Vitamins B6, B12, and folic acid can lower homocysteine levels and …

The personal loss of thousands of prized brain cells every day is not inevitable 

You’ve heard it so many times, it seems as if mother was the first to say, “the older you get, the more brains cells you lose.” Since then, it is probable that you have dreaded what you believed you were powerless to do anything about—the personal loss of thousands of those prized cells every day. This idea has been a centerpiece of scientific dogma and popular lore for nearly 60 years. But is it true?

With the recent advent of longitudinal magnetic resonance imaging (MRI) studies, the answer is now clear.1 Yes, it’s true. Moreover, it’s foretold even in cognitively healthy subjects. Given that the brain is the center of the nervous system and that its mechanisms determine who you are, the death of brain cells could add up to something terrible.

Our Most Precious Organ

The brain, in close connection with your primary sensory apparatus, affects what you see and hear, and what you taste and smell. It even allows you to remain on your feet and balance yourself. So too . . . what you think, what you feel, along with everything that affects your consciousness, your autonomic nervous system, and a great deal more. Crucially, the termination of brain cells can affect not only your senses, which provide the raw input to your brain, but your overall cognition, how you apprehend the world, and what you are able to do about it. Your brain is precious and when the loss of its cells leads to brain atrophy (aka, brain shrinkage) and consequential memory loss, this predicament can lead to great tragedy in your life.

In the last few years, scientists have frequently observed that shrinkage, especially in older individuals, is associated with cognitive decline. In the elderly, there is significant progressive atrophy, and as previously stated, atrophy occurs even in cognitively healthy subjects. However, it is much more advanced in patients suffering from Alzheimer’s disease, while in those with mild cognitive impairment (MCI), an intermediate rate of atrophy is found. Given that the rate of brain shrinkage speeds up in subjects with MCI, who then progress to Alzheimer’s disease, it is imperative to identify causes that underlie the rate of atrophy. If the rate of atrophy can be reduced, that alone should slow the conversion to Alzheimer’s disease.

The brain, as the center of the 
nervous system, determines who you 
are; thus the death of brain cells 
could add up to something terrible.

Scientists have also discovered that homocysteine is a risk factor for brain atrophy, cognitive impairment, and especially dementia. This has been shown in many cross-sectional and prospective studies. The concentrations of homocysteine in tissue and plasma are significantly determined by the body’s level of certain B vitamins (folate, B6and B12), which serve as cofactors or substrates for enzymes that alter homocysteine metabolism. Homocysteine can be recycled into methionine or converted into cysteine with the aid of B-vitamins, thereby diffusing its destructive potential. And as it turns out, that’s a good thing for preserving brain power and memory.

A Good Reason to Wake Up

A single-center, randomized, double-blind placebo-controlled trial has determined that supplementation with high-potency B vitamins can lower levels of total homocysteine, and slow the rate of brain atrophy in subjects with MCI by half.2 That’s quite extraordinary and an idea which by itself should enable a lot of people to get out of bed in the morning!

A new study has determined that 
supplementation with high-potency 
B vitamins can lower levels of 
total homocysteine, and slow the 
rate of brain atrophy in 
subjects with MCI by half.

The new study, conducted at Oxford University in the U.K., selected 271 individuals over the age of 70 years with MCI who were randomized to receive either high-dose folic acid, vitamins B6 and B12 or placebo. A subset of 187 volunteered to have cranial MRI scans at the beginning and end of the study and of these, 168—85 in vitamin treatment group; 83 in the placebo group—completed the MRI part of the trial. The vitamin group was given 800 mcg of folic acid per day, 500 mcg of vitamin B12 per day and 20 mg of vitamin B6 per day for 24 months, while the other group received placebo during the same period. The principal outcome measured was the change in brain volume with regard to the rate of atrophy evaluated by serial volumetric MRI scans.

Brain Volume Maintenance Means Better Memory

When the results came in, B vitamin treatment produced a difference in final homocysteine concentration of 31.7% compared with the placebo. Along with that, there was a reduction in the rate of brain atrophy of almost 30%. Because there were no safety issues, the researchers concluded that high doses of B vitamins can be used to reduce the rate of atrophy of the brain in elderly people with MCI. Furthermore, the treatment response correlated with baseline homocysteine levels: there was a 53% lower level of atrophy in the vitamin treatment group compared to the placebo group, suggesting that brain atrophy corresponds directly to homocysteine. In other words, the subjects who had the highest levels of homocysteine at the start of the trial benefited the most from treatment with high doses of B vitamins. But whatever the initial level of homocysteine in the B vitamin group, that alone did not prevent a reduction in brain atrophy. While some might suggest that that this finding proves the view that raised homocysteine is a direct cause of the atrophy, it does not exclude that idea that homocysteine is but a marker for low-normal levels of the vitamins, which are themselves causal.

An analysis done at the end of 
the study found that a greater rate of 
atrophy was associated with 
lower cognitive tests scores.

The researchers found that when either vitamin B12 status or folate status was increased, either was associated with a reduced rate of atrophy. They could not determine which of these two vitamins was the most important. However, the association of atrophy with the change in a marker of vitamin B6 status, could indicate that vitamin B6 plays a lesser role as a determinant. In a cross-sectional study, the supplementary intake of either vitamin B6 or vitamin B12, but not of folate, was associated with more regional gray matter volumes in an elderly cohort.3

Brain Atrophy Reduces Cognition

Even though the study was not designed to detect an effect of treatment on cognition (these findings are to be reported separately), a post hoc analysis found that a greater rate of atrophy was associated with lower cognitive tests scores at the end of the study. In other studies for longer periods (up to 5 years), the rate of whole brain atrophy in MCI has been correlated with cognitive decline in several tests, including the Mini-Mental State Examination.4 However, the bigger looming issue is misted in the feed waters of overall cognitive decline. Which is that 16% of those over 70 years of age have MCI and that about one half of those go on to develop Alzheimer’s disease. Furthermore, accelerated brain atrophy is characteristic of individuals who convert to Alzheimer’s disease.

There are few, if any, reports that 
would challenge the safety of 
the vitamin levels of folate, 
B6, and B12 given.

According to Dr. A. David Smith of Oxford University’s department of pharmacology, who co-led the trial, “This is a very dramatic and striking result. It’s much more than we could have predicted.”5 The scientists, all from Oxford, said their two-year clinical trial was the largest to date into the effect of B vitamins on MCI. Not surprising, “experts” commenting on the findings said they were important and called for larger, longer full-scale clinical trials to see if the safety and effectiveness of B vitamins in the prevention of neurodegenerative conditions could be confirmed.

Safety in a Non-Issue

But the study’s level of B vitamin use is quite common—and has been for many years in the U.S.—and there are few, if any, reports that would challenge the safety of the levels given. Yet co-leader Dr. Helga Refsum stressed that vitamins were given in extremely high doses. She said, “This is a drug, not a vitamin intervention.”3 Professor Refsum, M.D., Ph.D., is European, with positions at both the University of Norway and Oxford, and she should know that in the U.S. these levels are quite common. Think about it, where did they get the idea to test these levels? According to the nonprofit, nongovernmental Institute of Medicine6—one of the four United States National Academies—the Tolerable Upper Intake Levels for each of the vitamins is many times greater than the amount used. The Tolerable Upper Intake Level (UL) is “the highest level of daily nutrient intake that is likely to pose no risk of adverse health to almost all individuals in the general population. As intake increases above the UL, the risk of adverse effects increases.”

Delaying Alzheimer’s Disease

Continuing with expert comments, “It is our hope that this simple and safe treatment will delay development of Alzheimer’s in many people who suffer from mild memory problems.” Alzheimer’s is a mind-wasting disease for which there are few treatments, and those have limited value and do not represent a cure. It affects 26 million people the world over.

One has to wonder why a generally 
supplement-hostile press has given 
this study so much coverage?

The supplements used in the study, called TrioBe Plus,® were manufactured by a Swedish Pharmaceutical company Meda AB/Recip AB. This would seem to be another case of Big Pharma’s wolf in sheep’s clothing. To confirm this, the researchers warned that the results of the study can only be achieved with “very high” dosages of the vitamins (see Dr. Refsum quote above), which should only be administered under the supervision of a doctor. And—haven’t we heard this before—further studies are needed to confirm the safety of B vitamins. Moreover, the researchers were also quite clear in saying that the dosages used in the study are not likely to be found in a typical health food store or pharmacy. This may be true in Europe where the European Union’s legal restrictions for food supplements, combined with proposals from the European Commission to restrict dosages, have succeeded. But it’s not true in the U.S.

Doesn’t it seem as if the experts quoted by the press are in league? Their goal appears to be to prevent you from taking the initiative to save your memory from age-related memory loss by taking B vitamins? It certainly would appear that vested interests are at play, and that they want to scare people away from vitamins and supplements, all the while pushing them towards patented “drug” versions— TrioBe Plus is patented by one of the co-leaders of the study*—that can only be taken under the supervision of conventional doctors.

* Dr. A. D. Smith is an inventor on two patents held by the University of Oxford on the use of folic acid to treat Alzheimer’s disease (US6008221; US6127370); under the University’s rules it is possible that he could benefit financially. Drs. Refsum and A. D. Smith report received speaking honoraria from Recip AB, the company that donated the vitamin tablets, and from Axis-Shield, manufacturer of the equipment used to assay homocysteine. However, according to the “Competing Interests” note in the paper, these competing interests do not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials.

There is a similar game plan underway in the U.S., which is now in deployment elsewhere in the world, as well as in Europe. And that plan is to take natural products out of the hands of the consumer and transfer supplements into the hands of pharmaceutical giants and mainstream medicine. It is truly amazing that they are doing this, even when there is no risk to the consumer! One has to wonder why a generally supplement-hostile press has given this study so much coverage? It’s simple to understand when you realize that supplements are the envy of the pharmaceutical industry and they’d like to get their hands on the vitamin and supplement market with their patented vitamin drugs. Then they can dominate the market and increase profits substantially by driving the competition out, even if they must team-up with regulators and the media to get their misleading message across. But this is something that they already do (and help to sustain) with drugs.

Improved Cognition in Vitamin Takers

Although the trial was not designed to measure cognitive ability, the researchers found those people who had lowest rates of shrinkage had the highest scores in mental tests. Commenting on the study, Paul Matthews, a professor of clinical neurology at Imperial College London said that although the vitamins used are generally safe and inexpensive, the study “should not drive an immediate change in clinical practice.” Here again, we have the wait-forever attitude. Supposedly, those with MCI should wait until they develop Alzheimer’s disease, one could conclude. “Instead, it sets out important questions for further study and gives new confidence that effective treatments modifying the course of some dementias may be in sight,” he said.


If you aren’t already taking 
high levels of the vitamins (folate, 
B6 and B12) for which the data is so 
clear and the safety so apparent, 
it may be time to examine 
whether you already suffer from 
brain shrinkage.

If you aren’t already taking high levels of the vitamins (folate, B6 and B12), for which the data is so clear and the safety so apparent, it may be time to examine whether you already suffer from brain shrinkage. But, seriously, it’s never too late and the choice is yours.


  1. Resnick SM, Pham DL, Kraut MA, Zonderman AB, Davatzikos C. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci 2003;23: 3295–3301.
  2. Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, et al. (2010) Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS ONE [online journal]. 2010;5(9):e12244.
  3. Erickson KI, Suever BL, Prakash RS, Colcombe SJ, McAuley E, et al. Greater intake of vitamins B6 and B12 spares gray matter in healthy elderly: A voxel-based morphometry study. Brain Res 2008;1199:20–6.
  4. Jack CR, Jr., Shiung MM, Gunter JL, O’Brien PC, Weigand SD, et al. Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. Neurology 2004;62:591–600.
  5. Kelland K. B vitamins found to halve aging brain shrinkage. Reuters Health, September 9, 2010.
  6. Institute of Medicine, Food and Nutrition Board. Folate. In: Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington DC: National Academy Press; 1998, 196-305.