52 Comments

Thank you for your very good series on this issue. We have some pretty bad mental health issues and our family and of course are treating it with medication. I'm not saying we're going to go off of it due to this info, but it would be great to prevent severe episodes in my family members who have horrible anxiety, especially between meals.

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This reminds me of Andrew Cutler's idea about low-level mercury toxicity causing sensitivity to foods with high levels of unbound thiol compounds, which are all also foods high in sulfur (but not all foods high in sulfur are also high-thiol). Recommend remedies include avoiding those foods, eating a high-protein diet, and molybdenum supplementation.

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Fascinating - thank you!

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Thanks Chris! Two questons: Is S-sulfocysteine higher in diabetics? Does it generally increase overnight or when fasting due to gluconeogenesis? Thanks

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No one has researched any of this because no one cares because of what I explained at the end of the article.

Flux through the sulfate pathway declines overnight due to declining availability of sulfur amino acids as they are used up. However that could change if you provoke lean mass catabolism.

H2S is generally lower in diabetes I think but I haven’t researched it in any detail.

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This is huge! Very helpful indeed, and this helps me to possibly solve a mystery I have wondered about. I have tested my glucose levels during HypoGlycemia episodes and have found the levels very low at times, and 'normal' at other times with similar symptoms. Moreover, I have noticed that when I go meatless for a day or more, I never get HypoG symptoms even if i miss a meal by hours. I might get hungry, but I don't get that weak, irritable, shaky, desperate feeling that I do with classic HypoG. When I am eating meat regularly that is when I am most at risk for HypoG if I am late for or miss a meal. Your theory here solves that mystery for me. An all carb diet, which is supposed to make classic HypoG worse, actually works well for me in preventing HypoG episodes, but probably not so healthy so I generally try to eat a 'balanced' diet.

Next mystery, if what we think as HypoG is really sulfite problems, why are those symptoms alleviated by eating foods high in carbs, salt, and fat? When I am in that weak, shaky state, the number one combo my body craves is orange juice and potato chips. I rarely have these in the house, but that is what I crave. When I eat that, or similar sugar/fat/salt combinations, I get fairly rapid remission of symptoms (although I won't really feel fully recovered till the next day)

Does that combo somehow help clear sulfites/metabolites from the system?

Thank much Chris for sharing your research with us!!!

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Carbs shut off trans-sulfurartion. It makes complete sense.

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So I end up feeling terrible. Horrible anxiety after eating eggs and Parmesan cheese for breakfast. I will add an apple but I will still get the same horrible feelings of hypoglycemia and such. I am not a diabetic. Do you think that adding whole food starch to breakfast will help counteract this? Thank you. I've been dealing with this for many years. Trying to eat healthier and lower carb but had determined that vlc was not for me when I got tired of feeling like I was dying just about every single day from anxiety and allergy issues.

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I used to be like that, and I too believed carbs and fats were the answer. It would solve it completely, but my health overall was going downhill doing that, as obviously you will gain weight over time and be protein starved. So you are right it is not a solution. I now can eat lots of red meat without feeling shaky or irritable and the only thing different I'm doing is coffee enemas and activated charcoal morning and night. I also was using betaine hcl with meat meals for several months leading up to this new change. So I think you may be putrifying your meat possibly causing hydrogen sulfide production. And that absolutely puts a burden on the system. Try betaine hcl with meat. Or try hardwood activated charcoal morning and night. I bet you it clears up the shakiness after a few weeks!

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You don’t need microbes to turn meat into H2S.

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It seems for me it did have to do with digestion though as red meat used to be very hard for me to digest. I didn't have smelly gas though.

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I have learned that I have histamine intolerance issues. Trying to up my molybdenum without high histamine sources, such as legumes. Not sure I'll ever be able to eat legumes other than green peas or seeds/nuts again, as I get pretty severe brain detachment feeling a few minutes after consuming.

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Try going low and slow with beans. It gets better over time as you are binding up junk allergenic proteins in your bile and pooping them out instead of reabsorbing them over and over which causes allergies. Unfortunately avoiding foods gets worse over time.

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I also added black beans to my diet now that I don't get IBS from them after using charcoal. So that also helps digestion as well as it binds up toxic bile. Plus they have molybdenum often lacking in diets.

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That is awesome! I didn't know that charcoal could help in that way. I will add that to my list of things to try. I have thought about trying charcoal, but concerned about where it comes from and what toxins it might contain (heavy metals, etc). A lot of supplements come from countries with a lot of toxins in their environment. Maybe you can't say here, but do you have a source of charcoal that you trust is 'clean'?

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I've been using zen principle hardwood activated charcoal. Some people react to coconut charcoal.

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Thanks for sharing your experience. I will try that. I have taken HCL in the past but never linked it with an improvement in that area, but then I wasn't looking for that either. I don't have episodes of HypoG (or whatever is really is) very often now, mainly because I do a good job of avoiding those circumstances that precipitate it. That would be a real blessing if it works for me as it has for you. Thanks again.

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Orange juice or potato chips are almost like eating pure glucose. That's just your body wanting a rapid infusion of glucose.

Try alternating the sequence of protein and carbs. I find that some proteins taken before carbs induce hypoglycemia. If I take the carbs before the protein that does not happen.

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It would be nice if it were that simple. OJ only has a glycemic index of 48, a low GI food believe it or not. Potato chips are at 70, just above the medium range, so not so very high. If it were just sugar, any sugar source would be effective, but the OJ and potato chips combo works better than other things for some reason. Its relatively high in sodium and potassium, so those may help. The fats are also important (my body thinks so anyway) for some reason. Sugar carbs alone do not work well for me, including OJ alone. That's why I think Chris is onto something here - its not about low blood sugar. When I am low meat, I do not get hypoglycemia (after the first 24 hours), or if it does manifest it is very mild. I went for about 2 years and never had an episode of HypoG when I was totally off meat, but that is not a healthy option for other reasons. I believe his theory on sulfites explains why I am susceptible,, but not why the sugar, salt, and fat of my body's chosen treatment would remedy the situation. Is there something there that enhances the clearance of sulfites, or their conversion to sulfates?

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I think you completely misunderstand Chris' article. You reported being hypoglycemic after eating meat. Chris article is about being hungry when you are NOT hypoglycemic, so your facts already are not a match to his case. Nothing in Chris' article in any way explains your hypoglycemia. Chris' article is about getting out of a catabolic state by eating glucose when you were never hypoglycemic in the first place.

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The article is not about being hungry when you are not hypoglycemic. Its about being hangry. Hangry. Not the same. If you missed that at the beginning of the article.....

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No, I didn't miss the point, and hangry is just hunger with anger, basically a pseudoterm to explain symptoms that are similar to hypoglycemia in the absence of hypoglycemia. As Chris says:

"I know for myself, I have never been hypoglycemic when I “feel hypoglycemic.” I discovered this by measuring my glucose during those times."

...

"Thus, I propose that many people get hangry because they are generating S-sulfocysteine as collateral damage during protein catabolism."

So Chris is explaining a set of symptoms that happen IN THE ABSENCE OF HYPOGLYCEMIA.

Your symptoms include hypoglycemia, therefore by definition your case is not the case Chris is discussing.

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Dale I think you are confusing us a little because you state that these symptoms accompany both low and normal glucose and then you refer to the symptoms themselves as “hypoglycemia” without reference to your actual blood sugar.

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So what's the takeaway? Should people take more molybdenum? I can barely handle that supplement on its own, yet take it in my trace minerals supplement.

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People who need more should.

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No he means that keto adaptation has another benefit

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Chris, I'm wondering if this mechanism happens more in people who are not adapted to burning their own fat once their liver glycogen runs out. My understanding is that if one is fat adapted, then the cells that use fat for fuel (most cells except brain cells I believe) can run on fat, the brain cells can run on ketones, and then some glucose can be generated from triglycerides--enough to keep the blood glucose stable. Therefore, the body would not need to generate glucose from protein. Am I understanding that correctly?

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That is half right but very importantly wrong. It is under no circumstances ever possible to avoid using amino acids for gluconeogenesis. Even if that could be done during ketoadaptation, it will not stop protein catabolism because there is an obligate 1:1 loss of ammonia for ketones in the urine for acid-base balance. You might be able to get rid of this with bicarbonate or organic acid supplementation but not simply by keto-adapting.

I think you are right that the people who would break protein down the most would be the people who don’t get enough carbs yet are not keto-adapted.

However, I doubt S-sulfocysteine stays the same or goes down on a keto diet. I bet it goes up.

But you have net neruoinhibition due to the strong GABAergic effect of ketones.

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Sorry one other point is they just quantitatively glycerol is not in enough abundance to displace the majority of amino acids from being used for gluconeogenesis. It makes a partial contribution.

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Thanks for your reply. So my next question then is can you use molybdenum to counteract the s-sulfocysteine?

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I would think so. In theory you should be able to convert all sulfite to sulfate.

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But it’s not all about molybdenum. See my previous articles. I will have a consolidated guide on sulfur metabolism coming out soon.

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Isn't molybdenum just a required cofactor? It's not an accelerator, so if you already have sufficient molybdenum, taking more does not solve the problem here. There might be other aspects of the sulfite oxidase enzyme that are not working efficiently, and that might be genetic.

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That’s true but it’s also true that you almost certainly make more sulfite oxidase when you need more and that the molybdenum requirement goes up on high sulfur amino acid intake, which means that the DRI is of low utility and it’s never clear whether someone has “enough.”

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Without looking for the study, I am pretty sure that the keto diet - including people who adapt well to fat burning - upregulates conversion of protein to glucose. The body is in a simulated starvation state, so there must be all kinds of metabolic signals going out that the body needs to catabolize, and that would likely involve proteins. The fact that you suspect s-sulfocysteine is higher in keto diet would independently reinforce the same idea.

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Mar 23Edited

Coming from Carnivore and Ray Peat way of thinking I avoided many Molybdenum containing foods. Now introducing them back again, I can feel surprising effects

Libido back, Less hunger, more energy

Just from fava beans and oats, still experimenting. But thank you so much for shedding the light on Molybdenum

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Hey Chris,

Longtime fan - I saw this post on Reddit yesterday with an accompanying paper on Fructose and its impact on cellular metabolism.

Post - https://old.reddit.com/r/Biohackers/comments/1c4y652/tracing_the_roots_of_metabolic_dysfunction_a_case/

Paper - https://royalsocietypublishing.org/doi/10.1098/rstb.2022.0230

Would love to hear your take on it in a future post! Or if you've already covered it, then I can find it myself.

I wanted to bring it to your attention because it offers a compelling hypothesis for a number of questions I've had about my own energy levels and how certain foods/ingredients have directly impacted them.

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This is fascinating!

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Most diagrams of sulfite to sulfate metabolism show cysteine diverging to s-sulfocysteine, but after you get to sulfite that can also diverge to thiosulfate. I have read that both s-sulfocysteine and thiosulfate can test for sulfite oxidase deficiency:

https://pubmed.ncbi.nlm.nih.gov/24035933/

https://pubmed.ncbi.nlm.nih.gov/509724/

https://pubmed.ncbi.nlm.nih.gov/8605694/

NMS Labs has a $247 test for urinary thiosulfate. But the problem is they only sell to researchers, crime investigators, etc. They don't provide any kit. I think they would accept an order from a doctor but most doctors won't want to set up an account with a vendor for ordering a single test.

Chris, does your research suggest that thiosulfate would be an equally good marker for sulfite oxidase inefficiency? I think you should probably not refer to this as sulfite oxidase deficiency since people who have that rarely survive childhood and get massive brain damage along the way. The condition you are trying to describe is genetic polymorphisms - possibly made worse by diet - that result in excess sulfite accumulation.

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1) No, not on its own. HDRI has a panel with sulfate sulfite and thiosulfate.

2) I didn’t make any incorrect statements that I am aware of. I described the rarity of the fully manifest deficiencies. And regardless the medical binary diagnostic model is highly distort or if the reality.

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If you write another article on this topic, it would be incredibly interesting to see the metabolic diagram which shows s-sulfocysteine as well as thiosulfate. This one is from the Medscape article on sulfite oxidase deficiency:

https://img.medscapestatic.com/pi/meds/ckb/32/44132.jpg

Then maybe discuss why s-sulfocysteine is the preferred marker to measure. Finding a way to order from Mayo at all might be difficult, and probably they are not going to be cheap. I will cross my fingers that you find a way in there.

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Such a diagram is already in the works!

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I agree with all of this. I am just trying to find a term for people who do not have true deficiency but do have a problem. From experience with metabolic geneticists, I can tell you that the moment any of us asks them if we have "sulfite oxidase deficiency (SOD)" their eyes are going to roll, because that is a term that defines the very rare population that you discussed in the article. So shouldn't we create an official name for the genetic polymorphisms that cause a metabolic inefficiency, rather than the "disease" state known as SOD?

Again, I am trying to agree with you. I am just thinking there might be value in creating terminology for describing a novel new idea for the metabolic condition you are considering.

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I think most medical geneticists are absolutely awful and solve almost no one’s problems.

There are about a dozen people in that field globally who are smart, and they are almost impossible to see.

I agree with you on the need to move the field, but that is not the primary lever we can pull right now. There’s all kinds of headwind from regulations, insurance, dogma, cover-your-assery, and so on.

What is more important is to apply common sense to the terminology.

A “deficiency” is when you don’t have enough of something. Period.

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And this field in particular bastardizes language.

Like “mutation.”

They jealously guard this word as if they invented it when in fact it has a meaning in genetics and it has nothing to do whatsoever with clinical impact.

In fact literally every gene is mutated according to evolutionary biology.

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What’s the solution here, apart from getting tested? Molybdenum?

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I’ll be writing more on sulfur soon.

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Any ideas on how to get the Mayo Clinic panel? Call the Mayo Clinic and request an appointment with one of their physicians and then hopefully have that appointment done via telehealth?

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Working on it!

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Thanks, Chris!

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Should we be focusing more on being able to use glucose and glycogen well before a more advanced approach?

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Sure.

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