Tufts researchers report that eight key vitamins might affect dementia, cardiovascular disease, and other health conditions.
Eight vital nutrients form the group of B vitamins known as the B complex. Research at Tufts University and beyond has shown that these vitamins play a role in many areas of health, influencing brain function, heart health, recovery after gastric bypass surgery, the prevention of neural tube defects, and even the risk of cancer.
“It’s hard to study the B vitamins in isolation,” explains gastroenterologist Joel Mason, senior scientist at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) and professor at the Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy and Tufts University School of Medicine. “Four of these B-vitamins cooperate as co-factors in many critical activities in cells in what we call ‘one carbon metabolism’.”
One carbon metabolism refers to interconnected pathways that enable cells to transfer single-carbon units for vital functions such as DNA synthesis and amino acid processing. Because B vitamins are central to these processes, they are both indispensable to human health and difficult to evaluate individually, as their effects often overlap.
Mason, along with two other long-time B vitamin researchers, outlines what is currently understood about how five of the most extensively studied B vitamins influence both cognitive performance and cardiovascular health.
Cognitive Health, B12, and Folate
Cognitive health remains one of the most heavily studied areas of B vitamin research. According to Mason, by the time individuals reach ages 75 to 80, about 40% experience reduced ability to absorb food-bound vitamin B12. This shortage contributes to deterioration in nerve health, particularly in the brain and spinal cord, increasing the risk of dementia in older adults.
For many years, clinicians assumed that plasma B12 measurements were sufficient to determine whether supplementation was needed. Mason notes, however, that many older adults whose B12 levels fall within the “low to normal” range still develop neurological impairments caused by vitamin B12 deficiency.
“The contribution of vitamin B12 deficiency to cognitive decline and the vascular disease that results in many cases of dementia is underdiagnosed and underreported,” explains Irwin H. Rosenberg, Jean Mayer University Professor Emeritus at Tufts and former dean of the Friedman School of Nutrition Science and Policy, who also taught pharmacology at the School of Medicine.
“Age-related cognitive decline is not just Alzheimer’s,” Rosenberg adds. “We’ve lumped together many kinds of brain dysfunction under one name. And in doing so, we’ve overlooked how critical blood vessels—and by extension, nutrition—are to preserving brain function.”
Alzheimer’s disease has traditionally been associated with the buildup of two proteins in the brain, amyloid and tau, which aggregate into plaques and tangles believed to interfere with neuronal function.
Rosenberg points out, however, that cerebrovascular disease and small vessel disease—both of which may be influenced by B vitamin deficiencies—are more commonly linked to dementia and cognitive decline than the accumulation of these proteins. He emphasizes that drug treatments targeting protein buildup will not be effective if B12 deficiency is the underlying cause.
This makes it essential to test for B12 deficiency when evaluating dementia symptoms, Rosenberg argues.
“B12 tests measure all B12 in your system, even though approximately 80% is inactive,” says Paul Jacques, senior scientist at the HNRCA and professor at the Friedman School of Nutrition Science and Policy.
To properly diagnose a deficiency, two additional tests are required. The first, the MMA test, measures methylmalonic acid, a metabolic byproduct that rises when B12 levels are insufficient. “It can be elevated with even a mild B12 deficiency, indicating a potential higher risk of dementia,” Jacques explains.
The second test measures homocysteine, another compound produced during metabolism that also requires B12. If only homocysteine is elevated, folate deficiency may be the cause, but if both MMA and homocysteine are high, B12 deficiency is the most likely explanation.
Reversible causes of cognitive decline
If a patient presents with neurological issues or signs of dementia, conducting all three tests will narrow down if a B vitamin deficiency is involved—and which B vitamin it is.
“Unlike changes that we are unable to see in patients being given expensive anti-amyloid antibody drugs to treat Alzheimer’s disease, there is actually evidence that fairly early in the course of cognitive decline we can slow the process if the underlying cause is elevated homocysteine or B12-related deficiency,” says Rosenberg. “It’s my recommendation that patients, with or without anemia, should be screened for elevated homocysteine or B12 deficiency because that may be one of the reversible factors in their cognitive decline.”
This isn’t a new theory. Two decades ago, studies like the Framingham Heart Study showed that elevated homocysteine predicted brain atrophy and a higher risk of dementia. More recently, trials such as VITACOG and FACT have shown that B vitamin supplementation can slow brain shrinkage and improve cognitive performance in those at risk.
“There is an enormous amount of education needed around this issue,” Rosenberg says. “We hope to convince cardiologists, neurologists, and internists to measure B12 and homocysteine levels as part of the evaluation of cognitive impairment. Even the modest effects from vitamins that cost pennies a day can be very meaningful in those who will benefit, especially when you compare vitamin supplementation to costly drugs that are getting much more attention yet may have the same or even less benefit.”
“There is evidence that fairly early in the course of cognitive decline we can slow the process if the underlying cause is B12-related deficiency,” said Irwin H. Rosenberg, Jean Mayer University Professor Emeritus and former dean of the Friedman School of Nutrition Science and Policy
B12 and Dementia
Jacques and colleagues currently are leading a study using data from about 2,500 middle-aged and older adults in the Framingham Heart Study, all of whom were free of dementia in the 1990s and all of whom received B12, MMA, and homocysteine testing for the last 20+ years.
“The risk of dementia and late-stage Alzheimer’s begins to increase when one is 75 years old or older, but evidence suggests that some of the pathological changes associated with dementia and Alzheimer’s may start to develop 20+ years before clinical symptoms and diagnosis occurs,” says Jacques. “This study should give us a good handle on whether B12 is related to cognitive decline and dementia. If so, hopefully we can identify a simple, inexpensive intervention that could be started years in advance and before real damage occurs.”
Jacques is also looking at the role folate (B9) may play in the development of cognitive issues, specifically the influence high levels of folate might have on B12 and cognitive health.
In the 1950s, people with anemia were treated with folic acid, the synthetic form of folate. Unfortunately, it became clear that while pharmaceutical level treatment with folic acid alleviated anemia, it often masked or exacerbated B12 deficiency. “Scientists observed that people with low B12 and high folic acid concentrations tended to have cognitive issues,” Jacques says.
More recent research suggested that it wasn’t total B12 concentrations that folic acid might be affecting, but perhaps just one component, holoTC, which is the form of vitamin B12 that is crucial for transporting and using B12 in cells and is considered a potentially better indicator of vitamin B12 status.
Jacques and colleagues are conducting two studies to tease apart the issues involved. “In the first, our B vitamin and brain aging study, we will look at the influence high folate status has on the relationships between B12 and cognitive health. A second study we are doing in collaboration with Rutgers will look at the effect of high folic acid in the blood on the two forms of B12 —holoTC and unbound cobalamin.”
Heart Disease, Cholesterol, and Stroke
B vitamins have also stirred excitement among researchers because of their possible role in heart disease and stroke prevention, but thus far their utility as a clinical treatment remains limited.
Scientists discovered in the early 2000s that riboflavin (B2) could decrease blood pressure very effectively. It is believed that riboflavin improves a biochemical reaction mediated by a gene called MTHFR (methylenetetrahydrofolate reductase) that helps the body use folate. Riboflavin is only effective in reducing blood pressure specifically in patients with the MTHFR 677 TT genotype, however.
Vitamins B6, B12, and folate help the body rid itself of homocysteine, which in overabundance had been linked to an increased risk of heart attacks and strokes, as well as dementia. However, a number of clinical trials in the 1980s showed that B6, B12, and folate supplementation didn’t decrease heart attacks, but did slightly lower the risk of strokes.
Niacin (B3) can lower LDL (the so-called “bad cholesterol”) and raise HDL (the so-called “good cholesterol”). “But it has to be taken in such large doses that it often causes very uncomfortable flushing, like hot flashes,” says Mason. “People often can’t tolerate taking it, and other drug options are available that lower blood LDL that do not have such unpleasant side effects.”
Chronic Inflammation and B6
Perhaps most promising for the future is the role vitamin B6 may play in curbing inflammation, which has been identified as an underlying feature of many chronic diseases, from heart disease to diabetes to arthritis to dementia.
A number of animal studies, plus some human studies, suggest that supplemental B6 can reduce inflammation. “Again, we are talking about giving B vitamins at an appropriate pharmaceutical level under the care of a clinician,” cautions Mason. “B6 can be toxic in large amounts.” He sees this research as an area to watch in the years ahead.
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