Previously, we saw that your B vitamins are essential for most of your body’s systems, and they are particularly important in your methylation cycle.
We learned that Homocysteine is a sulfur-containing amino acid that can be converted to cystathionine and further to cysteine via the transsulfuration pathway (CBS) or remethylated to methionine. Additionally, Homocysteine is produced by the body through the chemical alteration of adenosine.
To learn more about adenosine, click here.
Do you know?
Migraine is a painful and often debilitating condition linked to inflammation and blood vessel dysfunction.
One possible trigger is elevated homocysteine levels, which can damage the endothelial lining of blood vessels in the brain, potentially setting off a migraine attack.
Researchers have long observed that migraines tend to run in families, suggesting a genetic link.
One contributing factor may be MTHFR gene variations, which can disrupt folate metabolism and raise homocysteine levels, increasing susceptibility to migraines in some individuals.
Do you know?
Epilepsy also has a connection to elevated levels of Homocysteine.
Systemic administration of high doses of homocysteine in animals produce convulsive seizures, a fact that has been exploited in models of experimental epilepsy. Furthermore, up to 20% of patients with homozygous CBS deficiency have seizures, and the high plasma concentrations of homocysteine in these patients (usually 50-200 µmol/L) may contribute to epilepsy. Whether less severe hyperhomocysteinemia (15-20 µmol/L) predisposes patients to epilepsy has not been established.
Homocysteine relates to 2 additional important issues in the management of patients with epilepsy. First, most anticonvulsants lower plasma folate levels, and as a result, almost half of patients treated with anticonvulsants had homocysteine levels sufficiently elevated to put them at high risk for vascular disease. Arteriosclerosis is an important issue for patients requiring long-term anticonvulsant therapy, particularly given the rising incidence of epilepsy in older age groups. The effectiveness of polyvitamin therapy in lowering homocysteine levels in the setting of anticonvulsant use has not been directly studied.
A second issue relates to putative teratogenic effects of high homocysteine levels. There is an increased risk of major congenital malformations in children whose mothers receive anticonvulsants during the first trimester. While the mechanism of teratogenicity in folate deficiency is unclear, recent data implicate elevations in homocysteine. First, fasting or PML hyperhomocysteinemia is commonly found in women who have given birth to infants with neural tube defects. Second, the C677T mutation in the MTHFRgene significantly increases the risk of neural tube defects. Finally, amniotic fluid homocysteine levels were found to be significantly higher in pregnancies complicated by neural tube defects. Observations such as these led to a practice parameter recently promulgated by the American Academy of Neurology, recommending that all women of childbearing potential who are taking anticonvulsants consume at least 0.4 mg/d of folic acid. Whether this or higher doses of folic acid are effective in lowering homocysteine levels or in decreasing the incidence of neural tube defects in epileptic women has not been studied. It is also unclear whether cyanocobalamin and pyridoxine hydrochloride supplements are necessary for this population.
Read the full article on Homocysteine and Neurologic Disease here.
Certain medications and natural compounds can raise homocysteine levels by interfering with folate absorption or the body’s ability to metabolise homocysteine properly. This can be an overlooked contributor to elevated homocysteine.
Some of the most common culprits include:
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Azaribine – Used for skin conditions like psoriasis.
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Caffeine – Can impair B-vitamin status in large amounts.
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Cholestyramine (Questran) – Lowers cholesterol but also reduces absorption of fat-soluble vitamins (A, D, E, K).
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Colestipol (Colestid) – Another cholesterol-lowering agent that interferes with bile acid recycling.
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Colchicine – Prescribed for gout; can impact nutrient absorption.
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Fenofibrate (Lipanthyl) – Used for high triglycerides and certain types of hyperlipoproteinemia.
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Levodopa (Sinemet, Madopar, etc.) – For Parkinson’s disease; affects methylation balance.
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Metformin – Common in type 2 diabetes; known to reduce B12 levels over time.
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Methotrexate (Methoblastin) – Blocks folate activation; used for autoimmune and inflammatory conditions.
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Niacin (Vitamin B3) – High doses may disrupt methylation pathways.
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Nitrous oxide – Depletes B12 and interferes with methylation.
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NSAIDs (non-steroidal anti-inflammatory drugs) – Long-term use can reduce nutrient absorption.
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Pemetrexed (Alimta) – Antifolate chemotherapy drug for lung cancer.
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Phenytoin (Epanutin, etc.) – Anticonvulsant that disrupts folate metabolism.
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Pyrimethamine (Daraprim) – Antimalarial with antifolate action.
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Sulfasalazine (Salazopyrin) – Used for IBD and rheumatoid arthritis; impairs folate absorption.
The Good News:
High homocysteine is manageable.
With the right nutrition and supplementation, levels can often be brought back into a healthy range.
Key nutrients that help lower homocysteine:
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Folate (B9)
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Vitamin B12
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Vitamin B6
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Vitamin B2
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Zinc
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Trimethylglycine (TMG)/Betaine
Standard folate or folic acid supplements may not always be effective. One key reason is that folic acid—the form commonly found in most supplements and fortified foods—is not sufficiently bioavailable to raise blood folate levels in individuals with certain health conditions or genetic variations, especially those with MTHFR mutations.
For folic acid to work clinically, it must first be converted into the active form, 5-methyltetrahydrofolate (5-MTHF). This conversion depends on several enzymes, healthy liver and gut function, and adequate levels of nutrients like niacin (B3), pyridoxine (B6), riboflavin (B2), vitamin C, and zinc. A further benefit of 5-MTHF is that it does not mask a vitamin B12 deficiency—a problem sometimes seen with folic acid. Folic acid can hide the blood-related symptoms of B12 deficiency without treating the neurological effects, making diagnosis more difficult.
Natural folates are also destroyed by cooking and food processing. While red blood cells can hold folate for 40–50 days after stopping supplementation, folic acid itself does not transport well to the brain and is quickly cleared from the central nervous system.
Recent research in patients with coronary artery disease showed that supplementing with bioactive folate (5-MTHF) led to higher plasma folate levels compared to folic acid, regardless of genotype. Overall, folic acid supplements are less effective than bioactive 5-MTHF in raising blood folate concentrations.
PLEASE NOTE: ANY VIEWS REGARDING THE RESULTS ARE MY UNDERSTANDING AND DO NOT SERVE AS PROFESSIONAL ADVICE. THE TREATMENT RECOMMENDATION IS STRICTLY RELATED TO ALEX’S RESULTS AND NOT MEANT FOR SELF-TREATMENT. ALWAYS SPEAK TO YOUR HEALTHCARE PROVIDER BEFORE STARTING ANY TREATMENTS.