You can find tons of people on thiamine facebook groups experiencing this, I think. They often call it "paradoxical effects", and some actually seem to snap out of it after a while, but quite a few don't. Personally, I experience similar issues with benfotiamine and biotin. Biotin is quite immediate, while benfo took a little longer to mess me up.
I'm very interested in what exactly is the biochemical process that generates the symptoms. I would assume that it's not just lactate itself, but also the superoxide or hydrogen peroxide produced in ETC in those who have issues with it or is it something else?
I had a similar thing happen on benfotiamine. 95 mg. I had a massive reaction, became very forgetful, and unfocused, I developed intensified long haul covid symptoms. I think I accelerated my metabolism and depleted my body of the supporting metabolites. I am curious to find in the literature which ones exactly may have been effected.
This would have happened to me but I stopped it when my lactate went to 2.5 in two days. Everyone should be doing what I did instead of randomly waiting around for a neurological disorder to set in.
I had nothing but positive experiences with 20 mg until I took 95 mg and then I had a reaction where I thought I was going to die. I stopped the benfo immediately and haven’t taken any since. That was almost 2 years ago and I still haven’t recovered.
I think you mentioned in another post that when you supplemented with riboflavin your lactate initially went up before it came down again. Might the same thing happen with thiamine?
Idk if this was meant for me, but I don’t know how I’m burdening it. I only take lipo GSH a few times a month and lately I haven’t taken it at all. The only sup I take more than once a week is vitamin D.
B2 and manganese are also part of the antioxidant system. I don't know what your issues are and how much trouble you are in, but generally, it seems that many/most people will have some kind of a pathogenic/overgrowth situation going on, which is at least a part of what drives and perpetuates the cycle of illness. So if you have such an issue, the temporary dysregulation that thiamine caused, may have allowed whatever pathogenic thing you have going on to get worse, so simply fixing nutrition nutition may not be enough.
I meant that the metabolic effects of megadosing may cause the underlying issues to get worse. Although yea, I think the direct feeding of something in the gut, may also play a role sometimes
Biotin was giving me blurry vision. I also noticed it was giving me sulfury gut issues. 400 mg of riboflavin a day has opened the door for me get to the root of the issue. Which test would confirm if I have an ACAD mutation?
Thanks for the information. Much appreciated. Can you please tell me where we might be able to purchase a NovaBiomedical Lactate plus in Australia. The website at the link you posted doesn't post internationally. If there is another brand you would recommend I'd be grateful if you would share it and I'll try to locate a supplier either in Australia or who is prepared to ship to Australia. Many thanks.
I'm in Oz too - looks like there a few reputable options out there used by athletes. Also, we can't get ketones measured on blood tests like the US but there are ketone trackers for sale here, I don't know that they measure the two that are needed.
I'm in Australia, so this is the one I found so far. I haven't verified it independently though as I only just started looking. There are others available too, that are more affordable. But again, I don't know about accuracy, usability etc.
Ketones measured on blood tests in labs? Or at home? At home, people can get the finger-prick tests and ketone strips, often used by diabetics. And for lab testing, there are definitely some ketone studies that can be done.
https://www.capitalpath.com.au/clinicians/online-tools/test-collection-manual/ and click on the 'View test collection manual' link, and you can search the tests available at capital/sonic. Laverty also has a guide somewhere that you can search for their offered tests. There are some others, but I haven't looked into them. There should be some blood tests on ketone studies offered, as well as more for urinary organic acids, although I dont really know what all of the results on those mean, and the compounds often have various names so search online and look for the other terms used.
I'm not sure if that's exactly what you were asking for, but thought it might help.
Thanks. I checked the Laverty manual - I'm a naturopath, so I have access to order tests. They offer lactate and "beta OH butyrate" (I assume this is beta hydroxy butyrate) but not pyruvate or acetoacetate.
Not sure about acetoacetate. Pyruvate I was only able to find as part of a urinary organic acids test, that was with Capital, but laverty might have it too. Laverty previously offered a blood test, but it has since been removed.
do you know if the at-home ketone tests measure both of them? Because when I looked at some products, they don't specify. So will have to email the manufacturers.
I would love to run some genetic tests on myself, but I have zero trust in the companies that do the testing. They keep getting caught selling private data or experiencing data breaches. When there is a way to control my own data, I will test, otherwise, never.
It would be interesting to repeat your experiment with biotin and thiamine, but adding extra magnesium +/- calcium. Eliot Overton has mentioned that his patients do much better on mega dose thiamine if they add magnesium. Chandler Marrs (who co-wrote the book upon which much of Eliot Overton's work is based) has mentioned that her patients do much better on mega dose of thiamine only if they add BOTH magnesium and calcium. I love the idea of using early morning lactate levels as a measure of the metabolic effect. If I decide to do this experiment myself, what protocol would you recommend. How many days in a row should you be on a supplement +/- co-factor before drawing a serum lactate?
I get plenty of Ca and Mg, and don't see how that would impact the effect on lactate. Thiamine would increase ATP production, which depends entirely on Mg, but whether Mg is there or not shouldn't impact whether it generates lactate.
And I have no interest in repeating something that gave me a temporary neurological disorder!
With regard to thiamine, I believe the reasoning is that conversion of thiamine to its active form by thiamine pyrophosphokinase requires magnesium. Therefore mega-dosing of thiamine will consume/sequester a lot magnesium. In a rat study, supplementation of thiamine markedly lowered magnesium levels (https://www.jstage.jst.go.jp/article/jnsv1954/18/3/18_3_159/_pdf). In multiple human clinical studies, a low-magnesium state is associated with increased lactate production.
It requires ATP, and everything requiring ATP required magnesium. It will not sequester more magnesium. It will just require ATP like everything else does. Magnesium doesn't get sequestered by TPP to my knowledge.
The paper you post shows thiamin has zero effect on magnesium status in the magnesium-adequate rats judged by both serum and RBC magnesium.
Thanks. But why was magnesium further decreased by thiamin in the magnesium-deficient mice? Why didn't the magnesium-deficient mice simply remain similarly deficient in magnesium? Also, even in the magnesium-adequate mice there was a downward trend of magnesium in the liver, kidney, and femur, and there was a downward trend in body weight. Anyway, no need to respond. I ordered my lactate meter yesterday. I'll let you know if my self-experimentation leads to any interesting results. I am currently eating the exact same diet every day, measuring everything to the gram, so it should be a fairly well-controlled experiment.
Well, like I said, the thiamin requires ATP to be activated and if it is in any manner limiting for ATP production it will increase ATP production, and ATP will chelate magnesium. However, if thiamin and magnesium are adequate for maximal ATP production, then all extra thiamin is likely to do is increase the turnover of ATP while it's being activated, which should increase the turnover of magnesium and perhaps cause transient decreases in free magnesium concentration, but that doesn't mean the magnesium is being depleted and it probably isn't being permanently or quasi-permanently sequestered.
Color me Not convinced that “nearly everyone has several highly idiosyncratic bottlenecks in energy metabolism” - the linked article supporting this claim is paywalled.
Thanks very much for these illuminating pieces. Do you have any advice on resolving an urgent high lactic acid issue? As in, how would you advise I bring it down quickly?
I know my lactic acid is high because it was high on my most recent OAT. I supplement higher dose B1, Biotin, and B6 (also B2 and other Bs). I was using bicarbonate in between meals but it wasn’t enough.
Now, the lactic acid build up is so bad that I can feel it all over my body. It is at its worst in the middle of the night/upon waking. This morning it was in my chest muscles and it felt difficult to breathe.
Today, I stopped the B1, Biotin, and B6 to give my body a break. I’ve got magnesium and potassium going. And I took an additional Mito-q. I had been taking additional B2, but I think it was making the lactic acid worse (perhaps this is the short term effect mentioned).
I am now more mindful of this 2 step process - and when I reintegrate the Step 1 group I will be more careful about making sure Step 2 is better supported (and maybe I don’t need that much in Step 1 after all).
I would be extremely grateful for guidance. Thank so much again.
Thank you, Chris. I feel like that piece speaks directly to me. I have yet to unmask the cause, though extremely high dose B2 combined with B2 r5p seems to help (I am not deficient in any of the B2 cofactors), but also does taking additional B1. Maybe I just keep flip-flopping between the states?
At my recent annual physical, I mentioned your investigation into nutrient-responsive heterozygous mutations to my GP. He was intrigued and thought it might be relevant for my case. I sent my full genome testing sample to Dante Labs a few weeks ago and I'll do take an OAT at the end of the month. I've signed up on the waiting list for a consultation with you (accidentally, twice - sorry!) and really hope that you're able to take me on as a client. I have got to figure this out. Thanks heaps again and best wishes for 2024 :)
Thanks to you, I understand that not only am I a resident of (or at least frequent visitor to) the blue pattern, but also that salicylates were likely poisoning me. Among other things, I recently quit the 1.5+ liter coconut water, which I used for potassium, and once I get my electrolytes sorted I am sure I will feel better without it. THANK YOU.
My B2 needs feel bonkers. For the past few weeks I’ve been at ~ 1 gram (!) (divided doses) of B2 and I get deficiency symptoms even if I miss just 1-2 doses. I am not low in any of the cofactors. I feel like something additional to other Bvits at high doses is driving this.
Thinking more on it ... is it possible that reducing salicylates would lower the B2 need? Or does it not work like this?
How is Step 2 best supported?
I'm sure this is relevant to lots of people with CFS and fibro regardless of taking biotin.
thanks Chris - always interesting and helpful!
However this article goes into some:
https://chrismasterjohnphd.substack.com/p/how-to-interpret-ketone-ratios-and
And I'll be writing more about it in the future.
There is no blanket answer to this. There are at least 297 things that can be wrong with it.
haha! makes sense. thank you :)
You can find tons of people on thiamine facebook groups experiencing this, I think. They often call it "paradoxical effects", and some actually seem to snap out of it after a while, but quite a few don't. Personally, I experience similar issues with benfotiamine and biotin. Biotin is quite immediate, while benfo took a little longer to mess me up.
I'm very interested in what exactly is the biochemical process that generates the symptoms. I would assume that it's not just lactate itself, but also the superoxide or hydrogen peroxide produced in ETC in those who have issues with it or is it something else?
I know this. The “paradoxical” thing is deeply misleading them.
It’s very likely NADH/NAD+ ratio backing up all the NAD+-dependent reactions.
Lactate is the indicator, not the culprit.
Wow that’s very interesting, and not surprising to me
I had a similar thing happen on benfotiamine. 95 mg. I had a massive reaction, became very forgetful, and unfocused, I developed intensified long haul covid symptoms. I think I accelerated my metabolism and depleted my body of the supporting metabolites. I am curious to find in the literature which ones exactly may have been effected.
This would have happened to me but I stopped it when my lactate went to 2.5 in two days. Everyone should be doing what I did instead of randomly waiting around for a neurological disorder to set in.
I had nothing but positive experiences with 20 mg until I took 95 mg and then I had a reaction where I thought I was going to die. I stopped the benfo immediately and haven’t taken any since. That was almost 2 years ago and I still haven’t recovered.
You have a respiratory chain issue you haven't looked into.
I think you mentioned in another post that when you supplemented with riboflavin your lactate initially went up before it came down again. Might the same thing happen with thiamine?
It didn't go up that dramatically and quickly, it looked like a very different phenomenon.
Chris will probably give you a better answer, but my bet would be on glutathione/antioxidant depletion.
I have read it’s more like b2, manganese. I take lipo GSH plus many other antioxidants. Getting slowly better but it’s been nearly 2 years
Seriously doubt it. You are burdening the respiratory chain.
Idk if this was meant for me, but I don’t know how I’m burdening it. I only take lipo GSH a few times a month and lately I haven’t taken it at all. The only sup I take more than once a week is vitamin D.
You were burdening it with 95 mg benfo, but removing the burden doesn't fix the actual issue, which you've never looked into before.
B2 and manganese are also part of the antioxidant system. I don't know what your issues are and how much trouble you are in, but generally, it seems that many/most people will have some kind of a pathogenic/overgrowth situation going on, which is at least a part of what drives and perpetuates the cycle of illness. So if you have such an issue, the temporary dysregulation that thiamine caused, may have allowed whatever pathogenic thing you have going on to get worse, so simply fixing nutrition nutition may not be enough.
You’re starting from an assumption that there is something normal or innocuous about megadosing vitamins.
I meant that the metabolic effects of megadosing may cause the underlying issues to get worse. Although yea, I think the direct feeding of something in the gut, may also play a role sometimes
Ok I agree with that.
Biotin was giving me blurry vision. I also noticed it was giving me sulfury gut issues. 400 mg of riboflavin a day has opened the door for me get to the root of the issue. Which test would confirm if I have an ACAD mutation?
whole genome sequencing
Great post! Are you planning on experimenting with lower doses of Biotin, say in the 300 mcg-1,000 mcg range?
Already have.
Thanks for the information. Much appreciated. Can you please tell me where we might be able to purchase a NovaBiomedical Lactate plus in Australia. The website at the link you posted doesn't post internationally. If there is another brand you would recommend I'd be grateful if you would share it and I'll try to locate a supplier either in Australia or who is prepared to ship to Australia. Many thanks.
I’m not sure. What meters do you get if you search Amazon or Google shopping for lactate meters?
I'm in Oz too - looks like there a few reputable options out there used by athletes. Also, we can't get ketones measured on blood tests like the US but there are ketone trackers for sale here, I don't know that they measure the two that are needed.
What are the reputable ones used by athletes? That should be good for other purposes.
I'm in Australia, so this is the one I found so far. I haven't verified it independently though as I only just started looking. There are others available too, that are more affordable. But again, I don't know about accuracy, usability etc.
https://www.hmgdirect.com.au/products/lactate-pro-2-analyser
Thank you!
Ketones measured on blood tests in labs? Or at home? At home, people can get the finger-prick tests and ketone strips, often used by diabetics. And for lab testing, there are definitely some ketone studies that can be done.
https://www.capitalpath.com.au/clinicians/online-tools/test-collection-manual/ and click on the 'View test collection manual' link, and you can search the tests available at capital/sonic. Laverty also has a guide somewhere that you can search for their offered tests. There are some others, but I haven't looked into them. There should be some blood tests on ketone studies offered, as well as more for urinary organic acids, although I dont really know what all of the results on those mean, and the compounds often have various names so search online and look for the other terms used.
I'm not sure if that's exactly what you were asking for, but thought it might help.
You cannot measure ketone ratios at home.
Thanks. I checked the Laverty manual - I'm a naturopath, so I have access to order tests. They offer lactate and "beta OH butyrate" (I assume this is beta hydroxy butyrate) but not pyruvate or acetoacetate.
Not sure about acetoacetate. Pyruvate I was only able to find as part of a urinary organic acids test, that was with Capital, but laverty might have it too. Laverty previously offered a blood test, but it has since been removed.
do you know if the at-home ketone tests measure both of them? Because when I looked at some products, they don't specify. So will have to email the manufacturers.
At home ketone tests do not measure both.
I'm not sure, I haven't looked into them in that much depth.
I would love to run some genetic tests on myself, but I have zero trust in the companies that do the testing. They keep getting caught selling private data or experiencing data breaches. When there is a way to control my own data, I will test, otherwise, never.
I understand your perspective. You don’t need to know the genetic basis to see if something is raising your lactate though.
It would be interesting to repeat your experiment with biotin and thiamine, but adding extra magnesium +/- calcium. Eliot Overton has mentioned that his patients do much better on mega dose thiamine if they add magnesium. Chandler Marrs (who co-wrote the book upon which much of Eliot Overton's work is based) has mentioned that her patients do much better on mega dose of thiamine only if they add BOTH magnesium and calcium. I love the idea of using early morning lactate levels as a measure of the metabolic effect. If I decide to do this experiment myself, what protocol would you recommend. How many days in a row should you be on a supplement +/- co-factor before drawing a serum lactate?
I get plenty of Ca and Mg, and don't see how that would impact the effect on lactate. Thiamine would increase ATP production, which depends entirely on Mg, but whether Mg is there or not shouldn't impact whether it generates lactate.
And I have no interest in repeating something that gave me a temporary neurological disorder!
Just do finger prick lactate at home.
With regard to thiamine, I believe the reasoning is that conversion of thiamine to its active form by thiamine pyrophosphokinase requires magnesium. Therefore mega-dosing of thiamine will consume/sequester a lot magnesium. In a rat study, supplementation of thiamine markedly lowered magnesium levels (https://www.jstage.jst.go.jp/article/jnsv1954/18/3/18_3_159/_pdf). In multiple human clinical studies, a low-magnesium state is associated with increased lactate production.
It requires ATP, and everything requiring ATP required magnesium. It will not sequester more magnesium. It will just require ATP like everything else does. Magnesium doesn't get sequestered by TPP to my knowledge.
The paper you post shows thiamin has zero effect on magnesium status in the magnesium-adequate rats judged by both serum and RBC magnesium.
Thanks. But why was magnesium further decreased by thiamin in the magnesium-deficient mice? Why didn't the magnesium-deficient mice simply remain similarly deficient in magnesium? Also, even in the magnesium-adequate mice there was a downward trend of magnesium in the liver, kidney, and femur, and there was a downward trend in body weight. Anyway, no need to respond. I ordered my lactate meter yesterday. I'll let you know if my self-experimentation leads to any interesting results. I am currently eating the exact same diet every day, measuring everything to the gram, so it should be a fairly well-controlled experiment.
Well, like I said, the thiamin requires ATP to be activated and if it is in any manner limiting for ATP production it will increase ATP production, and ATP will chelate magnesium. However, if thiamin and magnesium are adequate for maximal ATP production, then all extra thiamin is likely to do is increase the turnover of ATP while it's being activated, which should increase the turnover of magnesium and perhaps cause transient decreases in free magnesium concentration, but that doesn't mean the magnesium is being depleted and it probably isn't being permanently or quasi-permanently sequestered.
Color me Not convinced that “nearly everyone has several highly idiosyncratic bottlenecks in energy metabolism” - the linked article supporting this claim is paywalled.
Thanks very much for these illuminating pieces. Do you have any advice on resolving an urgent high lactic acid issue? As in, how would you advise I bring it down quickly?
I know my lactic acid is high because it was high on my most recent OAT. I supplement higher dose B1, Biotin, and B6 (also B2 and other Bs). I was using bicarbonate in between meals but it wasn’t enough.
Now, the lactic acid build up is so bad that I can feel it all over my body. It is at its worst in the middle of the night/upon waking. This morning it was in my chest muscles and it felt difficult to breathe.
Today, I stopped the B1, Biotin, and B6 to give my body a break. I’ve got magnesium and potassium going. And I took an additional Mito-q. I had been taking additional B2, but I think it was making the lactic acid worse (perhaps this is the short term effect mentioned).
I am now more mindful of this 2 step process - and when I reintegrate the Step 1 group I will be more careful about making sure Step 2 is better supported (and maybe I don’t need that much in Step 1 after all).
I would be extremely grateful for guidance. Thank so much again.
Remove the cause is certainly the first thing. Please see this article:
https://chrismasterjohnphd.substack.com/p/how-to-interpret-ketone-ratios-and
Thank you, Chris. I feel like that piece speaks directly to me. I have yet to unmask the cause, though extremely high dose B2 combined with B2 r5p seems to help (I am not deficient in any of the B2 cofactors), but also does taking additional B1. Maybe I just keep flip-flopping between the states?
At my recent annual physical, I mentioned your investigation into nutrient-responsive heterozygous mutations to my GP. He was intrigued and thought it might be relevant for my case. I sent my full genome testing sample to Dante Labs a few weeks ago and I'll do take an OAT at the end of the month. I've signed up on the waiting list for a consultation with you (accidentally, twice - sorry!) and really hope that you're able to take me on as a client. I have got to figure this out. Thanks heaps again and best wishes for 2024 :)
Hi Anne, I hope so too! If B1 and B2 need more help maybe you just need more of those.
Thanks to you, I understand that not only am I a resident of (or at least frequent visitor to) the blue pattern, but also that salicylates were likely poisoning me. Among other things, I recently quit the 1.5+ liter coconut water, which I used for potassium, and once I get my electrolytes sorted I am sure I will feel better without it. THANK YOU.
My B2 needs feel bonkers. For the past few weeks I’ve been at ~ 1 gram (!) (divided doses) of B2 and I get deficiency symptoms even if I miss just 1-2 doses. I am not low in any of the cofactors. I feel like something additional to other Bvits at high doses is driving this.
Thinking more on it ... is it possible that reducing salicylates would lower the B2 need? Or does it not work like this?