Homocysteine

An amino acid intermediate that accumulates when B12, folate or B6 handling falters, associated with cardiovascular and cognitive risk, though lowering it with B vitamins has not reduced events in trials.

What it is

Homocysteine sits in the middle of methionine metabolism. It is either recycled back to methionine, a step that needs vitamin B12 and folate, or converted onward to cysteine, a step that needs vitamin B6. When any of those routes is limited, homocysteine backs up in the blood.

That makes it a functional readout rather than a nutrient level. It can be elevated while B12 sits inside the reference range, which is one reason it is ordered alongside B12 and folate rather than instead of them.

The association and the trials

Elevated homocysteine is consistently associated with cardiovascular events, stroke and cognitive decline in observational studies. That looked like a treatable pathway.

It largely was not. Large randomized trials, including HOPE-2 and VITATOPS, lowered homocysteine substantially with folic acid and B vitamins and did not reduce cardiovascular events, although stroke signals were more favorable in some analyses. The current reading is that homocysteine is a marker of an underlying problem more than the problem itself.

When it is still worth measuring

It remains useful for detecting functional B12 or folate insufficiency, particularly in people on metformin, people with limited stomach acid or absorption, older adults, and vegetarians and vegans. Kidney impairment and hypothyroidism also raise it.

Correcting a deficiency is worth doing on its own terms. Treating the number in the absence of a deficiency is not supported.

Reference ranges

  • Typical laboratory reference: roughly 5 to 15 micromol/L. Assay and laboratory dependent. Population reference range, not a treatment target.

Homocysteine is a reasonable add to a longevity panel when B12 or folate status is in question. A Baseline consult can talk through whether it is worth adding, and any ordering is done by an independent licensed provider.

References

  1. Lonn E, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease (HOPE-2). N Engl J Med. 2006.
  2. VITATOPS Trial Study Group. B vitamins in patients with recent transient ischaemic attack or stroke. Lancet Neurol. 2010.
  3. Smith AD, Refsum H. Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 2016.