Trimethylaminuria is a disorder in which the body is unable to break down trimethylamine, a compound derived from the diet that has a strong odor of rotting fish.
What are the signs and symptoms of fish odor syndrome (trimethylaminuria)?
As trimethylamine builds up in the body, it causes affected people to give off a fish-like odor in their sweat, urine, and breath. The intensity of this odor may vary over time.
The strong body odor can interfere with many aspects of daily life, affecting a person’s relationships, social life, and career. Some people with trimethylaminuria experience depression and social isolation as a result of this condition.
What is the cause?
The bacteria in our bowel help us to digest foods such as eggs, beans and seafood. In the process, they produce a strong-smelling chemical called trimethylamine.
Normally, an enzyme (protein) called flavin-containing monooxygenase 3 (FMO3) is produced by the liver to turn trimethylamine into the odourless molecule trimethylamine N-oxide.
Most people have an FMO3 gene, which provides instructions for making this enzyme.
In most people with trimethylaminuria, the FMO3 enzyme is missing or their FMO3 gene doesn’t work as well as other people’s. This allows trimethylamine to build up in the body.
Usually, those with trimethylaminuria have inherited the faulty FMO3 gene from both their parents. In other words, each parent will carry one copy of the faulty gene and be a “carrier” of the condition.
Carrier parents may not have symptoms themselves, or may only have mild or temporary episodes of body odour.
It’s estimated that 1% of the UK population are carriers of the faulty gene that causes trimethylaminuria.
Not everyone with trimethylaminuria has the faulty FMO3 gene. Some cases may be caused by an excess of certain proteins in the diet, or an abnormal increase in the gut bacteria that produce trimethylamine.
A few cases of trimethylaminuria have been linked with liver or kidney disease, where the FMO3 enzyme is underactive.
Women are more likely than men to have the condition – possibly because female sex hormones such as progesterone and oestrogen aggravate the symptoms. Some cases appear to be worse around puberty and, in women, at the following times:
- just before or after periods
- after taking the contraceptive pill
- around the menopause
Temporary symptoms of this condition have also been identified in a small number of premature infants.
Stress and diet may also play a role in triggering the odour.
How is trimethylaminuria diagnosed?
Trimethylaminuria is diagnosed with a urine test that measures the ratio of trimethylamine (the fishy-smelling chemical) to trimethylamine N-oxide (the odourless version).
The test involves taking choline tablets and collecting several urine samples over the 24-hour period that follows.
If you have trimethylaminuria, you’ll have higher-than-normal levels of trimethylamine in your urine.
If it’s suspected you’re a carrier of the faulty gene that causes trimethylaminuria, you can take the “TMA challenge” (also called the “TMA load test”).
This involves taking a trimethylamine (TMA) pill and seeing how much is passed out in your urine. Carriers pass out 20-30% of trimethylamine in their urine, while non-carriers pass less than 13% and convert the rest.
The urine test is sometimes carried out in children by replacing the TMA pill with a meal including foods high in choline, such as:
- salt-water fish
- baked beans or soya beans
Gene testing can also be carried out, to look for any genetic changes in the FMO3 gene.
How common is fish odor syndrome (trimethylaminuria)?
Trimethylaminuria is an uncommon genetic disorder; its incidence is unknown.
What genes are related to fish odor syndrome (trimethylaminuria)?
Mutations in the FMO3 gene cause trimethylaminuria.
The FMO3 gene provides instructions for making an enzyme that breaks down nitrogen-containing compounds from the diet, including trimethylamine.
This compound is produced by bacteria in the intestine as they help digest proteins from eggs, liver, legumes (such as soybeans and peas), certain kinds of fish, and other foods.
Normally, the FMO3 enzyme converts fishy-smelling trimethylamine into another molecule that has no odor. If the enzyme is missing or its activity is reduced because of a mutation in the FMO3 gene, trimethylamine is not processed properly and can build up in the body.
As excess trimethylamine is released in a person’s 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.
How do people inherit fish odor syndrome (trimethylaminuria)?
Most cases of trimethylaminuria appear to be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations.
Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but typically do not show signs and symptoms of the condition.
Carriers of an FMO3 mutation, however, may have mild symptoms of trimethylaminuria or experience temporary episodes of fish-like body odor.
How is trimethylaminuria treated?
There’s currently no cure or approved drug to treat trimethylaminuria, but symptoms can be improved by making certain lifestyle changes and, if necessary, taking the medication outlined below.
You can reduce the odour by avoiding foods containing the chemicals trimethylamine, choline and trimethylamine N-oxide. This means avoiding:
- milk from wheat-fed cows
- soy products
- Brussels sprouts
- seafood (fish and crustaceans), although freshwater fish can be eaten
- lecithin and lecithin-containing fish oil supplements
Taking low doses of antibiotics can reduce the amount of bacteria in your gut and suppress the production of trimethylamine.
However, to avoid antibiotic resistance, these should only be used now and again, or alternated every two weeks.
Laxatives can speed up the passage of food through your bowel so less trimethylamine is produced in your gut.
You may also be able to decrease the concentration of trimethylamine in your urine by taking supplements such as:
- 750 milligrams (mg) of charcoal twice daily for 10 days
- 60mg copper chlorophyllin three times a day for three weeks
- riboflavin (vitamin B2) supplements to enhance any FMO3 enzyme activity
- Always seek the advice of your doctor before trying any of the above medications and supplements.
Other lifestyle measures
It’s a good idea to avoid anything that causes you to sweat excessively, such as intense exercise and stress. To help, try easy exercises and learn how to cope with stress.
Use soap and shampoos with a pH between 5.5 and 6.5. These help to remove traces of trimethylamine from your skin and hair.
Trimethylaminuria can be very upsetting, potentially affecting your personal life and career. Depression and social isolation are common.
Counselling may help you cope with any depression and other psychological symptoms. For more information, visit our pages on how to get help for stress, anxiety and depression.
Genetic counselling may help you understand how you developed the condition and the risks of passing it on to any children you have.