Long-term intermittent fasting may affect hair volume: A related study from Westlake University published online in the journal Cell.

“Intermittent fasting” is gaining popularity globally, but long-term practitioners may have to choose between fat loss and hair health. On December 14, 2023, the WeChat public account of West Lake University announced that the journal “Cell,” a leading international publication in the field of life sciences, published a study conducted by a research team led by Zhang Bing from the university’s School of Life Sciences. The research indicates that intermittent fasting can trigger apoptosis in activated hair follicle stem cells, thereby inhibiting hair follicle regeneration and hair growth.

While intermittent fasting, also referred to as light fasting, is known to aid weight loss and improve metabolic health, reduce inflammation, and enhance focus, its potential negative effects on the human body are seldom discussed. Zhang Bing’s team primarily investigates the regulatory mechanisms of various adult stem cells in response to systemic physiological changes such as mental stress, metabolism, and aging. During his postdoctoral research at Harvard University, Zhang identified the biological mechanism by which mental stress leads to gray hair, which was recognized as one of Nature’s top ten scientific discoveries in 2020.

Many scientific discoveries arise from “mistakes.” In the summer of 2021, a research intern at the stem cell and regenerative biology laboratory of West Lake University forgot to provide food for a group of mice, leading to them being starved for a day. Subsequent observations of hair follicle samples revealed several apoptotic hair follicle stem cells in the starved mouse.

“Could hunger kill hair follicle stem cells? If a single fasting episode can kill the hair follicle stem cells of a mouse, could intermittent fasting affect hair follicle regeneration and growth?” Zhang pondered. At that time, he was practicing “16/8 time-restricted eating,” consuming food only within an 8-hour window each day.

The “16/8 time-restricted eating” method is one of the most popular intermittent fasting approaches, with other common methods including alternate-day fasting and fasting for two days a week.

The research team designed three feeding regimens for the mice: a normal diet group, a 16/8 time-restricted eating group, and an alternate-day fasting group. All mice had their fur shaved before the experiment, and after 96 days, the mice in the normal diet group had their fur fully restored, while those in the 16/8 and alternate-day fasting groups only partially regrew fur, which appeared sparse.

The research group hypothesized that the issue with hair regeneration in the intermittent fasting group stemmed from a reduced total caloric intake. To accurately measure food intake and metabolic indicators, the mice were placed in “metabolic cages.”

Unexpectedly, the “plot” reversed. The mice undergoing intermittent fasting ate more when food was available than they typically did. Monitoring data indicated no significant differences in overall food consumption among the three groups of mice.

“Perhaps the apoptosis of hair follicle stem cells is related to the duration of each fasting period?” After adjusting the experimental protocols, the research team found a direct correlation between the severity of hair follicle stem cell apoptosis and the fasting duration. When fasting was extended to 21 hours a day, hair regeneration in the mice was nearly completely suppressed; conversely, reducing the fasting duration to 12 hours restored normal hair growth. The total caloric intake of these mice remained unchanged.

“Why does prolonged fasting kill hair follicle stem cells?” Through an in-depth study, a coordinated system response directed by the brain, involving multiple organs, was revealed. Research showed that during hunger, the secretion of leptin (a hormone released by adipose tissue) decreases in mice, activating the hypothalamic-pituitary-adrenal axis, leading the adrenal glands to release cortisol and adrenaline into the bloodstream. These hormones enter the skin, prompting dermal adipocytes to break down and release free fatty acids, which are a more efficient energy source compared to glucose.

Hair follicle regeneration is driven by stem cells within the hair follicle, which enter the growth phase when activated, promoting hair growth. Zhang Bing’s team discovered that the newly activated hair follicle stem cells “cannot tolerate” fatty acid metabolism. The high levels of free fatty acids released from dermal adipocytes surrounded the hair follicle stem cells, pushing them toward fatty acid oxidation metabolism. However, this fatty acid oxidation metabolism directly caused apoptosis in the activated hair follicle stem cells, effectively pausing hair follicle regeneration.

When the mice resumed eating, the dormant hair follicles were reactivated, only to undergo apoptosis in the subsequent fasting phase. Mice subjected to long-term intermittent fasting continuously transitioned their hair follicle stem cells from a dormant state to an active state, only to have them perish due to oxidative stress in the following fasting periods. This extended cycle of fasting excessively depleted the hair follicle stem cells.

Once the research team clarified this mechanism, they collaborated with Zheng Jusheng’s team at the West Lake University School of Medicine to conduct human trials on campus, where volunteers adhered to an intermittent fasting schedule and had one square centimeter of hair shaved from the back of their heads for observation. The results showed a significant reduction in hair growth rate due to intermittent fasting, though the degree was less severe compared to mice. In vitro cultures of human hair follicle stem cells also demonstrated that the utilization of free fatty acids led to elevated oxidative stress and cell apoptosis.

“From an evolutionary perspective, our ancestors’ access to food was random; hunger was the norm. The body adapted to the reality of alternating between feast and famine through refined responses, even the skin tissues have developed different survival strategies for epidermal stem cells and hair follicle stem cells,” Zhang stated. “Intermittent fasting appears to trigger an ancient ‘brake’ mechanism, pausing the regenerative activities of some tissues and organs to adapt to fluctuations in food supply. In this adaptive process, hair follicle regeneration and hair growth became the ‘sacrificial victims.'”

In their experiments, researchers attempted to provide antioxidant supplements daily to the fasting mice, successfully preventing the apoptosis of hair follicle stem cells, leading the mice to start regrowing hair. The team is now utilizing this discovery to seek new methods to promote hair follicle regeneration and accelerate hair growth in humans.

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