Intermittent fasting has proven benefits for metabolic health, but a new study shows that it could slow hair growth in mice by inhibiting hair follicle regeneration. A research team headed by scientists at Zhejiang University, and at Westlake University, Zhejiang, found that mice subjected to intermittent fasting regimes showed improved metabolic health but slower hair regeneration compared to mice with 24/7 access to food. Their study indicated that intermittent fasting selectively induced apoptosis—programmed cell death—in activated hair follicle stem cells (HFSCs).
The results of a small clinical trial also conducted by the team indicated that a similar process might occur in humans, although they suggest it’s likely to be less pronounced, as humans have a much slower metabolic rate and different hair growth patterns compared to mice.
“We don’t want to scare people away from practicing intermittent fasting because it is associated with a lot of beneficial effects—it’s just important to be aware that it might have some unintended effects,” says stem cell biologist Bing Zhang, PhD, at Westlake University. The team’s studies did also how it might be possible to prevent the inhibitory effect of intermittent fasting on hair follicle regeneration.
The researchers aim to collaborate with local hospitals to investigate how fasting may impact on different types of stem cells in the skin and other body systems. “We plan to examine how this process affects the regeneration activities in other tissues,” says Zhang. “We also want to figure out how fasting impacts skin wound healing and identify metabolites that could help the survival of HFSCs and promote hair growth during fasting.”
Senior author Zhang and colleagues reported on the results of their mouse study and small clinical study, in Cell, in a paper titled “Intermittent fasting triggers interorgan communication to suppress hair follicle regeneration.”
“The beneficial effects of intermittent fasting on body health are believed to stem from the periodic switching of metabolic fuel sources, which help optimize cellular energy utilization and induce adaptive cellular stress response,” the authors wrote. “This response enhances the expression of antioxidant defense and repair mechanisms, inhibits protein synthesis, and reduces cellular inflammation.”
But while previous studies have shown that in addition to its metabolic benefits, fasting can improve the stress resistance of stem cells associated with blood, intestinal, and muscle tissue, little is known about how it impacts peripheral tissues such as skin and hair. “Intermittent fasting has gained global popularity for its potential health benefits, although its impact on somatic stem cells and tissue biology remains elusive,” they stated.
The team further noted that prior clinical observations suggest that patients on very low-calorie diets for rapid weight loss may experience hair loss. “However, the effects of modern intermittent fasting regimens on hair follicle regeneration and hair growth remain unclear,” they added.
For their reported study, Zhang and colleagues examined hair regrowth in mice that were shaved and then subjected to different intermittent fasting regimes. “The well-defined behaviors of HFSCs and the visible nature of the hair make the hair follicle an ideal system for studying how various intermittent fasting regimens impact somatic stem cells and tissue biology,” they noted.
Some mice were fed on a time-restricted feeding (TRF) schedule that involved 8 hours of food access and 16 hours of fasting each day, while other mice were subjected to alternate-day feeding (ADF). Control mice were allowed ad libitum (AL) feeding.
The team was surprised to find that fasting inhibited hair regeneration in fasting animals. While control mice that had unlimited access to food had regrown most of their hair after 30 days, mice on both intermittent fasting regimes showed only partial hair regrowth after 96 days.
The team showed that fasting inhibited hair growth occurs because hair follicle stem cells (HFSCs) were unable to cope with the oxidative stress associated with switching from using glucose to fat. HFSCs go through phases of activity and dormancy, and hair regrowth depends on these cells becoming active. While HFSC activation in control mice started around day 20 post-shaving and this activation continued until their hair had regrown, activated HFSCs in the intermittent fasting mice underwent apoptosis during extended fasting periods.
Using genetic engineering methods, the team showed that this fasting-induced apoptosis was driven by an increased concentration of free fatty acids near the hair follicles, which caused a build-up of harmful radical oxygen species (ROS) within the HFSCs. Free fatty acids also caused human HFSCs to undergo apoptosis in vitro. “During fasting, adipose tissue starts to release free fatty acids, and these fatty acids enter the HFSCs that were recently activated, but these stem cells don’t have the right machinery to use them,” added Zhang.
Further experiments indicted that “… fasting activates crosstalk between adrenal glands and dermal adipocytes in the skin, triggering the rapid release of free fatty acids into the niche, which in turn disrupts the normal metabolism of HFSCs and elevates their cellular reactive oxygen species levels, causing oxidative damage and apoptosis,” the investigators reported.
In comparison, epidermal stem cells (EpiSCs), which are responsible for maintaining the epidermal skin barrier, were unaffected by intermittent fasting. The major difference between these stem cell types is that epidermal stem cells have a higher antioxidant capacity. When the team tested whether antioxidants could mitigate the effects of fasting on hair growth, they showed that both topical application of vitamin E and genetic upregulation of antioxidant capacity helped HFSCs survive fasting. “Importantly, we show that enhancing HFSCs’ antioxidant ability through the external supply of antioxidants can significantly alleviate the inhibitory effect of intermittent fasting on hair follicle regeneration, offering a promising strategy for counteracting its impact on hair growth in humans,” the scientists stated.
They separately conducted a small clinical trial with 49 healthy young adults to examine whether fasting similarly affects hair regrowth in humans. They showed that a time-restricted diet involving 18 hours of fasting per day reduced the average speed of hair growth by 18% compared to controls, although they pointed out that larger studies would be needed to verify this effect given the study’s small sample size and short duration (10 days).
“The human population is very heterogeneous, so the effects might be different for different people,” says Zhang. “Mice also have a very high metabolic rate compared with humans, so fasting and metabolic switching have a more severe effect on mouse HFSCs. We see a milder effect in humans—there are still apoptotic stem cells, but many HFSCs survive. So, there is still hair regrowth; it’s just a little bit slower than usual.”
In their paper the team suggested that, given the widespread adoption of intermittent fasting globally, the effects of different fasting regimens on different stem cell systems will need thorough investigation. “Understanding the complexity of responses across different stem cells and tissues is critical for optimizing these intervention strategies in humans and exploring ways to mitigate any unintended effects on tissue biology while retaining their benefit.”
