It is a curious fact that antidepressants are a common treatment for irritable bowel syndrome. But why give Prozac to someone with abdominal discomfort?
Antidepressants work because what happens in the gut does not stay in the gut — it travels to the brain. More than half of all patients with IBS are affected by a mood disorder.
The gut and brain are connected by the vagus nerve, sometimes called the gut-brain axis. The vagus nerve allows communication between the two. The conversation that takes place along this bidirectional superhighway is under the control of the microbiome, the collective name for the trillions of microorganisms coexisting in your bowel.
We’ve known about this gut-brain connection ever since an early, pivotal study found that germ-free mice experience ‘exaggerated physiological reactions to stress’ that can be reversed when their guts are colonised by healthy bacteria.
The serotonin connection
The neurotransmitter serotonin is found at both ends of the vagus nerve. It is an important mood regulator, and low levels are associated with depression. Dysfunctional serotonin production is considered to be ‘one of the main factors contributing to the development of depressive symptoms.’
Serotonin is the ‘happy’ chemical, influencing the way you feel. It’s also a precursor of melatonin, a hormone secreted in the brain’s pineal gland that regulates your internal body clock and helps you fall asleep at night.
Serotonin is crucial to brain function and mood, yet over 90% of the body’s serotonin supply is found in the gut.
On the surface, gut serotonin appears to have nothing to do with head serotonin. It cannot cross the blood-brain barrier, so the brain has to make its own supply.
For that reason, scientists did not believe (until recently) that the serotonin in the gut could in any way influence mood. But over the last decade or so, there has been a flurry of research activity, all suggesting otherwise.
Selective serotonin reuptake inhibitors (SSRIs), including Prozac, work by keeping serotonin in the brain. It is normally reabsorbed by the body once it has been used.
It appears that SSRI drugs don’t just work in the brain; they also work in the gut. In research on mice, the administration of SSRIs leads to ‘a significant increase in vagal activity’ and reduced depressive-type behaviour. Similarly in humans, electrical stimulation of the vagus nerve in people with ‘intractable’ depression transmits signals that result in reduced levels of depressive behaviour.
However, if the vagus nerve is blocked, the anti-depressant effects of SSRI come to a halt.
The serotonin in your gut may not enter the brain, but it sends messages to the brain via the vagus nerve, and the transmission of those messages is directed by the beneficial bacteria in your gut.
But whether or not all this goes according to plan depends on how much tryptophan you consume in your diet.
The role of tryptophan
Like all neurotransmitters, serotonin is made from the protein in your diet. Protein is constructed from amino acids, and serotonin synthesis requires the amino acid tryptophan.
How much serotonin is made in the brain depends on how much tryptophan is present in the brain — which in turn depends on how much tryptophan is present in the diet.
Tryptophan is an ‘indispensable’ amino acid, meaning that the body cannot make it; you must obtain it directly from food. It is able to cross the blood-brain barrier to enable serotonin synthesis by the central nervous system.
Low dietary intake of tryptophan has been shown to be associated with increased levels of depression.
‘In vulnerable populations, reducing the circulating concentrations of tryptophan has been shown to affect mood, and to reinstate depressive symptoms in patients who have successfully responded to selective serotonin reuptake inhibitors.”
A 2015 paper published in Archives of Psychiatric Nursing describes the changes in anxiety, depression and mood in 25 healthy, non-depressed young adults (average age 20.5), after eating a high or low tryptophan diet. A validated system of scoring depressive symptoms was used.
In this blinded, randomized, crossover study, mood improved significantly on a high tryptophan diet. Depressive symptoms and anxiety were low. However, after switching to a low tryptophan diet, the scores indicated that the participants’ mood had deteriorated so much that they had ‘reached thresholds for depression’.
Similar studies, conducted over a 40 year period, have consistently found that in people with major depressive disorders, tryptophan depletion decreases mood states.
Best sources of tryptophan
In the US, the recommended daily amount (RDA) of tryptophan for adults is 5mg/kg body weight per day. No RDA currently exists in the UK.
Complete protein sources such as meat and fish provide the highest and most bioavailable level of the amino acid tryptophan.
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With the right diet, you can increase the availability of tryptophan, and therefore serotonin, in the brain. The right diet is the one that gets the conversation going, and changes the way you feel.