This calculated ratio is called the ‘Met/Sulf Balance’ and it compares analytes between the methylation pathway and transsulfuration pathways.
Biomarker levels are compared proportionately allowing potential insight into which of the pathways is being favored.
The four analytes from the main methylation pathway that are used in the Met/Sulf Balance are SAM, SAH, methionine, and homocysteine. The four analytes from the transsulfuration pathway are cystathionine, cysteine, taurine, and glutathione.
Methylated Metabolites
- SAM
- SAH
- Methionine
- Homocysteine
Un-Methylated Metabolites
- Cystahionine
- Cysteine
- Taurine
- Gluthatione
There is a relative balance that exists between the methylation and transsulfuration pathways. This balance ensures that adequate levels of glutathione are produced to counteract oxidative stress and that an adequate amount of SAM is made for methylation reactions.
As with the Methylation Balance ratio, the Met/Sulf balance is a novel biochemical pathway analysis. Early Genova data analysis of this biomarker has demonstrated its ability to distinguish a healthy cohort from an unqualified cohort.
In the presence of increased oxidative stress, more homocysteine is used for glutathione production because oxidative stress induces enzymes in the transsulfuration pathway. Also, transsulfuration is induced by higher levels of intracellular SAM. Therefore, poor methylation status (Methylation Balance Ratio and SAM/ SAH Ratio) may be a risk for low glutathione production. As with the Methylation Balance ratio, the Met/Sulf ratio is based solely on biochemical pathway analysis.
LOW |
HIGH |
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SAM/SAH |
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Methylation Balance Ratio |
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Met/Sulf Ratio |
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May be a consequence of high levels of methyl products or potential “over-methylation”.
May be due to adequate methylation status and increased oxidative stress.
- Reduce exposure to oxidative stress – Support with antioxidants
- Potential high oxidative stress
- Ensure adequate methylation status
- Decrease oxidative stress exposure
Look at SAM/SAH ratio and Methylation Balance Ratio as well.
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Balanced shifted to Methylation.
- Look at Methylation Balance and SAM/SAH ratios;
- Consider methylation support to correct low methylation status
- Vitamin B6, especially if high homocysteine (consider adding vitamin B3 if high SAH levels)
- Consider Mg, iron
- Consider antioxidant support
- CBS SNP
- May be consequence of high SAM/SAH
- Evaluate oxidative stress and consider antioxidant support
- Consider glutathione if needed
- Evaluate whether high protein intake or high BMI could be contributing to elevated methylation metabolite
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Betaine, Betaine/Choline Ratio, Choline, Cyst(e)ine, Cystathionine, Dimethylglycine (DMG), Glutathione, Glycine, Homocysteine, Met/Sulf Balance Ratio, Methionine, Methylation Balance Ratio, Methylation Index (SAM/SAH Ratio), S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), Sarcosine, Serine, Taurine