Fasting Will Make You Bald! ... And How to Stop It

New research in the journal Cell describes how intermittent fasting, including 16-8 time restricted feeding and alternate day fasting, hurt hair growth. But there may be something you can do about it.

New research published in Cell has me scratching my beard… while I have it.

It shows how fasting can lead to hair loss.

I’m going to break down the data and convince you why this all makes sense and reveal what you can do to stop fasting-induced hair loss.

Preface

But first, let me be clear: this is not a “fasting is bad” post, 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 stem cell populations in the intestine, muscle, and hematopoietic system,” and generally endorses the health benefits of fasting.

However, there is nuance.

And to conduct intellectual gymnastics to “excuse” a potential negative effect of an intervention because we like said intervention is anti-scientific.

So, here … we … go…

Background

First, it’s important to understand a bit about the biology of hair growth.

In the skin, the hair follicles undergo cyclic phases of growth (anagen), regression (catagen), and rest (telogen) to produce new hairs. This is driven by the cyclic activation of hair follicle stem cells (HFSCs).

The stem cells reside in a “niche,” which is like a metabolic pocket within the body.

“Niches,” be they in the skin, gut or elsewhere, are critical because they allow for the integration of whole body (systemic) and local signaling to generate outcomes that are adaptive for the whole organism given a particular state or environmental stressor, like fasting.

The New Research

The researches began in mice, applying common intermittent fasting routines (16-8 time-restricted feeding [TRF] and alternate day fasting [ADF]), and found that each impaired hair follicle regeneration and slowed hair regrowth.

Figure 1B. Mice were shaved and their hair left to regrow. Time-restricted feeding (TRF) and alternate day fasting (ADF) clearly slowed hair regrowth.

Additionally, markers of programmed cell death (apoptosis) increased among the HFSCs. (If you forgot already, that stands for hair follicle stem cells. There. Don’t forget!)

Figure 2C. Shown are HFSC stained in red for a marker of apoptosis (active caspase-3). In other words, more red = more programmed cell death of the hair follicle stem cells, as quantified to the right.

Furthermore, there was a dose-response effect whereby longer fasts had a worse effect on hair growth.

Adaptation or Baldification?

Now, as with many things, sometimes the body can adapt. So, did the mice adapt well to chronic intermittent fasting. In other words, did the HFSCs and hair follicles become more resilient?

Umm… Nope.

Quoting from the paper, “Chronic application of intermittent fasting [for 8 months] resulted in baldness in some regions … Upon examination of hair follicles, we observed a significant reduction in HFSC number, hair follicle length, and HFSC compartment size, indicative of hair follicle degeneration driven by stem cell loss… [Thus], when applied chronically, they cause HFSC loss and hair follicle degeneration.”

Mechanism? It’s Fat!

So, what’s going on here?

Well, first off, it’s not a “calorie problem,” since caloric intake was largely stable, and the researchers concluded, “Therefore, the apoptosis of HFSCs cannot be attributed to a reduction in total calorie intake.” Additionally, the researchers found – perhaps to their surprise – the effect wasn’t mediated by the popular “mTOR1” protein complex, which is involved in classical nutrient sensing.

Fascinatingly, they found the mechanism had to do with fat burning.

Recall, I mentioned metabolic “niches” earlier. Well, the HFSC niche includes fat cells in the skin called “dermal adipocytes.” During fasting dermal adipocytes break down stored fat into free fatty acids and release these fatty acids into the niche at an alarming rate, leading to local fatty acid levels in the skin to far exceed those in the blood.

And when the researchers knocked out a key enzyme in dermal adipocytes responsible for fat burning (adipose triglyceride lipase, Atgl), the effect of fasting on the HFSCs was reduced.

In other words, when the fat cells in the skin couldn’t burn fat, the stem cells survived fasting.

They went on to find that the system depends on the adrenal glands.

Upon fasting, leptin levels fall, which signals to the brain’s hypothalamus to activate the hypothalamic-pituitary adrenal (HPA) axis, which tells the adrenals to make epinephrine and cortisol, which trigger fat burning in those dermal adipocytes, which then release free fatty acids onto the HFSC.

In fact, when adrenal glands were removed from mice, fasting no longer caused HFSC death.

Now, the next question, why would fatty acids released from dermal adipocytes kill the HFSC?

To make a long story short, the metabolism of the high levels of free fatty acids overwhelmed mitochondria in the HFSC, leading to oxidative stress, mitochondrial dysfunction, and apoptosis/death of the HFSC.

Summary of Mechanism: Fasting decreases leptin levels which activates the HPA axis and causes the adrenal glands to release cortisol and epinephrine, which signal to dermal adipocytes to release free fatty acids. The oxidation of free fatty acids by the HFSC leads to oxidative stress that overwhelms the antioxidant systems and triggers apoptosis (death).

Is this Bad or Beautiful?

This may sound bad, but it’s not. It’s adaptive.

Consider this, while oxidative stress and apoptosis are elevated in the dermal stem cell niche, systemic (whole body) oxidative stress was actually reduced, as measured from the blood. This discrepancy highlights that “changes in HFSCs’ cellular oxidative stress levels during intermittent fasting do not align with changes in systemic oxidative stress levels of the body,” and – more to the point – how metabolic phenomenon can be coordinated across an organism to accomplish an overall adaptive outcome for the organism.

In fact, stem cells in the epidermis – although right near by the hair stem cells – don’t have the same response to fasting and, instead, are have higher antioxidant capacity and are resilient such that the skin retains it’s important barrier function.

Thus, even in the skin, different stem cell populations are specialized to meet the metabolic needs of the system.

Saving Your Hair

But can anything be done about this, or is this just a quirk of biology with which those of us who love fasting will need to tangle?

Well, consider this: the effect is dependent on the metabolism of fatty acids generative oxidative stress to a degree that overcomes the antioxidant capacity of the niche.

So, what if we added a topical antioxidant, like vitamin E?

In fact, the researchers did just this in their animal models and… it worked!

Figure 6 I, J. Application of vitamin E protected the HFSC from apoptosis and restored hair regrowth during fasting

The authors write, “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.”

Human Randomized Controlled Trial

Now, I did mention they included human randomized controlled trial data data. Indeed, they collected data from 49 healthy young 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 animal models. So, it appears this mechanism does generalize to humans.

Summary & Takeaways

To review the mechanism once more: fasting leads to activation of the adrenal glands and release cortisol and epinephrine, which signal to fat cells in the skin to release free fatty acids. When these are burned by hair follicle stem cells, oxidative stress oxidative stress overwhelms the antioxidant systems and triggers stem cell death.

This is adaptive because tissue regeneration is a resource-demanding process. Therefore, it makes sense for different tissues and organs to respond differently. Hair growth is sacrificed, whereas other stem cells in other metabolic niches may flourish, including those in the epidermis (important for barrier function) and in the intestines (for nutrient absorption).

This may be treatable, as application of a topic anti-oxidant (Vitamin E) provided extra anti-oxidant defense against the oxidative stress generated by the local metabolism of free fatty acids in the hair follicle stem cell niche, as least in the rodent model. Will it work in humans… time and data will tell…

Or you can try an N = 1 and tell me! I’d offer up myself as a subject. But anyone who has seen my eyebrows knows well I’m an outlier in this department and might not make a good test subject #CaterpillarBrows.

Well, I hope you thought that was interesting. Isn’t biology amazing! #StayCurious