What is Homocysteine?
Homocysteine is a sulfur-containing amino acid produced during the metabolism of methionine, an essential amino acid obtained from dietary protein. Normally, homocysteine is rapidly converted to other beneficial compounds through two pathways:remethylation (converting back to methionine using folate and vitamin B12) or transsulfuration (converting to cysteine using vitamin B6). When these pathways are impaired, homocysteine accumulates in the blood.
Elevated homocysteine (hyperhomocysteinemia) is a powerful independent risk factor for cardiovascular disease, stroke, dementia, and all-cause mortality. High homocysteine damages blood vessel walls through oxidative stress, promotes blood clot formation, and accelerates atherosclerosis. It's also directly neurotoxic and associated with brain atrophy and Alzheimer's disease. The good news:elevated homocysteine is easily corrected with B-vitamin supplementation in most cases.
While standard labs consider homocysteine "normal"up to 15 µmol/L, longevity-focused practitioners target <7 µmol/L for optimal cardiovascular and brain protection. Levels above 10 µmol/L indicate methylation dysfunction and significantly increase disease risk. Homocysteine is one of the most actionable biomarkers—simple, inexpensive B-vitamin supplementation (folate, B12, B6) can normalize levels and reduce cardiovascular events by 10-25%.
Why Homocysteine Matters for Longevity
- Cardiovascular disease:Each 5 µmol/L increase in homocysteine increases cardiovascular risk by 20-30% and stroke risk by 50%. High homocysteine damages endothelial cells, promotes oxidative stress, and accelerates atherosclerosis through multiple mechanisms. It's as important as cholesterol for cardiovascular risk assessment.
- Brain health and dementia:Elevated homocysteine is strongly associated with cognitive decline, brain atrophy, and Alzheimer's disease. Levels >14 µmol/L double the risk of dementia. Homocysteine is directly neurotoxic and damages blood vessels in the brain. B-vitamin supplementation slows brain atrophy by 30-50% in those with elevated homocysteine.
- Methylation and aging:Homocysteine reflects the efficiency of methylation—one of the most important biochemical processes for longevity. Methylation regulates gene expression, DNA repair, detoxification, and neurotransmitter production. Impaired methylation accelerates aging and disease.
- Fracture risk:High homocysteine increases fracture risk by 30-90% by interfering with collagen cross-linking in bone and promoting bone resorption. This effect is independent of bone mineral density and vitamin D status.
- Pregnancy complications:Elevated homocysteine in pregnancy is associated with neural tube defects, preeclampsia, placental abruption, and recurrent miscarriage. This is why folate supplementation before and during pregnancy is standard care.
- All-cause mortality:Elevated homocysteine is associated with increased all-cause mortality in a dose-dependent manner. Lowering homocysteine through B-vitamin supplementation may reduce mortality risk, though trials have shown mixed results.
Optimal vs Standard Ranges
| Range Type | Level | Significance |
|---|
| Optimal (Longevity) | <7 µmol/L | Exceptional homocysteine level associated with minimal cardiovascular risk and optimal methylation function. This level is associated with lowest risk of cardiovascular events, dementia, and all-cause mortality. |
| Good (Standard) | 7-10 µmol/L | Adequate homocysteine level with acceptable cardiovascular and cognitive protection. Some longevity practitioners target <8 µmol/L, but levels in this range are generally considered safe. |
| Acceptable (Functional) | 10-12 µmol/L | Mildly elevated homocysteine indicating methylation dysfunction. Cardiovascular and dementia risk begin to increase significantly above 10 µmol/L. B-vitamin supplementation recommended. |
| Suboptimal (Standard) | 12-15 µmol/L | Moderately elevated homocysteine associated with 20-40% increased risk of cardiovascular disease and stroke. Clear indication for B-vitamin supplementation (folate, B12, B6) and investigation of underlying causes. |
Standard lab range: B12
How to Optimize Homocysteine
2. Very low homocysteine is rare and not concerning. May indicate vitamin B excess or very efficient methylation. No intervention needed.
Critical High
3. >15 µmol/L
Severely elevated homocysteine associated with >50% increased risk of cardiovascular events, stroke, and dementia. Aggressive B-vitamin supplementation required (5-15mg methylfolate, 1-5mg methylcobalamin, 50-100mg P5P). Investigate for genetic causes (MTHFR mutations, CBS mutations) or other underlying conditions (kidney disease, hypothyroidism).
4. Supplement with methylated B vitamins
B-Vitamin Supplementation
5. Take methylfolate (5-MTHF) 1-5mg, methylcobalamin (B12) 1-5mg, and pyridoxal-5-phosphate (P5P, active B6) 50-100mg daily. Methylated forms bypass genetic variations in folate metabolism (MTHFR mutations affect 30-40% of people) and are more effective than folic acid or cyanocobalamin. This combination normalizes homocysteine in 90% of cases within 8-12 weeks.
Optimize dietary B vitamins
Scientific Evidence
Homocysteine is partially cleared by the kidneys, so impaired kidney function (eGFR <60 mL/min/1.73m²) causes homocysteine elevation. Optimize kidney health through blood pressure control, adequate hydration, limiting nephrotoxic medications (NSAIDs), and managing diabetes if present. Even mild kidney dysfunction can significantly raise homocysteine.
Limit methionine and check thyroid
Source:Reduce Methionine &Support Thyroid
High dietary methionine (from animal protein) increases homocysteine production. While you don't need to avoid protein, consider moderating intake to 0.8-1.2g/kg body weight. Also check thyroid function (TSH, Free T4)—hypothyroidism impairs homocysteine metabolism. Treating hypothyroidism can significantly lower homocysteine.
Very low:Rare and not concerning
Source:Low Homocysteine Symptoms
Homocysteine below 5 µmol/L is rare and not associated with any negative health effects. No symptoms or interventions needed.
High:Often asymptomatic initially
Source:High Homocysteine Symptoms
Elevated homocysteine is usually asymptomatic until it causes disease. When very high (>30 µmol/L), may cause:premature atherosclerosis and cardiovascular disease in young adults, recurrent blood clots (deep vein thrombosis, pulmonary embolism), cognitive decline or dementia symptoms, peripheral neuropathy (tingling, numbness in hands/feet), psychiatric symptoms (depression, psychosis in severe cases), osteoporosis and fragility fractures. Note:Most people with homocysteine 10-20 µmol/L have no obvious symptoms but silently accumulating damage.
B vitamin deficiencies
Source:Causes of High Homocysteine
Folate deficiency (dietary insufficiency or malabsorption)|Vitamin B12 deficiency (common in vegans, elderly, those with pernicious anemia or taking metformin/PPIs)|Vitamin B6 deficiency (less common but important for transsulfuration pathway)|MTHFR gene mutations (C677T and A1298C polymorphisms affect 30-40% of population and reduce folate metabolism efficiency by 40-70%)|Kidney disease (impaired clearance of homocysteine)|Hypothyroidism (low thyroid function impairs homocysteine metabolism)|High methionine intake (excess animal protein consumption)|Medications that deplete B vitamins (metformin, PPIs, H2 blockers, methotrexate, anti-seizure medications)|Excessive coffee or alcohol consumption (depletes B vitamins)|Smoking (increases homocysteine by 10-20%)
N/A
Source:Causes of Low Homocysteine
Frequently Asked Questions
What does Homocysteine test for?
Homocysteine is a inflammation &immune markers biomarker. Amino acid linked to cardiovascular disease
The normal reference range is B12.
Which providers include Homocysteine?
14 of 22 providers include this test:Superpower, Blueprint, Mito Health, WHOOP and others.
How often should I test Homocysteine?
For most people, testing 2-4 times per year is recommended to establish baseline levels and track trends.
Consult your healthcare provider for personalized recommendations.
What is the optimal range?
The standard reference range is B12.
Many functional medicine practitioners recommend tighter optimal ranges for peak health.
Your ideal range may vary based on age, sex, and health goals.
Why is Homocysteine important?
Elevated levels increase cardiovascular and Alzheimer's disease risk. Lowered with B vitamins (B6
Superpower
WHOOP Advanced Labs
Labcorp OnDemand
InsideTracker
Function Health