Antioxidants, Multivitamins, Minerals, and Souvenaid

B Vitamins

In my video see.nf/homocysteine, you can learn what homocysteine is, what it does, and what preclinical and epidemiologic evidence exists for a link between homocysteine and dementia. In short, it is a toxic metabolite that is produced naturally in the body and whose level can be lowered with the help of three vitamins: folate, vitamin B12, and vitamin B6. A number of more recent systematic reviews and meta-analyses of randomized controlled trials on vitamin B supplements have found no effects on overall cognitive function in healthy or impaired individuals. The vitamins also do not appear to slow decline. Normally, the case would be closed at that point, but a deeper dive into the subject suggests that the situation is more complex.

The concern is that vitamin B deficiency could lead to homocysteine, and that in turn to dysfunction in the brain. If you give vitamin B supplements to people without that deficiency and without elevated homocysteine levels, then negative results do not help answer the question. In the VITACOG study, for example, hundreds of men and women with mild cognitive impairment were randomized for two years to either placebo or the B vitamins that lower homocysteine—folic acid (the supplemental form of folate), B12, and B6—without any overall benefit being found. However, when the analysis was limited to those who needed the supplement, meaning those who had an above-average homocysteine level at the start of the study, the scientists found a significant benefit for overall cognition and some memory measures. Even more remarkable was that the brain shrank less.

As we age, our brains slowly shrink. The brains of people at least 90 years old weigh about 10 percent less than those of people in their mid-50s. That corresponds to a loss of about 140 grams of brain. In Alzheimer’s patients, shrinkage progresses much faster; in people with mild cognitive impairment, at a moderate pace. In the VITACOG study, the rate of brain atrophy in subjects with high homocysteine levels who were randomized to receive B vitamins was cut in half. In regions that are particularly vulnerable to Alzheimer’s, the vitamin B supplements reduced shrinkage by as much as sevenfold. The scientists concluded: “We show that in mild cognitive impairment, a simple and safe treatment of homocysteine can slow accelerated brain atrophy.”

But an adequate vitamin B status can explain only a fraction of the failed studies. The overwhelming majority of studies involved individuals with elevated homocysteine levels of over 12 µmol/l. A more far-reaching problem is the lack of baseline data on cognitive abilities. For about three quarters of study participants, they were not collected. The reason is that most large vitamin B supplementation trials were originally intended to investigate not the effects of lowering homocysteine on cognition, but on cardiovascular disease, and the researchers added the cognitive measures at the end merely as a secondary outcome. Why are baseline measures so important to us? If subjects are randomized to B vitamins or placebo and then months or years later all show the same brain values as at the beginning, doesn’t that prove that B vitamins have no cognitive benefit? Not if performance did not decline in either group. Only if there was measurable cognitive decline in the placebo group would the B vitamins have prevented anything. “In other words,” wrote a pair of reviewers, “you can’t prevent something that isn’t happening.”

The Alzheimer’s Disease Cooperative Study met both criteria to properly test vitamin B supplementation: high homocysteine levels at baseline and a worsening of mental performance in the placebo group. 18 months later, there was no overall difference in cognition between the two groups. A planned subgroup analysis, however, found a significant slowing of cognitive decline in the vitamin B group among people with mild dementia, but not in those with more advanced disease. How could nutrient deficiency be avoided from the start?

How to Lower Homocysteine

Most people get enough B12 and B6, but older individuals get stuck at a homocysteine level of 11 µmol/l because they do not consume enough folate. This should not be surprising, since folate is present in concentrated form in beans and vegetables. 96 percent of Americans do not eat even the recommended minimum amount of beans and dark green vegetables.

Because folate is generally the B vitamin that is consumed the least in the population, in the FACIT study more than 800 older men and women were randomized for three years to receive folic acid supplements or placebo. In the folic acid group, homocysteine dropped from an average of 13 to 10, which demonstrably improved cognitive abilities—and quite markedly. The scientists estimated that because of the extra folic acid, people were 4.7 years younger in memory performance, 1.7 years younger in sensorimotor speed, 2.1 years younger in information processing, and 1.5 years younger in overall cognitive function. And all of that for two cents a day.

So should all older adults take folic acid supplements? Everyone needs enough folate, and that is one of the many reasons I recommend daily consumption of dark green leafy vegetables and legumes. But folic acid is not folate, and it is not completely harmless. So it is best simply to eat folate.

Just one week of a plant-based diet can lower homocysteine by 20 percent, from about 11 µmol/l down to 9 µmol/l, a normal value for people who consume plenty of B vitamins. This may be due directly to folate-rich vegetables and beans or indirectly to plant fiber. Every gram of fiber per day increases folate levels in the blood by almost 2 percent, possibly by stimulating folate production by our friendly colon bacteria.

Another explanation for the rapid improvement could be reduced intake of methionine, an amino acid that comes mainly from animal protein. Homocysteine is a breakdown product of methionine. After a breakfast of bacon and eggs and a steak for dinner, homocysteine levels in the blood shoot up. So lower methionine intake on a plant-based diet is another factor for lower, safer homocysteine levels.

The irony is that people who eat a plant-based diet long-term can develop terribly high homocysteine levels. Meat eaters average 11 µmol/l, but among vegetarians it can be almost 14 µmol/l, and among vegans 16 µmol/l. Why? Vegetarians and vegans eat lots of fiber and folic acid, but not enough vitamin B12, which in modern times can be found reliably only in animal products, fortified foods, or supplements. As I mentioned earlier, a regular, reliable source of vitamin B12 is critically important for anyone eating a plant-based diet. (Leonardo da Vinci’s stroke may possibly be traced to his vegetarian diet not fortified with B12, which increased his homocysteine level.) But when vegans take B12, their homocysteine levels drop below 5 µmol/l. Why not to 11 µmol/l like the rest of the population? Because the general population is probably folate-deficient. Once vegans are adequately supplied with B12, they can finally fully reap the benefits of their fiber- and folate-rich plant-based diet and reach the lowest levels of all.