Keep yer hair on Jimmeh!

The man in the photobooth is Rab C Nesbitt. Earl of alopecia and king of the combover, he was also occasional point man for Hamlet cigars (1). And his hair loss problem is growing.

There are different patterns and types of hair loss. Two of the most common are androgenic alopecia, or male pattern hair loss; and alopecia areata, an auto-immune condition characterised by the sudden appearance of circular bald patches which can emerge on the scalp or anywhere else on the body.

The global epidemiology of hair loss is not well documented but the incidence appears to be rising, and the condition is emerging at earlier ages. The multiple interacting drivers include dietary factors and subsequent endocrine and immunological changes. Reversing these drivers using pharmaco-nutrition is not a cure-all, but should help more of us hold on to our hair for longer.

Alopecia areata is increasing (ie 2, 3), and the same is reportedly true for other forms of hair loss. One likely cause is the rising incidence of obesity, which among other things accelerates the ageing of the hair follicles (4); but a number of other environmental factors appear to be involved also.

As we have seen with other conditions such as allergy and IBD, all-cause hair thinning may be increasing in the West but seems to be increasing more rapidly, from a lower stating point, in other parts of the globe. This kind of pattern immediately makes one think of negative dietary trends, where the West leads and the rest of the world generally follows.

The West. 

A 1998 community-based USA study (5) found male pattern hair loss (MPHL) affecting 42%, ranging from 16% of males aged 18-29 to 53% of males aged 40-49. A 2000 Norwegian community study of males aged 25-50 reported 63% with hair loss, a quarter of whom reported moderate to severe loss (6), and contemporary figures for non-autoimmune hair loss are in the same area (7). In 2018, anecdotal reports emerged suggesting that hair loss in the West was increasing and that Millennials (ages 22-37) were particularly affected (8).

The East. 

In 2010, a large China community study (9) found MPHL in 21.3% in males aged 18-59, a figure significantly lower than Caucasians and similar to Koreans at that time. Since that time hair loss of all types is reported to have increased in China (10-12), as it has in South Korea (13-15), in both cases particularly affecting younger adults. In South Korea, hair loss in young adults has even become an election issue (16).

A 2018 Chinese survey of male and female university students aged 18-24 recorded slightly over 60% with some degree of hair loss (10-12), and a 2015 Turkish study of alopecia in high school students aged 12-18 reported incidence of hair thinning in 37% (17). 

What might these trends signify?

If the reports of increased incidence and earlier onset of hair loss are substantiated, the alopecias start to look like yet another non-communicable degenerative condition – so let’s take this further.  I am aware of ten potential contributory factors. All of these have increased over the last two generations, and the first nine are affected by diet. The tenth refers to modern pollutants.

1. The incidence of autoimmune diseases has increased (18), and several of these are associated with a higher risk of developing alopecia areata (19-21).

2. PCOS increases the risk of female pattern hair loss and androgenic alopecia (22, 23). The increasing incidence of PCOS among females in some regions (24) is probably therefore contributing to overall alopecia figures.

3. The average age of puberty has fallen in both sexes (ie 25-27), which would be expected to advance the onset of androgenic alopecia.

4. Chronic low-grade inflammation is thought to be involved in hair loss in both sexes (27-32). This is likely exacerbated by recent dietary shifts, which have shifted the balance of anti-and pro-inflammatory dietary factors in favor of the latter (33-37). 

5. Falling intakes and/or reduced bio-functionality of iodine (38, 39) and selenium (40, 41) have likely contributed to rising rates of hypothyroidism (42, 43), which is linked to hair thinning in both sexes.

6. Diabetes and its metabolic constituents have been linked to increased central scalp hair loss in women (44, 45) and to androgenic alopecia (46-49). The remarkable increase in NIDDM may therefore be another driver of hair loss.

7. Significant differences in hair volume between identical male twins with androgenic alopecia (50) indicate a role for external (51) and epigenetic (52) factors involving histone modification (51-54).

8. Histone methylation and acetylation rates are affected by the availability of dietary methyl groups and intakes of prebiotic fiber respectively, and by ancillary dietary compounds including isothiocyanates, polyphenols, carotenoids, omega 3 HUFA’s, vitamin D and others which impact mRNA expression (55).

9. The recent dietary shift from basic produce to ultra-processed foods has reduced dietary intakes of all the above compounds; the phytonutrient density of ultra-processed foods is reduced by dilution with sugars, starches and plant oils (56).

10a.    Exposure to endocrine-disrupting chemicals (EDC’s) has increased (ie 57). There appears to be a relationship between EDC exposure and advanced age of puberty, but it is a highly complex one (58, 59); the effects are gender- and compound-specific, and depend on the exposure window. 

10b.    There may also be a link between EDC exposure and PCOS. EDC’s bind to and alter hormone receptors including estrogen, progesterone, androgen, and glucocorticoid receptors (60, 61); and there is evidence that pre-natal exposure may predispose to PCOS in later life (61).

10c.    EDC’s are routinely found in hair and urine samples, even in children (57). They even occur in a significant number of hair products (63), which deliver high concentrations of these compounds directly to the scalp. 

So much for potential causes of hair loss. Let us move on to consider treatments.

The limitations and adverse effects of the two pharmaceutical staples, minoxidil and finasteride, are well known. The most recent oral treatment for alopecia areata Olumiant (baricitinib), a JAK inhibitor originally designated for the treatment of RA, comes with a boxed warning for serious infections, mortality, malignancy, major adverse cardiovascular events and thrombosis. While these adverse effects may be a reasonable trade-off against a painful and crippling disorder such as severe RA, they seem excessive in the context of hair loss.

Nutritional remedies for hair loss include various B vitamins, vitamin D, trace elements, amino acids, garlic gel, marine proteins, capsaicin, melatonin and onion juice. All have some evidential support, albeit weak (64), but the vitamins, trace elements and amino acids can only rectify deficiency states.

Herbal remedies with some evidence behind them include Curcuma aeruginosa, Trifolium pratense, Panax ginseng and Serenoa repens. All of these are thought to act primarily via the inhibition of 5α-reductase (65), with all the limitations that this mechanism entails.

Recent research underpins the role of PGD2 and its receptors GPR44 and PTGDR in alopecia. PGD2, a pro-inflammatory mediator (66), is elevated in bald areas of the scalp in males with androgenic alopecia, and reduces anagenic hair lengthening (67). 

The selective GPR44 receptor antagonist Septiprant was relatively ineffective as an anti-inflammatory agent in seasonal allergic rhinitis (68) and failed as a hair loss treatment (69). 

However, an extract of Leea indica (Bandicoot berry) leaves with inter alia PGD2 synthase inhibitory activity showed enhanced hair growth in a pre-clinical model (70). More convincingly, an alkaloid-free extract of Ageratum conyzoides (Billygoat Weed), which inhibited PGD2 synthesis, 5-alpha reductase and possibly CB-1, increased hair growth in males and females in two clinical trials (71, 72). The second of these was reasonably robust, being randomized, double-blinded and placebo-controlled.

The microbiome is also, inevitably, involved.

Colonic dysbiosis plays a crucial role in many disease states, both in the gut and in almost all other tissues, to the extent that a fibre-depleted diet is associated with a 30% increased risk of early death (73). Colonic and dermal dysbiosis alter systemic and local immune responses, and are suspected of promoting the development of skin diseases including atopic dermatitis, psoriasis, acne vulgaris, dandruff and skin cancer (74, 75). We should consider adding hair loss to that list.

In some specific cases, the mechanism linking colonic dysbiosis and hair loss is relatively well characterized. Colonic dysbiosis characterized by overgrowth of Lactobacillus murinus reduces biotin in the gut, and causes alopecia (76). Biotin deficiency causes alopecia in pre-clinical models (74) and humans (77), giving these findings coherency. Taking a blended prebiotic supplement to correct dysbiosis (78) and at the same time exert systemic anti-inflammatory effects (79), will therefore likely help to slow or stabilize some cases of hair loss.

The dermal microbiota is also significant, and estimated at 10 to the 12^th (80, 81). The hair follicle environment contains not only stem cells and immune cells, but also a complex population of bacteria, fungi and bacteriophages. A healthy microbial profile in the follicle plays a role in setting appropriately low (physiological) levels of inflammatory stress, involved in homeostasis and innate immune defense (80, 81). Dermal dysbiosis can upset this delicate balance.

The bulb and bulb regions are immune-privileged (82, 83). Higher levels of pathogenic taxa in the hair follicle disrupt immune-privilege (84, 85), contributing to a pro-inflammatory state in the scalp (85-86) which can damage or destroy the follicle (86). This is in line with recent findings that chronic inflammatory stress is involved in alopecia areata (87) and androgenic alopecia (88, 89) 

The above suggests that the modern pro-inflammatory diet, and the related plague of pro-inflammatory obesity are likely contributing to the noted increases in hair loss. If so, a shift to a broadly anti-inflammatory diet should be hair-protective; and there are some data which support this (90, 91).

Diet, colonic dysbiosis, dermal dysbiosis and follicular health all appear, indeed, to be inter-linked. 

There is some evidence that colonic dysbiosis may, possibly by inducing gastrointestinal and then systemic inflammation and also possibly via more direct gut-dermis connections, increase inflammatory stress in the hair follicle and damage hair growth (84, 85, 89, 91). Colonic species such as Clostridium difficile (92), as well as dermal species including the yeast Malassezia (93) and the gram-positive bacterium Propionibacterium acnes (94), have all been implicated in hair loss.

The link with Clostridium difficile is an odd one. It emerged from a clinical group which was using fecal transplants to treat patients with severe gut disease. In two patients who also had alopecia, the treatment resulted in hair regrowth (92). This is hardly a user-friendly cure for balding. 

Given their shared embryological origins, the structural/functional similarity of gut and skin and hand-mouth microbial transfer, the possibility of a more direct relationship between colonic and dermal microbiota cannot be excluded (89, 92, 95, 96). This provides another rationale for utilizing prebiotic fibers to re-establish a healthy colonic microbiota. 

Metabolic disease, so common today, is also involved.

The skin microbiota is markedly affected by diabetes (97), and diabetes and its metabolic components have been linked to an increased incidence of hair loss (45-49). More recently, Type 2 diabetes was associated with significantly increased central-scalp hair loss in women (45), an association which was unaffected by diabetic treatment. 

Diabetes causes immune dysfunction (98), chronic inflammatory stress (99) and altered skin pH (100) and microbiota (97), providing multiple possible mechanistic links to alopecia. Here again, the role of prebiotic fibers in supporting glycemic control (101) may be relevant. Given the established use of non-medical tools (reduced intakes of digestible carbohydrate and increased levels of physical activity) in improving and reversing Type 2 diabetes (102-109), with resulting normalisation of cardiovascular, metabolic and hepatic parameters (108, 109), these lifestyle strategies may impact positively on hair growth also. 

Dietary shift involving a move away from basic produce toward increasing consumption of ultra-processed foods (110-112) is associated with rising rates of most if not all of the non-communicable chronic degenerative diseases (112-117). This shift has reduced intakes of key anti-inflammatory nutrients such as the polyphenols and omega 3 HUFA’s, contributing to wide-spread chronic inflammation (118-120) and to a situation where poor diet has become the leading cause of death world-wide (120).

This excessively inflammatory background has been shown to impact adversely on immune-privileged processes in males and females (122, 123), and it is reasonable to assume that similar effects may be present in the immune-privileged hair follicle also. This would be expected to increase the tendency to anagenic curtailment and androgenic alopecia (124), as mentioned earlier. 

Alopecia has likely always been with us, as shown by the fact that other non-human primates may present with alopecia (125-127), and genome-wide association studies which have identified susceptibility loci accounting for roughly two fifths of the heritability of androgenic alopecia (128).  However, multiple factors associated with the modern diet and lifestyle may be contributing to an increased incidence of androgenic alopecia and alopecia areata over and above the genetically disposed. This is hinted at in many of the references cited above.

By inducing chronic inflammatory stress, dysbiosis, and metabolic and epigenetic disruption, the modern diet and lifestyle increase the incidence of non-communicable degenerative conditions; and it may well be useful to consider the alopecias within this context. Reducing these harms via restoration of pre-transitional nutritional and therefore metabolic and epigenetic profiles will likely reduce the numbers of non-genetically determined cases of hair loss.

• An amended version of this post was published as a scientific paper. ‘Is Alopecia a Non-Communicable Degenerative Disease?’ Clayton P, Hair Ther. Transplant. (2022), 12(1)

Next week: The Book of Deuteronomy, and a new insight into cancer.

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