Why lipoic acid should never be supplemented

The sodium-dependent multivitamin transporter transports biotin, pantothenic acid and lipoate (Prasad et al. 1997). The three vitamins competitively inhibit transport of each other. Lipoate inhibits the transport of biotin and pantothenic acid (Prasad et al. 1998). Biotin is taken in microgram quanties while lipoic acid is taken in 600 milligram and higher quantites. What is more lipoate is synthesized on proteins whereby there is no need for free lipoic acid. All supplemental lipoic acid would be doing is blocking the transport of biotin and pantothenic acid.

The most attractive supplements can be the most dangerous supplements

In terms of alternative and complimentary medicine 5-MTHF, alpha lipoic acid, folate and N acetyl cysteine are mainline treatments for depression.

There are lots of grounds to think these supplements could be very unsafe. Lipoic acid shares the same transporter with biotin and pantothentic acid. Lipoate inhibits the transport of pantothenic acid and biotin. The body uses miniscule quantities of biotin. 300 milligrams of lipoic acid twice a day could have a large negative affect on biotin transport. Lipoic acid does not work in bipolar depression which is not suprising, See the page on Bipolar Depression.

N-acetyl cysteine is associated with musculoskeletal adverse side effects. These musculoskeletal adverse side effects are almost totally impossible to get rid of and can be horrendous. Clincal trials are usually about 6 weeks long but musculoskeletal effects accumulate over time and can persist long after N-acetyl cysteine is stopped.

There are no grounds whatsover to hold than S-adenosyl methionine taken long term would not affect DNA methylation and histone methylation. Abberrant DNA methylation is associated with cancer, aging and mental illnesses. Minimally an explantion as to why greatly increasing S-adenosyl-l-methionine levels does not affect DNA and histone methylation long term has to be given but no explanatiton is provided.

5-methyltetrahydrofolate inhibts glycine-N-methyltransferase which degrades S-adenosyl methionine. With 5-methyltetrahydrofolate supplementation S-adenosyl methionine levels would again be expected to greatly increase with again unknown consequences to DNA methylation and histone methylation. No consequences would be very surprising. Despite great early enthusiasm folic acid supplementation has been a bust in the prevention of a range of illnesses associated with high homocysteine levels.

What is it about these supplements that makes them so attractive? One very definitely notices these supplements when one takes them.

Treating the negative symptoms of schizophrenia

The negative symptoms of schizophrenia are at least partly due to a shortage of coenzyme A which is used by the E2 unit of the 2-oxoglutarate dehydrogenase complex and the E2 unit of the pyruvate dehydrogenase complex in the citric acid cycle. What is needed is to increase levels of coenzyme A which can be done by supplemental pantothenic acid.

Why are coenzyme A levels low in schizophrenia? L-cysteine is required to synthesize coenzyme A. Due dysregulation of the transsulfuration pathway in schizophrenia, as explained in my paper Treatment-resistant schizophrenia: focus on the transsulfuration pathway, intracellular levels of L-cysteine can be low in schizophrenia which will decrease synthesis of coenzyme A.

Supplementation with L-carnitine from carnitine tartrate is needed as L-carnitine reverses the inhibition of pantothenic kinase by coenzyme A and acetyl-coenzyme A. Pantothenic kinase is the rate-limiting enzyme in coenzyme A synthesis. Supplementation with acetyl-l-carnitine is avoided as palmitonylcarnitine , which is what actually reverses the inhibition of pantothenic kinase, is synthesized from L-carnitine not acetyl-L-carnitine. For reasons I will not go into here the L-carnitine must be L-carnitine from L-carnitine tartrate. L-carnitine fumarate must be avoided.

Supplementation with sulbutiamine will also be helpful in the treatment of the negative symptoms of schizophrenia. Sulbutiamine is a fat-soluble form of thiamine which can greatly increase thiamine diphosphate levels . Thiamine diphoshpate is used by the E1 unit of the 2-oxogularate dehydrogenase complex and the E1 subunit of the pyruvate dehydrogenase complex.

Supplementation with sublingual biotin would be useful. The sodium-dependent multivitamin transporter (SMVT) transports pantothenic acid, biotin and lipoate. Biotinyalition of histones associated with with the sodium-dependent multivitamin transporter silences transcription of the sodium-dependent multivitamin transporter gene. High dosages of pantothenic acid could competitively biotin transport in the gut but this would be avoided with sublingual biotin. Very surprisingly coenzyme Q10 must be taken when biotin is supplemented. Biotin apparently can have a large effect on the TCA cycle. If the TCA cycle hangs up at the succinate dehydrogenase step supplemental biotin is not of assistance.

Acetyl-coenzyme A can be synthesized from fatty acids. EPA + DHA where EPA makes up 65 to 70% of the EPA + DHA combination will be helpful. A EPA + DHA combination has been extensively studied and has good safety profile.

Supplemental coenzyme Q10 is also required. Succinate dehydrogenase which is an iron-sulfur protein in the citric acid cycle, requires coenzyme Q10. Biotin is not useful without coenzyme Q10. If the citric acid cycle gets hung up at the succinate dehydrogenase step biotin is not helpful.

Activities of the E3 subunits of the pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex, which have NAD+ as substrates, unstimulated by supplements are  completely acceptable as is.

If niacin, niacin derivatives,  riboflavin and/or lipoic acid are supplemented pantothenic acid and thiamine will not work against the negative symptoms of schizophrenia.  A B-50 supplement is a terrible supplement. What not to supplement with is as important as what to supplement with.  Lipoic acid increases l-cysteine levels by reducing cystine to L-cysteine but cystine must be present to enter cells by way of the cystine/glutamate antiporter. Once in cells cystine is rapidly reduced to L-cysteine.  In any case lipoic acid is synthesized on lysine residues of proteins so supplemental lipoic acid would not boost activities of the  E2 subunit of the pyruvate dehydrogenase complex and E2 subunit of the 2-oxoglutarate complex. Do not supplement with pantethine. Pantethine depletes cystine.

The supplements must be taken with food. Taking the supplements with food makes a huge difference.

Can pantothenic acid, sulbutiamine, sublingual biotin, EPA + DHA, coenzyme Q10 and l-carnitine be effective againstĀ  the negative symptoms of schizophrenia when taken alone? I don’t know. Minimally, to be avoided supplements as listed on the Treatment page should be avoided.