Betaine

Optimal Result: 21 - 71 micromol/L.

Betaine, also known as trimethylglycine, is an amino acid - so named because it was first discovered as a beet byproduct. It is also found in wheat, shellfish, and spinach.

It can be produced via choline oxidation. Betaine is a major methyl donor and acts as an osmolyte in the cell to regulate cell volume.

Betaine donates a methyl group, using the enzyme betaine homocysteine methyltransferase (BHMT), to re-methylate homocysteine back to methionine. 

The product of this methyl transfer is dimethylglycine (DMG), which is then available for further methyl donation.

In folate deficiency, this betaine pathway compensates to maintain Homocysteine re-methylation. Folate-deficient people have elevated serum DMG levels, as would be expected with the increased betaine use as a methyl source.

Because the betaine pathway is a salvage pathway to remethylate Homocysteine, betaine is a significant determinant of plasma Homocysteine levels, particularly in folate deficiency. 

Betaine supplementation lowers Homocysteine after methionine load.

References:
- https://pubmed.ncbi.nlm.nih.gov/24022817/
- https://pubmed.ncbi.nlm.nih.gov/18716669/
- https://pubmed.ncbi.nlm.nih.gov/20346934/

What does it mean if your Betaine result is too low?

- Can be due to decreased dietary choline intake
- Low betaine, high choline is a risk

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Betaine deficiencies have many clinical implications, including: 
- metabolic syndrome, 
- diabetes, 
- vascular disease, 
- liver diseases, 
- cancer, 
- and fetal abnormalities.

Not surprisingly, supplementation with betaine has been shown to be beneficial in many conditions associated with poor methylation status and higher homocysteine, such as metabolic syndrome.

What does it mean if your Betaine result is too high?

- Can be due to supplementation
- Can be due to high dietary betaine (i.e. beets, wheat, shellfish, and spinach) or choline intake.

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An elevated Betaine on a Methylation Panel can signify several things. Betaine, a methyl donor, plays a crucial role in the BHMT (betaine-homocysteine methyltransferase) pathway, where it remethylates homocysteine to methionine when MTR (methionine synthase) activity is inhibited. Elevations in Betaine levels might suggest an increased demand for methylation reactions or a compensatory mechanism due to MTR inhibition. Moreover, Betaine's role in inflammation and its impact on DNA methylation patterns indicate its involvement in various cellular processes. However, further clinical evaluation is necessary to determine the specific implications of elevated Betaine in an individual's methylation status.

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