Vitamins B and the healthy body: new data on old facts for future aimed interventions

Introduction

Eight essential nutrients make up the suite of B vitamins also known as the B complex. Researchers from Tufts University and elsewhere have revealed that these B vitamins influence a vast spectrum of human health and disease, including cognitive function, cardiovascular health, gastric bypass recovery, neural tube defects and even cancer. Four of these B-vitamins cooperate as co-factors in many critical activities in cells in what we call ‘one carbon metabolism’. This is a series of pathways that allow for the transfer of single-carbon units to cells for essential processes such as DNA synthesis, amino acid metabolism, and more. It’s their role in all these crucial biological functions that make the B vitamins so important-and so challenging to tease out how they contribute positively and, perhaps negatively, to human health.

Heart disease, cholesterol and stroke

B vitamins have 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 (vitamin 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. Also Niacin (B₃) can lower LDL (“bad cholesterol”) and raise HDL (“good cholesterol”). But it has to be taken in such large doses that it often causes very uncomfortable flushing because the vitamin is taken under the form of nicotinic acid (which causes vblood vessel dilation). 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. HOwever, these drugs have nothing of metabolic interaction compared to a metabolite like vitamin B3.

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, since vitamin B₆ can be toxic in large amounts. Since the substance may conver itself in several cofactor forms (hydroxymethyl, methylamino- and pyridoxal or aldehyde), large amounts in the body may scramble these conversions, since each cofactrial form is needed for specific enzymatic reactions and not others.

B vitamins and pregnancy

In the United States, corn, rice, and wheat flours have been fortified with thiamine (B₁), riboflavin (B₂), and niacin (B₃) since the 1940s, which helps prevent the spread of diseases such as pellagra and beriberi. Folic acid, the synthetically produced version of folate (B₉), was added to the mandatory fortification process in the U.S. in 1998 to ensure pregnant people consumed enough of the vitamin to help prevent neural tube defects in developing fetuses. The neural tube develops into the brain and spinal cord of a fetus early in pregnancy, often before someone knows they have conceived. Because as many as 50% of pregnancies are unplanned, the U.S. government is among approximately 70 countries that mandate fortifying grains with folic acid to prevent neural tube defects. Efforts like these to increase folate levels have resulted in as much as a 70% decrease in birth defects in the central nervous system.

Folate and cancer

Research over the past 30 years has produced compelling data that shows people who consume too little folate also have an increased risk of certain cancers. More recent research at Tufts University, mostly focused on colon cancer, has shown in both animals and humans that those who chronically consume too little folate have a sizably increased risk of colon cancer, and perhaps also pancreatic and post-menopausal breast cancer. Data from animals has also suggested, however, that consuming too much folic acid might paradoxically increase the risk of certain cancers developing. And this is where controversy brews. Through their research, Tufts scientists started to notice that while adequate levels of folate are good, a super-supply yields more cancer in animals.

Intuitively, this makes sense since stimulates cellular proliferation. If you have a few cells floating around that contain mutations that could turn them into cancer cells, and mutated cancer and precancer cells multiply rapidly naturally, sprinkling a fertilizer like folate on them could likely make them multiply much more quickly. However, several large epidemiological studies have shown that the paradoxical cancer-promoting effect is not a widespread issue and, if the phenomenon actually exists, those high levels of intake are probably only achieved among people taking multiple sources of folic acid supplements.

Folate, vitamin B12 and cognition

One of the most active areas for B vitamin research is cognitive health. By the age of 75-80, 40% of people have a diminished ability to absorb food-bound B₁₂, says Mason. This deficiency leads to a decline in nerve health, particularly in the spine and brain, which can contribute to the risk of developing dementia in older adults.  For decades, clinicians and researchers thought measuring plasma B₁₂ was accurate enough to determine if supplementation was needed. However, while many elderly people may have B₁₂ levels that are in the ‘low to normal’ range, they are simultaneously developing neurological deficits linked to vitamin B₁₂ deficiency. The pathology of Alzheimer’s disease described the abnormal buildup of amyloid and tau which clump together, forming plaques and tangles which are believed to disrupt brain cell function.

Professor Rosenberg stated: “Age-related cognitive decline is not just Alzheimer’s. 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”. Yet Rosenberg says cerebrovascular disease and small vessel disease, which in some cases are connected to B vitamin deficiency, is more prevalent with cognitive decline and dementia than the buildup of harmful proteins in the brain, which has been the focus of so much research and drug development to treat Alzheimer. Treating people with drugs meant to address the protein buildup will not work if the cause of dementia symptoms is a B₁₂ deficiency.

To pinpoint a B₁₂ deficiency requires two additional tests. One, called the MMA test, measures levels of methymalonic acid, an acid produced during certain aspects of metabolism requiring adequate B₁₂. “It can be elevated with even a mild B₁₂ deficiency, indicating a potential higher risk of dementia,” says Jacques. A second test measures levels of an amino acid, homocysteine, which is also a byproduct of metabolism requiring B₁₂. If only homocysteine levels are elevated, a folate deficiency may be the problem. If both MMA and homocysteine are high, a B₁₂ deficiency is the likely culprit. 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.

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 in cellular backgraounds where there was a concrete loss of vitamin B12 or folate or and increase in homocysteine. Professor Rosenberg stated that 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.

Vitamin 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. This study should give a good handle on whether B₁₂ is related to cognitive decline and dementia. If so, hopefully scientists 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. More recent data 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.

One last critical noteworthy issue is the age- and disease-related dementia that occurs or might occur in type 2 diabetic patients. Type 2 diabetes is widely managed with metformin, which is commonly used, inexpensive and generally safe. However, it is known in time it leads to vitamin B12 depletion, making diabetic patients more vulnerable to develop cognitive impairments independently from the correct management of the disease.

• Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Miller JW et al. J Alzheimers Dis. 2025 Aug; 106(3):920-924.

Gordon S, Hoey L et al. BMC Med. 2025 Jul 28; 23(1):440.

Lin WZ, Yu D et al. Alzheimers Dement. 2025; 21(1):e14376.

Ekundayo BE et al. Eur J Pharmacol. 2024; 982:176958.

Li T, Steibel JP, Willette AA. Nutrients. 2024; 16(13):2050.