In women, symptoms may worsen just before and during menstrual periods, after taking oral contraceptives, and around menopause.The odor seems to vary depending on many known factors, including diet, hormonal changes, stress level, amount of sweat, other odors in the space, and the observers sense of smell. Genetics
Most cases of trimethylaminuria appear to be inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. The parents of an individual with an autosomal recessive disorder are both carriers of one copy of the altered gene. Carriers may have mild symptoms of trimethylaminuria or experience temporary episodes of fish-like body odor.Mutations in the FMO3 gene, which is found on the long arm of chromosome 1, cause trimethylaminuria. The FMO3 gene makes an enzyme that breaks down nitrogen-containing compounds from the diet, including trimethylamine. These compounds are produced by bacteria in the intestine as they digest proteins from eggs, meat, soy, and other foods. Normally, the FMO3 enzyme converts fishy-smelling trimethylamine into trimethylamine N-oxide which has no odor. If the enzyme is missing or its activity is reduced because of a mutation in the FMO3 gene, trimethylamine is not broken down and instead builds up in the body. As the compound is released in a persons sweat, urine, and breath, it causes the strong odor characteristic of trimethylaminuria. Researchers believe that stress and diet also play a role in triggering symptoms.There are more than 40 known mutations associated with TMAU.
Additionally, when a food substance, supplement or medicine containing a precursor (choline or carnitine) is ingested, bacteria in the gut convert a portion of those precursors to TMA. Moderate amounts of precursor are absorbed in the small intestine before reaching the gut, however if precursor rich food saturates the transport capacity of the intestine, excess precursor ends up in the gut. The proportion of precursor converted to TMA is related to the amount of specific bacteria in the gut.TMA in the gut is absorbed through the intestinal lining and enters the bloodstream, where it is filtered by the liver. The liver usually produces an abundance of the enzyme FMO3, which neutralises the TMA by oxidising it to odourless TMAO, and passes it through to the bladder. If FMO3 enzyme production is compromised, or there is too much TMA for the amount of enzyme, then TMA will continue to circulate in the bloodstream until enough enzyme is produced. While TMA is in the bloodstream, it is slowly exits the body via bodily fluids; urine, sweat, saliva, reproductive fluids and breath (See fluid balance for rates of fluid loss). TMA has no known interactions with any known internal or organ function. Although lecithin, creatinine and betaine are technically precursors to TMA, studies have shown no significant effect on the production of excess TMA/TMAO in urinary analysis at normal dietary levels of consumption. Symptoms and signs
Trimethylamine is most noticeable in urine, as it is captured, concentrated and released in intervals.