Interesting, thanks for posting this summary and review. Would be fascinating to hear a video/podcast conversation between you and Dr. Burt Berkson talking about ALA and how it functions, clinical use, etc. He has treated patients for years with it, conditions related to liver disease, cancer treatment, autoimmune, and some others, and he has some remarkable published case studies. I heard he advises b complex injections after ALA infusions due to it depleting their levels in some way, but I couldn’t find a citation for that claim to know the mechanism of how that happens.
So fascinating - thank you. I just listed to your podcast on niacin as well and deeply appreciate your insight on how these two supplements can have a huge negative impact on methylation.
I have been taking 480mg of R-Lipoic Acid (Life extension brand) daily for almost 8 years now, all at breakfast. I am always grumpy and my strength levels have not been improving in years. Last year, I fasted before my blood test and homocysteine was just over 9 (so that would be the leftover from the day before). After reading your article, I asked my doc if I could test your hypothesis and he said yes, so I fasted except I took the 480mg of R-Liopic acid 1 hour and 5 mins before the blood test was drawn. I'll post here when I see the homocysteine results, but might be a few weeks.
Interesting! I've been taking 600mg/day of the Jarrow product for oh, must be 25+ years now. It's evidently racemic, since it doesn't say otherwise, and is 2/3 sustained-release. I haven't noticed any of the symptoms you mentioned, but I'll keep an eye out for them.
Very interesting, Chris. Thanks for this. I have been toying a bit with Dmitry Kats' protocol since I have long Covid from a delta infection in early January, and one thing I've noticed is significantly decreased muscle mass, exercise capacity, and even my skin is looking wrinkly and bad, all of which are unusual. I already dropped the niacin dosage significantly because I was already concerned about depleting methyl groups (I'm taking 50mg of nicotinic acid BID now) but I had no idea that the 600mg of Na-R-ALA that I've been taking was also likely depleting methyl groups! I am so glad that I read this because I'm going to switch gears and focus on increasing Methionine, Choline, TMG, Creatine, etc now, which feels like a much better tactic since the NA/ALA protocol is not helping my energy or exercise capacity! : )
According to this article food decreases absorption by 30%, why do you suggest spreading it with meals? Gleiter, C. H., Schug, B. S., Hermann, R., Elze, M., Blume, H. H., and Gundert-Remy, U. Influence of food intake on the bioavailability of thioctic acid enantiomers. Eur.J Clin Pharmacol. 1996;50(6):513-514
Very interesting! I'm thinking people have had SNPs that affect methylation for generations and lived very well, without consequences associated with poor methylation. Why it's such an issue now is heavy metals, including mercury, further impede the methylation cycle. The dithiol group is what chelates mercury. Given the difficulty in getting DMSA and DMPS as mercury chelators, could ALA be more beneficial to methylation in the long run as a mercury chelator?
Also, I'm reading Sean Carson's comment below and it seems he's taking the approach of supplementing at each step of the methylation cycle (methionine, TMG, creatine, etc.) to make sure all his bases are covered. What do you think of that approach?
Very interesting and insightful article. You mention that one of the effects in the rat study was "The SAH in the plasma increased 10-20-fold" so it seems like impact on SAH was a much more pronounced effect than homocysteine. I was wondering whether you'd see this study (S-adenosyl-L-homocysteine extends lifespan through methionine restriction effects https://pubmed.ncbi.nlm.nih.gov/35388610/ ...it was in Caenorhabditis elegans so very preliminary).
I am sure there are too many variables to consider this, but taken as a standalone supplementation issue, is there any factor, axiom or even a shaky suggestion as to what dose of TMG would be prophylaxis for methyl depletion/mg R-ALA?
This is an interesting aspect of ALA. How would you predict individuals with low homocysteine (range of 4-5) to react with ALA with partially impaired methylation (heterozygous 677T)? Any recommendations?
Interesting, thanks for posting this summary and review. Would be fascinating to hear a video/podcast conversation between you and Dr. Burt Berkson talking about ALA and how it functions, clinical use, etc. He has treated patients for years with it, conditions related to liver disease, cancer treatment, autoimmune, and some others, and he has some remarkable published case studies. I heard he advises b complex injections after ALA infusions due to it depleting their levels in some way, but I couldn’t find a citation for that claim to know the mechanism of how that happens.
So fascinating - thank you. I just listed to your podcast on niacin as well and deeply appreciate your insight on how these two supplements can have a huge negative impact on methylation.
Awesome info! Thank you for writing this article! What do you think about ALA as a heavy metal chelator?
I have been taking 480mg of R-Lipoic Acid (Life extension brand) daily for almost 8 years now, all at breakfast. I am always grumpy and my strength levels have not been improving in years. Last year, I fasted before my blood test and homocysteine was just over 9 (so that would be the leftover from the day before). After reading your article, I asked my doc if I could test your hypothesis and he said yes, so I fasted except I took the 480mg of R-Liopic acid 1 hour and 5 mins before the blood test was drawn. I'll post here when I see the homocysteine results, but might be a few weeks.
Interesting! I've been taking 600mg/day of the Jarrow product for oh, must be 25+ years now. It's evidently racemic, since it doesn't say otherwise, and is 2/3 sustained-release. I haven't noticed any of the symptoms you mentioned, but I'll keep an eye out for them.
Very interesting, Chris. Thanks for this. I have been toying a bit with Dmitry Kats' protocol since I have long Covid from a delta infection in early January, and one thing I've noticed is significantly decreased muscle mass, exercise capacity, and even my skin is looking wrinkly and bad, all of which are unusual. I already dropped the niacin dosage significantly because I was already concerned about depleting methyl groups (I'm taking 50mg of nicotinic acid BID now) but I had no idea that the 600mg of Na-R-ALA that I've been taking was also likely depleting methyl groups! I am so glad that I read this because I'm going to switch gears and focus on increasing Methionine, Choline, TMG, Creatine, etc now, which feels like a much better tactic since the NA/ALA protocol is not helping my energy or exercise capacity! : )
I used to measure the ratio between SAH and SAM...in mice livers. Now I am an out of work molecular biologist. Good article!
Would MSM help?
According to this article food decreases absorption by 30%, why do you suggest spreading it with meals? Gleiter, C. H., Schug, B. S., Hermann, R., Elze, M., Blume, H. H., and Gundert-Remy, U. Influence of food intake on the bioavailability of thioctic acid enantiomers. Eur.J Clin Pharmacol. 1996;50(6):513-514
Very interesting! I'm thinking people have had SNPs that affect methylation for generations and lived very well, without consequences associated with poor methylation. Why it's such an issue now is heavy metals, including mercury, further impede the methylation cycle. The dithiol group is what chelates mercury. Given the difficulty in getting DMSA and DMPS as mercury chelators, could ALA be more beneficial to methylation in the long run as a mercury chelator?
Also, I'm reading Sean Carson's comment below and it seems he's taking the approach of supplementing at each step of the methylation cycle (methionine, TMG, creatine, etc.) to make sure all his bases are covered. What do you think of that approach?
Very interesting and insightful article. You mention that one of the effects in the rat study was "The SAH in the plasma increased 10-20-fold" so it seems like impact on SAH was a much more pronounced effect than homocysteine. I was wondering whether you'd see this study (S-adenosyl-L-homocysteine extends lifespan through methionine restriction effects https://pubmed.ncbi.nlm.nih.gov/35388610/ ...it was in Caenorhabditis elegans so very preliminary).
I am sure there are too many variables to consider this, but taken as a standalone supplementation issue, is there any factor, axiom or even a shaky suggestion as to what dose of TMG would be prophylaxis for methyl depletion/mg R-ALA?
MTHFR imo is the body trying to unmethylate and block B6 pyroxidine which is rocket fuel for leukemia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389897/
So maybe alpha lipoic acid can help block B6 or stub leukemia?
Yes kinda:
https://pubmed.ncbi.nlm.nih.gov/27461609/
This is an interesting aspect of ALA. How would you predict individuals with low homocysteine (range of 4-5) to react with ALA with partially impaired methylation (heterozygous 677T)? Any recommendations?