Folate & B Vitamins
Methylation-cycle vitamins that lower homocysteine and slowed brain atrophy in MCI, but excess folate may fuel cancer.
Summary
B6, B12 and folate convert homocysteine back to methionine; in a 2-year placebo-controlled trial in people over 70 with MCI they slowed brain atrophy, especially when homocysteine was high, and higher DHA enhanced the effect. At the same time, she argues more folate is not always better: trials and cohorts link high-dose folic acid, higher methylfolate levels, and even high dietary folate to increased risk of colorectal adenomas, bladder cancer recurrence, overall cancer and skin cancer. A preprint pooling intervention studies found B12 plus folate had no effect on biological age. She takes creatine or a low dose of methylfolate, reasoning that creatine synthesis uses about 40% of methyl groups.
Alternates creatine with 'a low dose of methylfolate' and gets folate and choline from diet, but concludes 'more is not always better' with folate.From My Current Supplement Stack for Longevity
The evidence
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Human trial
In a 2-year randomized placebo-controlled trial of 271 people over 70 with mild cognitive impairment, B6, B12 and folate slowed brain atrophy, by 53% in those with homocysteine above 13 µmol/L.
Read the study Discussed in B Vitamins in Mild Cognitive Impairment -
Human trial
In a randomized placebo-controlled trial of 987 adults, 1 mg/day folic acid was linked to a 67% higher relative risk of recurrent advanced adenomas at later follow-up (3-5 years after the first three).
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Human trial
In long-term follow-up of an osteoporosis trial in 2,524 adults, folic acid (400 µg) plus B12 (500 µg) was associated with a 13% higher relative risk of overall cancer and 77% higher risk of colorectal cancer vs placebo.
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Human trial
In a trial of 240 people with MCI, folic acid plus B12 for 6 months improved homocysteine, inflammatory cytokines and cognitive function versus control and folic acid alone.
Read the study Discussed in B Vitamins in Mild Cognitive Impairment -
Human trial
In adults aged 50-70 with high homocysteine, 800 mcg/day folic acid for three years improved cognitive scores, but only in those with low omega-3 levels.
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Human obs.
Higher blood methylfolate (5-MTHF) was associated with a 58% higher relative risk of advanced or multiple adenomas, while unmetabolized folic acid was not.
Doses used in studies
Amounts reported in the research, not dosing recommendations.
| Dose | Context |
|---|---|
| 1 mg/day folic acid | Colorectal adenoma prevention RCT, 987 adults, 6-8 years follow-up |
| 400 µg folic acid + 500 µg vitamin B12 | Osteoporosis prevention trial, 2,524 adults, long-term cancer follow-up |
| 800 mcg/day folic acid | Adults with high homocysteine and high blood pressure; and adults aged 50-70 with high homocysteine for three years (cognition) |
| RDA 400 mcg/day DFE; tolerable upper limit 1,000 mcg/day from supplements or fortification | US adult reference values |
Cautions
- Folate helps cancer cells grow once a mutation takes hold; high folic acid intake was linked to more colorectal adenoma recurrence and 65-80% higher bladder cancer recurrence in higher-risk adults.
- High-dose (1 mg) folic acid in pregnancy was associated with increased childhood cancer risk, especially in mothers with epilepsy.
- Some 1 mg folic acid supplements were recalled in Canada for containing carcinogenic N-nitroso-folic acid; folate above 400 mcg/day with high-nitrate water was linked to 40% higher breast cancer risk.
- Fortified cereal, bread and rice can add substantial folic acid even without supplements.
- Folate is one of her examples of supplements with a cancer trade-off; her precautionary principle is to err on the side of caution or cycle such supplements. 'An excess may not be a good idea.'