01/27/2026
B12 + Folate + B6: are the methylation triad 🧬🫀🧠
When one is low, the entire pathway can bottleneck.
These three B-vitamins work as a tightly linked system that drives one-carbon metabolism, the biochemical process behind DNA synthesis, red blood cell production, neurotransmitter balance, and homocysteine regulation.
That’s why B12, folate, and B6 are often discussed together, not as isolated nutrients, but as a functional triad supporting cardiovascular, neurological, and metabolic health.
Why this combo matters
• Supports healthy homocysteine metabolism (a cardiovascular risk marker)
• Required for DNA synthesis and repair
• Supports red blood cell formation (distinct from iron)
• Plays a key role in nerve function and energy metabolism
RDAs vs real-world needs ⚖️
RDAs are designed to prevent overt deficiency in the general population, not necessarily to optimize function in people with:
• Elevated homocysteine
• Malabsorption issues
• Increased demand (pregnancy, aging, stress)
• Certain dietary patterns (low animal foods, restricted diets)
As a result, some individuals require supplemental doses above the RDA, under appropriate guidance.
Practical protocol:
Baseline intake (RDA level):
• Vitamin B12: 2.4 mcg/day
• Folate: 400 mcg DFE/day (600 mcg DFE during pregnancy)
• Vitamin B6: 1.3–1.7 mg/day
Common supplemental ranges used clinically (not required for everyone):
• B12: 25–500 mcg/day (higher doses often used for deficiency or absorption issues)
• Folate (B9): 400–800 mcg DFE/day
• B6: 5–25 mg/day
⚠️ Important considerations
• High folate intake can mask a B12 deficiency, especially in older adults
• B6 has an established upper limit. Chronic megadoses may not be appropriate
• These vitamins work best together, not in isolation
Who may benefit most
• Individuals with elevated homocysteine
• Older adults or those with reduced B12 absorption
• Pregnancy and pre-conception (folate is critical)
• People with fatigue, anemia, or confirmed deficiencies