Huntington's disease: Clinical and chemical effects of choline administration

Abstract

Choline (Ch) administration sequentially increases blood Ch, brain Ch, and brain acetylcholine (ACh) levels in the rat and might be useful in Huntington's disease, a brain disorder thought to be associated with deficient cholinergic tone. Ten patients with Huntington's disease took Ch orally (8 to 20 gm per day) after the extent of their disabilities had been documented by clinical examination, movies, and combined electromyogram-accelerometer recordings. Choline levels in blood and cerebrospinal fluid increased markedly during treatment with Ch, affirming that oral Ch administration increases the amount of ACh precursor delivered to the brain. Although some of the patients exhibited transient improvement in speech, balance, and gait, treatment with Ch failed to bring about consistent or lasting improvement in any of the subjects.

Dietary Reference Values for choline

“…The US Institute of Medicine (IOM, ) defined a UL for adults based on a study in seven patients with Alzheimer's dementia, where the oral administration of 7.5 g/day of choline (as chloride) had a hypotensive effect accompanied by nausea and diarrhoea (Boyd et al., ). Similar gastrointestinal effects and a fishy body odour were observed in therapeutic studies with choline (8–20 g/day) on individuals with tardive dyskinesia and Huntington's disease (Growdon et al., ; Gelenberg et al., ; Lawrence et al., ). The IOM considered 7.5 g/day of choline as the Lowest Observed Adverse Effect Level (LOAEL), and after the application of an uncertainty factor of 2 and rounding, set a UL of 3.5 g choline/day for adults.…”

Trimethylaminuria (fish‐odour syndrome) and oral malodour

“…Exposure to unusually high levels of such precursors may hasten a fish malodour syndrome especially if the individual is a haplotype for certain mutations. Large oral therapeutic doses of choline (8–20 g day −1 ) have been used to treat Huntington's chorea, with patients complaining of a striking fish‐like odour that was attributed to the generation of excessive amounts of trimethylamine overloading their N‐oxidation capacity (Growdan et al , 1977). Similar problems have also been reported following choline therapy for Alzheimer's disease (Etienne et al , 1978).…”

Nutrition and Behavior

“…However, this was not generally the case. Moreover, improvements were transient and did not persist for longer than two weeks, despite continued choline administration (Davis et al 1976;Aquilonius and Eckernas 1977;Growden, Cohen, and Wurtman 1977;Growden 1979).…”