Intermittent fasting boosts libido by lowering brain serotonin

A new study published in Cell Metabolism has found that intermittent fasting enhances sexual behavior in aging male mice—not by improving sperm quality or hormone levels, but by shifting brain chemistry. The dietary intervention led to more frequent mating and higher reproductive success in older males by decreasing brain serotonin levels, which in turn disinhibited sexual behavior. The researchers identified a novel biological pathway linking dietary patterns, amino acid availability, and reproductive behavior.

The research team, led by Dan Ehninger of DZNE in Germany and Yu Zhou of Qingdao University in China, originally set out to study the offspring of fasting male mice. But when they noticed that older males on an intermittent fasting regimen were fathering more offspring than their normally fed counterparts, their focus shifted. The surprising discovery prompted a deeper investigation into what might be driving the increased fertility in these aging animals.

The scientists knew that male reproductive health tends to decline with age in both humans and animals. Older males typically show reduced testosterone levels, lower sperm count, and diminished sperm motility. These changes are often accompanied by decreased sexual motivation. In mice, as in humans, libido tends to fade with age, and mating behavior becomes less frequent and less successful. The researchers wanted to find out whether intermittent fasting could offset these declines—and if so, how.

To test this, they divided male C57BL/6J mice into two groups starting at 8 weeks of age. One group had constant access to food (ad libitum), while the other followed an intermittent fasting schedule in which food was available every other day. The researchers monitored these mice as they aged, conducting mating experiments at 8 months (young adults) and again at 24 months (roughly equivalent to an elderly human age).

Among the 24-month-old mice, those on the intermittent fasting regimen were more than twice as likely to sire offspring compared to those who had unrestricted access to food. In contrast, all 8-month-old males—regardless of diet—successfully reproduced. The data suggested that intermittent fasting effectively preserved reproductive success into old age, despite the typical age-related physiological declines.

However, when the researchers looked at traditional measures of reproductive health—such as testis weight, sperm count, sperm motility, and testosterone levels—they found little evidence that intermittent fasting improved these markers. In some cases, the fasting mice even showed slightly worse outcomes. This ruled out the possibility that the improved fertility was due to better sperm or hormonal health.

The answer, they discovered, lay in behavior. In a series of controlled mating trials, older mice that had followed the fasting regimen showed greater sexual activity. They spent more time interacting with females, initiated mounting more quickly, and engaged in more frequent mating. In other words, they were simply more interested in sex.

The researchers turned to neurochemical analyses to understand what might be driving this increase in libido. They measured levels of key neurotransmitters in the brain and found that serotonin levels were elevated in older mice on the standard diet, while those on the intermittent fasting regimen had significantly lower serotonin levels. At the same time, brain dopamine levels—another neurotransmitter associated with motivation—declined with age in all groups and were not influenced by diet.

Serotonin is known to inhibit sexual behavior, and high levels can suppress libido. The researchers hypothesized that intermittent fasting might be reducing serotonin availability in the brain, lifting this inhibitory signal and increasing sexual drive. To test this, they administered 5-hydroxytryptophan (5-HTP), a chemical that boosts serotonin production, to the fasted mice. As expected, this reduced their mating activity, confirming that serotonin was acting as a brake on sexual behavior.

But what was causing the drop in serotonin in the fasted mice? The team focused on tryptophan, an amino acid obtained from the diet that serves as a precursor for serotonin. They found that plasma tryptophan levels were lower in the fasting mice, even though these animals consumed more food during feeding periods than the non-fasting mice. Importantly, the researchers observed that intermittent fasting led to increased uptake of tryptophan into peripheral tissues like skeletal muscle, reducing the amount available for serotonin synthesis in the brain.

Further experiments showed that tryptophan levels in the brain were also lower in fasted mice, and that this reduction fully explained the diet-related differences in serotonin. There were no changes in the expression of serotonin-related enzymes or transporters, suggesting that the key factor was simply the availability of tryptophan in the bloodstream and brain.

This mechanism was supported by isotope labeling studies, where fasted mice were fed a tryptophan-rich diet containing a detectable nitrogen isotope. The fasted mice showed greater incorporation of the labeled amino acid into muscle proteins, confirming that more dietary tryptophan was being diverted to peripheral tissues rather than reaching the brain.

Taken together, the findings reveal a clear chain of events: intermittent fasting alters tryptophan metabolism, leading to reduced serotonin synthesis in the brain, which in turn lifts the inhibition on sexual behavior. This behavioral boost compensates for the age-related declines in sperm quality and testosterone, resulting in higher reproductive success.

Although these experiments were conducted in a single strain of lab mice, the results suggest broader implications for understanding the links between diet, brain chemistry, and reproductive behavior. The researchers note that human aging is also associated with reduced libido and that serotonin plays a similar inhibitory role in sexual desire in people. This raises the possibility that dietary interventions like intermittent fasting might help alleviate age-related sexual dysfunction, including conditions such as hypoactive sexual desire disorder.

However, the study also has several limitations. It is not yet clear whether similar effects would be seen in other mouse strains or in humans. The researchers did not test other dietary restriction methods like chronic calorie reduction or time-restricted feeding. They also did not determine the minimum length of time required for the behavioral changes to emerge. Short-term fasting (six weeks) was not sufficient to increase sexual behavior, suggesting that long-term adherence may be necessary.

The study, “Intermittent fasting boosts sexual behavior by limiting the central availability of tryptophan and serotonin,” was authored by Kan Xie, Chengfeng Wang, Enzo Scifo, Brandon Pearson, Devon Ryan, Kristin Henzel, Astrid Markert, Kristina Schaaf, Xue Mi, Xin Tian, Jiajia Jia, Meiqin Wang, Stefan Bonn, Manuel Schölling, Christoph Möhl, Daniele Bano, Yu Zhou, and Dan Ehninger.