How Do Serotonin Receptors Affect Weight Gain? (HTR2C)

Stress Management

Stress may make the brain resistant to the effects of serotonin and desensitize 5-HT2C receptors. This in turn may increase appetite and food intake as more food is required to produce the same rewarding effects [R, R, R, R].

However, other studies suggest that stress could increase 5-HT2C receptors in some cases [R].

Stress is known to cause weight gain in some people. Stress increases cortisol and dynorphin, both of which cause weight gain [R, R, R, R].

It also increases glutamate, which increases appetite, while decreases NGF and BDNF, both of which are appetite suppressants [R].

Exercise

Exercise is well-known to improve mood; one of its mechanisms for doing so may be increased serotonin in the brain, which could reduce appetite [R].

However, animal research suggests that exercise may reduce 5-HT2C receptor activity in some parts of the brain [R, R].

Despite this, high-intensity exercise is probably the best strategy to lose weight. In addition to promoting fat burning, the increased norepinephrine production may suppress food intake according to a study in rats [R].

Being active burns calories and jump-starts metabolism. Some studies suggest it also increases BDNF, which supports mental health and might cause us to eat less [R].

Exercise also increases endorphins, which activates mu-opioid receptors and also suppresses appetite [R].

Aerobic exercise (like walking, running, swimming, etc) has also been shown to cause major reductions in belly fat in multiple studies [R, R].

Although the reason is not fully understood, yoga can be a useful tool for weight loss too [R, R, R].

Moderate Sun Exposure

Sunlight exposure is believed to increase brain serotonin, and vitamin D may be important for the function of serotonin signalling neurons. Vitamin D has also been specifically studied for its potential to counteract antipsychotic-induced weight gain (which, as we’ve discussed, can be caused by 5-HTR2C being blocked) [R, R, R].

Vitamin D deficiency is suspected to contribute to obesity in some cases, though more research is needed [R].

UV light is hypothesized to prevent obesity in animals, whether or not they are deficient in vitamin D [R].

In one study, intense light exposure, particularly in the morning, was associated with a lower BMI independent of sleep duration and timing [R].

Specifically, having a majority of the average daily light exposure above 500 lux earlier in the day was associated with a lower BMI [R].

Exposure to at least 45 minutes of morning light (between 6-9 am at 1,300 lux) for 3 weeks in obese women resulted in reduced body fat and appetite. Although encouraging, more research is needed to verify the link between sunlight exposure and weight loss [R].

Stress management, physical exercise, and moderate sun exposure are three relatively simple strategies that may increase brain serotonin and reduce appetite.

Olive Oil

In rats, the omega-3 and omega-6 fatty acids abundant in olive oil increased serotonin levels in the brain [R].

An olive oil-enriched diet brought about greater weight loss than a lower-fat diet in an 8-week comparison. Scientists are investigating whether oleic acid, the main fatty acid found in olive oil, excites neurons that cause weight loss (POMC) [R, R].

Dark Chocolate

Eating dark chocolate may increase the amount of tryptophan that enters the brain, which may increase the synthesis and availability of serotonin. This is a proposed mechanism for the mood-boosting effects of chocolate, but it may help with appetite as well [R, R].

Some animal research also indicates that eating dark chocolate may directly increase serotonin levels throughout the body. The authors suggest [R].

Cocoa contains polyphenols that are believed to promote weight loss, though clinical studies are few and far between. In one study, daily consumption of 49 grams of dark chocolate reduced the quantity of snacks eaten by adults, suggesting that cocoa might decrease appetite or cravings [R].

In a study in rats, those fed cocoa had less fat production in the belly [R].

In mice, cocoa consumption reduced weight gain and fat uptake in the gut. Cocoa also reduced inflammation associated with obesity and improved insulin resistance [R].

Dark chocolate may increase tryptophan in the brain, providing the building blocks to make serotonin. Cocoa has also been found to reduce appetite and fat production.

Resistant Starch

Butyrate is a fatty acid produced by good bacteria in the gut when they digest resistant starches and fibers that we can’t digest on our own. The cells of the colon wall use this compound for energy [R].

Some animal research suggests that butyrate’s antidepressant properties stem from increased concentration of serotonin in the brain [R].

Some evidence suggests that resistant starch (and the butyrate produced as a result) may help promote weight loss in certain circumstances.

In a trial of 118 overweight people, fiber supplements (which the gut flora convert to butyrate) also led to reduced body weight and BMI. Animal studies have also generally found butyrate to be protective against weight gain [R, R].

In obesity-prone rats, dietary resistant starch and regular exercise prevented weight gain, apparently by reducing energy intake [R].

It reduces fat accumulation and blood glucose levels and increases the breakdown of fat through fermentation in the intestines, thus potentially improving weight control [R, R].

Resistant starch may stimulate fat burning by:

• Reducing fat accumulation and increasing fat oxidation after meals [R].
• Forcing the body to burn fat by lowering blood glucose [R].
• Decreasing fat production while increasing the production of phospholipids [R].

Butyrate, which is produced by good bacteria digesting resistant starches, may increase the concentration of serotonin in the brain. Butyrate and resistant starch have both also been linked to weight loss.

Tryptophan

Tryptophan is an amino acid that is used to make serotonin. It is a component of dietary protein and most abundant in high-protein foods [R].

Some research suggests that getting more calories from protein (as opposed to either carbohydrates or fat) may support weight loss, metabolism, and satiety. High-protein diets appeared to increase fat burning and weight loss and reduce appetite in a handful of human studies [R, R, R].

Probiotics

Some probiotics (such as B. infantis, B. longum, and L. rhamnosus) have been found to produce similar effects to selective serotonin receptor inhibitors (SSRIs), a class of antidepressants [R, R].

In a clinical trial of 125 obese adults, L. rhamnosus induced weight loss, reduced fat mass, and reduced circulating leptin [R].

Additionally, L. rhamnosus CGMCC1.3724 improved liver parameters in a small trial of 20 obese children with liver dysfunction noncompliant with lifestyle interventions [R].

Oral administration of B. longum, B. bifidum, B. infantis, and B. animalis decreased glucose levels, ameliorated insulin resistance, and reduced the expressions of inflammatory adipocytokines in obese mice [R].

Some strains of probiotic bacteria may increase available serotonin in the brain and have been linked with weight loss.

Garcinia

Garcinia cambogia is a plant that produces a sour, acidic fruit that looks like a small yellow pumpkin. It is somewhat popular as a weight loss supplement, and it produces enough of a spike in brain serotonin that there are warnings about combining it with antidepressants that also increase serotonin [R, R, R].

In a clinical trial on 99 obese men, Garcinia cambogia together with a weight-loss drug (orlistat), lowered BMI, belly fat, overall fat under the skin, and waist circumference in 3 months [56].

In two 12-week studies on over 100 overweight and obese people, Garcinia cambogia reduced weight by about 3.6 kilos [R, R].

After 16 weeks, Garcinia cambogia extract decreased total fat, belly fat, and fat under the skin in a clinical trial on 39 overweight people [R].

In two 8-week studies on almost 150 overweight and obese adults, hydroxycitric acid decreased the body weight and BMI by 5%-6% [R, R].

In an 8-week study on 40 obese adults, Garcinia cambogia reduced belly and under-the-skin fat better than the placebo [R].

Garcinia cambogia extract reduced body weight by 4.67% in 30 overweight or obese adults (compared to only 0.63% in 28 adults receiving placebo) in a 60-day study [R].

Hydroxycitric acid decreased body weight in a study of 21 obese adults after 2 weeks [R].

A 2011 review of 12 studies on Garcinia cambogia found that, on average, it was associated with weight loss of about 2 pounds (0.88 kg) over several weeks [R].

Garcinia cambogia is a sour fruit that increases available serotonin and may promote weight loss.

Vitamin D & DHA

Some researchers have proposed that vitamin D and DHA may both be important in the process that makes new serotonin [R].

As previously noted, vitamin D deficiency may contribute to obesity, though the precise relationship is unclear [R].

In young, overweight men, the inclusion of either lean or fatty fish or fish oil, which is rich in DHA, as part of an energy-restricted diet resulted in approximately 1 kg more weight loss after 4 weeks compared to a similar diet without seafood or a supplement [R, R].

On the other hand, fish oil actually decreased 5-HTR2C levels in experimental rats with very high serotonin and low appetite. The relationship between DHA and 5-HTR2C is likely complex [R].