Brilliant! Love the "D-Lactate Shuttle" & the discussion adding other mitochondrial complexes to support this idea. The A.G.E linkage with methylglyoxal is particularly noteworthy as well as the resultant neurotoxicity. Including the oxalate effects and possible involvement with autism is also of great significance.
Will you recommend the use of calcium citrate since it is more effective? if yes is the dose per meal still 300mg to 400mg per meal?
Just came across these 2 research , Crystals in the Substantia Nigra ( https://pubmed.ncbi.nlm.nih.gov/31257859/ ) and Potentially Pathogenic Calcium Oxalate Dihydrate and Titanium Dioxide Crystals in the Alzheimer's Disease Entorhinal Cortex ( https://pubmed.ncbi.nlm.nih.gov/32804151/ ) . With these 2 papers, we should avoid using sunscreen containing titanium dioxide.
Some people including e.g. Kressler, claim that 3x300-400mg of supplemental calcium will only lead to calcification of tissues. You're not afraid of this? Sure, it would be better to get that much calcium from food, but that's another level complicating one's diet, so supplements would be quite convenient here. Thanks.
Calcium is the most effective thing you can do to shut down calcification because it inhibits bone resorption, and excess bone resorption is the most pro-calcification condition you can have. At best, that concern is justified for taking calcium on an empty stomach, which is easily solved by taking it after a meal, and most likely the concern is limited to the average person taking calcium supplements which are older adults with osteopenia and osteoporosis getting their calcium up to 2000 mg/d. The amount I just cited is the RDA for calcium.
You MAY have just helped me figure out what in the world is wrong with my husband. He has been suffering for more than a decade (possibly the same thing since childhood), with crippling nausea/vomiting/vertigo episodes, other gastrointestinal distress, and within the last year, stroke-like episodes. It has becomes so frequent that he has been unable to work since August 8 last year. I received an email with the contents of this post, which got my wheels turning. It's rare that I read something and go, "Wow, those symptoms sound a lot like what my husband experiences." He's special. I don't know anybody like him. We've only ever had every medical practitioner he come in contact with tell us, "We have no idea what is wrong with you," and some suggest a psychological evaluation (which he is currently getting anyway). It's even more difficult with us being in Canada, and one of the worst provinces for healthcare, at that (we've had to travel out of province, twice, to see a specialist). He doesn't have short bowel syndrome, and because of this post, I found the contact for one of the doctors involved in writing about one of the four reports of D-lactate dehydrogenase. This doctor was involved with a family that also had elevated levels of uric acid and had gout (my husband also has elevated levels of uric acid, and has episodes of swollen joints/tendons, but never "officially" diagnosed with gout), and has d-lactate dehydrogenase deficiency. I feel like I'm completely going out on a limb, since (naturally), his d-lactate levels have never been tested, but I really feel like I have finally put together the puzzle. Last year, he had Whole Genome Sequencing done by Nebula Genomics, and the aforementioned doctor is currently looking at his genome (I assume the LDHD gene). Thank you SO MUCH for writing this!!! I will definitely give an update when I have one.
These symptoms are totally non-specific. He definitely has an inborn error of metabolism but it could be many. You’d be hitting total luck if it’s this. I wish you the best in figuring it out.
He's had both his plasma amino acids urine organic acids tested (while non-symptomatic and symptomatic), and the urine organic acids were reported as "unremarkable" (with a refusal to release what the breakdown is), and the plasma amino acids had mildly elevated leucine, isoleucine, and valine while symptomatic (isoleucine within range when not symptomatic). The raised BCAA was explained as the result of catabolism (from "prolonged fasting/vomiting and dehydration"; even though he had some vomiting, but still able to drink water and it wasn't prolonged). While symptomatic, his hydroxyproline was way low (< 5; normal range 40-90), serine mildly low, and cysteine as well. Although I realize that even this can be non-specific.
Mostly normal test results, except mildly low Total CO2, mildly low creatinine, and mildly low calcium.
He's a complete enigma, which is why it all gets dismissed as psychosomatic. I can't see things like MSUD as being responsible, as 1. he doesn't have the characteristic smell of maple syrup or anything resembling as sweet; 2. His blood glucose is always normal (maybe even a bit on the "elevated" side of 6.0) and blood ketones nearly non-existent.
He had his porphyrin precursors tested while symptomatic and it came back as normal.
In December, he was told two options by local genetics: MELAS and CADASIL. Nothing is really happening with testing for either. It doesn't sound like CADASIL, and his serum lactate (l-lactate) always comes back as normal during an episode (well; mildly elevated; 2.47 max). He had a failed lumbar puncture a couple of weeks ago to check his CSF for oligoclonal antibodies (MS inflammatory markers) and l-lactate (while non-symptomatic). However, when I was in contact with Children's Hospital fo Philadelphia, someone looked over his mitochondria, and while they did get hits regarding MELAS, they were all very low frequency and they said it's unlikely. They also had a neurologist look over his MRI, and said that the more than 20 white matter lesions across both hemispheres on it wasn't consistent with MELAS.
Several months ago, we applied to two different Mayo Clinics (internal medicine), but they both rejected him.
It's like nobody wants to touch him, shrug their shoulders, and just say, "We don't know."
So when I was reading about what high levels of d-lactate can do, namely, make someone appear like they're blackout drunk AND it can give off a smell... that's why I suspected something to do with d-lactate.
Hey Chris, new sub here. You’ve spoke about when you load up on step 1 of energy metabolism ( nutrients such as thiamine , b6 , biotin) your over burden the respiratory chain. Can you speak about the reverse… what happened when step 2 is supported too much. I’ve noticed when I supplement with Coq10 or riboflavin I get 2 of the exact same feelings: extreme muscle weakness and I get very tired and sleepy. Can you explain maybe why this is
What they share in common is promoting fat oxidation and oxidation of lysine tryptophan and BCAAs, converting sarcosine and dimethylglycine to glycine, bypassing complex I in the respiratory chain, converting hydrogen sulfide to sulfite, converting dihydroorotate to orotate , and converting proline to P5C.
You could experiment with any of the variables above to try to narrow it down.
Hi Chris, also a question relating to this! I had an initial honeymoon period with high dose thiamine last year. After 2 months it left me wrecked until I found high dose riboflavin. Now supporting riboflavin and b12 had immense benefit in symptoms. A big issue I deal with is lactic acid feeling, burning/tingling weak legs so I got the lactate meter. I usually run high with fasting lactate of around 1-1.2. Tried bringing small amounts of thiamine back in and it would bring down the lactate the next day before raising it to 1.5. I’ve tried biotin in various doses which do not bring the lactate down either. Any thoughts? Thanks
Does that mean D-lactate also get produced in muscle during exercise?
And if oxalate binds to minerals, could you take a magnesium supplement with a high dose biotin supplement, and expect any extra oxalate to bind to the magnesium for kidney excretion instead of being redistributed? Was wondering if biotin frees enough oxalate to overload methylation and other pathways, then maybe we could consume something like a magnesium or calcium supplement to chelate it.
Thought some mineral supplements were occasionally used to break down kidney stones, of which I thought some are oxalate. Not sure if that's even effective for kidney stones but if it is then why not for much smaller crystals in the blood too?
I think some would be produced in the muscle during exercise, and that you'd have to biopsy it to find it because it would not be likely to exit into the blood.
Oxalate is much more specifically attracted to calcium.
Brilliant! Love the "D-Lactate Shuttle" & the discussion adding other mitochondrial complexes to support this idea. The A.G.E linkage with methylglyoxal is particularly noteworthy as well as the resultant neurotoxicity. Including the oxalate effects and possible involvement with autism is also of great significance.
Will you recommend the use of calcium citrate since it is more effective? if yes is the dose per meal still 300mg to 400mg per meal?
Just came across these 2 research , Crystals in the Substantia Nigra ( https://pubmed.ncbi.nlm.nih.gov/31257859/ ) and Potentially Pathogenic Calcium Oxalate Dihydrate and Titanium Dioxide Crystals in the Alzheimer's Disease Entorhinal Cortex ( https://pubmed.ncbi.nlm.nih.gov/32804151/ ) . With these 2 papers, we should avoid using sunscreen containing titanium dioxide.
"More effective" doesn't mean anything without being followed by an "at ________."
300-400 mg calcium per meal is enough to substantially reduce oxalate absorption and also lines up with the general requirement for calcium.
Some people including e.g. Kressler, claim that 3x300-400mg of supplemental calcium will only lead to calcification of tissues. You're not afraid of this? Sure, it would be better to get that much calcium from food, but that's another level complicating one's diet, so supplements would be quite convenient here. Thanks.
Calcium is the most effective thing you can do to shut down calcification because it inhibits bone resorption, and excess bone resorption is the most pro-calcification condition you can have. At best, that concern is justified for taking calcium on an empty stomach, which is easily solved by taking it after a meal, and most likely the concern is limited to the average person taking calcium supplements which are older adults with osteopenia and osteoporosis getting their calcium up to 2000 mg/d. The amount I just cited is the RDA for calcium.
Thanks for this. A lot.
You MAY have just helped me figure out what in the world is wrong with my husband. He has been suffering for more than a decade (possibly the same thing since childhood), with crippling nausea/vomiting/vertigo episodes, other gastrointestinal distress, and within the last year, stroke-like episodes. It has becomes so frequent that he has been unable to work since August 8 last year. I received an email with the contents of this post, which got my wheels turning. It's rare that I read something and go, "Wow, those symptoms sound a lot like what my husband experiences." He's special. I don't know anybody like him. We've only ever had every medical practitioner he come in contact with tell us, "We have no idea what is wrong with you," and some suggest a psychological evaluation (which he is currently getting anyway). It's even more difficult with us being in Canada, and one of the worst provinces for healthcare, at that (we've had to travel out of province, twice, to see a specialist). He doesn't have short bowel syndrome, and because of this post, I found the contact for one of the doctors involved in writing about one of the four reports of D-lactate dehydrogenase. This doctor was involved with a family that also had elevated levels of uric acid and had gout (my husband also has elevated levels of uric acid, and has episodes of swollen joints/tendons, but never "officially" diagnosed with gout), and has d-lactate dehydrogenase deficiency. I feel like I'm completely going out on a limb, since (naturally), his d-lactate levels have never been tested, but I really feel like I have finally put together the puzzle. Last year, he had Whole Genome Sequencing done by Nebula Genomics, and the aforementioned doctor is currently looking at his genome (I assume the LDHD gene). Thank you SO MUCH for writing this!!! I will definitely give an update when I have one.
These symptoms are totally non-specific. He definitely has an inborn error of metabolism but it could be many. You’d be hitting total luck if it’s this. I wish you the best in figuring it out.
He's had both his plasma amino acids urine organic acids tested (while non-symptomatic and symptomatic), and the urine organic acids were reported as "unremarkable" (with a refusal to release what the breakdown is), and the plasma amino acids had mildly elevated leucine, isoleucine, and valine while symptomatic (isoleucine within range when not symptomatic). The raised BCAA was explained as the result of catabolism (from "prolonged fasting/vomiting and dehydration"; even though he had some vomiting, but still able to drink water and it wasn't prolonged). While symptomatic, his hydroxyproline was way low (< 5; normal range 40-90), serine mildly low, and cysteine as well. Although I realize that even this can be non-specific.
Mostly normal test results, except mildly low Total CO2, mildly low creatinine, and mildly low calcium.
He's a complete enigma, which is why it all gets dismissed as psychosomatic. I can't see things like MSUD as being responsible, as 1. he doesn't have the characteristic smell of maple syrup or anything resembling as sweet; 2. His blood glucose is always normal (maybe even a bit on the "elevated" side of 6.0) and blood ketones nearly non-existent.
He had his porphyrin precursors tested while symptomatic and it came back as normal.
In December, he was told two options by local genetics: MELAS and CADASIL. Nothing is really happening with testing for either. It doesn't sound like CADASIL, and his serum lactate (l-lactate) always comes back as normal during an episode (well; mildly elevated; 2.47 max). He had a failed lumbar puncture a couple of weeks ago to check his CSF for oligoclonal antibodies (MS inflammatory markers) and l-lactate (while non-symptomatic). However, when I was in contact with Children's Hospital fo Philadelphia, someone looked over his mitochondria, and while they did get hits regarding MELAS, they were all very low frequency and they said it's unlikely. They also had a neurologist look over his MRI, and said that the more than 20 white matter lesions across both hemispheres on it wasn't consistent with MELAS.
Several months ago, we applied to two different Mayo Clinics (internal medicine), but they both rejected him.
It's like nobody wants to touch him, shrug their shoulders, and just say, "We don't know."
So when I was reading about what high levels of d-lactate can do, namely, make someone appear like they're blackout drunk AND it can give off a smell... that's why I suspected something to do with d-lactate.
Hey Chris, new sub here. You’ve spoke about when you load up on step 1 of energy metabolism ( nutrients such as thiamine , b6 , biotin) your over burden the respiratory chain. Can you speak about the reverse… what happened when step 2 is supported too much. I’ve noticed when I supplement with Coq10 or riboflavin I get 2 of the exact same feelings: extreme muscle weakness and I get very tired and sleepy. Can you explain maybe why this is
What they share in common is promoting fat oxidation and oxidation of lysine tryptophan and BCAAs, converting sarcosine and dimethylglycine to glycine, bypassing complex I in the respiratory chain, converting hydrogen sulfide to sulfite, converting dihydroorotate to orotate , and converting proline to P5C.
You could experiment with any of the variables above to try to narrow it down.
Hi Chris, also a question relating to this! I had an initial honeymoon period with high dose thiamine last year. After 2 months it left me wrecked until I found high dose riboflavin. Now supporting riboflavin and b12 had immense benefit in symptoms. A big issue I deal with is lactic acid feeling, burning/tingling weak legs so I got the lactate meter. I usually run high with fasting lactate of around 1-1.2. Tried bringing small amounts of thiamine back in and it would bring down the lactate the next day before raising it to 1.5. I’ve tried biotin in various doses which do not bring the lactate down either. Any thoughts? Thanks
Hey Chris, excellent article! Do you have an ETA for your oxalate manual? Thanks.
I do not. Thanks!
Does that mean D-lactate also get produced in muscle during exercise?
And if oxalate binds to minerals, could you take a magnesium supplement with a high dose biotin supplement, and expect any extra oxalate to bind to the magnesium for kidney excretion instead of being redistributed? Was wondering if biotin frees enough oxalate to overload methylation and other pathways, then maybe we could consume something like a magnesium or calcium supplement to chelate it.
Thought some mineral supplements were occasionally used to break down kidney stones, of which I thought some are oxalate. Not sure if that's even effective for kidney stones but if it is then why not for much smaller crystals in the blood too?
I think some would be produced in the muscle during exercise, and that you'd have to biopsy it to find it because it would not be likely to exit into the blood.
Oxalate is much more specifically attracted to calcium.