Nov. 24 2015

Does Tryptophan in Turkey Make You Sleepy?

Mady Hornig Takes Us on a Thanksgiving Journey from the Gut to the Brain

Not long after you finish your second, generous helping of turkey, sweet potatoes, and all the fixings, a pleasant but insistent torpor will take hold this Thanksgiving. But don’t blame tryptophan for your postprandial slumber.

The real reason: overindulgence. According to Mady Hornig, director of translational research at the Mailman School’s Center for Infection and Immunity, a big meal taxes digestion, making us sleepy, especially after a glass or two of wine. Yet there is a kernel of truth to the tryptophan myth: the amino acid is an essential ingredient in neurochemicals that manage our mood and sleep cycle.  

First tryptophan takes an amazing journey from the gut to the brain.

Starting as a forkful of turkey or any other protein source, the amino acid emerges a few hours later in the small intestine where it is absorbed into the bloodstream. From there, it hitches a ride in the body on shuttle protein called albumin. Next stop is the brain, but getting inside means crossing the blood-brain barrier. To do that, tryptophan must contend with a “large neutral amino acid transporter” that acts like a bouncer for the nightclub that is the brain, and is anything but neutral.

Most of the time, the brain’s gatekeeper doesn’t like tryptophan as much as other neutral amino acids and sends it to the back of the line. It turns out there’s only one sure way in: carbs. “When you raid the refrigerator for the extra piece of pie, you get an insulin spike,” says Hornig, “that suppresses the blood levels of all the other large neutral amino acids except for tryptophan.” A sugary snack is tryptophan’s ticket to ride into the brain where the magic can happen.

Once inside, enzymes go to work transforming tryptophan into serotonin, the neurotransmitter best known for regulating mood and sex drive. (It also plays an important role in digestion; 95 percent of the serotonin found in our bodies, along with the receptors for serotonin, are in the gut.) Then when it’s late at night and the lights are low, serotonin undergoes its own metamorphosis into melatonin, which regulates the sleep cycle; melatonin doesn’t actually make us drowsy, rather it aligns our body clock: the circadian rhythm.

A Window Into Brain Disorders

According to Hornig, an associate professor of Epidemiology, understanding the tryptophan journey could uncover triggers for brain disorders like autism and chronic fatigue syndrome.

One area of interest is what’s called the tryptophan degradation pathway, also known as the kynurenine pathway. When we get sick or stressed, tryptophan will sometimes take a different route through the body. “You can eat all the tryptophan you want, but if the kynurenine pathway is overly active,” says Hornig, “you are shunting tryptophan away from serotonin synthesis and ultimately away from melatonin synthesis.”

Most of the time, this is business as usual: we all depend on the kynurenine pathway and its tryptophan metabolites to synthesize niacin, an essential B vitamin, to produce some important neuro-protective compounds, and to dampen down inflammatory processes after the immune system is activated by an infection or other serious stressor. “Health depends on striking an intricate and dynamic balance,” says Hornig, “between maintaining a supply of tryptophan and degrading just the right amounts required to activate these vital functions.”

Yet sometimes, chemicals produced along the kynurenine pathway can trigger or block receptors for certain neurotransmitters, and these have the potential to both harm and help the brain and the immune system. One of the affected neurochemical pathways centers on the neurotransmitter glutamate.

“We know that glutamate pathway abnormalities have been implicated in autism, and potentially chronic fatigue syndrome as well,” explains Hornig. “We don’t know yet whether there is a particular defective component in [the serotonin or kynurenine pathways] that sets things awry in either of these disorders.”

Hornig suspects that we will eventually find that these faulty processes arise not only from an improper balance of tryptophan and other nutrients in the foods we eat but also from disturbances in the gut microbiome—the ecosystem of bacteria and other microorganisms that live in intestines. It turns out that our cells aren’t the only ones metabolizing tryptophan: certain bacteria of the microbiome also break it down into metabolites that are important in controlling inflammation, gastrointestinal function, and other key bodily processes. When these tryptophan-degrading bacteria are out of balance, unusually high levels of the amino acid can build up in the intestine, leading to excessively high levels of both tryptophan and serotonin in the intestine, potentially triggering adverse effects on gastrointestinal and immune system function.

But if everything is on track this Thanksgiving, stuffing ourselves with turkey and other tryptophan-bearing foods will have a predictable upside. Hours later and after an assist from a slice of carbohydrate-rich pie, the neuroactive products of tryptophan will send us off into sweet slumber.