Methylfolate (5-MTHF) vs Pantothenic Acid (B5)

Mechanism

5-methyltetrahydrofolate (5-MTHF) is the biologically active form of folate and the primary methyl donor for remethylation of homocysteine to methionine via methionine synthase (requires B12). This reaction generates SAMe (S-adenosylmethionine), the universal methyl donor for >200 methyltransferase reactions including DNA methylation (gene expression), histone methylation (epigenetics), neurotransmitter synthesis (serotonin, melatonin, norepinephrine), creatine synthesis, and phospholipid methylation (phosphatidylcholine). 5-MTHF crosses the blood-brain barrier via folate receptors.

Standard Dosing

400-800 mcg daily (general health); 5-15mg for depression/MTHFR homozygous

Timing

Morning with B-complex. Start low and titrate up, especially in COMT slow metabolizers.

Cycle Duration

ongoing

Side Effects

• Anxiety/irritability (overmethylation, especially COMT slow)
• Insomnia
• Headache
• Joint pain
• Nausea
• Depression paradoxical worsening (overmethylation)

Contraindications

• Active methotrexate cancer therapy (discuss with oncologist — leucovorin rescue is different)
• Untreated B12 deficiency (folate can mask B12 deficiency, allowing neurological damage to progress)
• Some COMT slow metabolizers may not tolerate high doses

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Mechanism

Pantothenic acid is converted to Coenzyme A (CoA), the universal acyl-group carrier essential for >100 metabolic reactions. CoA is required for: fatty acid synthesis and beta-oxidation, citric acid cycle (acetyl-CoA entry), steroid hormone synthesis (pregnenolone from cholesterol), acetylcholine synthesis, melatonin synthesis, and Phase II detoxification (acetylation reactions). Pantethine (the active form) supports healthy lipid metabolism by inhibiting hepatic HMG-CoA reductase and fatty acid synthase, while stimulating fatty acid oxidation.

Standard Dosing

500mg pantothenic acid or 300mg pantethine twice daily

Timing

With meals. Split doses for pantethine.

Cycle Duration

ongoing

Side Effects

• Diarrhea at high doses
• GI discomfort
• Contact dermatitis (topical dexpanthenol)

Contraindications

• Hemophilia (theoretical concern: pantethine may have mild antiplatelet effect at high doses)

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