Entire body hurts

[youngsinatra]

I disagree. Past basic vitamin deficiency, the problem here is hypoxia, not decreased COX. The inhibition of PDH is greater than that of COX, that is, PDH is the bottleneck. That's provable by a high dose of B1.

Hypoxia generates lactate, obviously by depleting COX of oxygen, but also by shutting off glucose input into Krebs's. HIF/PDK are responsible for this, and having enough oxygen but not enough Cu/Fe would not downregulate PDH to this extent. In other words, with a normal oxygen supply, your PDH should still be fairly functional even though its regulated by NADH. Without ample oxygen, its exacerbated further.

I think it's more of a POTS/capillary problem. Interestingly, HIF induces VEGF, EPO, and GLUT1 transcription, which some conditions such as CIRS supposedly interfere with. CIRS also supposedly dysregulates overall mitochondrial gene expression, which could explain any irregularities in iron or general metabolism..

I personally never gained huge benefit from thiamine (and the many forms of it) or other B vitamins, except for the initial stage of fixing a deficiency maybe. I still take a daily dose of liquid thiamine pyrophosphate (10mg & holding it for ~10min in my mouth) to ensure normal B1 status.

The main thing that I struggle with is a really bad copper deficiency that did not resolve with copper-rich foods or any kind of copper supplement. (even the fancy copper-1 mitosynergy bulk powder did nothing)

I struggled with that piece of my physiology for almost 2 years. I also had elevated lactate, symptoms of hypoxia (extreme dark circles under my eyes, air hunger, blue/white nails, extremely pale skin) but without any anemia.

No B vitamin deficiency on blood work, and pretty much unresponsive to most of them. I tried high dose B vitamin protocols without long-term success. (High dose B1, B2, B3, B5, B6, B7, Methylation Protocols with B9/B12)

The only thing that really made a big difference so far has been supplementing thyroid hormone (T4/T3) together with lots of magnesium.

I‘ll get blood work tomorrow and see if my hypothesis is true, that thyroid will correct this low copper/ceruloplasmin/low cytochrome C oxidase phenomenon.

 

[brightside]

I personally never gained huge benefit from thiamine (and the many forms of it) or other B vitamins, except for the initial stage of fixing a deficiency maybe. I still take a daily dose of liquid thiamine pyrophosphate (10mg & holding it for ~10min in my mouth) to ensure normal B1 status.

The main thing that I struggle with is a really bad copper deficiency that did not resolve with copper-rich foods or any kind of copper supplement. (even the fancy copper-1 mitosynergy bulk powder did nothing)

I struggled with that piece of my physiology for almost 2 years. I also had elevated lactate, symptoms of hypoxia (extreme dark circles under my eyes, air hunger, blue/white nails, extremely pale skin) but without any anemia.

No B vitamin deficiency on blood work, and pretty much unresponsive to most of them. I tried high dose B vitamin protocols without long-term success. (High dose B1, B2, B3, B5, B6, B7, Methylation Protocols with B9/B12)

The only thing that really made a big difference so far has been supplementing thyroid hormone (T4/T3) together with lots of magnesium.

I‘ll get blood work tomorrow and see if my hypothesis is true, that thyroid will correct this low copper/ceruloplasmin/low cytochrome C oxidase phenomenon.

I think that it's two different pathologies, copper mismanagement and hypoxia. The copper mismanagement should mimic hypoxia, but not to the extent that I had. (where without PDK blockers (thiamine), I was essentially bedridden ) Basically, if you have a copper deficiency, your decreased COX would be the primary bottleneck, and you would only produce as much lactate as COX is decreased. With hypoxia, you're artificially creating more lactate, since PDH is also being blocked. Like I said, you would obviously have NADH coming around and reducing PDH activity, since you would have a slowdown due to the decreased COX, but either way, you wouldn't have HIF activation that would be artificially driving things lower.

That's kind of my theory/opinion, but it does explain things for me. I could very well have the same copper mismanagement you are talking about, but that would be in addition to the hypoxia from capillary dysfunction. I don't think copper problems would explain things, and they clearly don't, since B1 works for me to get me out of bed and at least walking around. (past that, copper could be an explanation, though). If I didn't make it clear, I'm doubtful that you could be in such deep lactic acidosis without hypoxia. I don't think that's possible, otherwise you would have a mitochondrial mutation, severe vitamin deficiency, or insulin deficiency.

My skin looks very healthy, and I tan easily too (potentially good copper management), but I get cold skin. The more active I am, the colder it gets. I could be doing some intense physical labor, sweating, on a hot summer day, and my skin would be ice cold to the touch. So there's something off there for sure.

I have seen a number of your posts/threads over the past few years, so your new endeavor is interesting. It's definitely a solid theory, and I'm curious to see what your results and experiments show. What set off your symptoms initially?

I also find high dose B's to lose their potency, usually very quickly, but in the case of B1, it's still >0. And the mito copper is definitely a gimmick lol. I mean, it's definitely more potent, but that's about it.

 

[youngsinatra]

I think that it's two different pathologies, copper mismanagement and hypoxia. The copper mismanagement should mimic hypoxia, but not to the extent that I had. (where without PDK blockers (thiamine), I was essentially bedridden ) Basically, if you have a copper deficiency, your decreased COX would be the primary bottleneck, and you would only produce as much lactate as COX is decreased. With hypoxia, you're artificially creating more lactate, since PDH is also being blocked. Like I said, you would obviously have NADH coming around and reducing PDH activity, since you would have a slowdown due to the decreased COX, but either way, you wouldn't have HIF activation that would be artificially driving things lower.

That's kind of my theory/opinion, but it does explain things for me. I could very well have the same copper mismanagement you are talking about, but that would be in addition to the hypoxia from capillary dysfunction. I don't think copper problems would explain things, and they clearly don't, since B1 works for me to get me out of bed and at least walking around. (past that, copper could be an explanation, though). If I didn't make it clear, I'm doubtful that you could be in such deep lactic acidosis without hypoxia. I don't think that's possible, otherwise you would have a mitochondrial mutation, severe vitamin deficiency, or insulin deficiency.

My skin looks very healthy, and I tan easily too (potentially good copper management), but I get cold skin. The more active I am, the colder it gets. I could be doing some intense physical labor, sweating, on a hot summer day, and my skin would be ice cold to the touch. So there's something off there for sure.

I have seen a number of your posts/threads over the past few years, so your new endeavor is interesting. It's definitely a solid theory, and I'm curious to see what your results and experiments show. What set off your symptoms initially?

I also find high dose B's to lose their potency, usually very quickly, but in the case of B1, it's still >0. And the mito copper is definitely a gimmick lol. I mean, it's definitely more potent, but that's about it.

Thanks for the throughout reply.

Have you ever gotten a serum copper and ceruloplasmin blood test? I see it flagged „low“ all the time in the people I speak to. Especially people with CFS, neurological disease (MS), chronic GI conditions (colitis..) and esp. those with EDS. (Ehler-Dahnlos-Syndrome)

 

[brightside]

Thanks for the throughout reply.

Have you ever gotten a serum copper and ceruloplasmin blood test? I see it flagged „low“ all the time in the people I speak to. Especially people with CFS, neurological disease (MS), chronic GI conditions (colitis..) and esp. those with EDS. (Ehler-Dahnlos-Syndrome)

Unfortunately, no, I haven't. I wouldn't be surprised if it's low, though. Supplemental copper is helpful, but not curative.

I'm curious if you have ever tried Cholestyramine (CSM). CSM has an interesting capability to bind negatively charged toxins (because it's positively charged), unlike the common detoxifiers that are all negatively charged.. or so I heard. Regardless, it's still a potent bile binder, and it does seem to really help CIRS patients detox toxins when they recirculated in their enterohepatic circulation. I know you used fibers, oatmeal, and other techniques to improve liver detox, but CSM has a special mechanism that you probably won't get from other binders.

 

[Dutchie]

Unfortunately, no, I haven't. I wouldn't be surprised if it's low, though. Supplemental copper is helpful, but not curative.

I'm curious if you have ever tried Cholestyramine (CSM). CSM has an interesting capability to bind negatively charged toxins (because it's positively charged), unlike the common detoxifiers that are all negatively charged.. or so I heard. Regardless, it's still a potent bile binder, and it does seem to really help CIRS patients detox toxins when they recirculated in their enterohepatic circulation. I know you used fibers, oatmeal, and other techniques to improve liver detox, but CSM has a special mechanism that you probably won't get from other binders.

My understanding has always been that mold, pollution etc. toxins are positive charged, so wouldn't you need a negative charge binder in that case?

which toxins are negative charged?

 

[brightside]

My understanding has always been that mold, pollution etc. toxins are positive charged, so wouldn't you need a negative charge binder in that case?

which toxins are negative charged?

I honestly don't know, I just heard it in a CIRS lecture. I might have gotten it reversed. FWIW, I noticed definite benefit even from light CSM use, whereas large doses of charcoal, or increased fibers is useless.

 

[Dutchie]

I honestly don't know, I just heard it in a CIRS lecture. I might have gotten it reversed. FWIW, I noticed definite benefit even from light CSM use, whereas large doses of charcoal, or increased fibers is useless.

Yeah, I'd heard of CSM from the Lyme community but have never used it (can't get a prescription for it anyway).
Powdered binders always made me constipated, so I don't know if they would've worked for me.

At the moment, I take about 1-1 1/2tsp of pectin daily. I take it to keep my gut moving (and hopefully feed the good guys) as zerofiber/meatbased led to H2S issues.
Pectin is supposed to be (a weak?) binder as well....tbh I have no idea what it"s doing or what I have going on inside.

 

[brightside]

Yeah, I'd heard of CSM from the Lyme community but have never used it (can't get a prescription for it anyway).
Powdered binders always made me constipated, so I don't know if they would've worked for me.

At the moment, I take about 1-1 1/2tsp of pectin daily. I take it to keep my gut moving (and hopefully feed the good guys) as zerofiber/meatbased led to H2S issues.
Pectin is supposed to be (a weak?) binder as well....tbh I have no idea what it"s doing or what I have going on inside.

You can get it from a CIRS specialist, but IDK of the realism and costs of that. You can also buy it from farmacia del nino. It's expensive, but so is being sick.

How does the pectin compare to psyllium husk, if you tried that? And what are your symptoms that you are trying to fix?

Pectin is supposed to be (a weak?) binder as well....

Probably, but I'm skeptical that it would work as well, if at all, like CSM. If that would be true, you could get well from eating fruit, it would just take longer.
Okra supposedly binds bile up to 34% as strong as CSM, but even then, it's chemical structure might not be ideal for binding the toxins.

I do have one big question concerning the necessity of CSM. If mold has been around forever, then why can't we detox its toxins? Or rather, why is that only CSM works well? But then if you decide to believe the entire CIRS theory, then it's somewhat answered. I'm not sure about the mechanisms of that, but at least it makes some sense.

 

[Dutchie]

You can get it from a CIRS specialist, but IDK of the realism and costs of that. You can also buy it from farmacia del nino. It's expensive, but so is being sick.

How does the pectin compare to psyllium husk, if you tried that? And what are your symptoms that you are trying to fix?

CIRS specialists need to prescribe it as well here....and they need to have the authority to prescribe medication. (Generally, it's naturopaths whom you need to turn to for CIRS...and they don't have that authority).
Ordering from outside The EU sadly is not an option (due to Customs).

I have tried psyllium in the past and it didn't work well for me....also felt constipatory. Why?....I dunno..maybe it's bc it's from a seed?
Pectin feels gentle on my gut.

In regards of the pectin, it's not that I'm using it as a binder to fix something.
I take it to hopefully keep my bowels moving and have a better microbiome so I can tolerate more foods again (though I don't feel like anything else for now).
Btw, I'm not saying I have CIRS.....

Probably, but I'm skeptical that it would work as well, if at all, like CSM. If that would be true, you could get well from eating fruit, it would just take longer.

You're absolutely right that it is a slow healing process, but I've come to realize that my body likes these gentler (slower) healing methods best....lol, much to my frustration at times.

For me personally, the pectin powder works bc there are no other substances involved (carbs, planttoxins etc which my body reacts to.) which you would have with fruits&veg.

I do have one big question concerning the necessity of CSM. If mold has been around forever, then why can't we detox its toxins? Or rather, why is that only CSM works well? But then if you decide to believe the entire CIRS theory, then it's somewhat answered. I'm not sure about the mechanisms of that, but at least it makes some sense.

Good questions.
I don't know.....I do know that there are certain gene defects to make one susceptible to having difficulty clearing out mold toxins. Maybe also methylation and detoxifying issues in general?
Also, a naturopath I saw once said, that we all basically would need 2 livers to deal with all the toxins from our (Western) modernday society.

 

[achillea]

When achy joints leads to medical terms, like fibromyalgia, there is a lot of research on magnesium and its benefits in connection to it. Inflammation is always at the spot.
But something else comes to mind that I don't think we realize, though. I had made the mistake taking Vit D. when going Peat for all these years. Now, in reading Cu-re Your Fatigue, I've learned that it can raise inflammation and susceptibility to infection. Sunlight exposure is how we make it naturally. Mangin published in a scientific journal Inflammation Research in 2014, "This molecule is transported to the liver where it is used to produce calcidiol [storage D]. This storage form of Vit D [25(OH)D} is transported to the kidneys where it is converted to the active form of Vit D called calcitriol [1,25 dihydroxyvitamin-D]. Kicker alert that Morley found, she writes. "In sick people, low calcidiol (often labled as Vit D deficiency) and high calcitriol are markers of a chronic inflammatory process. Low calcidiol is a consequence of a disease process, not a cause. Supplementing with Vit D increases the level of calcidiol, making it easier to produce calcitriol, which increases inflammatory symtoms." So when I hear people taking Vit D, and a lot of us do or did doing Peat, I wish I could express my regret to them, for having taken it for all these years and that I hadn't known how bad it really was for me. But now I do and without a lot of testing and complication to finding an answer, think about Vit D and ask if it could be suspect. A lot of people are taking it, I see it everywhere I look.
"Mo-Maggie" (magnesium) says Morley Robbins of RCP and I think he's right.
My problem was the type of magnesium, the BiCarb and the sulphate form is what I can tolerate, the others cause me problems. After I get the T-3 back in, (which is something I dropped for experimental purposes) I'll be interested to see if the glycinate form will work too.
Happily, a quick change came when I used BiCarb with DMSO and progesterone. I hope this helps make a simple transition to feeling better.

 

[iLoveSugar]

@brightside you have posted that I don't believe in lactic acidosis being an issue for me. That isn't true. I'm just in such a disoriented, beatdown, hyperfogged, and terrible state of health, that nothing has worked thus far. I'm exhausted, hurt, and just completely drained. I'm currently taking 300 mg of thiamine a day along with some magnesium glycinate, and 300-400 mg of aspirin per day. Just literally nothing is helping. I'm also drinking quite a bit of homemade lemonade which we make with carbonated water and sugar.

 

[mostlylurking]

@brightside you have posted that I don't believe in lactic acidosis being an issue for me. That isn't true. I'm just in such a disoriented, beatdown, hyperfogged, and terrible state of health, that nothing has worked thus far. I'm exhausted, hurt, and just completely drained. I'm currently taking 300 mg of thiamine a day along with some magnesium glycinate, and 300-400 mg of aspirin per day. Just literally nothing is helping. I'm also drinking quite a bit of homemade lemonade which we make with carbonated water and sugar.

What type of thiamine are you taking? What are you taking it with? Are you spacing all sugar at least 30 minutes away from taking the thiamine? How much sugar/sweet things do you consume in a day? Do you drink coffee or tea?

 

[purple pill]

@brightside you have posted that I don't believe in lactic acidosis being an issue for me. That isn't true. I'm just in such a disoriented, beatdown, hyperfogged, and terrible state of health, that nothing has worked thus far. I'm exhausted, hurt, and just completely drained. I'm currently taking 300 mg of thiamine a day along with some magnesium glycinate, and 300-400 mg of aspirin per day. Just literally nothing is helping. I'm also drinking quite a bit of homemade lemonade which we make with carbonated water and sugar.

I feel ya, my medicine cabinet is bursting with supplements i had high hopes for after reading some study or anecdote on here or elsewhere....all leading to empty pockets and dissapointment. Sodium bicarbonate has been the only supplement for a long time thats actually made a difference to my general aches and pains and slowed down and relaxed my breathing, even made a huge difference to the dark circles under my eyes ive always had which someone here mentioned was caused by hypoxia. I wouldve hoped the homemade lemonade would have brought some relief if it was lactic acidosis but maybe not enough. still im sure you have some old baking soda lying around for a 1/4-1/2 teaspoon or so in your coffee as a quick and free experiment thiamine, magnesium or even aspirin never done jack ***t for me either, if anything they probably made me more acidic minus the magnesium but still done nothing even in gram doses got some potassium citrate in the post too, hopefully turn that car into a bicycle soon lol

 

[brightside]

@brightside you have posted that I don't believe in lactic acidosis being an issue for me. That isn't true. I'm just in such a disoriented, beatdown, hyperfogged, and terrible state of health, that nothing has worked thus far. I'm exhausted, hurt, and just completely drained. I'm currently taking 300 mg of thiamine a day along with some magnesium glycinate, and 300-400 mg of aspirin per day. Just literally nothing is helping. I'm also drinking quite a bit of homemade lemonade which we make with carbonated water and sugar.

I’m sorry, I do know how you feel. It sucks.

I said that because I’ve explained to you about (high dose) thiamine before but you didn’t seem interested, so I dropped it. Recently, I saw one of your threads again and couldn’t help not commenting, since it’s something that could potentially really help.

Have you actually tried 2 grams at once on an empty stomach with water, though? In my experience, even that wasn’t quite enough, and TTFD is what I need. So if you get only mild improvement at 2g, then trying TTFD could be a good idea.

 

[iLoveSugar]

What type of thiamine are you taking? What are you taking it with? Are you spacing all sugar at least 30 minutes away from taking the thiamine? How much sugar/sweet things do you consume in a day? Do you drink coffee or tea?

I have attached the screenshot of what I am taking. I typically take it with nothing else except a sip of something to chase it, such as lemonade, milk, etc. I drink lots of homemade lemonade in a day which is loaded with sugar, along with 2-3 cups of iced decaf coffee that we make. I don't do well with caffeine right now.

 

[iLoveSugar]

I feel ya, my medicine cabinet is bursting with supplements i had high hopes for after reading some study or anecdote on here or elsewhere....all leading to empty pockets and dissapointment. Sodium bicarbonate has been the only supplement for a long time thats actually made a difference to my general aches and pains and slowed down and relaxed my breathing, even made a huge difference to the dark circles under my eyes ive always had which someone here mentioned was caused by hypoxia. I wouldve hoped the homemade lemonade would have brought some relief if it was lactic acidosis but maybe not enough. still im sure you have some old baking soda lying around for a 1/4-1/2 teaspoon or so in your coffee as a quick and free experiment thiamine, magnesium or even aspirin never done jack ***t for me either, if anything they probably made me more acidic minus the magnesium but still done nothing even in gram doses got some potassium citrate in the post too, hopefully turn that car into a bicycle soon lol

To be honest with you, I have taken sodium bicarbonate in the past, but never tried an extended experiment with it. It's always been something I have taken and then just stopped after 1 or 2 times.

 

[iLoveSugar]

I’m sorry, I do know how you feel. It sucks.

I said that because I’ve explained to you about (high dose) thiamine before but you didn’t seem interested, so I dropped it. Recently, I saw one of your threads again and couldn’t help not commenting, since it’s something that could potentially really help.

Have you actually tried 2 grams at once on an empty stomach with water, though? In my experience, even that wasn’t quite enough, and TTFD is what I need. So if you get only mild improvement at 2g, then trying TTFD could be a good idea.

I have not taken 2 grams at once. I guess it's just me being scared since I always react so bad to literally every supplement, whether good or bad. Many times, it's probably just physiological. I have noticed several times that when I wake up in the morning to go to the bathroom, urine seems to smell like it, so I'm likely excreting some. Is that normal?

 

[Waynish]

Fixed? Have you tried going off everything (including caffeine) for a week to see what your baseline is like?

 

[mostlylurking]

I have attached the screenshot of what I am taking. I typically take it with nothing else except a sip of something to chase it, such as lemonade, milk, etc. I drink lots of homemade lemonade in a day which is loaded with sugar, along with 2-3 cups of iced decaf coffee that we make. I don't do well with caffeine right now.

"loaded with sugar" will cancel out your thiamine and cause a deficiency. It isn't the caffeine that blocks thiamine, so decaffeinated coffee would still be a problem.

I realize this negative perspective about sugar is counter to Ray Peat's teaching and Ray was pretty vocal about his distaste for John Yudkin and his book warning about sugar. However, when it comes to someone with a thiamine deficiency or functional blockage, sugar in the diet is a real problem. The concept is pretty straightforward.

Thiamine Deficiency and Sugar in Diabetes - Hormones Matter

Sugar requires thiamine to metabolize it, in much the same way as gasoline requires a spark plug to burn it. Eating sugar easily overwhelms the power of thiamine to carry out its function.

www.hormonesmatter.com

"Because sugar requires vitamin B 1 to metabolize it, in much the same way as gasoline requires a spark plug to burn it, taking sugar on its own in the form of empty calories easily overwhelms the power of thiamine to carry out its function."

Hiding in Plain Sight: Modern Thiamine Deficiency

Thiamine or vitamin B1 is an essential, water-soluble vitamin required for mitochondrial energetics—the production of adenosine triphosphate (ATP). It is a critical and rate-limiting cofactor to multiple enzymes involved in this process, including ...

www.ncbi.nlm.nih.gov

"Finally, caffeic acid, chlorogenic acid, and tannic acid in coffee, tea, and energy drinks, oxidize the thiazole ring of the thiamine molecule, impairing its absorption, while the added sugars, flavors and other substances to enhance taste, increase thiamine demand. Sixty-two percent of Americans consume an average of three cups of coffee per day [163], suggesting this popular food item may contribute more to TD than acknowledged."

My suggestion is to try your benfotiamine WITHOUT any sugar and WITHOUT any coffee (including the decaf) in your diet at all. You could still have milk, just not with added sugar. Take the benfotiamine with a full glass of water; space it 30 minutes away from consuming anything else.

I am not familiar with the recommended dosing amounts for benfotiamine.
This article discusses benfotiamine as well as other thiamine types:

Navigating Thiamine Supplements- Hormones Matter

Understanding the different forms of vitamin B1.

www.hormonesmatter.com

I have not taken 2 grams at once. I guess it's just me being scared since I always react so bad to literally every supplement, whether good or bad. Many times, it's probably just physiological. I have noticed several times that when I wake up in the morning to go to the bathroom, urine seems to smell like it, so I'm likely excreting some. Is that normal?

Diabetics are known to waste thiamine via the kidneys.

Diabetes and Thiamine: A Novel Treatment Opportunity

A growing body of evidence links Type 1 and Type 2 diabetes to thiamine deficiency.

www.hormonesmatter.com

"With diabetes, thiamine deficiencies are common, though likely under-recognized. Diabetics are susceptible to thiamine deficiencies mediated by diet and exposures like most of the Western world, but also have added risk factors associated with the disease itself. In diabetics, kidney function is altered which decreases thiamine reabsorption while increasing thiamine excretion. In some people, diabetic and non-diabetic alike, thiamine deficiency can be exacerbated even further by a mutation in the thiamine transporter protein that brings thiamine into the cells."

However, I don't have diabetes and I can report that my urine was pretty stinky for months when high dosing thiamine hcl. It isn't that way anymore though and I'm still high dosing thiamine hcl.

 

[mostlylurking]

@iLoveSugar , can you tell me if you have any amalgam (silver) fillings in your mouth, also do you have any root canals? Thanks.