Hangry hairs: intermittent fasting linked to hair loss

Chen and colleagues explore links between intermittent fasting (IF) and skin health, focusing on the effect of IF on hair growth, and discover that hair regeneration is blocked during IF periods.

Intermittent fasting (IF) is a dietary pattern relying on extended periods of fasting each day. This pattern has shown to be almost universally beneficial to overall health in experimental organism models promoting longevity, gut health, and cognition.¹ However, more recent data from murine and human models paint a more nuanced picture.^2,3,4 Some of the purported positive effects from this regimen have been linked to the regeneration of different types of stem cells throughout the body such as intestinal and hematopoietic stem cells.⁵ Chen et al.⁶ performed a comprehensive study of the effect of IF on hair growth as controlled by hair follicle stem cells (HFSCs). HFSCs are present in each hair follicle and serve to initiate the production of an active hair germ which then creates a new growing follicle and hair shaft. Chen et al. explored the effect of IF on HFSCs and uncovered connections between neurological signals induced by fasting and hair growth.

The authors employed two commonly used IF regimen: 16/8 time-restricted feeding and alternate-day fasting, both of which consistently show similar effects throughout the study. 16/8 time-restricted feeding equates eating during an 8 h period and fasting for 16 h. Alternate-day fasting involves alternating between eating days and fasting days. The authors found that mice on these fasting regimens exhibited disrupted hair growth compared to mice with constant feeding. Interestingly, the mice displayed positive metabolic benefits from the fasting regimen, and yet still hair growth was negatively affected. Delving deeper into the cause of hair growth disruption in the fasting mice, the authors examined HFSCs and found that they underwent cell death by apoptosis in the fasting mice. The authors found that longer periods of fasting prompted increased numbers of dying HFSCs, and a longer time required to complete a hair cycle. To illuminate the cause of HFSC apoptosis during fasting, the authors first focused on nutrient sensing pathways known to be important for HFSCs, however, they found that cellular nutrient sensor such as mTORC1 was not involved.

Chen et al. then explored a relation to adipocytes because fasting triggers the breakdown of fats and the skin harbors a robust adipocyte layer, in or near HFSC niches, and these are known to play a role in hair growth and stem cell maintenance. They hypothesized that adipocytes were communicating with HFSCs and somehow driving them to become apoptotic. They discovered that during fasting, adipocytes underwent lipolysis, a process where fat cells are broken down. During lipolysis, triglycerides were broken down releasing free fatty acids into the HFSC niche. Through a variety of genetic knockouts manipulating fatty acid oxidation, they found a reduction of HFSC apoptosis when fatty acid oxidation was blocked. To verify this, they injected free fatty acids into the skin of mice that were not fasting and found that this induced apoptosis in HFSCs. Moreover, Chen et al. identified fasting as the cause of lipolysis which then caused HFSC apoptosis. While others have shown that the adipocyte layer in the skin is a key regulator of HFSC homeostasis, this was not previously linked to lipolysis and diet.⁷

This prompted a rigorous exploration of the contribution of adrenal glands, which are known to respond to fasting by releasing hormones such as cortisol and epinephrine into the bloodstream. Previous work from the Hsu lab showed that these hormones have a strong effect on HFSC activation.^8,9 Here, Chen et al. showed that both hormones can function to induce lipolysis in the skin, and that both of these hormones were increased during fasting in mice (Fig. 1). This is interesting in light of the Hsu studies showing that increases in cortisol associated with stress blocked the hair cycle. After injecting cortisol and epinephrine into the skin, Chen et al. found widespread lipolysis in the skin and apoptosis in HFSCs, further confirming the direct relationship between these hormones and the downstream effects observed throughout the study. These interesting findings emphasize that communication between multiple organs can occur in response to physiological changes such as dietary alteration.