address inaccurate conclusions put forward in the media.
What was the objective of this study?
The stated objective of this research was to determine whether Vitamin B therapy could be used to slow the progression of diabetic nephropathy and prevent vascular complications. Diabetic nephropathy is damage to the kidneys caused by the disease of diabetes. It is an important cause of chronic kidney disease and kidney failure.
How was the study designed?
Researchers of the JAMA study, including lead author Dr. David Spence (MD), professor of neurology and clinical pharmacology at the University of Western Ontario and director of the Stroke Prevention & Atherosclerosis Research Centre at the Robarts Research Institute, designed a randomized, double-blind, placebo-controlled trial at five university medical centres across Canada.
The study ran from May 2001, to July 2007, and it included 238 participants, all of whom had Type I or Type II diabetes. All participants had previously been diagnosed with damage to their kidneys from their chronic diabetic condition and, to qualify for the study, it was a requirement that each participant have at least 300 mg/daily of urinary albumin excretion (or 500 mg/daily of proteinuria).
Each participant was given either a single-tablet B Vitamin — containing folic acid (2.5 mg/daily), Vitamin B6 (25 mg/daily) and Vitamin B12 (1 mg/daily) — or a placebo.
Was the methodology sound?
The researchers were investigating how to lower homocysteine, which greatly increases the risk of cardiovascular disease and stroke. The problem with the study design is that the researchers focused on the wrong vitamin. Folic acid and Vitamin B12, not Vitamin B6, are known to lower homocysteine. The researchers, therefore, tested the wrong B Vitamin in the largest daily dose.
Another major factor skewing the results is that all participants were already suffering from kidney disease. To qualify for the study, participants had at least 300 mg/d of urinary albumin excretion (or 500 mg/d of proteinuria). Urinary albumin levels are used to measure both the risk of kidney disease and cardiovascular disease. Levels below 300 are considered normal. So all participants were above the normal range. This suggests that each participant already had a fairly advanced risk of kidney disease and, perhaps, heart disease.
Perhaps the most significant oversight was the researchers’ failure to control for diet, exercise, smoking and other lifestyle factors associated with heart disease. Such variables have a more profound impact on kidney and heart health than a water-soluble Vitamin B6. It raises the question: was the worsening cardiovascular condition due to other risk factors, such as weight, diet or smoking?
Diabetics also experience altered leptin (the satiety hormone from fat cells) and altered levels of cortisol (the stress hormone). Both leptin and cortisol adversely affect indicators of kidney health and the clearance of electrolytes and water-soluble vitamins, any of which could distort their findings.
What did the researchers report?
The researchers primarily monitored the progression of kidney disease and then followed up by examining other health issues, including dialysis, occurrence of vascular events, all-cause mortality, cognitive decline and amputation.
Among patients with existing kidney damage, the use of B Vitamins, compared to a placebo, resulted in a greater decrease in GFR (or glomerular filtration rate), which is the best test to measure kidney function and the stage of kidney disease. The vitamin group also showed an increase in vascular events, such as heart attack, stroke, angioplasty and cardiac bypass. The data showed that total blood homocysteine levels decreased in the vitamin group compared to the placebo group. There was no difference in requirement of dialysis between the B Vitamin and placebo groups.
Is this study significant?
The study sample size is statistically insignificant. Of the 238 participants who joined the study, only 118 remained after three years.
Given the patient sample and the researchers’ failure to control for lifestyle issues, it is a stretch to conclude that 25 mg of Vitamin B6, similar to a single serving of a spinach salad, could adversely affect health.
Further investigation may need to take place to identify meaningful conclusions as the study yielded contradictory findings, such as reductions in homocysteine levels and increased cardiovascular disease. But these opposing findings may be the result of lifestyle and the prior existence of serious health conditions.
The greatest disservice to the public may be the inflammatory headlines in the daily news, which link Vitamin B to an increased risk of heart events and kidney disease among diabetics. This study does not establish such a claim. Diabetes alone, especially in its advanced form, increases the risk of kidney disease and cardiovascular disease. This study has only demonstrated that the selected B Vitamin complex does not appear to significantly reverse the serious known health conditions associated with diabetes.
What impact should this study have on my use of B vitamins?
Absolutely none. If you are in normal health, you should continue to feel confident in the safety and efficacy of consuming recommended amounts of B Vitamins as part of an overall healthy lifestyle.
People with serious chronic diseases, such as diabetes and kidney disease, should always consult their healthcare practitioners when taking natural health products. What are the key benefits of B Vitamins?
Millions of people around the world take B Vitamin supplements in complex combination formulas — typically on the advice of their doctor. The B vitamins have been associated with reductions in homocysteine levels and stress (both contributing factors in heart disease), increases in energy levels and improved nerve, liver, muscle and brain function. The B vitamins also enhance skin health. These benefits are heightened for the elderly and people on carbohydrate-reduced diets.
In Canada and the United States, studies have shown that deaths from stroke have been reduced by 10 to 15 percent lower since folic acid was added to wheat.
The family of B vitamins is also known to prevent spina bifida and neural tube defects. In 2007, the Society of Obstetricians and Gynaecologists of Canada (SOGC) noted that as many as half of all birth defects could be prevented if women of childbearing age consumed adequate folic acid. In 2007, the SOGC compiled a 15-person expert panel to affirm new guidelines recommending that, barring special health considerations, women in the childbearing years should maintain “a good diet of folate-rich foods and daily supplementation with a multivitamin with folic acid (0.4–1.0 mg) for at least two to three months before conception and throughout pregnancy and the postpartum period (4–6 weeks) and as long as breastfeeding continues.”
More than 30 case-control and prospective cohort studies have reported that folate could play a role in reducing the risk of colorectal cancer by nearly half. Anecdotally, we know that since mandatory fortification in Canada and the United States, the incidence of cancer, in particular lung cancer, has declined.
Furthermore, nearly 50,000 participants around the world are involved in 11 other major medical studies designed to illuminate the benefits of B Vitamins and help determine whether folic acid should be preventatively added to wheat in developing countries.
It has also been widely reported that supplementation with Vitamin B6 appears to offer significant protection against the development of diabetic neuropathy, or diseases of the nervous system caused by diabetes. Diabetics with neuropathy have been shown to be deficient in Vitamin B6 and they benefit from supplementation.
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