Thiamin is a vitamin (B1) found in a variety of foods including meat, legumes, and whole, fortified and enriched grain products. Thiamin’s main role in the body is to act as a helper to enzymes used to release energy from foods. Thiamin also plays a role in fatty acid synthesis, membrane and nerve conduction and amino acid metabolism.
The metabolism of branched-chain amino acids (BCAA) involves several enzymatic steps and complexes. The first step involves removing the amino group to create a-ketoacids. This step is catalyzed by an enzyme known as branched chain aminotransferase (BCAT), and occurs normally in MSUD. The next step involves a branched-chain a-ketoacid dehydrogenase complex (BCKAD). MSUD is caused by a defect in this enzyme complex, resulting in a buildup of BCAAs and their a-ketoacids. Thiamin is part of a cofactor needed for this enzyme to work.
One form of MSUD is considered to be thiamin-responsive. This variant of the disease is less severe than the classic form, and has some enzyme activity. The daily requirement for thiamin in healthy people is approximately 1.1 mg daily for adults, but the amount needed to improve enzyme function is much greater and depends on the amount of enzyme activity present. Thiamin dosages used to treat MSUD range from 10-100mg each day. Individuals who have thiamin-responsive MSUD can also tolerate more protein in their diet as compared with other more severe types of the disease.
The first observed thiamin-responsive patient was reported by Scriver and associates in 1971. This French Canadian female infant was admitted to Montreal Children's Hospital with moderately elevated plasma BCAA concentrations. She was provided with a 10 mg per day oral supplement of thiamin hydrochloride and her plasma BCAA concentrations were drastically reduced to normal levels without the restricting BCAA intake. The withdrawal of the vitamin supplement caused a fast return of plasma BCAA concentrations to the pre-thiamin levels. This was followed by another sharp decline of BCAA concentrations upon reintroduction of the thiamin supplement (Chuang, 2006).
Researchers hypothesize that large doses of thiamin increase the amount of the cofactor which is needed for proper enzyme function, allowing the enzyme to function normally (Rosenberg 2008 pg 669). Large doses are safe as they do not cause toxicity and excess amounts are excreted in the urine.
This method of treatment only works for MSUD individuals who are thiamin-responsive. Those with classic MSUD do not respond as they have minimal or no enzyme activity of the BCKAD complex. Thiamine supplementation is not an alternative to diet for individuals with this type of MSUD. It should be understood that while thiamine is a vitamin, when administered in these very large doses it acts more as a drug making monitoring by a physician essential.
Chuang, D., Chuang, J., & Wynn, R. (2006). Lessons from genetic disorders of branched chain amino acid metabolism. The Journal of Nutrition, 136(1), 2435-2495.
Rosenberg, R., DiMauro, S., Paulson, H., Ptacek, L., & Nestler, E. (2008). The Molecular and Genetic Basis of Neurologic and Psychiatric disease. (4th ed., p. 669). Philadelphia: Lippincott Williams & Wilkins.