My homocysteine is 9.6, I've been taking P5P for about 6 months but only recently increased it to about 15mg. I get weird side effects from P5P and B6 and even after 6 months those side effects haven't improved. I was taking it in the hope it would lower my homocysteine but I'm wondering if all it's doing is speeding up the CBS pathway? Don't know if anyone can make sense of this but I've been told my CBS pathway is upregulated, so I assume that means it's sped up very fast, and that's why my homocysteine is accumulating? Or do I have it the wrong way round, is CBS slowed down because B6 is low and that's why homocysteine is accumulating? My methionine is high as well, so I don't think taking folate/B12 would help. I'm taking Allithamine/Benfotamine, R5P, Niacitol, Niacinamide (some days), Biotin, Zinc, Manganese, Selenium (all of these were low). I've read P5P can increase quinnolic acid (which mine was high) so I wonder if that's why I'm having issues with P5P. Or is it just that my other B's are possibly still too low to introduce P5P/B6 yet?
In one of my OAT tests 2-Hydroxybutyric reports as being high, this seems to indicate the CBS pathway is sped up.
According to Great plains laboratory, 2-Hydroxybutyric is a marker of cysteine accumulation, they describe it here:
https://www.greatplainslaboratory.com/gpl-blog-source/2016/4/14/dna-methylation-pathway
Great plains also says this about 2-Hydroxybutyric acid in the OAT report:
In one of my OAT tests 2-Hydroxybutyric reports as being high, this seems to indicate the CBS pathway is sped up.
According to Great plains laboratory, 2-Hydroxybutyric is a marker of cysteine accumulation, they describe it here:
https://www.greatplainslaboratory.com/gpl-blog-source/2016/4/14/dna-methylation-pathway
CBS
Cystathione beta-synthase (CBS) is a pyridoxal-5’-phosphate (vitamin B6) dependent enzyme that converts L-serine and L-homocysteine into L-cystathionine. L-cystathionine is later converted into the amino acid cysteine. Mutations to the CBS gene are the most common cause of hereditary hyperhomocysteinemia. The adverse effects of homocysteine accumulation in the body are related to the substitution of homocysteine for methionine in protein synthesis. The resulting complications include an increase in immune response, increase in cell death, and protein damage. The degree of homocysteinemia is relative to the mutation. Hyperhomocysteinemia has been linked to multiple mutations to the CBS gene. The most common of these are the Ile278Thr and the Gly307Ser, which cause homocysteine to build up in the blood. Complications of hyperhomocysteinemia include mental retardation, seizures, and vascular disease. One of the most common causes of death for patients with homocystinuria (CBS deficiency) is heart attack. Patients with CBS polymorphisms are recommended to take glutathione and B6. There are reports that the CBS polymorphisms A360A (rs1801181) and N212N (rs2298758) can lead to an increase in CBS activity. Some claim that these mutations lead to a buildup of ammonia and decrease in glutathione. Since ammonia is a very unstable compound that must be measured STAT for accurate results, the better marker for increased ammonia is orotic acid which is very stable and accumulates when excessive amines are filtered through the urea cycle. I recommend that patients with this mutation do an Organic Acid test (OAT) and look at marker 60 (orotic acid) for ammonia and markers 58-59 (Pyroglutamic and 2-hydroxybutyric acid) for glutathione synthesis and cysteine accumulation respectively.
Great plains also says this about 2-Hydroxybutyric acid in the OAT report:
High 2-hydroxybutyric acid (Marker 59) This organic acid is elevated when there is increased production of sulfur
amino acids derived from homocysteine. The reasons for an increase can be due to the following reasons (which are
not mutually exclusive):
1. There is increased need for glutathione to detoxify a host of toxic chemicals, resulting in increased shunting of
homocysteine into the production of cysteine for glutathione. This is the most common reason.
2. There are genetic variants of the DNA such that methylation of homocysteine by betaine homocysteine methyl
transferase or methionine synthase is impaired.
3. There are nutritional deficiencies of betaine, methylcobalamin, or methyltetrahydrofolate that reduce the
enzyme activities of the enzymes in #2 above.
4. There is a genetic variant in cystathionine beta synthase (CBS) enzyme such that there is excessive shunting
of homocysteine into cysteine production that results in excessive 2-hydroxybutyric acid formation.
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