Review article
Open Access
A Scientific Hypothesis on the Role of Nutritional
Supplements for Effective Management of Hair Loss
and Promoting Hair Regrowth
Rajendrasingh Rajput*
Hair Transplant Surgeon, Member ISHRS, IAT, & AHRS India
*Corresponding author: Rajendrasingh Rajput, Hair Restore, 401 Saffire, 65B, Linking Road, Santacruz west, Mumbai 400054, Tel: +91-
9821308411, E-mail:
@
Received: March 28, 2018; Accepted: May 04, 2018; Published: May 11, 2018
Citation: Rajendrasingh Rajput (2018) A Scientific Hypothesis on the Role of Nutritional Supplements for Effective Management of Hair Loss and Promoting Hair Regrowth. J Nutrition Health Food Sci 6(3): 1-11
DOI:
10.15226/jnhfs.2018.001132
Abstract
Our quest for establishing a cause and effect relationship has lead
us to accept that only androgens and DHT causes hair loss. However
there are various other internal and external factors resulting in hair
loss due to dysregulation of the hair growth cycles. There are non
hormonal factors that influence and carry out metabolic interactions
maintaining a cellular environment to ensure the intricate balance
of hair growth cycles. Oxidative stress generated by ROS (Reactive
Oxygen Species) from external exposure to pollution, smoking,
pesticides in foods, contamination of soil, water, etc. as well as
excessive ROS formation due to internal metabolic derangements,
can lead to hair loss. Vitamin and mineral deficiencies have been
clinically detected in hair loss patients and are known to alter the
immune response. Though the prevalence of nutritional deficiencies
is common these are covert deficiencies. The nutrient deficiencies
cannot always be detected clinically as the deficiencies are masked
and compensated by self regulating processes of redistributing the
utilization of nutrients in the body, arresting hair growth during stress,
sickness, exertion, recovery, etc. which we know as telogen effluvium,
and by novel mechanisms like autophagy. In deficiency states body
conserves the nutrients by restricting hair growth. It is worthy to note
that apparent deficiency of a single nutrient has a cascading effect
on optimum utilization of multiple other nutrients and functioning
of other body systems. When we desire to stimulate or ensure hair
growth it is logical to ensure a supply of building blocks, which are the
necessary nutrients, in order to support cell division and growth. We
have been investigating hair loss all the time. Let us now change our
perspective and direct our efforts on how to strengthen the hair roots
to withstand the onslaught of damage and enhance hair growth. In the
present review, a low dose comprehensive cyclical nutrient therapy,
for hair growth utilized in our practice is included. Here we propose
the hypothesis and discuss the scientific basis and mechanism of how
to achieve hair growth with the use of nutritional supplements.
Introduction
Common approach of treating any condition by eradicating
the cause has lead to a singular ideology of treating hair loss
only with DHT (dihydrotestosterone) blockers. Studies reporting
benefits of nutritional supplements in hair loss management
have dismal support due to the previous scientific belief that
DHT and androgens causes hair loss. One is perplexed as to how
can nutritional supplements counter DHT and correct hormonal
imbalance? Recent scientific evidence confirms that DHT acts by
promoting the accumulation of free radicals in androgen sensitive
cells which then leads to the release of hair growth inhibiting
factor TGF ß1, resulting in hair loss. Direct experimental results
show that the accumulation of free radicals or ROS (Reactive
Oxygen Species) in response to DHT can be blocked successfully
by the use of free radical scavengers, (antioxidants) in androgen
sensitive cell cultures [1-5]. There is also more evidence on how
nutrients can strengthen the hair roots and promote growth. Let
us look at it from a new perspective, with an open mind.
Multiple Factors Other than DHT Can Lead to Hair
Loss
The understanding of hair loss is changing. At present hair
loss is agreed to be a multifactorial combination of various
intertwined mechanisms [6, 7]. We previously believed that
hair loss was genetic, but it can occur without any genetic
predisposition or family history [8]. We believed hair loss was
caused by androgens, but it is known to occur even if androgen
levels are normal and not raised [9-12]. Several research workers
have doubted the present theory of androgenetic alopecia and
insisted on the need for a better insight into the understanding
of the mechanism of hair loss [13-15]. Due to lack of consistent
evidence of family history or raised androgens, the condition is
no more referred to as androgenic alopecia but now referred to
as Male Pattern Hair Loss (MPHL) and Female Pattern Hair Loss
(FPHL).
Patterned Hair Loss Reported in Androgen
Insensitivity and Hypogonadism
Cousen and Messenger have reported patterned hair loss in
a patient with complete androgen insensitivity syndrome, Orme
and Cullen observed it in patients with hypogonadism while
Birch and Norwood have recorded patterned hair loss occurring
before puberty [16-19]. The clinical observations of these
research workers challenge the age old consideration that DHT
or androgens are the sole contributing factor to patterned hair
loss or androgenic alopecia [16]. There are many predisposing
factors other than androgens, which weaken the follicle making
it sensitive to normal levels of androgens and leading to hair loss.
Can correction of these factors and strengthening of the follicles
restore hair growth without using anti androgens? We have
reviewed and explored this option.
Androgen Levels in Hair Loss Patients a Rarely
Raised
It has been found that raised androgen levels are rarely
detected in hair loss patients. Several research workers have now
proposed and agreed that not the raised androgens but various
factors causing increased sensitivity of the hair follicle cells to
normal androgens, leads to poor hair growth and baldness [20-
22]. Clinically there is another dilemma to deal with. Most people
think they are going bald because the hair is falling and insist that
the hair fall should stop. But scientifically it is the lack of fallen
hair being replaced with new hair or the lack of continuation of
hair growth cycles that leads to baldness.
Under Unfavourable Conditions Follicles Remain
in Prolonged Resting Phase
The interruption of hair growth cycles, premature telogen and
subsequently the follicles remaining in a continued, prolonged
telogen or resting phase, is responsible for gradual progressive
thinning and baldness. When the conditions are not favourable
or ideal for growth, the hair follicles continue to remain in resting
phase and do not come back to the anagen. This new empty follicle
stage described as ‘kenogen’ has been recorded and described by
Rebora and Guarrera [23, 24].
Table 1: Some of the factors causing hair loss due to dysregulation of
hair cycle or unfavourable conditions for hair growth without any role
of DHT
Internal Factors |
External Factors |
Iron, calcium deficiency |
Smoking, Hookah, Passive smoking, |
Vit. A, C, E, D deficiency |
Tobacco, Pan, Beetle nut, Tea |
Overuse of Vit. & Supplements |
Alcohol |
Thyroid hypo or hyper |
Hard water areas, |
Side effect of medications |
Stress, Lifestyle, |
Metabolic disease, diabetes, gout |
Lack of sleep, |
Siborrhoeic scalp |
Exposure to excess heat or cold |
Prolonged illness |
Dryness of the Scalp |
Crash Dieting |
Exposure to Dust, Pollution, |
Poor fluid intake |
Continuous Air Conditioning |
Fat free Diet, |
Exposure to chemical fumes |
High Protein Diet |
Mining areas, Construction work |
Derangement of liver function |
Pressurised Airline Cabins |
Derangement of Kidney function |
Over use of Hair Products |
Post Pregnancy Hair loss |
Blow drying |
Various internal and external factors can make the cellular
environment unfavourable for hair growth. These factors cause
an imbalance or dysregulation of the hair growth cycles. Factors
causing hair thinning and hair loss without the involvement of
the DHT mechanism are listed in table 1. The factors cause non
hormonal hair loss. These non hormonal factors are on the rise.
These various factors also weaken the hair follicle and affect the
dermal papilla cells making them sensitive to normal androgen
levels and leading to hair loss [25]. Researchers today agree
that, hair loss could be genetic, androgenic, immune mediated,
inflammatory, nutritional or due to internal or external factors
leading to slowing down and dysregulation of the hair growth
cycles [26-28]. We shall try to elaborate on how nutritional
support can help in growing more hair and fighting hair loss.
Approach to the Hair Problem
There are two sides to having good hair. Either reduce the
hair loss or promote more hair growth. For the treatment of
falling hair you require DHT blockers, anti androgens, anti
inflammatory, steroids or other medications. These remedies are
not a permanent cure, these are only supportive for better hair
growth and need to be continued for a long time. Effective hair
growth is seen only as long as these remedies are being used. The
moment you discontinue the treatment you begin to suffer hair
loss again. Therefore the treatment has to be continued for a very
long time, probably lifelong, therefore, increasing the possibility
of side effects. There is a need to consider, weather we can achieve
hair growth without the use of DHT blockers and offer remedies
which are safe for long term use. The parody is that though DHT
blockers are recommended for treatment of practically every
patient of hair loss, the levels of DHT or other androgens in these
patients are rarely found to be raised [26]. The clinical levels of
DHT or androgens do not correlate with the grades, severity or
the progress of hair loss seen clinically [26].
New Perspective to Strengthen the Follicles and
Promote Growth
Researchers in this field have now concluded that not the
raised DHT or androgens but the increased sensitivity of the hair
roots is responsible for hair loss [22-24]. We therefore, propose
a change of perspective. Instead of fighting the hair loss with
long term use of DHT blockers and other medications, having
possibility of side effects, why not direct our efforts towards
strengthening the hair roots and promoting better growth. Good
strong, robust hair roots can stand withstand any cause. At any
given time 10-12% of the hair is in telogen or fall phase and 1%
is in catagen. We are missing the fact that remaining 87-89% hair
which is not in these stages is willing to grow. All this hair needs
initiation and propagation of anagen. Hair regrowth can be seen,
if we provide stimulation for hair growth, nutritional support
and maintain scalp hygiene. We have found this approach to
be clinically effective in our practice of hair restoration and we
hereby try to share the scientific basis of this therapy.
Oxidative Stress in Hair Loss
Hair loss is now being seen in younger age groups, which in
our experience is due to rising competitive life, stress, lack of sleep,
exposure to pollution, wrong food choice, erratic lifestyle and
some of the additional causes as listed in table 2. All these causes
are a source of generating free radicals or ROS (Reactive Oxygen
Species) in the body. The role of ROS and oxidative damage in
hair loss was first recognised after detecting raised levels of nitric
oxide, lipid peroxidation and glutathione derivatives in hair loss
patients [29-32]. These are the markers or indicators of oxidative
damage to the cells. Such oxidative damage can be successfully
countered by use of free radical scavengers and antioxidants, in
order to make the internal environment favourable to achieve
hair growth.
Table 2: Some of the causes of hair loss seen at early age
No. |
Causes |
1 |
Competitive Lifestyle Stress, lack of sleep, |
2 |
Lack of sports and good breathing exercise |
3 |
Poor eating habits – wrong time, wrong choice of food |
4 |
Gym supplements, Whey Protein, Overuse of Vitamins |
5 |
Fad Diets – High Protein, No Carbohydrates, Fat free Diet |
6 |
Restricted eating has become a social practice |
7 |
Attraction for Sugar foods and processed foods |
8 |
Increased pollution in air, water and atmosphere |
9 |
Depleted Ozone layer exposing to UV rays |
10 |
Hormones, antibiotics, in meat |
11 |
Fertilizers, insecticides, pesticides, fast growing hybrids |
12 |
Endocrine Disrupting Chemicals, EDCs in food products |
Antioxidants Can Counter the Action of DHT
While working on androgen sensitive cell cultures, Inui,
Fukuzato and Itami found that inhibition of hair growth by DHT
occurs through release of hair growth inhibiting factor, TGFß1
[33-35]. Interestingly, the research and analysis continued by
Hee, Shin, Yoo and Inui into the secretion of TGF ß1 in response to
DHT discovered that the effect is mediated through accumulation
of ROS or free radicals in androgen sensitive cells [36, 37]. DHT
leads to accumulation of ROS in the cells which then leads to the
release of TGF ß1. In this experiment it was further discovered
that the use of ROS scavengers successfully blocked the release
of hair growth inhibiting factor TGF ß1, preventing the inhibition
of hair growth [36, 37]. The work establishes a scientific basis
for use of free radical scavengers and anti oxidants instead of
anti androgens and enzyme blockers to prevent the action of
DHT. From these experiments it can therefore be concluded that
accumulation of free radicals has a definitive role in mediating
the effect of DHT and use of antioxidants can provide protection
to sensitive hair roots from damage inflicted by DHT.
ROS Alters Immune Response and Promotes
Inflammation
The role of immunity and micro inflammation in hair loss
has been established through the publications of Trueb and
scientific studies by Kubibidila, Yu et al. who have determined
the alteration of immunity in malnutrition [38, 39]. Freker and
King have recorded the reprogramming of the immune system in
zinc deficiency such derangements in immunity can trigger and
sustain a continuous mechanisms of hair loss [40].
ROS Bind and Changes Immune Signature of
Intracellular Proteins
Details of another mechanism leading to altered immune
response, autoimmune response and propagation of
inflammation by ROS have come from the work of Kalkan, Seçkin
et al. [41]. Their research has postulated that, after entering
inside the cells, the ROS form several covalent bonds by binding
and combining with the endogenous, intracellular proteins in
the cells. The newly created bonds change the structure of the
intracellular proteins. This change in the molecular structure
alters the immune recognition pattern of the proteins. As a
result the normal proteins are now recognised as new antigens,
making them targets of immunity, autoimmune reactions, and
inflammation. The altered cell response and metabolism, lead to
release of intracellular cytokines, interlukin-1alpha, interlukin-
1beta, which are known to inhibit hair elongation [34, 35]. This
response is the same as which is generated by Monocyte chemo
attractant protein-1 (MCP-1) and chemokines which have been
identified to be active in hair follicles and sebaceous glands of
patients having androgenetic alopecia [42, 43]. Thus there is
another mechanism that supports scientific basis and rationale,
for the use of antioxidants to neutralize the ROS in hair loss
management. Use of antioxidants and free radical scavengers can
prevent a cascade of events and protect the cells from various
mechanisms of repeated continuous damage that leads to hair
loss [41].
Hair Loss Due to Pollution
Exposure to free radicals and ROS has now increased through
rising air pollution along with contamination of food and water.
Sensitive scalp syndrome was defined by Fabio Rinaldi who studied
the effects of pollutants on the scalp, and it’s relation to hair loss
[44]. Philpott demonstrated that pollution increases oxidative
stress leading to increased hair shedding, by a mechanism similar
androgenic alopecia [25]. The particle size of the pollutants itself
triggers oxidative stress in addition to combination of ROS which
bind to the particles and reach deeper into the cells. Continued
exposure to pollutants, creates chronic low grade inflammation
leading to fibrosis and hair loss [45]. Our previous published
work has described the mechanism in detail and reported
clinical benefit and new hair growth, with use of antioxidants
and nutritional supplements in the management of hair loss due
to pollution [46]. The study reported reduced itching, dandruff,
correction of dryness of scalp, burning and pain in the hair
roots by the end of 4 months. While trichoscopy showed 9-12%
improvement in density and 5-7% improvement in hair calibre
[46]. The review of the current research demonstrates that, use of
antioxidants can prevent the propagation of inflammation, avoid
altered immune response, protect the hair follicles from damage,
control hair loss and promote hair regrowth [46].
Role of Nutrition in Hair Loss Due to Smoking
Studies on oxidative stress and smoking by Trueb highlight
release of cytokines resulting in micro inflammation, peri
follicular fibrosis and hair loss caused by direct pro oxidant effect
of smoking [47]. These effects can be successfully countered
with the use of antioxidants. Studies by Alberg, Dietrich et al. and
Bloomer have confirmed reduced levels of antioxidants in smokers
[46, 48, 50]. D’Agostini et al. showed that the effects smoking and
cell apoptosis could be treated with supplements of L-cysteine
and Vit B6 [51]. Galan et al. found reduced serum concentrations
of beta-carotene, vitamins C and E, zinc and selenium in smokers
[52]. The work by all these researchers supports the use of
antioxidants, vitamins, minerals and nutritional supplements, in
hair loss patients with history of smoking. Though smoking is
known to make the follicles sensitive to DHT, the damage cannot
be prevented by the use of DHT blockers. As reported in an earlier
publication, we have successfully reversed hair loss in smokers
and in passive smokers, with the use of low dose antioxidants,
nutrients and minerals which strengthen the hair follicles and
successfully promote regrowth of the thin, weak, slow growing
hair [53]. The study reported 28% improvement in hair counts,
8% improvement in hair calibre and with 50% reduction in villus
hair counts within 4 months.
Role of Nutrition in Immunity and Inflammation
Chronic micro inflammation and altered immune response
are an established mechanism of hair loss [38]. Individual studies
confirm the importance of antioxidants, vitamins and minerals
in maintaining immunity and preventing inflammation. Eugenio
Mocchegiani pointed out that micronutrients like zinc, copper
and selenium maintain immunity, control inflammation and also
preserve antioxidant activity of the cells [54, 55]. Thurnham
warns that micronutrients have interactions, with other nutrients,
diet, non-nutrients, prescribed medicines, and lifestyle factors
like smoking, tea and alcohol, with leading to hair loss [56]. The
study emphasises use of nutrient supplements and minerals to
maintain immunity and prevent inflammation [56]. The influence
of Vitamin C and Vitamin D on immunity, T cells phagocytosis,
formation of antibodies, autoimmune response and resistance
to infection was reported by Ströhle, Wolters and Hahn [57, 58].
They also confirmed the importance of micronutrients as essential
components of transcription factors, epigenetic modulators,
enzymes, cofactors and structural links in antioxidant systems
for normal cell functions [57, 58]. Zinc plays an important role
in hair growth [59, 60]. Studies by Freker have noted that zinc
deficiency can initiate apoptosis and programmed cell death by
inducing secretion of glucocorticoids [61]. Thus there is adequate
data to indicate role of nutrients and minerals in maintaining the
immune status and preventing micro inflammation which are
known mechanisms leading to hair loss.
Role of Vitamins in Hair Growth
Reichrath, Lehmann, et al. have suggested in their study
that, due to the regulatory role of Vitamin A and Vitamin D in
epithelial integrity and immunity, these should be considered
as hormones [62]. The hair-inductive capacity of dermal papilla
cells is directly modulated by Vitamin D3 as proven in the
research of Aoi, Inoue, et al. [63]. Vitamin D should therefore form
an integral part of all hair growth treatments. Beoy, Woei and
Hay reported 34% improvement in hair counts due to effective
inhibition of lipid peroxidation and reduction of oxidative stress
from the combined use of tocotrienol and alpha tocopherol [64].
Kwack and Shin reported hair growth and hair elongation by
ascorbic acid derivative mediated release of Insulin like Growth
Factor, IGF 1 [65]. The scientific facts suggest that providing
adequate vitamins and avoiding deficiency states can play a role
in preventing hair loss and achieving new hair growth. Table 3
summarises the functional role of individual vitamins, minerals
and nutrients which contributes towards better hair growth and
helps in hair loss management.
Table 3: Role of various nutrients in hair growth
No |
Vitamin Mineral Nutrient |
Role through which it benefits Hair growth |
1 |
Biotin – Vitamin B7 |
Hair growth & Dry skin |
2 |
Nicotinamide – Vitamin B3 |
Anti inflamatory |
3 |
Cyanocobalamine – Vitamin B12 |
Prevents Anemia |
4 |
Pyridoxin HCl – Vitamin B6 |
Prevents Anemia & water retention |
5 |
Vit C |
Antioxidant, Collagen synthesis, |
6 |
Vit A |
Antioxidant, |
7 |
Vit.E |
Protects cell membrane from free radicals |
8 |
Folic acid – B9 |
Prevents Anemia, Required for DNA synthesis |
9 |
Vit D3 |
Calcium Metabolism |
10 |
Tyrosin |
Improves Hair growth |
11 |
Lysine mono HCl |
Hair growth in telogen effluvium |
12 |
L – Ornithine |
DNA & protein synthesis |
13 |
L - Arginine |
Rapid cell division, repair & endothelial stability |
14 |
Taurine (2 aminoetahesulphonic acid) |
Protects from exercise induced & other toxicity |
15 |
Glycine |
Precursor to bio synthesis of various proteins |
16 |
L –Selenomethionine / Sodium Selenate |
Rapidly absorbed antioxidant, Elasticity, UV damage& aging |
17 |
Sulphur – Methyl sulphonyl methane |
Prevents brittle and dry hair |
18 |
L – Histidine hydrochloride |
Protein Metabolism |
19 |
Ferrous Fumerate |
Prevention of Anemia |
20 |
Calcium D – Pantothenate – B5 |
Hair color & premature aging, CoA & TCA cycle |
21 |
Magnesium hydroxide |
Calcium, Potassium, Parathyroid & Insulin Metabolism |
22 |
Cupric oxide / sulphate |
Hair elasticity, pigmentation & skin tone |
23 |
Zinc Gluconate / Zinc sulphate (25mg), elemental Zinc 7mg |
Cell division, collagen formation & oxidative damage |
24 |
Manganese Sulphate |
Accelerates hair growth & prevents UV damage |
25 |
Iodine |
Growth, protein synthesis & cell metabolism |
26 |
Molybdenum |
Assists use of iron stores, fat burning, |
27 |
Vanadium Sulphate |
Insulin like anabolic, Na & K transport |
28 |
Gama Linolenic acid |
Anti inflammatory |
29 |
Chromium Polynicotinate |
Cellular metabolism |
30 |
Para amino benzoic acid |
Prevents premature graying of hair |
31 |
Inositol |
Prevents hair thinning |
32 |
Green Apple Extract - Proanthocyanidin |
Flavonoid & free radical scavenger |
33 |
Green Tea Extract – Catechins |
Antioxidant & protection from UV damage |
34 |
Saw Palmeto |
Anti androgenic |
35 |
Co Enzyme Q10 |
Rapid energy for growing cells |
Review of Mineral Analysis Conducted in Hair
Loss Patients
Research workers have direct evidence of lower mineral
levels in hair loss patients. When compared to healthy men,
lower levels of zinc, copper, iron and manganese were found in
the hair of patients with male pattern alopecia in the study by
Jin, Zhu and Wug [66]. Low BMI and low levels of zinc, copper in
hair, serum and urine of Turkish male patients were reported in
patients with androgenetic alopecia in their study by Ozturk et,
al. [60]. The study also noted that cell division, important cellular
and metabolic functions, nucleic acid metabolism, enzymes and
coenzymes like collagenase, polymerase, superoxide dismutase,
carbonic anhydrase, require zinc, copper, minerals and trace
elements to complete their biological functions [60]. Zinc and
Copper by themselves have inherent antioxidant activity. Zinc
stabilizes cell membrane and prevents oxidative destruction by
free radicals [60]. Deshwali et al. in their review mention that zinc
has a combined role of action with most of the metabolic enzyme
functions. Zinc inhibits miniaturization, follicle regression and
promotes hair growth [67]. Zinc deficiency is also associated with
hypothyroidism and anaemia which are known causes for hair
loss [67]. Skalnaya et al. compared the mineral content of falling
hair from frontal area with better growing hair from occipital
area and detected lower copper and zinc content in the frontal
hair [68]. These research studies have evidence that maintaining
mineral balance in the body is essential for good growing hair.
Minerals supplements thus have a well defined role in preventing
hair loss and inducing regrowth of healthy hair.
The Controversy of Iron Deficiency and Role of
Ferritin in Hair Loss
Deshwali et al. mention that hair follicles are storage sites
for ferritin which is utilized in case of deficiency by arresting or
compromising the hair growth and maintaining more important
functions, as of the blood and bone marrow cells [67]. Which
means the iron deficiency in circulation, will get corrected but then
there shall be hair loss or telogen effluvium with contradictory
lab tests depicting that the iron levels in circulation have been
maintained normal despite restricted hair growth. The deficiency
being compensated by utilizing iron from the follicles and arresting
hair growth is not clinically detectable. Park, Na, et al. reviewed
the role of iron deficiency and found it had a significant role in
hair loss [69]. Research by Ruston et al., Moeinvaziri et al., Kantor,
Kessler et al., and Deloche, Bastien et al., have found correlation
between iron deficiency and hair loss [70-73]. Whereas Sinclair,
Bregy, Trueb et al., and Olsen, who studied serum Ferritin as the
representative of iron stores in the body, have found no relation
between iron deficiency and hair loss [74-76]. The contrasting
findings were criticized by Ruston, Bergfeld et al. it is important
to know about nutrient interactions to decipher the controversial
findings [77]. The fact is that iron deficiency would be masked as
hair growth is arrested, follicles are shifted to telogen and ferritin
stores in the follicle are utilized to compensate low ferritin levels
[67]. Thus clinically serum ferritin levels continue to appear as
normal.
At times normal serum ferritin may not be biologically utilized
due to other coexisting deficiencies. Thakachan et al. and Diaz et al.
have impressed the role of vitamin C in absorption and utilization
of iron [78, 79]. Deshwali et al. have reviewed the importance of
copper in formation of haemoglobin and providing the oxygen
carrying capacity to the RBCs [67]. Mejia, Chew and García-Casal
et al. have determined the role of combined supplementation of
vitamin A and beta carotene which, aid in iron absorption [80,81].
Studies by Semba, Bloem et al, and Suharno, West et al. have found
that vitamin A is also required for mobilizing the stored iron to
the sites of generation of Red Blood Cells (RBC) and formation of
haemoglobin [82, 83]. Importance of zinc for erythropoiesis has
been stressed by Kelkitli, Ozturk et al. [84]. Optimum functioning
of nutrients is interrelated. A balance of all nutrients is required
to ensure the effective utilization of iron [85]. Therefore patients
with normal values of storage iron represented by serum ferritin
can have coexisting deficiencies of vitamin A, vitamin C, zinc or
copper, leading to poor incorporation of iron into RBC or reduced
oxygen carrying capacity, resulting in hair loss, despite apparent
normal iron ferritin, storage levels making us conclude there is no
relation between serum iron and hair loss. Iron levels are essential
for good hair growth and require to be corrected with a balance
of other associated vitamins, minerals and nutrients without
excess of any. We can conclude that a balance of micro nutrients
and vitamins is required to achieve the required metabolic
functions in the body. Individual single nutrient replacements
could be ineffective and individual deficiencies detected may not
provide a correct interpretation of the nutritional balance of the
homeostasis or internal environment.
Multiple Deficiencies
A deficiency may manifest as a single nutrient but these are
often, associated with other, covert or subclinical deficiencies.
Single nutrient replacement never works. You need to replace a
combined set of nutrients which will help each other work better.
Zimmermann and Hess have described the details of various
ways in which iron deficiency and availability of micronutrients,
affects thyroid function [86, 87]. The role of calorie restriction,
low intake of fatty acids, crash dieting, starvation, zinc and iron
deficiency in diffuse hair loss has been emphasised by Harrison
and Bergfeld [88]. Though thyroid hormone is made up of
tyrosine and iodine, other nutrients are also required to support
the conjugation and creation of the hormone. Iron has a role in
conversion of storage form of thyroid hormone T4 to the active
form T3. The above mentioned studies and the report by Betsy,
Binitha and Sarita highlight the association between zinc, copper,
selenium deficiencies and altered thyroid function leading to hair
loss [89]. A study of hair loss after Bariatric Surgery by Rojas and
Gosch detected lower hair loss in patients who maintained zinc,
iron, copper, selenium levels [90]. All these studies establish a
direct role of micronutrients, vitamins, minerals in hair loss
management. Thus comprehensive overall, nutritional correction
is essential in order to preserve hair quality, prevent hair loss and
promote healthy hair growth.
Nutritional Deficiencies are clinically Difficult to
Detect in Hair Loss Patients
Patients continue to lose hair despite clinical tests being
normal making it very difficult to convincingly determine a
cause and effect relationship. Let us examine why it is difficult
to detect existing nutrient deficiencies in hair loss patients? First
important research that explains the masking or compensation
of nutrient deficiencies by replacing them, is autophagy. The
work on autophagy by Yoshinori Oshumi of Japan received the
2016 Nobel Prize for Medicine. The research shows that under
conditions of starvation, malnutrition and calorie restriction,
there is a programmed breakdown of intracellular organelles
in order to retrieve the required nutrients which are found to
be deficient. The process is termed as autophagy. The nutrients
retrieved by autophagy are provide to maintain normal body
functions and restore normal levels in circulation [91, 92]. Similar
mechanism with respect to hair growth is being arrested and
ferritin being utilized for more indispensible body functions has
been also described by Deshwali , et al. [67]. Thus we find normal
circulating levels of nutrients in the blood making the nutrient
deficiencies undetectable. The deficiencies are auto corrected,
compensated and masked by redistribution of priorities and
by mechanism of autophagy. Therefore deficiencies cannot be
detected on laboratory tests. The moment you begin low dose
supplement support the patient responds with hair growth within
2-3 months. Clinically we should not wait to detect deficiencies
but start low dose nutritional support for patients who suffer
from hair loss. Correlating these nutritional priority theories
clinically with hair loss cycles, we do find that telogen effluvium
is triggered whenever there is higher demand from other body
systems. High fever, illness, mental trauma, stress, recovery from
surgery, extreme climatic changes, intestinal problems, crash
dieting all lead to acute telogen which shuts off hair growth
under unfavourable conditions. Hair growth may spontaneously
resume when the conditions are corrected or may continue until
the nutritional and functional balance of the body is restored.
Subclinical and Covert Deficiencies
Another status of nutritional deficiencies described by
nutritional research is subclinical or covert deficiencies. These
deficiencies are hidden and may not manifest unless there is
increased demand from sickness, stress or events like wound
healing. The patients are apparently healthy and the deficiencies
are not clinically detectable. In such a state the body metabolism
is regulated, reset and adapted to continue functioning with low
levels of nutrients. The prevalence of such hidden deficiencies is
much higher than we can realise [93, 94]. The role of subclinical
dietary deficiencies in non scarring hair loss was enlisted twenty
three years ago by Dawyer in a publication in the year 1994
[95]. Dry skin, hair breakage, pain in the hair roots, flaky scalp,
generalized thinning of hair, loss of shine, bounce, lustre in the
hair, may be partial presentations of developing alopecia and
may represent, uncorrected subclinical deficiencies. Covert
deficiency of one nutrient can lead to inadequate functioning of
a number of other nutrients. Cellular metabolism is inter linked.
Subclinical deficiency of nutrients is found to affect the entire
thyroid pituitary axis [96]. Iodine deficiency is a known cause
of hypothyroidism leading to hair loss. However, subclinical
deficiencies of vitamin A, vitamin D, iron and selenium also lead
to poor functioning of the thyroid gland and require concomitant
correction [97-100].
More than one subclinical deficiencies may exist in an
apparently healthy person. Clinically we may not be able to
detect single or multiple nutrient deficiencies. Therefore, a single
nutrient support for hair loss may be inadequate; we need to
provide a balance of various essential nutrients to ensure better
functioning of the body systems which would then ensure good
hair growth.
Comprehensive Low Dose Nutrient Therapy
Nutritional deficiencies are on the rise. Supplements are
required for normal healthy living. Inter nutrient reactions can
reduce the absorption and efficiency when multiple nutrients
are administered together. Manifestation of a single nutrient
deficiency is a sign of other associated subclinical deficiencies. A
comprehensive balanced use of supplements is required to ensure
synergistic action and prevent overdose. Whereas, it is customary
to advice nutritional supplements as regular daily doses all
throughout seven days a week, we have adopted a program of using
each supplement once in three days which translates to twice a
week instead of the common trend of daily dosage. The approach
allows the inclusion of more number of different supplements in
the comprehensive program, while restricting the total dose of
individual supplements to remain much below the safe limits and
avoid the possibility of an overdose. One such combination used
in our clinic for hair growth is presented in table 4. Use of ten
nutrients is distributed over three days in a repeating cycle. The
approach has been found to be beneficial in hair loss management
and achieving new hair growth in various indications [46, 53,
101-105]. A clinical trial with 100 patients in each group, having a
control group and treatment group comparing 2% minoxidil plus
finasteride in men and only 2% minoxidil in women has been
published earlier [106]. The density and calibre were measured
by tattooed, computerized trichoscopy analysis. The average
improvement in density was 18% at 2 months and 30% and at
4 months. The average improvement in calibre in 2 months was
9% and at 4 months was 21%. Hair loss was controlled in all the
patients in treatment group, within 4-6 weeks. A photographic
representation of these male and female results is included in this
review. Figure 1a, 1b show improvement after four months of low
dose once in three days, in a case of grade III hereditary hair loss
in a male patient which has reversed to grade II, without the use
of minoxidil or finasteride. While figure 2a, 2b show a result of similar
therapy for four months in grade II female pattern hair loss which
has reversed to grade I.
Table 4: Cyclical Nutrient Therapy two supplement per day in a 3 – day
Cycles
Monday & Thursday |
Antioxidant, Calcium, Vitamin D3 |
Tuesday & Friday |
Iron, Folic Acid, Vitamin C, Omega 3 |
Wednesday & Saturday |
Essential Aminoacids, B-Complex, Biotin |
Sunday – no medicines |
Detox on Sunday OR add extra a dose of another nutrient as per individual status if required |
Provides ten different nutrient combinations that are synergistic with
each other over three days preventing overdose and inter nutrient
interaction.
Figure 1a: Hereditary hair loss in a male patient
Figure 1b: Improvement in hair quality, density and calibre after 4
months of nutritional therapy
Figure 2a: Female pattern hair loss
Figure 2b: Improvement in hair quality, density and calibre after 4
months of nutritional therapy
Conclusion
Anti androgens is not the only basis of treating hair loss.
Weak hair roots become sensitive and susceptible to multiple
factors. Whereas, strong hair roots can stand for any cause. Hair
loss is multifactorial. Nobody goes bald due to hair fall, people go
bald as fallen hair is not replaced with new hair, because the hair
growth cycles are disrupted or discontinued. Instead of fighting
hair loss with medications which have possibility of side effects,
we can change our perspective to strengthening the hair roots
and promoting better hair growth. Research shows that altered
immunity, inflammation, hormonal imbalance and dysregulation
of hair growth cycles can be improved with nutritional support.
There is evidence that the action of DHT is mediated through
ROS and can be successfully blocked with antioxidants. Low
mineral levels have been clinically detected to be associated
with hair loss and require correction. Nutrient deficiencies
may not always be clinically detectable due to compensation
by autophagy and presence of subclinical covert deficiencies. A
single deficiency often is a representative of several underlying
deficiencies, interlinked with derangement of numerous cellular
functions at multiple levels. A corrective balance of multiple
nutrients requires to be provided in order to ensure consistent
results. The nutritional support also has to continue for a long
time to maintain active hair growth. A comprehensive correction
of nutrients without utilizing any single nutrient in excess
is recommended as a low dose once in three days cycle. The
approach has been successfully utilized to achieve hair growth
for various indications without the use of anti androgens, DHT
blockers or Finasteride.
- Inui S, Fukuzato Y, Nakajima T, Yoshikawa K, Itami S. Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth. FASEB J. 2002;16(14):1967-1969.
- Inui S, Fukuzato Y, Nakajima T Yoshikawa K, Itami S. Identification of androgen-inducible TGF-beta1 derived from dermal papilla cells as a key mediator in androgenetic alopecia. J Investig Dermatol Symp Proc. 2003;8(1):69-71.
- Itami S. Pathomechanism of androgenetic alopecia and new treatment . Article in Japanese, Nihon Ronen Igakkai Zasshi. 2004;41(6):598-600. doi: 10.3143/geriatrics.41.598
- Hee Chul E. The involvement of ROS on androgen inducible TGF beta 1 regulation derived from dermal papilla cells; a suggestive implication of ROS on androgenetic alopecia. Journal of the American Academy of Dermatology. 2008;58(2):AB84. Suppl 2.
- Shin H, Yoo H G, Inui S, Itami S, Kim I G, A-Ri Cho,et.al. Induction of transforming growth factor-beta 1 by androgen is mediated by reactive oxygen species in hair follicle dermal papilla cells. BMB Rep. 2013;46(9):460-464. doi: 10.5483/BMBRep.2013.46.9.228
- Wolff H, Fischer T W, Blume-Peytavi U. The Diagnosis and Treatment of Hair and Scalp Diseases. Dtsch Arztebl Int. 2016;113(21): 377–386. doi: 10.3238/arztebl.2016.0377
- Trueb R M, Pharmacologic interventions in aging hair. Clinical Interventions in Aging. 2006:1(2);121–129.
- Lee W-S, Lee H-J. Characteristics of Androgenetic Alopecia in Asian. Ann Dermatol. 2012;24(3):243-252. doi:10.5021/ad.2012.24.3.243
- Cranwell W, Sinclair R. Male Androgenetic Alopecia. In:De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000
- Pitts R L. Serum elevation of dehydroepiandrosterone sulfate associated with male pattern baldness in young men. Journal of the American Academy of Dermatology. 1987;16(3):571-573.
- Schmidt J B. Hormonal basis of male and female androgenic alopecia: clinical relevance. Skin pharmacology : the official journal of the Skin Pharmacology Society. 1994;7:61-66.
- Schmidt J B, Lindmaier A, Trenz A, Schurz B, Spona J. Hormone studies in females with androgenic hairloss. Gynecologic and obstetric investigation. 1991;31(4):235-239.
- Dawber R P. Aetiology and pathophysiology of hair loss. Dermatologica. 1987;175 Suppl 2:23-28.
- Jahoda C A. Cellular and developmental aspects of androgenetic alopecia. Exp Dermatol. 1998 ;7(5):235-48.
- Ellis J A, Sinclair R, Harrap S B. Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med. 2002:4(22):1-11.
- Cousen P, Messenger A. Female pattern hair loss in complete androgen insensitivity syndrome. Br J Dermatol. 2010; 162(5):1135–1137. doi: 10.1111/j.1365-2133.2010.09661.x
- Orme S, Cullen DR, Messenger AG. Diffuse female hair loss: are androgens necessary?. Br J Dermatol. 1999;141(3):521-523.
- Birch MP, Messenger JF, Messenger AG. Hair density, hair diameter and the prevalence of female pattern hair loss. Br J Dermatol. 2001;144(2):297-304.
- Norwood OT. Incidence of female androgenetic alopecia (female pattern alopecia). Dermatol Surg. 2001;27(1):53-54.
- Ustuner ET. Cause of Androgenic Alopecia: Crux of the Matter. Plast Reconstr Surg Glob Open. 2013;1(7):e64. doi: 10.1097/GOX.0000000000000005
- Kaufman KD. Androgens and alopecia. Mol Cell Endocrinol. 2002;198(1-2):89–95.
- Sawaya ME, Price VH. Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of woman and men with androgenetic alopecia. J Invest Dermatol.1997;109(3):296-300.
- Rebora A, Guarrera M. Kenogen. A new phase of hair cycle. Dermatology. 2002;205(2):108-110.
- Guarrera M, Rebora A. Kenogen in female androgenetic alopecia. A longitudinal study. Dermatology. 2005;210(1):18-20.
- Philpott MP, Farjo N , Farjo B, Bahta AW. Premature senescence of balding dermal papilla cells in vitro is associated with p16 (INK4a) expression. J Invest Dermatol. 2008;128(5):1088–1094.
- Urysiak-Czubatka, Kmieć ML, Broniarczyk-Dyła G. Assessment of the usefulness of dihydrotestosterone in the diagnostics of patients with androgenetic alopecia. Postepy Dermatol Alergol. 2014;31(4):207-215. doi: 10.5114/pdia.2014.40925
- Headington JT. Telogen effluvium: new concepts and review. Arch Dermatol. 1993;129(3):356–363.
- Kligman AM. Pathologic dynamics of human hair loss. I. Telogen effluvium. Arch Dermatol. 1961;83:175–198.
- Giralt M, Cervello I, Nogues MR, Puerto AM, Ortin F, Argany N, et al. Glutathione, glutathione S-transferase and reactive oxygen species of human scalp sebaceous glands in male pattern baldness. J Invest Dermatol. 1996;107(2):154–158.
- Naziroglu M, Kokcam I. Antioxidants and lipid peroxidation status in the blood of patients with alopecia. Cell Biochem Funct. 2000;18(3):169–173.
- Akar A, Arca E, Erbil H, Akay C, Sayal A, Gur AR. Antioxidant enzymes and lipid peroxidation in the scalp of patients with alopecia areata. J Dermatol Sci. 2002;29(2):85–90.
- Koca R, Armutcu F, Altinyazar H, Gurel A. Evaluation of lipid peroxidation, oxidant/antioxidant status and serum nitric oxide levels in alopecia areata. Med Sci Monit. 2005;11(6):296–299.
- Inui S, Fukuzato Y, Nakajima T, Yoshikawa K, Itami S. Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth. FASEB J. 2002;16(14):1967-1969.
- Inui S, Fukuzato Y, Nakajima T, Yoshikawa K, Itami S. Identification of androgen-inducible TGF-beta1 derived from dermal papilla cells as a key mediator in androgenetic alopecia. J Investig Dermatol Symp Proc. 2003;8(1):69-71.
- Itami S. Pathomechanism of androgenetic alopecia and new treatment. Nihon Ronen Igakkai Zasshi. 2004;41(6):598-600.
- Hee CE. The involvement of ROS on androgen inducible TGF beta 1 regulation derived from dermal papilla cells; a suggestive implication of ROS on androgenetic alopecia. Journal of the American Academy of Dermatology. 2008;58(2):AB84.
- Shin H, Yoo HG, Inui S, Itami S, et.al. Induction of transforming growth factor-beta 1 by androgen is mediated by reactive oxygen species in hair follicle dermal papilla cells. BMB Rep. 2013;46(9):460-464.
- Trüeb RM. Molecular mechanisms of androgenetic alopecia. Exp Gerontol. 2002;37(8-9):981-990.
- Kubibidila S, Yu L, Ode D, Warrier RP. The immune response in protein-energy malnutrition and single nutrient deficiencies. 1993;8;121–155. Plenum Press, New York, NY.
- Fraker PJ, King LE. Reprogramming of the immune system during zinc deficiency. Ann Rev Nutr. 2004;24: 277–298.
- Kalkan G, Seçkin HY, Benli, et al. Relationship between manganese superoxide dismutase (MnSODAla-9Val) and glutathione peroxidase (GPx1 Pro 197 Leu) gene polymorphisms and alopecia areata. Int J Clin Exp Med. 2015;8(11):21533-21540.
- Mahe YF, Michelet JF, Billoni N, et al. Androgenetic Alopecia and microinflammation. Int J Dermatol. 2000;39(8): 576-584.
- Smith RS, Smith TJ, Bleden TM, et al. Fibroblasts as sentinel cells. Synthesis of chemokines and regulation of inflammation. Am J Pathol. 1997;151(2): 317-322.
- Rinaldi F. Pollution, scalp and hair transplant. Hair Transplant Forum Int. 2008;18:227.
- Vierkötter A, Schikowski T, Ranft U, Sugiri D, Matsui M, Krämer U, et al. Airborne Particle Exposure and Extrinsic Skin Aging. J Invest Dermatol. 2010;130(12):2719–2726. doi: 10.1038/jid.2010.204
- Rajput R. Understanding Hair Loss due to Air Pollution and the Approach to Management. Hair Ther Transplant. 2015;5:133. doi:10.4172/21670951.1000133
- Trüeb RM. Association between smoking and hair loss: Another opportunity for health education against smoking? Dermatology. 2003;206(3):189-191.
- Alberg AJ, Chen JC, Zhao H, Hoffman SC, Comstock GW, Helzlsouer KJ. Household exposure to passive cigarette smoking and serum micronutrient concentrations. Am J Clin Nutr. 2000;72(6):1576-1582.
- Alberg A. The influence of cigarette smoking on circulating concentrations of antioxidant micronutrients. Toxicology. 2002;15;180(2):121-137.
- Bloomer RJ. Decreased blood antioxidant capacity and increased lipid peroxidation in young cigarette smokers compared to nonsmokers: Impact of dietary intake. Nutr J. 2007;6:39. doi: 10.1186/1475-2891-6-39
- D'Agostini F, Fiallo P, Pennisi TM, De Flora S. Chemoprevention of smoke-induced alopecia in mice by oral administration of L-cystine and vitamin B6. J Dermatol Sci. 2007;46(3):189-198.
- Galan P, Viteri FE, Bertrais S, Czernichow S, Faure H, Arnaud J, et al. Serum concentrations of beta-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population. Eur J Clin Nutr. 2005;59(10):1181-1190.
- Rajput RS. Benefit from Vitamin Therapy in Smoker’s Hair. Hair Ther Transplant. 2016;6:141. doi: 10.4172/2167-0951.1000141
- Eugenio Mocchegiani, Laura Costarelli, Robertina Giacconi, Francesco Piacenza, Andrea Basso, Marco Malavolta. Micronutrient (Zn, Cu, Fe)–gene interactions in ageing and inflammatory age-related diseases: Implications for treatments. Ageing Res Rev. 2019;11(2):297– 319. doi: 10.1016/j.arr.2012.01.004
- Mocchegiani E, Costarelli L, Giacconi R, Malavolta M, Basso A, Piacenza F, et al. Micronutrient-gene interactions related to inflammatory/immune response and antioxidant activity in ageing and inflammation. A systematic review. Mech Ageing Dev. 2014;136-137:29-49. doi: 10.1016/j.mad.2013.12.007
- Thurnham DI. An overview of interactions between micronutrients and of micronutrients with drugs, genes and immune mechanisms. Nutr Res Rev. 2004;17(2):211-240. doi: 10.1079/NRR200486
- Ströhle A, Wolters M, Hahn A. Micronutrients at the interface between inflammation and infection--ascorbic acid and calciferol: part 1, general overview with a focus on ascorbic acid. Inflamm Allergy Drug Targets. 2011;10(1):54-63.
- Ströhle A, Wolters M, Hahn A. Micronutrients at the interface between inflammation and infection--ascorbic acid and calciferol. Part 2: calciferol and the significance of nutrient supplements. Inflamm Allergy Drug Targets. 2011;10(1):64-74.
- Betsy A, Binitha M, Sarita S. Zinc Deficiency Associated with Hypothyroidism: An Overlooked Cause of Severe Alopecia. Int J Trichology. 2013;5(1):40-42. doi: 10.4103/0974-7753.114714
- Ozturk P, Kurutas E, Ataseven A, Dokur N, Gumusalan Y, Gorur A, et al. BMI and levels of zinc, copper in hair, serum and urine of Turkish male patients with androgenetic alopecia. J Trace Elem Med Biol. 2014;28(3):266-270. doi: 10.1016/j.jtemb.2014.03.003
- Fraker Pamela J. Roles for Cell Death in Zinc Deficiency. J Nutr. 2005;135(3):359-362.
- Reichrath J, Lehmann B, et al. Vitamins as hormones. Horm Metab Res. 2007;39(2):71-84.
- Aoi N, Inoue K, Chikanishi T, et al. 1α, 25-dihydroxyvitamin D3 modulates the hair-inductive capacity of dermal papilla cells: therapeutic potential for hair regeneration. Stem Cells Transl Med. 2012;1(8):615–626. doi: 10.5966/sctm.2012-0032
- Beoy LA, Woei WJ, Hay YK. Effects of Tocotrienol Supplementation on Hair Growth in Human Volunteers. Trop Life Sci Res. 2010;21(2):91-99.
- Kwack MH, Shin SH, Kim SR, Im SU, Han IS, Kim MK, et al. l-Ascorbic acid 2-phosphate promotes elongation of hair shafts via the secretion of insulin-like growth factor-1 from dermal papilla cells through phosphatidylinositol 3-kinase. Br J Dermatol. 2009;160(6):1157-1162. doi: 10.1111/j.1365-2133.2009.09108.x
- Jin W, Zhu Z, Wu S, Zhang X, Zhou X. Determination of zinc, copper, iron and manganese contents in hair for MPA patients and healthy men. Guang Pu Xue Yu Guang Pu Fen Xi. 1998;18(1):91–93.
- Deshwali S, Kare PK, Agrawal BK, Alex A. Study of serum zinc, copper and ferritin levels in alopecia patients. Int J Adv Res Biol. Sci. 2015;2(7): 94–96.
- Skalnaya MG, Tkachev VP. Trace elements content and hormonal profiles in women with androgenetic alopecia. J Trace Elem Med Biol. 2011;25:50–53. doi: 10.1016/j.jtemb.2010.10.006
- Park SY, Na SY, Kim JH, Cho S, Lee JH. Iron Plays a Certain Role in Patterned Hair Loss. J Korean Med Sci. 2013;28(6):934-938.
- Rushton DH, Norris MJ, Dover R, Busuttil N. Causes of hair loss and the developments in hair rejuvenation. Int J Cosmet Sci. 2002;24(1):17–23. doi: 10.1046/j.0412-5463.2001.00110.x
- Moeinvaziri M, Mansoori P, Holakooee K, Safaee Naraghi Z, Abbasi A. Iron status in diffuse telogen hair loss among women. Acta Dermatovenerol Croat. 2009;17(4):279–284.
- Kantor J, Kessler LJ, Brooks DG, Cotsarelis G. Decreased serum ferritin is associated with alopecia in women. J Invest Dermatol. 2003;121(5):985–988.
- Deloche C, Bastien P, Chadoutaud S, Galan P, Bertrais S, Hercberg S, et al. Low iron stores: a risk factor for excessive hair loss in non-menopausal women. Eur J Dermatol. 2007;17(6):507–512.
- Sinclair R. There is no clear association between low serum ferritin and chronic diffuse telogen hair loss. Br J Dermatol. 2002;147(5):982–984.
- Bregy A, Trueb RM. No association between serum ferritin levels >10 microg/l and hair loss activity in women. Dermatology. 2008;217(1):1–6. doi: 10.1159/000118505
- Olsen EA, Reed KB, Cacchio PB, Caudill L. Iron deficiency in female pattern hair loss, chronic telogen effluvium, and control groups. J Am Acad Dermatol. 2010;63(6):991–999. doi: 10.1016/j.jaad.2009.12.006
- Rushton DH, Bergfeld WF, Gilkes JJ, Van Neste D. Iron deficiency and hair loss: nothing new? J Am Acad Dermatol. 2011;65(1):203–204. doi: 10.1016/j.jaad.2011.02.020
- Thankachan P, Walczyk T, Muthayya S, Kurpad AV, Hurrell RF. Iron absorption in young Indian women: the interaction of iron status with the influence of tea and ascorbic acid. Am J Clin Nutr. 2008; 87(4):881-886.
- DiazM, Rosado JL, Allen LH, Abrams S, Garcia OP. The efficacy of a local ascorbic acid-rich food in improving iron absorption from Mexican diets: a field study using stable isotopes. Am J Clin Nutr. 2003;78(3):436–440.
- Mejia, LA, Chew V. Hematological effect of supplementing iron with results of Mejia (1986), who demonstrated interactions be- vitamin A alone and in combination with iron. Am J Clin Nutr. 1988;48:595–600.
- García-Casal MN, Layrisse M, Solano L, et al. Vitamin A b -carotene can improve nonheme iron absorption from rice wheat and corn by humans. J Nutr. 1998;28:646-650.
- Semba RD, Bloem MW. The anemia of vitamin A deficiency: epidemiology and pathogenesis. Eur J Clin Nutr. 2002;56(4):271-281.
- Suharno D, West CE, Muhilal, Karyadi D, Hautvast JG. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet. 1993;342(8883):1325–1328.
- Kelkitli E, Ozturk N, Aslan NA. Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia. Ann Hematol. 2016;95(5):751-756. doi: 10.1007/s00277-016-2628-8
- Lynch SR. Interaction of iron with other nutrients. Nutr Rev. 1997;55(4):102-110.
- Zimmermann MB. The influence of iron status on iodine utilization and thyroid function. Annu Rev Nutr. 2006;26:367-389. doi: 10.1146/annurev.nutr.26.061505.111236
- Hess SY. The impact of common micronutrient deficiencies on iodine and thyroid metabolism: the evidence from human studies. Best Pract Res Clin Endocrinol Metab. 2010;24(1):117-132. doi: 10.1016/j.beem.2009.08.012
- S Harrison, W Bergfeld. Diffuse hair loss: Its triggers and management. Cleveland Clinic Journal of Medicine. 2009;76(6): 361-367. doi: 10.3949/ccjm.76a.08080
- Betsy A, Binitha M, Sarita S. Zinc Deficiency Associated with Hypothyroidism: An Overlooked Cause of Severe Alopecia. International Journal of Trichology. 2013;5(1):40-42. doi: 10.4103/0974-7753.114714
- Rojas P, Gosch M, Basfi-Fer K, Carrasco F, Codoceo J, Inostroza J, et al. Alopecia in women with severe and morbid obesity who undergo bariatric surgery. Nutr Hosp. 2011;26(4):856–862. doi: 10.3305/nh.2011.26.4.5199
- Guimaraes C. and Linden R. Programmed cell deaths. Apoptosis and alternate deathstyles. Eur J Biochem. 2004;271(9):1638–1650. doi: 10.1111/j.1432-1033.2004.04084.x
- Yoshimori, T. Autophagy: A regulated bulk degradation process inside cells. Biochem Biophys Res Commun. 2004;313(2): 453–458.
- Bender AE. Subclinical and covert malnutrition. Bull Schweiz Akad Med Wiss. 1976;31(4-6):279-290.
- Bailey RL, West Jr KP, Black RE. The Epidemiology of Global Micronutrient Deficiencies. Ann Nutr Metab. 2015;66(suppl 2):22-33. doi: 10.1159/000371618
- Dwyer JT. Vegetarian eating patterns: Science, values, and food choices -- Where do we go from here?. Am J Clin Nutr. 1994;59(5 Suppl): 1255S-1262S.
- Zimmermann MB. Interactions of vitamin A and iodine deficiencies: effects on the pituitary-thyroid axis. Int J Vitam Nutr Res. 2007;77(3):236-240. doi: 10.1024/0300-9831.77.3.236
- El-Eshmawy MM, Arafa MM, Elzehery RR, Elhelaly RM, Elrakhawy MM, El-Baiomy AA. Relationship between vitamin A deficiency and the thyroid axis in clinically stable patients with liver cirrhosis related to hepatitis C virus. Appl Physiol Nutr Metab. 2016;41(9):985-991. doi: 10.1139/apnm-2016-0056.
- Yilmaz H, Cakmak M, Darcin T, Inan O, Gurel OM, Bilgic MA, Bavbek N, Akcay A. Subclinical hypothyroidism in combination with vitamin D deficiency increases the risk of impaired left ventricular diastolic function. Endocr Regul. 2015;49(2):84-90.
- Chanoine JP. Selenium and thyroid function in infants, children and adolescents. Bio factors. 2003;19(3-4):137-143.
- Ravanbod M, Asadipooya K, Kalantarhormozi M, Nabipour I, Omrani GR. Treatment of iron-deficiency anemia in patients with subclinical hypothyroidism. Am J Med. 2013;126(5):420-424. doi: 10.1016/j.amjmed.2012.12.009
- Rajput RJ. Cyclical Medicine for Hair loss Management and Improving Results in Hair Transplantation. Hair Transplant Forum International. 2008;18:208.
- Rajput RJ. Is there a Role for Adjuvants in the Management of Male pattern hair loss? Published in Journal of Cutaneous and Aesthetic Surgery. 2010;3(2): 82–86. doi: 10.4103/0974-2077.69016
- Rajendrasingh JR. Role of Non Androgenic Factors in Hair loss and Hair Regrowth. J Cosmo Trichol. 2017;3(2):118. doi: 10.4172/2471-9323.1000118
- Rajput R. Improvement in Hair Loss and Better Hair Quality with Vitamin Therapy in Monilethrix. J Cosmo Trichol. 2016;2(3): 113. doi: 10.4172/2471-9323.1000113
- Rajput R. Hair Loss due to Electromagnetic Radiation from Overuse of Cell Phone. J Cosmo Trichol. 2016;2:114.
- Rajput RJ. Controlled clinical trial for evaluation of hair growth with low dose cyclical nutrition therapy in men and women without the use of finasteride. Plast Aesthet Res. 2017;4:161-173.