I have created chronological notes for this episode of the Ben Greenfield Podcast with guest Teri Cochrane here. I have created summaries of my understanding of these notes below.
This podcast may be the most impacting I’ve found regarding my health. Nutrigenomics may prove more significant even than BJJ, a regular right of passage adopted from the same place I found Ben Greenfield, JRE. Hail Joe Rogan (is he a Clown?).
I have been plagued with chronic health issues going back a long way, which understanding this podcast may all be wrapped up in Genetics. Despite circling around this topic for some time, I was never able to connect the many dots until this episode of Bens podcast.
Removing sulfur and oxilates from my diet the last few days has proved very impressive for my state of mind and cognitive ability. From here I can continue to improve my understanding with supplementation and testing.
So what are we talking about? Sulfur, Oxilates, Amyloids, MTHFR and other genetic polymorphisms
Amyloids
Easy, indigestible proteins found in conventionally farmed animals. Avoid..
CBS and SUOX
These are enzymes which can suffer from genetic defects, impairing their function. These defects can be identified using Genetic testing (23 and me). Both these enzymes have cofactors, which catalyze their function.
The CBS aka the “sulfate drain” enzyme pathway removes sulfur containing amino acids. B6 is a cofactor for the CBS enzyme converting
homocystine into Cystathionine.
If CBS is slow, may result in high homocystine. High homocystine may also be due to low B6, methylfolate among other things (from here). CBS is covered here and is pretty complex relating to specific alleles.
Chronic oxidative and inflammatory stress conditions divert the usual Methyl functions and lead to a bunch of bad things, especially important when these pathways are genetically compromised.
Looking at the screenshot above, after becoming Cystathionine through the CBS enzyme it becomes Cysteine before eventually partially converting into Sulfite. It then goes through the SUOX enzyme, which uses molybdenum as a cofactor to convert it to Sulfate to be pee’d out.
If your breath/arm pits smell like sulfur, your body is trying to eliminate it. Cysteine can also be converted into Glutathione for storage.
Too much protein in the diet is bad as it will push the nitrogen balance off and cause elevated ammonia, this will push the CBS enzyme.
The CBS polymorphism can apparently result in under-performance of this enzyme pathway, presenting as high homocystine, which can be helped with B6. Note that heartfixer.com refers more to over active CBS.
“Many of you with CBS and BHMT abnormalities will also bear MTHFR (compromising methyl-folate generation) and MTRR (compromising methyl-B12) abnormalities, and thus you will need and benefit from corresponding supplementation (with these molecules that you are having trouble making). However, if we treat you with methyl-folate, methyl-B12, or BH4, before we have the CBS problem under control (sulfite/sulfate levels low enough to allow for appropriate glutathione and cysteine assimilation) then we will be subjecting you to “incomplete detoxification”. You will feel great for 1-2 days, as beneficial neurotransmitters are generated. Detox pathways then open up, creating toxic intermediates that cannot be metabolized further due to the block in glutathione utilization (Dr. Yasko’s position) and possibly other genomic/nutritional blocks in Phase I and Phase II detoxification which we need to work on – and you will feel horrible. Thus we need to resist the temptation to treat your MTHFR/MTRR abnormalities until CBS/BHMT are under control.” from here.
“To address this constellation of alleles I will recommend: Moderate* animal protein intake (anything with eyes) and avoid sulfur rich vegetables, sulfur containing supplements, and sulfur containing drugs…”
“OUR FIRST GOALS WILL BE TO REDUCE YOUR BURDENS OF SULFITE/SULFATE, AMMONIA AND GLUTAMATE”
Sulfur (Methylation)
- From here: The term “methyl group” refers to CH3, one carbon atom attached to three hydrogens. The enzymes of the Methyl Cycle add or subtract a methyl group from another molecule to open or close biochemical pathways, to open our DNA when it should be read, or to close it when it would not be in our best interest to decode a specific gene.
- The metabolism of Sulfur happens in the bodys Methylation pathways (sulfur is turned into sulfate)
- RoundUp (Glyphosphate) impairs sulfur metabolism (according to Teri).
Understanding how to incorporate the science of Methyl Cycle Genomics in to your treatment program, and how best to monitor your individual response, will be a challenge to both of us.
http://www.heartfixer.com/AMRI-Nutrigenomics.htm
MTHFR
From here: Methylenetetrahydrofolate reductase (MTHFR), is the key enzyme for the metabolization of homocysteine. When there are mutations to the MTHFR gene, control of homocysteine levels may be altered. MTHFR mutation is a common genetic variant that causes diminishment of normal function of the enzyme.
MTHFR C677T +/+ or +/-
“Here ½ (+/-) or all (+/+) of your MTHFR enzymes are having trouble converting folic acid (or more precisely 5,10-methylene tetrahydrofolate) into 5-methyl folate. Without 5-methyl-folate (which we will shorten to methyl-folate) MTR cannot methylate homocysteine in to methionine and SAMe regeneration will be compromised. Methyl folate has another role – it can neutralize peroxynitrite. When NOS (nitric oxide synthase) is not functioning normally (i.e. when BH4 is deficient or if eNOS reduced function alleles are present), arginine is converted not in to the vasoprotective molecule nitric oxide, but rather in to the damaging free radicals superoxide and peroxynitrite.” We can easily bypass the MTHFR C677T block with 5-methyl folate supplementation.
Supplementation for MTHFR is specific to which alleals (variants) are present for a gene.
From here: “as your sulfate and ammonia burdens fall, so will your requirement for supplementation.”
Testing (here again)
- Vitamin D, homocysteine, and blood ammonia levels will likely change in response to our treatments and we will wish to follow these parameters.
- Urine sulfate and/or sulfite testing is critical –QUANTOFIX Sulfate
- We will need to follow your mineral status, (we often see deficiencies in Molybdenum, Boron, and Copper)
- If ammonia shows up, and you do not work with fertilizer or cleaning solutions, you likely have a problem in trans-sulfuration (CBS and or BHMT) or…
- GenovaLabs NutrEval. (serine and/or P-5-P)
Supplementation
- To stimulate SUOX activity, please add Vitamin E Succinate 400 IU/day, sublingual hydroxy-B12 2000 mcg/day, and Molybdenum (500 mcg daily) and Boron (3 mg daily) to your program
- Creatine supplementation is another means available to reduce SAMe and methyl group “demand” (from here).
- Ornithine stimulates the urea cycle, breaking down ammonia