Induction of deficiencies by thiamine

Elliot has posted a screenshot of an article (R2) that suggests that high doses of thiamine may cause B2 and B3 deficiencies if those other vitamins are not taken at the same time.

References (4) and (5) suggest that initiation of thiamine treatment may cause dumping of riboflavin (in rats and rabbits).

In this post I will try to gather all the sources of this information.

Original quote from a journal

In the recent study of vitamin metabolism, it has been noted hat absorption, utilization and excretion of each member of vitamin B complex are influenced by the administration of the other members.

Sydenstricker (1) (R3) reported that the administration of one of vitamin B complex was followed by the manifestation of deficiency states of other members of the B complex in a patient suffering from pellagra.

Leitner (2) (R4) observed that a large dose of thiamine given parenterally was followed by ariboflavinosis such as angular stomatitis. Manifestation of riboflavin deficiency following administration of a large lose of thiamine was also observed in rats by Unna (3) (R5).

Furthermore, Klopp (4) (R6) reported that the administration of large amounts of thiamine to a human being was followed by transitorily increased excretion of riboflavin in urine, and suggested that the administration of large amounts of thiamine to the subjects might have initiated a release of riboflavin from the tissue, and some portions of the released riboflavin were spilled into the urine. Increased urinary excretion of riboflavin following administration of large amounts of thiamine was also demonstrated in rabbits by Shinagawa (5) (R7), and as the mechanism of this phenomenon a possibility that thiamine might inhibit the phosphorylation of riboflavin was assumed. However, the details of the mechanism remain unknown.

In the previous paper (6) (R8) it was suggested that the increase of urinary excretion of riboflavin following administration of antibiotics might be caused by releasing FAD and its derivative compounds from flavinenzyme by competition with the antibiotics.

Suspecting the analogical relationship between the administration of thiamine and the increase of urinary excretion of riboflavin, the author has studied the effects of thiamine and its derivative compounds on D-amino acid oxidase, one of the representative flavinenzymes.

The present paper deals with the data that thiamine and thiamine diphosphate (TDP) inhibit the enzymatic activity. A possibility that binding of thiamine or TDP to the enzyme might result in the release of FAD is suggested.

References in the article

Sydenstricker, V. P., Ann. Int. Med., 15, 45 (1941). (R3)

Leitner, Z. A., Brit. Med. J. 1, 609 (1945). (R4)

Unna, K., and Clark, J. D., Am. J. Med. Sci., 204, 364 (1942). (R5)

Klopp, C. T., Abels, J. C., and Rhoads, C. P., Am. J. Med. Sci., 205, 852 (1943). (R6)

Shinagawa, T., Baba, T., and Takeuchi, Y., J. Vitaminol., 3, 135 (1957). (R7)

Nakamaru, T., J. Vitaminol., 5, 277 (1959). (R8)

Friedenwald, J. S., and Maengwyn-Davies, G. D., A Symposium on the Mechanism of Enzyme Action, 154 (1954).

Shinagawa, T., Vitamins, 12, 243 (1957).

Chevillard, L., and Thoai, N. V., Bull. Soc. Chim. Biol., 33, 1147 (1951)

Thiamine inhibits DAAO

The original article provides findings that thiamine inhibits D-amino acid oxidase - an enzyme that breaks down D-amino acids, such as D-Serine:

D-amino acid oxidase (DAAO; also OXDA, DAMOX) is an enzyme with the function on a molecular level to oxidize D-amino acids to the corresponding α-keto acids, producing ammonia and hydrogen peroxide. This results in a number of physiological effects in various systems, most notably the brain.

The enzyme is most active toward neutral D-amino acids, and not active toward acidic D-amino acids. One of its most important targets in mammals is D-Serine in the central nervous system. By targeting this and other D-amino acids in vertebrates, DAAO is important in detoxification.

DAAO also plays a role in both biotechnological and medical advancements. Risperidone and sodium benzoate are inhibitors of DAAO. (Wikipedia)