Homocysteine
Inflammation marker
Homocysteine
Amino acid in the blood. Elevated levels are an independent risk factor for cardiovascular disease, stroke, blood clots, and cognitive decline. Metabolised by B-vitamins (B6, B12, Folate).
PED Notes
An often-overlooked cardiovascular risk marker for PED users. Elevated homocysteine damages blood vessel walls and promotes clotting -- compounding the cardiovascular risk from AAS-worsened lipids and elevated haematocrit. Some AAS may affect homocysteine metabolism. Target <10 umol/L for optimal cardiovascular protection.
When high
Supplements (first-line -- B-vitamin cofactors):
- B12 (Methylcobalamin) -- 1000mcg/day
- Folate (Methylfolate) -- 800mcg/day
- B6 (P5P) -- 50mg/day
Lifestyle:
- Reduce alcohol, improve overall diet quality
If persistently elevated: Consider MTHFR genetic testing -- gene variants can impair homocysteine metabolism
Pharmacological/methylation options (when methylated B-vitamins are insufficient):
- Note that dedicated pharmacological homocysteine-lowering agents do not exist; management is almost entirely methyl donors, B-vitamin cofactors, and lifestyle. Outcome trials (HOPE-2, VISP, NORVIT) showed B-vitamin therapy lowers homocysteine but does not reduce cardiovascular events, so aggressive pharmacology is not warranted.
- Betaine (TMG, trimethylglycine) -- 500-3000mg/day (up to 6g/day in MTHFR carriers); alternative methyl donor that bypasses MTHFR; reduces homocysteine by 10-20% as standalone or alongside B-vitamins; especially valuable when MTHFR C677T or A1298C variant is confirmed
- Choline -- 500mg/day; substrate for betaine synthesis; supportive role alongside TMG
- N-acetyl cysteine (NAC) -- 600-1200mg/day; lowers homocysteine independent of B-vitamin status via cysteine conjugation
- Creatine -- 3-5g/day; reduces homocysteine modestly by sparing methyl groups (endogenous creatine synthesis is a major methyl consumer)
- Address upstream drivers before escalating: alcohol, smoking, caffeine excess, renal impairment, hypothyroidism
- TRT may modestly elevate homocysteine in some users (mechanism unclear, possibly via increased methionine turnover from accelerated protein synthesis); co-supplement methylated B-vitamins prophylactically if baseline homocysteine >10 umol/L
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