• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

CBS / Ammonia / Glutathione

Messages
95
Methyl Head, so if I have low moly as well as low in copper than would Molybenum be an issue? Since Moly will further reduce copper levels? Can that be a reason I get headaches when I take Moly? Can I coorect the CBS pathway without taking Moly? Even if my Moly is low? Would fixing the leaky gut and correcting the pathway through Ornithine and Yucca etc be enough to correct the CBS?
 
Messages
95
Well I will know for sure about my copper levels once i get my blood tests back. I have been reading about copper a lot and hanging out in the Magnesium Advocacy Group. Apparantly, high copper can really be low copper. It shows high cuz it's not metabolizing in my body. It's free unbound so it appears high. When I had the Biofeedback she said I had zero copper. But it is suggested to get plasma magnesium/copper/ zinc and serra something test to know for sure. But since I am deficient in everything it wouldn't make sense that my copper would really be high. Some people in the group have CBS mutation and they just take Moly for a short period of time and than resume the rest of the protocol. I am really jiving with the protocol, listening to videos. it makes sense to me. Still don't get why I get headaches from Moly. My guess is that is't depleting my copper. It is not recommended to take copper. Only fast oxidizers . The Barley Grass I'm taking an abundance of has a lot of zinc and copper so I think that will help a lot and fixing my gut. So how much Moly should I take at the least? I'm taking the ionic mineral itself. Is that ok? I can't take supplements with additives in it.
 
Messages
73
if someone could comment on my SNPs I would be hugely grateful :)
 

Attachments

  • Livwello Report.pdf
    87.8 KB · Views: 19
Messages
12
anyone? please!

my guess is I need folate and choline, but would love some advice

Just like me, you've got CBS 699T (hetero) and BHMT (hetero; all of them). This effectively constitutes a strong up-regulation of CBS. You've also got NOS3 mutations (homozygous; mine is hetero). This is not a good combination. You have a few COMT, the particularly problematic COMT V158M is good. You are COMT (-/-) and VDR Taq (-/-) and this combination is good. So you should be able to tolerate methyl groups (you actually may need it depending on VDR Taq status).

To stimulate BHMT, yes, you would need choline.


Search for "Methylation Nutrigenomics --HeartFixer" PDF.
 
Messages
12
@Methyl Head Is this combination (and dosages) of B-vits/mg/serine(BHMT&NR3C1) OK to start supporting CBS and related pathways ?

Screen Shot 2019-02-16 at 5.36.50 pm.png
 

Methyl Head

Sumptus salutis, amissio libertatis.
Messages
38
Location
Ohio
@dbose - This is perfect for you! I'm always wary about giving dosages without knowing what your deficiencies and other health needs are but the supplements themselves are perfect. I like the low dose use of Niacin, back off of it even more if you feel like you're getting microphagy symptoms. Which form of Niacin is it? Also, any word on the magnesium threonate? I've become curious about it recently.
 
Messages
12
@dbose - This is perfect for you! I'm always wary about giving dosages without knowing what your deficiencies and other health needs are but the supplements themselves are perfect. I like the low dose use of Niacin, back off of it even more if you feel like you're getting microphagy symptoms. Which form of Niacin is it? Also, any word on the magnesium threonate? I've become curious about it recently.

Thanks @Methyl Head

Trying this version from LifeEx, along with Curcumin LongVida as curcumin being methyl donor can create problems. But overall I'm feeling calm and relaxed. MgLT is something that is based upon thorough research. Next going to try PharmaGABA (along with Mg / B6 / Zn to stimulate GABA formation). Do you know any good GABA that gets absorbed well ?
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
Abstract
The effects of ornithine alpha-ketoglutarate (OKG) on ammonium acetate induced hepatotoxicity were studied biochemically in rats. The levels of urea, nonprotein nitrogen, and thiobarbituric acid reactive substances were significantly increased in ammonium acetate treated rats; these levels were significantly decreased in rats treated with ammonium acetate and OKG. Similar patterns of alterations were observed in the levels of free fatty acids, triglycerides, and phospholipids. Furthermore, nonenzymatic antioxidants (vitamins C and E) were significantly decreased in ammonium acetate treated rats, when compared with control rats, and increased in OKG and ammonium acetate treated rats. The biochemical alterations during OKG treatment could be (1) by detoxifying excess ammonia; (2) by participating in nonenzymatic oxidative decarboxylation in the hydrogen peroxide decomposition process, and (3) by enhancing the proper metabolism of fats which could suppress oxygen radical generation and thus prevent the lipid peroxidative damages in rats.

Copyright 2002 S. Karger AG, Basel
PMID 12169850 [Indexed for MEDLINE]
Looks like yes. Allergy Research Ornithime aspartate works well for me. Helped me sleep, too.
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
I don't know if you actually have CBS but I'm sure you know there are stages to treating and clearing the transsulfuration pathway if it is a problem. If you have a high urine sulfate reading you may qualify for this approach as the transsulfuration pathway has to be cleared first before moving on to any other methylation treatment. If you don't solve this problem first, you're not only flushing all the Mcbl, P-5-P and MTHF down the drain you're also causing yourself damage because your good nutrients will convert to ammonia and sulfites then release into the body which will make things worse in the long run/raise taurine and further exacerbate glutathione production issues because they share the same pathway. With that in mind, there is a stage type approach to methylation when CBS is involved, and early on in treating this problem especially, because certain things will only aggravate symptoms. Here is a link that justifies my views.

http://resqua.com/702188759/what-does-a-cbs-gene-mutation-mean

This way of thinking is not only valid, it's been designed by Dr. Amy Yasko and it's been confirmed in the link above. I'm not saying this will work for everyone but I can say that it worked for me when I first tested for and found CBS, I was very sick and it took me a while to clear everything before I could handle other supplements, and my sulfate readings were about the same as dbose's. I understand the body needs sulfur and the same goes for glycine, it's about timing though, like I stated in my first response to dbose, be careful and really feel what works for you because you might not be ready for some things yet.

No disrespect @Methyl Head, but I just thought perhaps you hadn't heard that Yasko's 'CBS upregulation' hypothesis has been thoroughly and repeatedly discredited since her original work 10+ years ago. As has her claim that one needs to avoid sulfur to address that polymorphism.

Here's just one link from one of the many times it's been mentioned here on PR:

https://forums.phoenixrising.me/thr...l-and-have-questions.49663/page-3#post-860965
 
Last edited:
Messages
12
@Methyl Head @dannybex and others,

I now have evidence that the hyperammonemia may not be caused by 10x up-regulation of CBS (discrediting Yasko). Most probably it's being caused by Mitochondrial defects (genetic or acquired as Mitos are very dynamic) systemic or liver-specific. In liver, mitos play a very special role in ammonia processing. Subtle defects in mtDNAs may act like a case of hyperammonemia.

Careful, one of Yasko's suggestions for fixing CBS (which may have been exaggerated) - Yucca Root contains potent saponins which are known to make leaky-gut worse. And leaky-gut itself may be caused my mito dysfunction. Mitos are known to participate in cross-talks with our gut microbiome and often butyrate is involved. There are papers available for it. So low butyrate and microbiome imbalance can actually be an subtle effect of harbouring dysfunctional mitos and colon/uterus are sensitive to such dysfunction (heart and brain cells are have already divided and matured ?)

And mito-dysfunction will cascade to glutathione issues for sure. Cu/Zn balance can be explained by increased production of Zn-dependent mtSOD2 etc. So yeah, Yasko has created a CBS-cult. But science is about continuous exploration.

What you can do to make sure that it's not a mito dysfuntion

- MitoSwab test

Protocols now I'm taking to better overall health and mito-health is to go through a cycle of mito fission and fusion inducing strategies. A senolytic protocol would be good prerequisite before embarking on that protocol.
And try to take as much as natural foods as opposed to supplements, unless you are at a very bad shape genetically.

Senolytic Protocol
------
Quercetin + Fisetin (strawberries and onions, onions and onions; but supplement here is better)

Infrequently once in 2/3 months

Fission-Fusion Protocol (3 days)
------

Defective mitos are usually fused and avoid mitophagy. The idea is to induce fission or at least encourage it via precision protocols. NAD+/NADH ratio, AMPK, mTOR all influences mitophagy

- 20hs+ or 18:6 IF Fasting (its pro-fusion and but more % of fission happens at early phase overnight)
- Apigenin (celery + parsely)
- Nicotinamide+Ribose (careful as it induces NAD+. so a solid senolytic protocol must proceed this)
- Yogic Intermittent Hypoxia (YIH)
- Weight Lifting
etc.

As mitos are fragmented evolutionarily preserved proteins Drp1 starts tagging dysfunctional mitos (after fragmentation its easier for a cell to identify poor performers) for a sweeping mitophagy

Fusion (2 days)
--

CoQ10 / Ubiquinol
PQQ
Vitamin C
Aerobics (cycling)
In fact most of the anti-oxidants are pro-fusion and protects the mitos directly or indirectly via NRF2-glutahione/SOD1/2

Rest: 1/2 day(s)

Cycle this for couple of rounds and measure VO2-Max, HR variability (as cardic metrics will improve with better mitos) and repeat MitoSwab, if you have money.
 

renski

Senior Member
Messages
338
Location
Honolulu
Even though curcumin / turmeric shifts the pathway to Glutathione formation, I believe curcuin does it magic via activating Nrf2 pathway which is really a low-stress-training for cells. If you activate Nrf2 pathway and you don’t have necessary cofactors present, you essentially will going to face increased oxidative stress.

What you all think about this simplified protocol ?

This is a good point, Chris Shade mentions getting phase III working better (bile, etc) before using Nrf2 upregulators.
 

Methyl Head

Sumptus salutis, amissio libertatis.
Messages
38
Location
Ohio
@dbose

I discovered this a while back and even addressed how and why she was wrong in a previous post about methylmalonic acid and the end products of CBS. The entire point of my post was to address the fact that our CBS enzyme is feeding directly into the Krebs Cycle. I intentionally left yucca and night shares off of my suggestions because I don't know other people's sensitivity to these things and like you said they can cause problems. This is absolutely solid though. My chronic fatigue has been successfully eliminated since I improved on my protocol and tweaked my copper and zinc levels by increasing CP thereby increasing folate levels because folate absorption is zinc-dependent. You clearly expressed my concerns from the previous post and have definitely done the CBS community a favor.
 

Methyl Head

Sumptus salutis, amissio libertatis.
Messages
38
Location
Ohio
I'm not endorsing Andrew Cutler's protocol, I'm using this as a template because we may have high mercury as a consequence of our genetics but the root problem is sulfur and ammonia and more specifically high thiol containing (literally called mercaptans because they are also very efficient with capturing mercury) foods that are extremely efficient at accelerating the metabolism of sulfur because they are sulfur analogues of alcohols and a sulfhyrdryl group replaces the oxygen group. This means 2 things: 1. They break down very quickly and we know that CBS as an up regulation is already over functioning so that's why we experience symptoms nwhen we consume them. 2. they're actually more acidic for us (yes inside the body after being deprotonated if we can't metabolism them properly!) so if we have thiolates in high numbers bonded to mercury that would explain a lot of metabolic issues. (Those of you that suspect ANION Gap or Metabolic Acidosis and have severely increased CBS activity (high level toxicity) and correlated end product dysfunction, ATP/mtDNA issues will love what that the next part means).

This means also means that one of the biochemical end products of CBS (AKB NOT AKG!!!! Yasko is wrong here. Please spread this as that's a big thing among those of us that have ME/CFS because it changes the structure and direction of some programs entirely...) used as a very important aspect of mtDNA and ATP production is functioning in a sub-optimal fashion and potentially causing thyroid dysfunction, decreased energy production and chronic illness. AKB is one of the most important aspects of the mitochondrial matrix and krebs cycle so for those of us with Thyroid disfunction and under performing mtDNA related issues here's a potential answer along with IgA and IgE or TPH antibody involvement. (long side bar, this is why I suggested biotin, vitamin E succinate and adenosly/hydroxy b12 in my first post to you a long time ago, people probably thought I was nuts but now you'll see why, and this will answer your magnesium threonate question as well): AKB is the result of the lysis of Cystathione and is one of the degradation products of threonine and the catabolism of the amino acid threonine dehydratase. It's also produced by the degradation of homocysteine and the metabolism of methionine. Here is the conversion from AKB => Succinyl CoA and entry to the Krebs Cycle

AKB, Alpha Keto Acid Dehydrogenase -> Proprionyl CoA, Proprionyl CoA Carboxylase + biotin = (S) Methylmalonyl CoA => (R) Methylmalonly CoA, Methylmalonyl CoA Epemirase -> Methmalonyl CoA Mutase + AdoCbl = Succinyl CoA -> Krebs Cycle. This reaction helps generate functional platforms for new mtDNA and ATP synthesis. So treating any immune disturbances you have while nurturing this will greatly help you improve.

I'm explaining here, VERY POORLY, that high sulfur isn't a product of CBS defects and in fact only applies with mercury toxicity (hence the Cutler reference) and the parenthesis around high-level toxicity. Those who have CBS, as you said, likely have mtDNA dysfunction and an accommodating zn/cu imbalance. The next question is how many of us have Aceruloplasminemia because copper bound to this protein is absolutely pivotal in the creation of new ATP.
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
Everyone has a CBS gene.

There are many other factors affecting mitichondria.

I don't seem to have a zinc/copper imbalance or aceruplasminemia but I do have problems with ATP synthesis.

I'd kike to understand more of what you're saying, though, but its hard to deduce it frim your dense text. Coukd you provixe some diagrams or references that explain more about this, please?
 

Methyl Head

Sumptus salutis, amissio libertatis.
Messages
38
Location
Ohio
@Learner1 I don't entirely understand what I've done yet. I know that I was severely deficient in a few co-factors related to Methmalonyl CoA. Extensive sessions of Nicotinamide and Niacinamide induced a profound healing state. I was also taking other supplements that helped immensely. I felt like I was becoming an entirely new person. This phenomenon has continued as well. I don't understand what, exactly, is happening though. Give me time to figure this out and I might have some answers. I have a protocol for different things that I took over that period. I'll post it soon.