Homocysteine
- An intermediate of various biochemical pathways
- Involved with production of glutathione, transfer of methyl groups
- Elevated homocysteine also called hyperhomocysteinemia contributes to inflammation and damage to blood vessels and other organ systems
- Optimal levels of homocysteine are <9
- High homocysteine levels indicate a deficiency of folic acid, B-6, B-12 and methyl donors
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Methyl Donors
- Methionine and homocysteine are identical except that methionine has an extra methyl (CH3) group
- Methyl donors are needed to reconvert homocysteine to methionine
- Methyl donors include 5-methyl folate and tri-methyl-glycine (also known as anhydrous betaine), choline, lethicin
MTHFR (Methylene Tetrahydrofolate Reductase)
- An important enzyme that helps biotransform 5,10 methylene tetrahydrofolate into methylated folate
- Some people have a variant of the normal gene known as the MTHFR gene (a single nucleotide polymorphism) which impairs proper methylation
- An MTHFR SNP can contribute to high homocysteine and related diseases
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MTHFR Variants (or single nucleotide polymorphisms =SNP)
- There are two relatively common SNP’s:
- A1298C – clinically irrelevant – will not effect homocysteine levels – does not require any specific supplementation
- C677T – can effect homocysteine levels – patient may need more folate or 5-methyl-folate
- Utilizing the methionine pathway by adding methyl donors like trimethyglycine and choline can bypass the problem of MTHFR variants
Manifestations of Elevated Homocysteine
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Sources of Methyl Groups
- B vitamins – folate, B-6, B-12
- Trimethylglycine (betaine)
- Choline
- Methionine
- SAMe
Metabolically Directed Approach to Elevated Homocysteine
- Look for root causes of homocysteine elevation – chronic inflammation, hypothyroidism, poor diet, MTHFR variants
- When replacing needed B vitamins, take into account the patient’s individual metabolic needs
- For example, a Dysaerobic patient will benefit from folate, but may suffer from increased Dysaerobic imbalance from B-6 and B-12.
- On the other hand, the Anaerobic patient’s imbalance will be exacerbated by folate, yet may benefit more from B-12 and B-6
- In summary, the treatment for elevated homocysteine is best personalized depending on the patient’s individualized metabolic requirements and balance
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Other Considerations
- Avoid sugar, smoking and caffeine – all can increase homocysteine
- Low B-12 levels are not necessarily caused by low intake or decreased absorption, but also by increased utilization by abnormal bowel flora
Hypothyroidism raises homocysteine