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In a nutshell
- Intermittent fasting dramatically improved reproductive success in aging male mice (83% success rate) compared to continuously-fed mice (38% success rate).
- The benefits came from enhanced mating behavior, not improved sperm quality or hormones, through reduced brain serotonin levels.
- The mechanism works through decreased tryptophan availability to the brain, as muscles take up more tryptophan during fasting/refeeding cycles.
BONN, Germany — Male sexual desire tends to decline with age—it’s a biological fact that many men face as the years pass. By age 70, about a quarter of men report a noticeable drop in sexual drive. But what if there were a relatively simple dietary approach that could help maintain libido well into later years?
A fascinating study published in Cell Metabolism reveals that intermittent fasting significantly boosts sexual behavior in male mice by altering brain chemistry in ways that enhance sexual motivation. The research suggests that brain chemistry might matter more than physical reproductive metrics when it comes to maintaining sexual function with age.
Scientists from the German Center for Neurodegenerative Diseases and University of Health and Rehabilitation Sciences in China discovered that mice subjected to intermittent fasting—alternating 24-hour periods of eating and not eating—maintained much higher reproductive success rates in old age compared to their continuously-fed counterparts. While only 38% of aged mice with unlimited food access successfully reproduced, a remarkable 83% of intermittently fasted mice remained fertile.
What makes this finding truly surprising isn’t just the striking difference in reproductive success, but the mechanism behind it. The fasting regimen didn’t improve traditional markers of reproductive health like testosterone levels, sperm count, or sperm quality. In fact, the fasting mice actually showed greater testis weight reduction than continuously-fed mice. The secret to their reproductive success lay entirely in behavior—the fasting mice simply showed more interest in mating.
The research team, led by Kan Xie, Yu Zhou, and Dan Ehninger, identified a clear chemical pathway for this behavioral change. Aging typically raises levels of serotonin in the brain, which acts as a sexual inhibitor. Intermittent fasting prevented this age-related serotonin increase by reducing the amount of its precursor, the amino acid tryptophan, available to the brain.
Study authors explain that this mechanism works through a unique metabolic pathway. When mice fast and then refeed, their skeletal muscles draw more tryptophan from the bloodstream. With less tryptophan circulating in the blood, less crosses into the brain, resulting in lower serotonin production and consequently less inhibition of sexual behavior.
To confirm their findings, the researchers administered 5-HTP—a direct precursor to serotonin that bypasses the rate-limiting step in serotonin synthesis—to fasting mice. This promptly reversed the behavioral benefits, with the treated mice showing decreased sexual interest. This confirmed that reduced brain serotonin was indeed responsible for the enhanced sexual behavior in fasting mice.
While the study was conducted in mice, the core biochemical pathways involved function similarly in humans. Tryptophan metabolism and serotonin synthesis operate through comparable mechanisms across mammalian species, suggesting the potential for similar effects in humans.
The intermittent fasting regimen used in the study wasn’t extreme. The mice alternated between 24 hours of unlimited food access and 24 hours of fasting. During feeding days, they ate more than usual, compensating for fasting days. Overall, they consumed only about 13% fewer calories than continuously-fed mice. This modest reduction in calorie intake, combined with the cyclical fasting/feeding pattern, produced significant effects on brain chemistry.
It’s worth noting that the benefits weren’t immediate—a brief six-week intervention didn’t improve sexual behavior. The changes required longer-term adaptation, suggesting that lasting modifications to brain chemistry take time to develop.
For men concerned about age-related decline in sexual interest, this research offers food for thought. While human studies are needed to confirm similar effects, the fundamental biological mechanisms are plausible. Before making any changes to your dietary routine, it’s important to speak with your doctor first.
From an evolutionary perspective, these findings challenge the notion that dietary restriction necessarily suppresses reproduction. While many theories suggest organisms redirect resources from reproduction to survival during food scarcity, this research indicates that certain patterns of food availability might actually enhance reproductive behavior, at least in males.
It’s something many of us probably haven’t thought of before, but perhaps what happens in the kitchen might influence what happens in the bedroom. While results from animal studies don’t automatically transfer to humans, the fundamental mechanisms involved are similar enough to warrant further investigation. After all, when it comes to maintaining quality of life with age, few aspects matter more than preserving the capacity for romantic connection.
Paper Summary
Methodology
The research team designed a meticulous experimental protocol comparing male mice on intermittent fasting with those allowed unlimited food access. The intermittent fasting consisted of alternating 24-hour periods of free access to food followed by complete food deprivation, beginning when mice were 8 weeks old and continuing throughout their lives. To test fertility, males from both feeding regimens were paired with young female mice in controlled mating scenarios.
Researchers conducted detailed analyses of mating behaviors, measuring factors like mounting frequency and time spent interacting with females. They also performed thorough examinations of the male reproductive system, including testosterone levels, sperm counts, sperm motility, testis weight, and molecular analyses of gene expression in reproductive tissues.
To investigate brain chemistry, the team measured various neurotransmitter levels in brain samples and used pharmacological interventions (like 5-HTP administration) to validate their proposed mechanism. They also evaluated tryptophan levels in blood plasma and conducted isotope-labeling experiments to track how this amino acid moved through the body.
Results
The study found that intermittent fasting dramatically improved reproductive success in aged male mice, with 83% of 24-month-old fasting mice successfully reproducing compared to only 38% of continuously-fed controls of the same age. This improvement occurred despite the fasting mice showing no benefits—and sometimes worse outcomes—in traditional reproductive metrics like testis weight and sperm quality.
Behavioral analysis revealed that fasting mice spent more time interacting with females, mounted more frequently, and showed reduced latency to initiate mating behaviors. Brain chemistry examinations showed that aging normally increases brain serotonin levels (which inhibit sexual behavior), while intermittent fasting prevented this increase.
The beneficial effects of fasting were eliminated when mice were treated with 5-HTP (the immediate precursor to serotonin), confirming that reduced serotonin played a central role in the behavioral changes. Analysis of blood samples showed that fasting reduced plasma tryptophan concentrations, limiting its availability for conversion to serotonin in the brain. Isotope-labeling experiments demonstrated increased tryptophan uptake into skeletal muscle in fasting mice, explaining the reduced blood levels.
Limitations
This study, while groundbreaking, has several important limitations. First, the experiments were conducted exclusively in one strain of laboratory mice (C57BL/6J), so the findings may not generalize to other mouse strains or to humans. The research didn’t identify the minimum effective duration of intermittent fasting needed to produce benefits—while six weeks proved insufficient, the researchers didn’t determine exactly when the effects begin to manifest.
The study focused solely on male reproductive behavior without examining potential effects on females. It also didn’t explore whether other fasting protocols (like time-restricted feeding or different fasting/feeding ratios) would produce similar results. While the researchers established a clear connection between tryptophan availability, brain serotonin, and sexual behavior, they didn’t fully explore whether fasting affects other neurotransmitter systems or brain regions involved in sexual motivation.
Finally, the research was conducted in controlled laboratory conditions that don’t fully reflect the complexity of human dietary patterns, social dynamics, and reproductive behaviors in real-world settings.
Discussion and Takeaways
This research challenges traditional thinking about aging and reproduction. While reproductive decline with age has typically been viewed primarily through the lens of physiological changes—decreasing hormone levels, declining sperm quality, and physical alterations—this study suggests that behavioral factors regulated by brain chemistry may be equally or more important for overall reproductive success.
The work provides fresh insight into how dietary patterns can influence brain function and behavior, showing how food intake patterns affect amino acid metabolism and subsequently alter neurotransmitter systems in ways that significantly impact behavior. These findings suggest potential new approaches to addressing age-related decline in sexual desire, focusing on interventions that modulate brain serotonin levels rather than exclusively targeting hormonal systems or physical aspects of sexual function.
The study also has broader implications for understanding how dietary patterns affect brain chemistry beyond sexual function. The same mechanisms might influence mood, cognitive abilities, and other behaviors regulated by serotonergic systems. From an evolutionary perspective, the findings challenge the notion that dietary restriction necessarily reduces reproductive effort, indicating that certain patterns of food availability might actually enhance reproductive behavior.
Funding and Disclosures
The research was supported by grants from the Helmholtz Future Topic Program AMPro (Aging and Metabolic Programming). Several researchers were members of the ETERNITY project consortium, funded by the European Union through Horizon Europe Marie Skłodowska-Curie Actions Doctoral Networks. Additional support came from the National Natural Science Foundation of China and the Natural Science Foundation of Shandong Province. The researchers declared no competing interests that might have influenced the study design or interpretation of results.
Publication Information
This research article, titled “Intermittent fasting boosts sexual behavior by limiting the central availability of tryptophan and serotonin,” was authored by Kan Xie, Chengfeng Wang, Enzo Scifo, and numerous collaborators, with Yu Zhou and Dan Ehninger serving as corresponding authors. It was published in Cell Metabolism (Volume 37, pages 1-17) on May 6, 2025, and is available online at https://doi.org/10.1016/j.cmet.2025.03.001.
