“Let food be thy medicine and medicine be thy food” is a proverb originally attributed
to Hippocrates, the father of medicine. Hippocrates was among the first to establish
the role of diet in health and disease. He proposed lifestyle modifications, including
dietary factors, to prevent or treat diseases, and yet, there is hardly another field
with so much prejudice, misconception, and debate as diet and health, let alone hair
health. In his publication, “How Doctors Think,” Jerome Groopman from Harvard Medical
School focuses on the thinking errors in medicine and among them succinctly states
that “Aside from relatively common dietary deficiencies – lack of Vitamin B12 causing
pernicious anemia, or insufficient Vitamin C giving rise to scurvy – little is known
about the effects of nutrition on many bodily functions.”[1]
The fact is that quantity and quality of hair are closely related to the nutritional
state of an individual. Normal supply, uptake, and transport of proteins, calories,
trace elements, and vitamins are of fundamental importance in tissues with a high
biosynthetic activity such as the hair follicle. Because hair shaft is composed almost
entirely of protein, namely, keratin, the protein component of diet is critical for
the production of normal healthy hair. The rate of mitosis is sensitive to the calorific
value of the diet, provided mainly by carbohydrates. Finally, a sufficient supply
of vitamins and trace metals is essential for the biosynthetic and energetic metabolism
of the follicle.
Since an important commercial interest lies in the nutritional value of nutritional
supplements, a central question that arises is whether increasing the content of a
seemingly adequate diet with specific amino acids, vitamins, and/or trace elements
may further promote hair growth and quality. Pharmacy aisles and Internet drugstores
are full of nutritional supplements promising full, thick, luscious hair for prices
that range from suspiciously cheap to dishearteningly exorbitant. It would appear
that, unless hair loss is due to a specific nutritional deficiency, there is only
so much that nutritional therapies can do to enhance hair growth and quality.
Bahta et al.[2] originally cultured dermal hair papilla cells (DPCs) from both balding
and nonbalding human scalps and demonstrated that balding DPCs grew slower in vitro
than nonbalding DPCs. Loss of proliferative capacity of balding DPCs was associated
with changes in cell morphology, expression of senescence-associated markers of oxidative
stress as well as DNA damage, and decreased expression of markers of cell proliferation.
This suggests that balding DPCs are particularly sensitive to environmental stressors
such as cigarette smoke[3] and ultraviolet radiation (UVR).[4] These findings, along
with the existing unmet needs in the management of androgenetic alopecia beyond the
current evidence-based therapies,[5] suggest that further pathogenic pathways contributing
to hair loss may be relevant and represent opportunities for further therapeutic strategies
to include nutritional therapy.
Ingesting keratin does not help hair growth, as the protein cannot be broken down
and absorbed. Therefore, constituent amino acids, from which the hair follicle can
build up the keratin, need to be consumed. Cysteine is catabolized in the gastrointestinal
tract and blood plasma, whereas cystine travels safely through the gastrointestinal
tract and blood plasma and is promptly reduced to two cysteine molecules upon cell
entry. Originally, the role of cystine in the production of wool was investigated
starting in the 1960s, and it was found that enrichment of even what appeared to be
a normal diet with the sulfur-containing amino acids cysteine and methionine increased
wool production in sheep.[6
7]
When considering which dietary supplements could be used for the improvement of hair
growth in humans, L-cystine in combination with B-complex vitamins was, therefore,
considered. Starting in the early 1990s, studies on the effect of dietary supplements
containing L-cystine, medicinal yeast (a rich natural source of amino acids and B
vitamins), thiamine (Vitamin B1), and pantothenic acid (Vitamin B5) were performed,
showing improvement in the trichogram, in hair swelling as a criterion for hair quality,
and in the tensile strength of the hair fiber.[8
9] Eventually, Lengg et al.[10] performed the first double-blind, placebo-controlled
study in women with telogen effluvium and demonstrated that the L-cystine, medicinal
yeast, thiamine, and pantothenic acid-based dietary supplements increased and normalized
the anagen hair rates within 6 months of treatment, while placebo did not. Combining
with topical minoxidil in the treatment of androgenetic alopecia was predicted to
add extra benefit, since it had previously been shown in whole hair follicle cultures
that minoxidil not only increases the incorporation of thymidine as a marker of cell
division but also leads to increased uptake of cysteine by the hair follicle.[11]
This was underlined by the fact that regression analysis in the study performed by
Lengg et al. showed that the presence of androgenetic alopecia in women with telogen
effluvium did not negatively affect treatment efficacy.
In this issue, Gadzhigoroeva et al. finally provide the evidence for the superiority
of a combination therapy of female androgenetic alopecia (FAGA) with a nutritional
treatment (Panto[vi] gar®, Merz Pharmaceuticals GmbH, Frankfurt, Germany) and topical
minoxidil over minoxidil monotherapy.
Topical minoxidil solution is the drug with the highest level of medical evidence
and first-line treatment for FAGA, though its efficacy has limitations in terms of
reducing hair loss or inducing new hair growth. The limited success rate of topical
minoxidil for the treatment of FAGA means that further pathogenic pathways must be
taken into account. Clinical and investigative advances have helped us to understand
some of the pathogenic steps, leading to FAGA: besides genetic imbalance and peculiarities
of sex hormone metabolism, additional pathogenic factors are suspected such as resident
microbial flora, endogenous and exogenous stress, microinflammation, and others.[12]
An experiment performed on C57BL/6 mice, which developed hair loss when exposed to
cigarette smoke, demonstrated that this effect could be prevented by the oral administration
of N-acetylcysteine, an analog and precursor of cysteine and reduced glutathione,
as well as cystine, the oxidized form of cysteine, in combination with Vitamin B6.[13]
The effect was interpreted by the authors as to be possibly related to the glutathione-related
detoxification system, an enzymatic antioxidant. Ultimately, the DPCs in androgenetic
alopecia are understood to have a higher sensitivity to oxidative stress.[14]
Obviously, the hair, like the skin, is exposed to a variety of noxious environmental
factors, of which UVR has been among the most studied in the skin. While the consequences
of sustained UVR on unprotected skin are well appreciated, mainly aging and photocarcinogenesis,
the effects of UVR on the hair are less understood. However, clinical and morphologic
observations, as well as theoretical considerations, suggest that UVR does have some
negative effects on hair growth.[4]
Finally, Hengl et al.[15] from Merz Pharmaceuticals GmbH, Frankfurt, Germany, provided
the in vitro evidence that L-cystine and thiamine are essential for proliferation
of normal human epidermal keratinocytes (NHEKs) under growth-limited conditions mimicking
telogen effluvium and also exert an UVR-protective effect on growth-limited NHEKs
in vitro as a model for environmental stress.
Hand in hand with the growing evidence for the modes of action and clinical efficacy
of L-cystine and B Vitamin-based nutritional treatment for telogen effluvium, the
results of the presented clinical study ultimately represent a proof of concept for
the superiority of combination treatment versus monotherapy of FAGA.