Longevity Knowledge BETA
Vitamin B
Table of Contents
Eight vitamins, one family
The B vitamins are a group of eight water-soluble nutrients: thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9), and cobalamin (B12). Your body can't store them in meaningful amounts, so you need a steady daily supply from food or supplements. Together, they act as coenzymes in more than 300 enzymatic reactions, converting food into energy, building neurotransmitters, supporting DNA repair, and keeping your nervous system running [1].
Deficiency in even one B vitamin can cause cascading problems: fatigue, brain fog, anemia, numbness in hands and feet. And because these vitamins depend on each other, fixing a shortfall often means addressing several of them at once rather than supplementing just one.
How B vitamins power your cells
B1, B2, B3, and B5 work together in the mitochondria to extract ATP from carbohydrates, fats, and proteins. B1 feeds pyruvate into the citric acid cycle. B2 donates electron carriers (FAD) to the electron transport chain. B3 is the precursor to NAD+, a molecule that has gained enormous attention in longevity research because NAD+ levels decline with age, and restoring them appears to improve mitochondrial function in animal studies [2]. B5 builds coenzyme A, which is needed for fatty acid oxidation. Without adequate B vitamins, your mitochondria simply can't produce energy efficiently.
B6 has a different job. It forms pyridoxal-5-phosphate (PLP), the coenzyme behind serotonin, dopamine, GABA, and melatonin synthesis. Low B6 can show up as irritability, poor sleep, or depressed mood before any blood test flags a deficiency.
Methylation, homocysteine, and aging
Folate (B9) and B12 are the workhorses of one-carbon metabolism, the biochemical cycle that supplies methyl groups for DNA synthesis, gene regulation, and detoxification. When this pathway stalls, homocysteine accumulates. Elevated homocysteine is linked to increased cardiovascular risk, cognitive decline, and bone fractures [3].
About 10-15% of people carry the MTHFR C677T gene variant, which slows the conversion of dietary folate into its active form, methylfolate. For these individuals, standard folic acid supplements are less effective; methylfolate or folinic acid may work better. A 2024 study found that targeted supplementation with methylfolate, P5P (active B6), and methylcobalamin lowered homocysteine by 30% in MTHFR carriers over six months [4].
A 2025 meta-analysis of B vitamin supplementation in older adults found high-certainty evidence for a small but real cognitive benefit, particularly in regions without mandatory folic acid food fortification [5]. Combined B6, B9, and B12 supplementation also reduced stroke risk in a separate meta-analysis, especially at moderate doses [6].
B12 absorption declines with age
Of all the B vitamins, B12 deserves special attention for anyone over 50. Between 10% and 30% of older adults have reduced ability to absorb B12 from food, mainly because the stomach produces less acid and intrinsic factor with age [7]. Proton pump inhibitors (PPIs) and metformin make this worse. The tricky part is that standard serum B12 tests can look normal while functional deficiency is already present. Testing methylmalonic acid (MMA) and homocysteine alongside serum B12 gives a much clearer picture.
Untreated B12 deficiency damages the myelin sheath around nerves, leading to tingling, balance problems, and memory loss that can become permanent. Sublingual or injectable B12 bypasses the stomach entirely, making these forms more reliable for people with absorption issues.
B6 toxicity: the exception to "more is better"
Most B vitamins are safe even at high doses because you excrete what you don't need. B6 is the exception. Chronic intake above 100 mg per day can cause peripheral neuropathy, the very symptom that B6 deficiency also produces. Recent case reports have described nerve symptoms at doses as low as 25 mg per day taken over months [8]. The European Food Safety Authority lowered its tolerable upper limit to 12 mg per day in 2023. Stick to a B-complex supplement with physiologic doses rather than megadosing individual B vitamins.
Who benefits most from supplementation
- Adults over 50 (impaired B12 absorption)
- Vegans and vegetarians (B12 is found almost exclusively in animal products)
- People on metformin, PPIs, or oral contraceptives (these drugs deplete B vitamins)
- Those with MTHFR variants (methylated forms may be more effective)
- Anyone with elevated homocysteine on blood work
- Pregnant women (folate prevents neural tube defects; B6 can reduce nausea)
References
- 1. Kennedy (2016): B Vitamins and the Brain: Mechanisms, Dose and Efficacy — A Review (Nutrients)
- 2. Garrido-Maraver et al. (2020): The Lifespan Extension Ability of Nicotinic Acid Depends on Whether the Intracellular NAD+ Level Is Lower than the Sirt...
- 3. Smith et al. (2018): Homocysteine and Dementia: An International Consensus Statement (J Alzheimers Dis)
- 4. MTHFR polymorphisms and vitamin B12 deficiency: correlation between MTHFR polymorphisms and clinical and laboratory findings (2024, Frontiers)
- 5. Efficacy of B Vitamin Supplementation on Global Cognitive Function in Older Adults: A Systematic Review and Meta-analysis (2025, Nutrition Reviews)
- 6. Zhao et al. (2023): The effect of B-vitamins on the prevention and treatment of cardiovascular diseases: a systematic review and meta-analysis (Nutr R...
- 7. Mouchaileh et al. (2023): Vitamin B12 deficiency in older people: a practical approach to recognition and management (J Pharm Pract Res)
- 8. The Role of Vitamin B6 in Peripheral Neuropathy: A Systematic Review (2023, Nutrients)
Test homocysteine, not just B12
Check your MTHFR status
Use sublingual B12 if you're over 50
Don't megadose vitamin B6
Watch for drug interactions
What are the symptoms of vitamin B deficiency?
Should I take individual B vitamins or a B-complex?
Can B vitamins help with fatigue and low energy?
What is the connection between B vitamins and brain health?
Do vegans need to supplement B vitamins?
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