In this YouTube video, Nick Norwitz reviews a recent Cell paper that demonstrates intermittent fasting (IF) can impair hair follicle regeneration. The study combines mouse mechanistic experiments and a small human randomized controlled trial (RCT). In mice, common IF regimens (16:8, alternate‑day, 20:4) repeatedly activate and then eliminate hair follicle stem cells (HFSCs), leading to dose‑dependent hair growth inhibition and, after chronic IF, regional baldness. The mechanism is not caloric restriction but a cascade: fasting lowers leptin, activating the hypothalamic‑pituitary‑adrenal (HPA) axis, which releases epinephrine and cortisol. These stress hormones trigger dermal adipocyte lipolysis via adipose triglyceride lipase (ATGL), flooding the HFSC niche with free fatty acids. Excess fatty acids overwhelm HFSC mitochondria, causing oxidative stress, mitochondrial dysfunction, and apoptosis. Knocking out ATGL in dermal adipocytes or adrenalectomy prevents HFSC loss, confirming the pathway. A human RCT with 49 participants on an 18:6 IF schedule showed an 18% reduction in hair regrowth, mirroring mouse findings. Topical application of vitamin E, an antioxidant, rescued hair growth in mice, suggesting a simple countermeasure. The video concludes with commentary from the senior researcher, emphasizing tissue‑specific effects of IF, the need for more human studies, and validation of vitamin E as a potential therapeutic.
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New research published in the journal Cell has me scratching my beard while I still have it. It reveals that intermittent fasting, as practiced by many people, including yours truly, can harm hair growth. It unravels the mechanism, drawing from both animal and human controlled data, and it presents a potential and easy solution to protect your hair. I'm going to break down the data, convince you why this all makes sense, share with you the solution, and at the end, you'll get to hear right from the senior researcher himself. But first, let me be clear. This is not a "Dangers of Fasting" or "Fasting is Bad" video, nor does the new research try to make that claim. To the contrary, the paper reads, "Fasting improves the function and stress resistance of multiple somatic body stem cell populations in the intestines, muscles, hematopoietic system, the blood system, and generally endorses the health benefits of fasting. However, there is nuance. There's always nuance. And to conduct intellectual gymnastics to excuse a potential negative effect of an intervention just because we like it is anti-scientific. And we're better than that on this channel. So, here we go. First, it's important to understand just a little bit about the biology of hair growth. In the skin, hair follicles undergo cyclic phases of growth. This is driven by the cyclic activation of hair follicle stem cells, or HFSCs for short. The stem cells reside in a niche, which is like a metabolic pocket within the body. Niches, be they in the skin or the gut or elsewhere, are critical because they allow the integration of whole body systemic signaling with local signaling in order to generate an outcome that's adaptive for the whole organism, the whole me, the whole you, given a particular state or environmental or nutrient stressor like intermittent fasting. Now, the researchers began working in mice because they wanted to dissect the mechanism in a tightly controlled fashion, which is best done in animals. And they subjected the mice to common intermittent fasting routines, including 16:8 fasting, where you fast for 16 hours a day and then feed for 8, and alternate-day fasting, where you eat every day. And they found that each fasting regimen impaired hair follicle regeneration. And additionally that fasting increased markers of programmed cell death in the hair follicle stem cells. So quoting from the paper: "During the feeding period, more hair follicle stem cells were activated, only to be eliminated again by fasting. And as a result, hair follicle stem cells were activated and eliminated repeatedly during intermittent fasting, leading to ultimately inhibited hair follicle growth. And furthermore, there was a dose-response effect whereby longer fasts had worse effects on hair growth. That means eating in a 20:4 pattern with 20 hours of fasting per day and 4 hours of feeding would be worse than eating in a 16:8 pattern. With 16 hours of fasting per day and 8 hours of feeding. Now, as with many things, sometimes the body can adapt. We're so adaptable. So did the mice adapt well to chronic intermittent fasting over 8 months? Did the stem cells and hair follicles become more resilient? No. No, they did not. Quoting from the paper, chronic application of intermittent fasting, in this case for 8 months, resulted in baldness in some regions. This is indicative of hair follicle degeneration driven by stem cell loss. Thus, when applied chronically, fasting causes follicle loss and degeneration. So, what's going on here? What's the mechanism? Well, first off, let's get this out of the way, it's not a calorie deprivation problem since caloric intake was actually largely stable. And the research team concluded, therefore, the apoptosis of the stem cells cannot be attributed to a reduction in total caloric intake. Fascinatingly, they found that the mechanism actually had to do with fat burning. Burning more fat linked to burning of the hair follicles, at least metaphorically speaking. Recall earlier I mentioned the metabolic niches. Well, the hair follicle stem cell niche includes fat cells in the skin.— not under the skin, but in the skin, called dermal adipocytes. And during fasting, dermal adipocytes break down stored fat to release free fatty acids and release these free fatty acids into the niche at an alarming rate, leading to local fatty acid levels in the skin that far exceed those in the blood. And when the researchers knocked out a key enzyme in these skin fat cells, the dermal adipocytes, responsible for fat burning— the enzyme's not really important, but it's called adipose triglyceride lipase, or ATGL is the gene— the effect of fasting on the stem cells was reduced. In other words, to simplify it, when fat cells in the skin couldn't burn fat, the hair follicle stem cells survived fasting. Isn't that weird? They then went on to find that the whole system depends on the adrenal glands. And here's how it works. Upon fasting, leptin levels— leptin is a hormone that's released from fat cells— drop, which signals the brain to activate the hypothalamic-pituitary-adrenal axis, which tells the adrenals to make stress hormones, epinephrine and cortisol. And those hormones trigger fat burning in those dermal adipocytes, those fat cells in the skin, which then release free fatty acids onto the hair follicle stem cells. In fact, as a cool aside, when the adrenal glands were removed from mice, fasting no longer caused death of the hair follicle stem cells. So it is dependent on the adrenal glands, although I don't recommend having your adrenals removed to spare your hair. I have a better solution for you. Now the next question is, why would fatty acids released from the dermal adipocytes kill the stem cells? And to make a long story short, the metabolism of high levels of free fatty acids in the stem cell niche in the skin overwhelm the mitochondria of very sensitive hair follicle stem cells, leading to oxidative stress, mitochondrial dysfunction, as you see here, and apoptosis—death—of the hair follicle stem cells. And that might sound bad, but it's not. It's highly adaptive. Of course it makes sense that we evolved in such a way that hair growth effectively sacrifices itself as a function during fasting. Since why would we expend valuable energy on regrowing hair when we also want to maintain our gut linings for eventual nutrient replenishment and our skin's barrier function and our immune system function? And also consider this: while oxidative stress and apoptosis are elevated in hair follicle stem cells in that niche, systemic whole body oxidative stress was actually reduced with fasting as measured in the blood. And this discrepancy highlights how metabolic phenomenon can be coordinated across an organism, sometimes in opposite ways in the skin stem cell niche versus the whole body, the blood, to accomplish an overall adaptive outcome for the whole organism. But can anything be done about this? This is probably why you're really watching the video. Or is this just a quirk of biology with which those of us who love fasting will need to tangle? Well, maybe not tangle your hair since you'll be losing it. But anyway, consider this now: the effect is dependent on the metabolism of fatty acids in the skin generating oxidative stress to a degree that overwhelms the antioxidant capacity in the hair follicle stem cell niche. So what if you just added some topical antioxidant to bolster the defenses, like some topical vitamin E? In fact, the researchers did just this in their animal models and, lo and behold, it worked! Hair saved with just some topical vitamin E. The authors write, "Importantly, we show that enhancing hair follicle stem cell antioxidant ability through external supply of antioxidants can significantly alleviate the inhibitory effect of intermittent fasting on hair follicle regeneration." offering a promising strategy for counteracting its impacts—fasting's impacts—on hair growth in humans. Now, I did mention they included human randomized controlled trial data. Indeed, they collected data from 49 healthy individuals subjected to 18:6 intermittent fasting and found it reduced hair regrowth by 18%, in association with other changes that paralleled those seen in their mouse model. So it appears this mechanism does generalize to humans. So what's the actual point here? Am I arguing that fasting will actually make you bald, like dropping an anvil on your foot will probably break some toes? No, it's not that black and white. It's not that simple. What I am saying is this is legitimate and interesting science that tells us a fascinating metabolic story of how the body's different metabolic niches have evolved to survive environmental challenges, in this case fasting, in a manner that is sensible, adaptive, and oh so biologically beautiful, if I do say so myself. And in understanding these mechanisms, we can leverage them for our own purposes. In this case, it might be as simple as rubbing some antioxidants on your skin as a nice thank you, but no thanks to evolution and natural selection. And if you followed me in this video all the way to this point, kudos. You're a nuance ninja who loves deep thought, or you're bald and desperate. It's one of the two. Anyway, now for some thoughts by the senior researcher recorded especially for you. Stay curious and enjoy what he has to say.
Alright, thank you, Nick, for reaching out about our research. To answer your questions, intermittent fasting has been shown to have many beneficial effects on the body, but the exact impact on tissue health remains unclear. So, our study suggests that intermittent fasting may affect different tissues in different ways. So, this variability may be linked to the unique characteristics of stem cells and their microenvironment within different tissues. So for the next steps, I think it is essential to identify the specific effect of different intermittent fasting methods on different stem cell systems. And additionally, we need to develop strategies to optimize these methods to maximize the beneficial effect to the body while minimizing any negative effect. So although animal studies suggest that the topical application of vitamin E can mitigate the effect of fasting on hair growth, and human hair follicle stem cells exhibit similar apoptosis when metabolizing fat. I think it is necessary to conduct more detailed studies in humans to evaluate the effect of vitamin E.
