The brain atrophies (shrinks) in the elderly, even in those without cognitive decline. In people with Alzheimer’s, there is an accelerated rate of brain atrophy.
One biomarker that is moderately elevated on average in Alzheimer’s is homocysteine. Higher levels of homocysteine are also linked to an increased risk of heart disease. Homocysteine is an amino acid that is involved in the methylation cycle and is usually kept at a normal level through recycling and conversion into methionine or cysteine.
Vitamin B6, B12, and B9 (folate) is needed for the normal processes involving converting homocysteine to methionine.
A 2010 study showed that supplemental B vitamins (B6, B12, and B9) were able to slow the rate of atrophy in elderly people with mild cognitive impairment (MCI), which can be the early stages of Alzheimer’s.
The study involved 271 people over age 70 with mild cognitive impairment. They were divided randomly to receive B vitamins or a placebo for 2 years. About 2/3 of the group underwent cranial MRIs before and after the intervention.
The group taking B vitamins had significantly less brain atrophy compared to the placebo group. However, the bigger effect was seen in people who initially had higher homocysteine levels.
The results were as follows:
“The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.” [ref]
Another study looked at the effect of B vitamin intake (foods, supplements) on the odds of cognitive decline over 2 years in more than 2,500 people. The results showed that adequate dietary folate, vitamin B6, and vitamin B12 intake “were significantly associated with better cognitive reserve.”[ref]
Vitamins B12, B6, and B9 are important in the methylation cycle, and the methylation status of specific redox-related genes is different for people with mild cognitive impairment (MCI).
A placebo-controlled trial of vitamins B6, B12, and B9 was also conducted in older individuals in China, about half of whom had high homocysteine levels. The trial looked at improvements in cognitive function. After 14 weeks, the B vitamin group had improvements in cognitive function scores and the placebo group did not.[ref]
Another study with 240 participants with MCI divided participants into four groups: folic acid alone, B12 alone, folic acid plus B12, or control group. The results at 6 months showed that the folic acid plus B12 group had improvements in homocysteine, inflammatory cytokines, and in cognitive function compared to the control group and to the folic acid alone group.[ref]
The basics:
In preventing cognitive decline and brain atrophy, the basics of getting adequate nutrition, especially B vitamins, is something that we all need to ensure. High homocysteine levels can be lowered for most people with B6, B12, and B9. For cognitive function in aging, supplemental B vitamins seem more likely to be effective for people who have high homocysteine levels.
Going one step further:
The initial 2 year long placebo-controlled B-vitamin study was taken one step further, and the plasma DHA and EPA (omega-3 fatty acid) levels were tested. For the B-vitamin arm of the trial, those who had higher levels of DHA “alone significantly enhanced the cognitive effects of B vitamins”. The results showed EPA levels weren’t significantly important.[ref] DHA and EPA are found in fish, krill, and algae oils.
What isn’t covered in these studies:
There are two forms of supplemental folate available: folic acid and methylfolate. The clinical trials all used folic acid, which has to be converted into the active form of methylfolate. Genetic variants impact how well people convert folic acid.
There are also multiple forms of B6 available: pyridoxine and pyridoxamine 5′ phosphate (active form). Again, genetic variants impact the need for B6.