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Heghine Khachatryan: Homocysteine – A Small Molecule with Big Clinical Consequences

Heghine Khachatryan/LinkedIn

Dec 5, 2025, 05:59

Heghine Khachatryan: Homocysteine – A Small Molecule with Big Clinical Consequences

Heghine Khachatryan, Editor-in-Chief of Hemostasis Today, Head of Hemophilia and Thrombosis Center at Yeolyan Hematology and Oncology Center, shared a post on LinkedIn:

“Homocysteine: a small molecule with big clinical consequences

Homocysteine is an amino acid formed during the metabolism of methionine, which we obtain from protein-rich foods (eggs, meat, fish, cheese, rice, soy, etc.). On its way through metabolic pathways, homocysteine should either be converted to glutathione – our key intracellular antioxidant – or to SAMe (S-adenosylmethionine), a universal methyl donor involved in hundreds of reactions.

Both pathways depend on adequate levels of specific cofactors:

For homocysteine → glutathione: vitamins B2, B6 and zinc
For homocysteine → SAMe: vitamins B2, B6, B9, B12, zinc, magnesium and trimethylglycine (TMG, betaine)

When these cofactors are deficient, the reactions slow down, homocysteine accumulates, and we face hyperhomocysteinaemia. In addition to nutritional deficiency, functionally significant variants of the MTHFR gene can impair conversion of folic acid to methylfolate and further disturb homocysteine metabolism.

From a clinical perspective, persistently elevated homocysteine (ideally we aim for <8–9 µmol/L; >20 µmol/L is considered high risk) is associated with:

Ischaemic stroke
Alzheimer’s and other dementias
Parkinson’s disease
Schizophrenia and other neuropsychiatric disorders
Atherosclerosis and cardiovascular disease
Osteoporosis
Adverse pregnancy outcomes

What can we do in practice?

Measure homocysteine in appropriate risk groups.
Assess and correct deficiencies of B-group vitamins, zinc and magnesium (through diet and, when necessary, supplementation).
Consider the impact of smoking, chronic stress and polypharmacy on micronutrient status.
In selected cases, evaluate for MTHFR variants and adapt folate therapy (e.g. methylfolate) accordingly.

Homocysteine is a simple marker that sits at the intersection of nutrition, genetics and vascular risk. It deserves more attention both in routine clinical practice and in patient education.”

Homocysteine