From the Guidelines
Homocysteine testing is not recommended for routine screening in the general population, but it may be considered in individuals with suspected MTHFR deficiency, particularly those with unexplained thrombosis, cardiovascular disease, or family history of these conditions. The relationship between homocysteine levels and cardiovascular risk is complex, and several studies have found that the association between homocysteine and cardiovascular disease is eliminated after adjustment for other cardiovascular risk factors or renal function 1.
Key Considerations
- Elevated levels of plasma homocysteine are associated with a 2- to 3-fold increased risk for atherosclerotic vascular disease, including stroke 1.
- The B-complex vitamins pyridoxine (B6), cobalamin (B12), and folic acid lower homocysteine levels, but most studies have found no benefit of homocysteine lowering by B-complex vitamin therapy on clinical cardiovascular end points 1.
- If an individual has an MTHFR gene variant and elevated homocysteine, treatment may include supplementation with activated forms of folate, vitamin B12, and vitamin B6, as well as diet modifications to include folate-rich foods.
Treatment and Monitoring
- Supplementation with activated forms of folate (methylfolate/L-methylfolate at 400-1000 mcg daily), vitamin B12 (methylcobalamin 500-1000 mcg daily), and vitamin B6 (pyridoxal-5-phosphate 25-50 mg daily) may be considered for individuals with MTHFR deficiency and elevated homocysteine levels.
- Regular monitoring of homocysteine levels every 3-6 months is advised to assess treatment effectiveness 1.
- It's essential to understand that having an MTHFR gene variant alone doesn't necessarily require treatment if homocysteine levels are normal, as many people with these variants maintain adequate enzyme function.
From the Research
Homocysteine Testing and MTHFR Deficiency
- Homocysteine testing is important in patients with unexplained neurological manifestations or thromboembolism, as hyperhomocysteinemia can result from hereditary defects affecting the transsulfuration pathway or methylation reaction 2.
- MTHFR deficiency can lead to various neurological symptoms, ranging from developmental delay to encephalopathy, including motor and gait abnormalities, seizures, psychiatric manifestations, and rarely strokes 2.
- The treatment of MTHFR deficiency can be efficiently managed by vitamin B12, folic acid, and betaine supplementation 2.
Relationship Between Homocysteine, Folate, Vitamin B12, and MTHFR
- Hyperhomocysteinemia is well documented in chronic renal failure (CRF) and premature and progressive occlusive vascular disease is common in CRF 3.
- The combined effects of renal failure, folate, and vitamin B12 levels, and a common mutation (C677T) in the MTHFR gene can lead to total plasma homocysteine elevation in CRF children 3.
- However, no significant difference was revealed between the mean homocysteine level and the CC, CT, and TT MTHFR genotypes in patients with a thrombotic event or recurrent fetal loss 4.
Effect of Folate, Vitamin B6, and Vitamin B12 Intake on Homocysteine Concentrations
- Plasma hyperhomocysteinemia is considered a risk factor for chronic allograft dysfunction (CAD), the main cause of functional loss in transplant recipients 5.
- Increased folate and vitamin B6 intakes seem to reduce homocysteine concentrations among transplant recipients with normal renal function, and could contribute to reducing the risk of CAD development 5.
- Supraphysiologic methylfolate, vitamins B6 and B12 supplementation in women with MTHFR mutations has a beneficial effect on pregnancy outcome, by lowering total homocysteine concentrations 6.