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Intermittent fasting triggers interorgan communication to suppress hair follicle regeneration 2024

Common intermittent fasting regimens inhibit hair follicle regeneration in mice
Fasting selectively eliminates activated HFSCs, but not EpiSCs that maintain epidermis
Activated adrenal gland-dermal adipocyte crosstalk mediates HFSC apoptosis
Intermittent fasting inhibits human hair growth in a randomized clinical trial

Intermittent fasting has gained global popularity for its potential health benefits, although its impact on somatic stem cells and tissue biology remains elusive. Here, we report that commonly used intermittent fasting regimens inhibit hair follicle regeneration by selectively inducing apoptosis in activated hair follicle stem cells (HFSCs). This effect is independent of calorie reduction, circadian rhythm alterations, or the mTORC1 cellular nutrient-sensing mechanism. Instead, 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. A randomized clinical trial (NCT05800730) indicates that intermittent fasting inhibits human hair growth. Our study uncovers an inhibitory effect of intermittent fasting on tissue regeneration and identifies interorgan communication that eliminates activated HFSCs and halts tissue regeneration during periods of unstable nutrient supply.

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#2

Pinging the hair expert @Virilius

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#3

So this is referring to time restricted eating? How does this compare in mice to humans? Why would anyone do time restricted eating?

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#4

First of all, mice are notoriously bad model organisms for studying the human hair cycle, even with transplanted hair from humans. While there are a few anecdotes of people’s hair falling out when fasting but it’s unclear whether this is related to nutrient deficiencies or other factors. Human clinical trials with rapamycin or fasting also don’t mention significant hair growth or fall. Judging from that, fasting has a negligible effect on hair growth.

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#5

From the paper: “A randomized clinical trial (NCT05800730) indicates that intermittent fasting inhibits human hair growth.”

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#6

Yes, but mice with transplanted human are still not a good model for the human hair growth cycle based on the low success rate seen when testing hair growth stimulants in humans that worked in mice.

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#7

Why are you talking about mice? It’s an RCT in humans.

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#8

Am i getting confused? There are a lot of mouse pictures in the study?

#9

Might be the first human-mice chimera.

#10

Can we just glue mice to our scalps?

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#11

They looked in mice and then confirmed the finding with an RCT in humans. All in the same paper.

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#12

I do TRF (time restricted feeding - 6 hours window) since two/three years ago and also supplement with GlyNAC daily, which acts restoring glutathione levels to youthful levels. Glutathione is well known for fighting ROS:

The alteration in the balance between reactive oxygen species (ROS) generation and antioxidant buffering capacity creates oxidative stress in the body that leads to disease on the body systems. The ROS are the operating agents to create an oxidative state of the body. There are biological mechanisms to tamper these agents and to reach a redox equilibrium, for promotion of health and avoid sickness. Some mechanisms of the oxidative stress will be discussed on the paper. The glutathione is a tripeptide, it the first line of defence against oxidative damage, being very important for the protection of the cells from oxidative damage and maintaining redox homeostasis.

Source .pdf

My question is for those of you in the know: as supplementing with GlyNAC allows our organism to get the glutathione building blocks for it to produce itself the ammount of glutathione our body needs, am I too wrong thinking it would be enough to compensate TRF negative effect on hair follicles the study mentions?.

Just my two cents 


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#13

Of course . . . this has been an option since the day glue was invented

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#14

Killer whales wear salmon
 why not a mouse?

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#15

You’re looking for a fix to a problem that shouldn’t exist. Just stop TRF.

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#16

With respect of the human study briefly mentioned in this paper, 49 people for 2 weeks divided in 3 groups, are these effects after 2 weeks of slowed hair growth in humans permanent or the hair growth resumes at previous rate when Intermittent fasting is stopped? Further it looks like this slow down happened in both calorie restricted and if groups. They don’t tell us how much calories if group consumed, though. So human study as I see it is incomplete.
With respect of mice study, as already mentioned extrapolating any effects of if to humans from it is far fetched. Instead doing longer, better powered and disclosing calorie intake of if group study in humans would be much more interesting.

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#17

Sure the study is not perfect. But the weight of evidence is now against intermittent fasting at least for those who want to keep their hair. Future papers might contradict that one. Time will tell


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#18

The killer whale equivalent of a comb over?

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#19

This turned out to be more interesting than expected. Hair follicles are an example of niche micro environments that behave differently to fasting (and other?) due to being considered a low priority system for survival which can be sacrificed for the good of the organism. What other systems are considered low priority (that I don’t want to give up)?

“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. This response enhances the expression of antioxidant defense and repair mechanisms, inhibits protein synthesis, and reduces cellular inflammation.

While similar responses were observed in hair follicle stem cells (HFSCs) upon intermittent fasting, the activated HFSCs were selectively eliminated during the extended fasting periods, leading to inhibited hair follicle regeneration.

Moreover, long-term intermittent fasting decreases the stem cell pool and induces hair follicle degeneration. Notably, fasting selectively harms HFSCs, but not epidermal stem cells (EpiSCs), that maintain the epidermis with vital barrier functions.

Previous studies have shown that in the gut, fasting and refeeding enhance intestinal stem cell function and intestinal epithelial repair, while in the muscle, fasting induces the muscle stem cells to enter a deep quiescent status and delays muscle regeneration upon injury.

While previous studies and our own data both indicated that intermittent fasting reduces markers of whole-body oxidative stress levels in circulation, for activated HFSCs with limited endogenous antioxidant capacity and thus primarily rely on glycolysis for energy production, switching to utilizing FFAs during fasting increases their cellular ROS production, leading to increased cellular oxidative damage and apoptosis.

This discrepancy in oxidative stress level changes between HFSCs and the whole-body underscores the unique metabolic demands and specific microenvironments (“niches”) of these stem cells. As tissue regeneration is a resource-demanding process, one potential explanation for the divergence in response to fasting among different stem cell populations and tissue types could be that it allows the body to allocate limited resources toward preserving essential organ systems for survival, such as the intestine for nutrient absorption and the skin epidermis for barrier function. 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.”

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#20

How long did they fast? If you eat a big mixed meal, it can take 6 hours or so for your glucose and insulin to return to baseline levels. There’s no way a piddly little 16 hour “fast” like most people use inhibits hair growth.