Homocysteine

Why Homocysteine Testing Matters

1. Critical Low

<5 µmol/L

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

Low Homocysteine

• B-Vitamin Rich Foods

Note: Eat folate-rich foods:dark leafy greens (spinach, kale), legumes (lentils, chickpeas), asparagus, broccoli. For B12:grass-fed beef, wild-caught fish, eggs, organ meats (liver). For B6:poultry, fish, potatoes, chickpeas, bananas. Note:Dietary changes alone rarely normalize elevated homocysteine;supplementation is usually needed.

High Homocysteine

• Support methylation with betaine (TMG)

Note: Betaine/TMG Supplementation

Low Homocysteine:

• Take trimethylglycine (TMG, also called betaine) 500-3000mg daily. TMG provides methyl groups directly and supports the remethylation pathway independent of folate and B12. Particularly helpful for those with MTHFR mutations or who don't respond fully to B vitamins alone. Start with 500mg and increase gradually.

High Homocysteine:

• Address kidney function

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%)

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Source:Causes of Low Homocysteine

Frequently Asked Questions About Homocysteine