Clinical efficacy of popular oral hair growth supplement ingredients

Abstract

Hair supplements are a vast and growing industry. Patients often turn to oral supplements to address hair concerns as they are easily accessible. There are numerous products on the market, many with thousands of reviews (both positive and negative). Nutritional supplements are regulated by the FDA as foods instead of drugs, meaning they do not have to prove their efficacy and safety before becoming available to consumers. While some oral supplements have strong evidence supporting their use for hair growth, many ingredients have not been tested in clinical trials, have only in vitro evidence for hair growth, or have only been tested in animals. Given these industry characteristics, it is important for dermatologists to be aware of the safety and utility of these ingredients to provide appropriate counseling to their patients. The goal of this review is to evaluate the efficacy of popular hair growth oral supplement ingredients and formulations. This review does not address the topical formulations of these ingredients and their effects on hair growth.

Full text

Review
Clinical efficacy of popular oral hair growth supplement
ingredients
Madeline J. Adelman
1
,BS, Lisa M. Bedford
2
,MD and Geoff A. Potts
2
,MD
1
School of Medicine, Wayne State
University, Detroit, USA, and
2
Department
of Dermatology, Wayne State University,
Detroit, USA
Correspondence
Madeline J. Adelman, BS
3150 Woodward Ave, Apt 521
Detroit
MI 48201
USA
E-mail: madelj@wayne.edu
Conflict of interest: None.
Funding source: None.
doi: 10.1111/ijd.15344
Abstract
Hair supplements are a vast and growing industry. Patients often turn to oral supplements
to address hair concerns as they are easily accessible. There are numerous products on
the market, many with thousands of reviews (both positive and negative). Nutritional
supplements are regulated by the FDA as foods instead of drugs, meaning they do not
have to prove their efficacy and safety before becoming available to consumers. While
some oral supplements have strong evidence supporting their use for hair growth, many
ingredients have not been tested in clinical trials, have only in vitro evidence for hair
growth, or have only been tested in animals. Given these industry characteristics, it is
important for dermatologists to be aware of the safety and utility of these ingredients to
provide appropriate counseling to their patients. The goal of this review is to evaluate the
efficacy of popular hair growth oral supplement ingredients and formulations. This review
does not address the topical formulations of these ingredients and their effects on hair
growth.
Vitamins
Vitamin A
Vitamin A represents a group of fat-soluble, retinoid derivatives
essential for cellular differentiation, vision, and immune function.
In general, a healthy diet provides the body with enough vitamin
A, and deficiency is rare in the United States. Preformed vita-
min A is obtained through consumption of animal-derived prod-
ucts (meat, fish, and eggs). Provitamin A, or beta-carotene, is
obtained through consumption of plants and nuts.
1
Dermatologic manifestations of vitamin A deficiency include
ichthyosis, fragile hair, and telogen effluvium.
2
There is no
upper intake level for beta-carotene;
1
however, over-supple-
mentation with preformed vitamin A can result in telogen efflu-
vium in addition to other systemic symptoms, such as
hepatotoxicity.
1
Therefore, it is important to consider which for-
mulation of vitamin A is being ingested.
Beta-carotene has both antioxidant and anti-inflammatory
properties.
3
It is able to avert damage by extinguishing free rad-
icals and photo-oxidation.
3
Naziroglu et al. evaluated the status
of serum beta-carotene in patients with alopecia areata (AA)
(n=37) compared to healthy controls (n=34).
4
Plasma beta-
carotene was significantly lower in patients with alopecia than in
controls.
4
However, inflammatory reactions result in a reduced
blood retinol and beta-carotene content; it is therefore most
plausible that these results represent a sequela of AA rather
than a trigger to the disease. Accordingly, beta-carotene and
other antioxidants may be useful in AA to decrease inflamma-
tion.
Iatrogenic hair loss induced by oral isotretinoin and acitretin for
treatment of acne has been reported. Kmie
cet al. evaluated the
effects of 0.5–1.0 mg/kg/day of isotretinoin in a 4–7 month
prospective study (n=30).
5
Total hair count, hair density, and
anagen hair rate were assessed by FotoFinder Dermoscope with
TrichoScan software before and after treatment.
5
Results
revealed a statistically significant reduction in total hair count, hair
density, and proportion of anagen hair.
5
However, these changes
were transient, with hair regrowth after discontinuation of treat-
ment. A similar 3-month study of patients on 0.5 mg/kg/day of
isotretinoin did not reveal a statistically significant change in hair
count, density, or percentage of anagen and telogen hairs; these
contradicting results may be because of the shorter study dura-
tion and decreased dosage.
6
Further studies are needed to eval-
uate the efficacy and role of vitamin A in hair loss.
Capsule summary
Clinical studies fail to support the efficacy of oral vitamin A sup-
plementation for hair growth. It is possible that the antioxidant
and anti-inflammatory properties of beta-carotene may be useful
in treating AA. However, no studies have demonstrated an
improvement in AA or other hair loss conditions with vitamin A
supplementation alone.
ª2020 the International Society of Dermatology International Journal of Dermatology 2020
1

Vitamin C
Vitamin C, also known as ascorbic acid, is a water-soluble vita-
min. Humans are unable to synthesize vitamin C and must
acquire it through consumption of citrus fruits and vegetables.
1
It is an important antioxidant and an essential cofactor in colla-
gen biosynthesis.
1
Vitamin C also enhances intestinal absorp-
tion of iron and iron mobilization, making vitamin C
supplementation an important adjunct in hair loss associated
with iron-deficiency anemia.
1
Vitamin C deficiency, also called
scurvy, may present with abnormal “corkscrew” hairs; however,
the condition does not result in hair loss (Fig. 1).
7
L-Ascorbic acid 2-phosphate (Asc 2-P), a long-acting ascor-
bic acid derivative, has been shown to induce hair growth in
animal studies and in in vitro human hair follicles.
8
However,
there are no clinical trials to date investigating the isolated
effects of oral vitamin C supplementation on human hair.
Capsule summary
Animal studies and in vitro human hair follicle studies support
that vitamin C, or its derivatives, plays a role in hair health and
growth. However, there is insufficient evidence that oral supple-
mentation in humans is beneficial to hair growth.
Vitamin D
Vitamin D is a fat-soluble vitamin that plays an essential role in
bone health, immunity, and calcium homeostasis. In the devel-
oped world, fortified foods, supplementation, and sunlight pro-
vide adequate levels of vitamin D.
2
The vitamin D receptor is present in hair follicle cells, and
studies have shown that it is involved in hair follicle cycling.
9
However, this is independent of vitamin D itself.
Low levels of vitamin D have been associated with multiple
hair loss conditions. Cerman et al. evaluated the status of
serum vitamin D in patients with AA (n=86), vitiligo (n=44),
and healthy controls (n=58) in a cross-sectional study.
10
Serum vitamin D levels were significantly lower in patients
with AA and inversely correlated with disease severity (Figs. 2
and 3).
10
Similarly, in a study comparing serum vitamin D in
females with telogen effluvium or female pattern hair loss
(FPHL) (n=80) to age-matched healthy controls (n=40),
serum vitamin D was significantly lower in telogen effluvium
and FPHL patients.
11
However, there have been no clinical
trials demonstrating that isolated supplementation with vitamin
D promotes hair growth.
Capsule summary
Patients with hair loss conditions, such as AA or telogen efflu-
vium, should be evaluated for low serum vitamin D and given
supplementation if low. However, given alone, there is no evi-
dence that oral vitamin D promotes hair growth.
Vitamin E
Vitamin E is a fat-soluble vitamin and an important antioxidant.
Deficiency is rare in healthy individuals and usually linked to
malabsorption conditions such as cystic fibrosis and Crohn’s
disease.
12
The most significant risk posed by consumption of
high doses of vitamin E is decreased hemostasis.
The major forms of vitamin E available in oral supplements
include tocopherols and tocotrienols.
12
Beoy et al. evaluated
the effects of 100 mg of oral tocotrienol in an 8-month ran-
domized, double-blind, placebo-controlled study (n=38) on
hair growth in patients with varying levels of hair loss.
13
Hair
count and hair weight measurements were obtained at base-
line and 4 and 8 months.
13
Tocotrienol supplementation
resulted in a significant increase in hair count compared to
placebo, but there was no increase in hair weight.
13
Further
studies are needed to evaluate the efficacy and role of vitamin
E in hair loss.
Capsule summary
Results of the study of Beoy et al. indicate that oral vitamin E
has a positive effect on hair count. Additional and larger clinical
trials are needed to fully investigate the risks and benefits of
vitamin E in hair growth oral supplement formulations.
Figure 1 Scurvy with perifollicular hemorrhage and corkscrew hairs
International Journal of Dermatology 2020 ª2020 the International Society of Dermatology
Review Oral hair growth supplement ingredients Adelman, Bedford, and Potts
2

Biotin
Biotin is a water-soluble B vitamin that plays a vital role in meta-
bolism, histone modification, cell signaling, and gene regulation.
1
Genetic causes of biotin deficiency secondary to enzyme defi-
ciencies manifest as severe dermatitis and alopecia in infancy.
1
Acquired deficiency can be caused by malabsorption, alcoholism,
pregnancy, antibiotics, and increased raw egg consumption.
1
Rahman et al. compared serum levels of biotin in patients with
telogen effluvium (n=60) to healthy controls (n=20) in a case-
control study.
14
There was no significant difference in biotin levels
between those with telogen effluvium and controls, with optimal
levels in both groups (>400 ng/l).
14
In a similar study, El-Esawy
et al. compared serum zinc and biotin levels in male patients with
androgenetic alopecia (n=60) to healthy controls (n=60).
15
Serum biotin levels were suboptimal (>300 and <400 ng/l) in
patients with androgenetic alopecia, with no correlation to patient
age, BMI, disease duration, or disease severity.
15
However, it is
important to note that serum biotin concentration is an unreliable
marker of biotin deficiency and may fluctuate up to 100% on a
daily basis.
16
While there is no upper limit for biotin intake, exogenous bio-
tin supplementation can negatively interfere with laboratory val-
ues, including precipitating a falsely low troponin test, leading
to a missed diagnosis of myocardial infarction.
1
It may also
result in a false positive TSH receptor antibody, suggestive of
Graves’ disease, and can interfere with some urinary hCG
devices.
1,17
In 2017, Patel et al. conducted a systematic literature review
of biotin supplements in hair and nail disorders.
18
In all cases
that showed clinical improvement after receiving biotin, patients
had an underlying condition and an established biotin defi-
ciency.
18
Biotin is one of the most advertised ingredients in hair growth
supplements. However, there is no published evidence support-
ing that biotin has a direct effect on hair follicle cycling or devel-
opment. Biotin has also never been studied independently as a
supplement in hair loss, and there is no published evidence
supporting that oral biotin supplements promote hair growth in
the absence of biotin deficiency.
Figure 2 Percentage of patients by deficiency level of vitamin D (25-hydroxyvitamin D). Vitamin D deficiency is defined as ≤20 ng/ml
ª2020 the International Society of Dermatology International Journal of Dermatology 2020
Adelman, Bedford, and Potts Oral hair growth supplement ingredients Review 3

Capsule summary
There is no evidence supporting the use of biotin as an oral
supplement for hair growth. Biotin may be considered in those
at risk for deficiency (pregnancy and malabsorption); however,
patients should be educated on potential laboratory test interfer-
ences and urged to inform their other providers who are taking
supplements to avoid false negative or positive results.
Niacin
Niacin, also known as vitamin B3, is another water-soluble vita-
min required for anabolic and catabolic metabolism, cellular sig-
naling, and gene expression.
19
It is naturally available in a wide
variety of animal- and plant-based foods in the forms of nicotinic
acid and nicotinamide.
19
Niacin deficiency results in pellagra, a triad of dermatitis, diar-
rhea, and dementia.
20
Alopecia may also be present. Pellagra is
rare in developed countries but may occur in those with malab-
sorption conditions, anorexia nervosa, and chronic alcoholism.
20
Topical application of niacin has shown to increase hair full-
ness in women with female pattern alopecia.
21
This outcome is
thought to be a result of niacin-induced increased blood flow,
optimizing oxygen, and nutrient delivery to the scalp.
21
However,
there is no available evidence that oral supplementation pro-
motes hair growth.
Capsule summary
Patients with hair loss as a result of pellagra will benefit from
niacin supplementation. However, there is insufficient evidence
supporting the use of niacin as an oral supplement for hair
growth in the absence of deficiency.
Minerals
Zinc
Zinc is an essential trace element involved in protein function,
cell signaling, and gene expression. Zinc is also crucial to
proper immune cell function and response.
2
As an essential ele-
ment, zinc must be supplied to the human body through diet.
One symptom of severe zinc deficiency is alopecia, with hair
regrowth after supplementation.
1
Yet, the exact role of zinc in
hair health is still unknown.
2
El-Esawy et al. compared serum zinc levels in male patients
with androgenetic alopecia (n=60) to healthy controls
(n=60).
15
Serum zinc was significantly lower in patients with
androgenetic alopecia compared to controls.
15
Similar results
were found in studies comparing patients with AA to controls
and comparing patients with female androgenetic alopecia to
controls, with significantly lower zinc in the diseased popula-
tion.
22,23
Figure 3 In the alopecia areata group, Severity of Alopecia Tool (SALT) scores were significantly and negatively correlated with serum
vitamin D (25-hydroxyvitamin D) concentrations (r=0.409; P<0.001)
International Journal of Dermatology 2020 ª2020 the International Society of Dermatology
Review Oral hair growth supplement ingredients Adelman, Bedford, and Potts
4

Ead et al. set out to evaluate the effect of oral zinc on AA in
a 3-month double-blind, placebo-controlled trial (n=308).
24
There was no improvement in the active group compared to the
placebo by objective or subjective assessment.
24
It is possible
that results were limited by the study’s short time frame.
A more recent trial reported different results regarding the
efficacy of oral zinc supplementation on hair growth. Siavash
et al. compared oral zinc sulfate, calcium pantothenate, a com-
bination of zinc and calcium, and 2% minoxidil solution on
women with hair loss in a 4-month, prospective, randomized
controlled trial (n=73).
25
All groups demonstrated positive out-
comes, with a significant change in hair thickness in the zinc
group.
25
Patient assessments showed that 88.8% receiving
minoxidil saw improvement, 85% in the combination group saw
improvement, while 55.5% receiving zinc alone reported
improvement.
25
Further studies are needed to evaluate the effi-
cacy and role of zinc in hair loss.
Capsule summary
Considering evaluation for serum zinc deficiency in patients with
hair loss, these patients may benefit from oral supplementation.
Oral zinc supplementation was shown to have no benefit on hair
growth in patients with AA in one study. There is mild support
for increase in hair thickness with zinc supplementation in
women with hair loss.
Iron
Iron is an essential element for red blood cell production,
enzyme and transcription factor function, oxidation-reduction
reactions, and DNA synthesis.
2
Iron deficiency is the most com-
mon nutritional deficiency in the world.
1
Low serum ferritin, an
iron-binding protein, is the most sensitive and specific marker of
iron deficiency.
2
However, in patients with inflammatory dis-
eases, infections, or cancer, ferritin may be elevated despite
low iron stores.
Vegans and vegetarians are at risk for iron deficiency as non-
heme iron from plant-based foods has a lower bioavailability
than heme iron in meats and poultry.
20
Vitamin C co-administra-
tion helps absorb more nonheme iron.
1
Menstruation and preg-
nancy are the most common causes of iron deficiency in
premenopausal women.
2
In men and postmenopausal women,
malabsorption and gastrointestinal blood loss are the most com-
mon causes of iron deficiency.
2
Other than acute overdose and
genetic conditions like hemochromatosis, adults with normal
functioning intestinal tracts and normal diets have a very low
risk of iron overload.
Data on iron levels in hair loss conditions are inconsistent. In
a study comparing serum ferritin in females with telogen efflu-
vium or FPHL (n=80) to age-matched healthy controls
(n=40), serum ferritin was significantly lower in telogen efflu-
vium and FPHL patients, using a cut-off value of 27.5 and
29.4 lg/l.
11
However, Olsen et al. compared serum ferritin in
women with FPHL and chronic telogen effluvium (CTE)
(n=381) to healthy controls (n=76) and found no statistically
significant difference in iron deficiency in FPHL or CTE com-
pared to controls.
26
Of note, oral ingestion of L-lysine has been reported to
improve iron absorption.
27
L-lysine is an essential amino acid
found in meat, fish, and eggs.
27
In one study evaluating iron
supplementation, some participants only achieved a modest
increase in serum ferritin with 50 mg twice daily oral elemental
iron; adding oral L-lysine (1.5–2 g/day) resulted in a significant
increase in mean serum ferritin.
27
The exact role essential
amino acids have on hair growth and trace element absorption
is still unclear.
27
Capsule summary
Iron supplementation may be beneficial in patients at risk for
deficiency and should be approached on a case-by-case basis
on objective ferritin levels. There is weak evidence supporting
the use of oral iron supplements in all hair loss patients.
Selenium
Selenium is a trace element that is essential for the proper func-
tion of multiple antioxidant and anti-inflammatory proteins.
1
Both
selenium deficiency and toxicity are associated with hair loss.
1
Deficiency is rare in the developed world; at-risk patients
include those with HIV, patients receiving dialysis, and patients
receiving total parenteral nutrition.
1
Chronic toxicity may result
from excessive Brazil nut consumption, and acute toxicity has
occurred from improperly formulated over-the-counter supple-
ments.
1
To date, no clinical trials have evaluated the effects of
selenium supplementation on hair growth.
Capsule summary
There is no existing evidence supporting selenium supplemen-
tation to promote hair growth.
Plant derivatives/nutraceuticals
Pumpkin seed oil
In recent years, pumpkin seed oil (PSO) has gained popularity
in the world of alternative medicine as clinical trials have
revealed its multi-beneficial effects as antidiabetic, antibacterial,
antioxidant, and anti-inflammatory agent.
28
PSO is a rich source
of zinc, iron, potassium, selenium, magnesium, and calcium.
29
Additionally, PSO is able to block 5-alpha reductase (which con-
verts testosterone to the more potent dihydrotestosterone),
making it antiandrogenic.
30
In theory, this function would make
it an optimal complementary treatment for androgenetic alope-
cia.
In a 24-week randomized, double-blind, placebo-controlled
trial by Cho et al., patients with androgenetic alopecia received
400 mg of oral PSO (n=76).
30
Hair count and hair diameter
were assessed by phototrichography at baseline and 12 and
24 weeks.
30
Phototrichography revealed a statistically
ª2020 the International Society of Dermatology International Journal of Dermatology 2020
Adelman, Bedford, and Potts Oral hair growth supplement ingredients Review 5

significant increase in hair count in the active group.
30
However,
the supplement contained additional ingredients, making the
exact effect of PSO uncertain. Additionally, this trial only evalu-
ated the effects in patients with androgenetic alopecia. More
studies are needed to evaluate the efficacy of oral PSO on hair
growth.
Capsule summary
There is mild evidence supporting the use of PSO as a comple-
mentary or alternative treatment in androgenetic alopecia. How-
ever, there is insufficient clinical evidence supporting its use in
all hair loss conditions.
Saw palmetto: Serenoa repens
Saw palmetto extract is one of the most expensive oils on the
pharmaceutical and health food market.
31
As a natural 5-alpha
reductase inhibitor, it is used widely for the treatment of benign
prostatic hyperplasia.
31
In theory, this mechanism would also
make it an optimal complementary treatment for androgenetic
alopecia.
Rossi et al. compared the effects of saw palmetto to finas-
teride in patients with androgenetic alopecia in a 2-year open-
label trial (n=100).
32
Patients received either saw palmetto
320 mg daily or finasteride 1 mg daily. FotoFinder Dermoscope
with TrichoScan analysis of standardized global photographs
was used to measure hair density at baseline and after
24 months.
32
Results showed an increase in hair growth in 68%
of patients treated with finasteride and 38% treated with saw
palmetto.
32
Rossi et al. concluded that saw palmetto is effica-
cious in the treatment of androgenetic alopecia.
32
Prager et al. evaluated the effectiveness of saw palmetto in
androgenetic alopecia in an 18-week randomized, double-blind,
placebo-controlled study (n=19).
31
Results showed that 60%
of patients in the active treatment group improved, compared to
only 11% in the placebo group.
31
However, there are no clinical
trials evaluating saw palmetto in other hair loss conditions. More
studies are needed to evaluate the effectiveness of oral saw
palmetto on hair growth.
Capsule summary
There is mild evidence supporting the use of saw palmetto as a
complementary or alternative treatment in androgenetic alope-
cia. However, there is insufficient clinical evidence supporting
its use in all hair loss conditions. More trials are necessary to
further validate the results of the studies of Rossi et al. and Pra-
ger et al. and determine proper use.
Ashwagandha: Withania somnifera
Ashwagandha is an antioxidant and adaptogen botanical that
has long been paramount to the practice of ayurvedic medi-
cine.
33
Adaptogens are herbs that claim to help the body main-
tain homeostasis through a greater stress response,
33
and
stress is a well-known catalyst for hair loss. Animal studies and
in vitro studies on human hair follicles have shown that stress-
mediated substances inhibit hair growth.
34
It is therefore plausi-
ble that the antistress properties of ashwagandha are beneficial
for hair growth.
35
In an 8-week randomized, double-blind, placebo-controlled
trial, Salve et al. investigated the effects of oral ashwagandha
supplementation in stressed healthy adults (n=60).
33
Stress
was assessed using a perceived stress scale (PSS) at baseline
and 4 and 8 weeks. Serum cortisol was measured at baseline
and at 8 weeks.
33
Salve et al. concluded that ashwagandha is
associated with a significant reduction of perceived stress and
noted a significant decrease in serum cortisol in the active treat-
ment group compared to placebo group.
33
These antistress
properties make ashwagandha a feasible complementary or
alternative anti-hair loss supplement.
Ashwagandha has also been shown to have effects on
testosterone.
36
In an 8-week, double-blind, placebo-controlled
study, Wankhede et al. evaluated the effects of oral ashwa-
gandha root (300 mg twice daily) on serum testosterone in
young males (n=57).
36
At 8 weeks, there was a significant
increase in testosterone levels in the treatment group relative to
the placebo group.
36
A separate 60-day randomized, double-blind, placebo-con-
trolled trial evaluated the efficacy and tolerability of ashwa-
gandha extract on stress, anxiety, and hormone production in
healthy adult females (n=23) and males (n=37).
37
Dehy-
droepiandrosterone-sulfate (DHEA-S), an inactive steroid pre-
cursor that can be converted into androgens and estrogens, is
secreted by the adrenal cortex and the most abundant circulat-
ing steroid in humans.
38
DHEA-S was measured at baseline
and 30 and 60 days, and testosterone was measured at base-
line and 60 days.
37
Both males and females in the treatment
group had a significant reduction in DHEA-S.
37
In the male
patients, testosterone increased by 11.4% in the active group
and 0.1% in controls; however, this increase was not statisti-
cally significant, likely because of small sample size.
37
Testos-
terone levels did not change significantly between females in
the active and control groups.
37
The implication of these find-
ings and their relationship to hair growth require further
research.
Another claimed that the mechanism in which ashwagandha
promotes hair growth is through induction of endothelial nitric
oxide synthase.
35
This results in improved blood flow and
increased oxygen and nutrient delivery to the scalp.
35
However,
there are no clinical trials evaluating the direct effect of ashwa-
gandha on hair growth.
Capsule summary
Based on current literature, there is some evidence supporting
the use of ashwagandha as a complementary or alternative
treatment through its antistress properties. However, there is
insufficient clinical evidence supporting its use in hair loss con-
ditions.
International Journal of Dermatology 2020 ª2020 the International Society of Dermatology
Review Oral hair growth supplement ingredients Adelman, Bedford, and Potts
6

Curcumin: Curcuma longa
Curcumin, made from turmeric, is another botanical that has
been used for centuries in ayurvedic medicine.
35
It is mostly
used in Western medicine as an anti-inflammatory, but it has
also been shown to exhibit antioxidant, antimicrobial, antineo-
plastic, antidiabetic, hepatoprotective, and cardioprotective prop-
erties.
35
It is believed that the anti-inflammatory and antioxidant
properties of curcumin may counteract the inflammatory compo-
nent of hair loss, promoting hair growth.
35
Additionally, in vitro studies on curcumin and prostate cancer
cell lines have shown that curcumin has an antiandrogenic
property as well.
35
This mechanism opens the possibility that
curcumin may have a role in treatment of androgenetic alope-
cia. However, there are no clinical trials evaluating the effect of
oral curcumin on hair growth.
Of note, oral ingestion of curcumin alone is poorly absorbed
and rapidly metabolized.
39
Piperine, a botanical found in black
pepper and long pepper, may be included in an oral supplement
formulation with curcumin to increase its bioavailability.
39
Piper-
ine inhibits the enzyme responsible for curcumin metabolism.
Comparative studies have shown that co-administration of
piperine with curcumin can increase curcumin bioavailability by
154% compared to curcumin alone.
39
Capsule summary
There is insufficient clinical evidence supporting the use of oral
curcumin in hair loss conditions.
Capsaicin
Capsaicin is the compound responsible for spiciness of hot pep-
pers.
40
Topical capsaicin-based formulations have long been
used in the treatment of neuropathic and musculoskeletal
pain.
40
Oral capsicum has been shown to exhibit antioxidant proper-
ties, improve metabolism, reduce insulin resistance, and
improve cardiovascular health.
40
Ehsani et al. compared the effects of topical capsaicin to clobe-
tasol ointment in patients with AA in a 12-week open-label trial.
41
There was a statistically significant increase in vellus and noncos-
metic hair growth in those using capsaicin compared to clobetasol
but no significant difference in cosmetically significant hairs.
41
In a 5-month study, Harada et al. evaluated the effects of oral
capsaicin (6 mg/day) and isoflavone (75 mg/day) to placebo on
serum insulin-like growth factor-1 (IGF-1) and global hair growth
in patients with alopecia (n=48).
42
IGF-1 inhibits apoptosis
and helps maintain hair follicles in the anagen stage.
43
Serum
IGF-1 was significantly increased from baseline in patients
receiving oral capsaicin and isoflavone compared to placebo.
42
The treatment group also experienced a significantly higher pro-
motion in hair growth (Fig. 4).
42
There is no published data
evaluating the effects of oral capsaicin alone on hair growth.
Capsule summary
There is insufficient clinical evidence supporting the use of oral
capsaicin in hair loss conditions.
Horsetail (Equisetum)
Horsetail is a herbaceous plant, long used in traditional medi-
cine for its anti-inflammatory, antioxidant, and antimicrobial
properties.
44
It has also been shown to inhibit 5-alpha reductase
in vitro, which may lead to prevention of hair loss.
45
Horsetail is
characterized by a high concentration of silicon, a mineral
important for optimal collagen synthesis.
46
A previous study
demonstrated that physiological concentrations of orthosilicic
acid are able to stimulate collagen type I synthesis by skin
fibroblasts.
46
It is hypothesized that stimulating fibroblasts in the
dermis may result in an increased volume and flow of nutrients
to the base of hair follicles, promoting hair growth and thick-
ness.
46
In a 20-week randomized, placebo-controlled, double-blind
study, Barel et al. evaluated the effects of oral choline-stabilized
orthosilicic acid (10 mg/day) on hair and nails in females with
photoaged skin (n=50).
47
Patients’ hair and nail brittleness
were evaluated at baseline and 20 weeks by a virtual analog
scale, with significantly lower scores in the active group at the
end of treatment compared to placebo.
47
Wickett et al. evaluated the effects of oral choline-stabilized
orthosilicic acid (10 mg/day) on hair morphology and tensile
strength in a 9-month randomized, place-controlled, double-
blind study in women with fine hair (n=48).
46
Although hair
elasticity decreased in both groups, the change was significantly
smaller in the active group.
46
The active group also showed a
Figure 4 Effect of oral administration of capsaicin and isoflavone
for 5 months on hair growth in four volunteers with alopecia.
Photographs at baseline and after treatment in (a) a 52-year-old
male with androgenetic alopecia, (b) a 29-year-old male with
alopecia totalis, (c) a 39-year-old female volunteer with
androgenetic alopecia, and (d) a 40-year-old female volunteer with
alopecia areata
ª2020 the International Society of Dermatology International Journal of Dermatology 2020
Adelman, Bedford, and Potts Oral hair growth supplement ingredients Review 7

significant change in cross-sectional area, indicating that oral
orthosilicic acid results in thicker hair.
46
Capsule summary
Based on current literature, there is some evidence supporting
the use of horsetail as a complementary or alternative treatment
to promote skin and hair health. More trials are necessary to
further validate the results of the studies of Barel et al. and
Wickett et al. and determine proper use.
Other
Methylsulfonylmethane (MSM)
Methylsulfonylmethane (MSM), a natural, sulfur-containing
compound found in plants and milk, has become a popular
anti-inflammatory supplement in arthritis and sports
medicine.
48
Oral supplementation is well tolerated with no
known risk of toxicity.
48
In dermatology, oral MSM has been
reported to improve skin firmness, tone, texture, and reduce
rhytides.
48
MSM is thought to promote skin, hair, and nail health through
donating sulfur to keratin amino acids.
49
In a 16-week, double-
blind study, Muizzuddin et al. evaluated the effects of oral MSM
on hair in healthy middle-aged women (n=63).
49
Measure-
ments included expert clinical grading of hair shine, volume, tri-
choptilosis (split ends), and subject self-assessment.
49
There
was a statistically significant increase in hair volume and
improvement in hair shine in the treatment groups.
49
Capsule summary
Based on current literature, there is some evidence supporting
the use of methylsulfonylmethane as a complementary or alter-
native treatment to promote skin and hair health. More trials are
necessary to further validate the results of the study of Muiz-
zuddin et al. and determine proper use.
Nutraceuticals
Nutraceutical refers to foods or supplements with biologically
active properties in addition to basic nutrition.
50
The colossal
diversity of marine ecosystems has provided numerous
resources and bioactive compounds to utilize in human
health.
50
Marine-derived formulations on the market offer an
array of benefits from neuroprotection and cardiovascular risk
reduction to antiaging effects.
50
AminoMar

marine complex
The AminoMar

marine complex is a proprietary blend of shark
and mollusk powder.
51
Multiple clinical trials have evaluated the
effects of oral AminoMar

supplementation on hair. AminoMar

is administered in a capsule with other ingredients, including
vitamin C, B vitamins, zinc, calcium, iron, and horsetail
extract.
52
Rizer et al. evaluated the effects of oral AminoMar

in pre-
menopausal women (n=96) with subclinical hair thinning in a
6-month randomized, double-blind, placebo-controlled study.
51
Hair shedding assessed by collection during shampooing and
hair diameter assessed by phototrichography were evaluated at
baseline and 3 and 6 months.
51
The active group demonstrated
a significant reduction in hair shedding and a statistically signifi-
cant increase in mean vellus-like hair diameter.
51
In a separate 6-month randomized, double-blind, placebo-
controlled study, Ablon et al. evaluated the effects of oral
AminoMar

in men with thinning hair.
52
Total hair count, hair
density, and anagen hair rate were assessed with TrichoScan
software at baseline and 3 and 6 months, along with hair pull
tests and self-assessment questionnaires.
52
All efficacy mea-
sures were significantly improved in the active treatment
group.
52
Lassus et al. evaluated the effects of oral AminoMar

com-
pared to fish extract in young men with hereditary androgenetic
alopecia (n=40) in a 6-month randomized, double-blind, pla-
cebo-controlled study.
53
Nonvellus hair counts were performed,
and punch biopsies were taken at baseline and 6 months.
53
At
the end of treatment, there was a mean increase of 38.1% of
new nonvellus hair in the active group compared to a mean
increase of 2.1% of new nonvellus hair in the control group.
53
Additionally, 19 of 20 patients in the active treatment group
showed no alopecia by histological examination, while 17 of 20
patients in the control group demonstrated histologic evidence
of alopecia with perifollicular inflammation.
53
Multiple other studies have demonstrated similar, statistically
significant beneficial effects of AminoMar

on males and
females with thinning hair, AA including alopecia totalis, and
hereditary androgenetic alopecia.
54
Synergen Complex

The Synergen Complex

contains hydrolyzed marine collagen
type I and type III and is administered in a capsule with other
ingredients, including phytoactive compounds such as ashwa-
gandha, saw palmetto, and curcumin.
Ablon et al. evaluated the effects of oral Synergen Complex

in women with self-perceived thinning hair in a 6-month random-
ized, double-blind, placebo-controlled study (n=40).
55
Total
hair count, terminal, and vellus hair counts were analyzed at
baseline and 3 and 6 months by phototrichogram.
55
Subjects
also completed self-assessment questionnaires, and blinded
investigators assessed global hair growth and quality improve-
ment.
55
All primary and secondary efficacy measures were sig-
nificantly improved in the active treatment group.
55
Nourkrin

Nourkrin

is another natural agent with marine proteins, vita-
mins, and minerals. The efficacy and tolerability of Nourkrin

was evaluated in a 6-month randomized, double-blind, placebo-
controlled study, in subjects with hair loss of different etiologies
International Journal of Dermatology 2020 ª2020 the International Society of Dermatology
Review Oral hair growth supplement ingredients Adelman, Bedford, and Potts
8

(n=55).
56
Hair counts at baseline and at 6 months from prede-
termined areas were performed along with subject self-evalua-
tion of satisfaction assessments.
56
The active group had an
average hair growth increase of 35.7%, while the placebo group
had an average growth of 1.5%.
56
There was also a highly sig-
nificant difference in self-evaluations between the groups, with a
higher degree of satisfaction in the active group.
56
Capsule summary
Based on current literature, there is strong evidence supporting
the use of AminoMar

as a complementary treatment to pro-
mote hair growth in hair loss conditions. There is evidence
from a small study supporting the use of Synergen Complex

as a complementary treatment to promote hair growth in hair
loss conditions. Based on current literature, there is evidence
from a small study supporting the use of Nourkrin

as a com-
plementary treatment to promote hair growth in hair loss condi-
tions.
Overall, there is evidence supporting the use of marine com-
plex formulations in hair loss conditions. The exact mechanism
of these complexes is still unknown. All marine complex
formulations are unique and administered with different vitamins
and minerals, many of which have not been shown to demon-
strate significant impact on hair growth. Further research of
these individual ingredients in larger prospective trials is needed
to elucidate their mechanisms and extent of effects on hair
growth.
Summary
Oral supplements are an increasingly popular category of over-
the-counter hair loss treatments. Patients often experiment with
supplements before seeking advice or treatment from a derma-
tologist or primary care physician. As supplements are not FDA
regulated, large, peer-reviewed clinical studies are crucial in
determining the efficacy and safety of ingredients in these sup-
plements. Table 1 provides a summary of all ingredients
reviewed in this paper.
Of the vitamins and minerals reviewed, vitamin A, vitamin D,
biotin, niacin, and selenium have no clinical evidence supporting
their use as an oral supplement alone. Vitamin C and iron have
weak evidence supporting their use in iron-deficient patients as
oral supplements. Vitamin E and zinc have mild evidence
Table 1 All reviewed oral hair supplement ingredients
Hair
count
increase Antiandrogen
Blood
flow
Improves bioavailability
of a different ingredient Antioxidant
Stress
modulation
Deficiency
affects
hair
Toxicity
affects
hair
Vitamins
Vitamin A X
5
(provitamin
A)
X
3
Vitamin C X
1
X (iron)
1
X
1
X
1
Vitamin D
Vitamin E X
12
X
1
X
1
Biotin (B7) X
1
Niacin (B3) X
20
X
19
Minerals
Zinc X
1
Iron
Selenium X
1
X
1
Plant derivatives
Pumpkin seed oil X
28
X
28
X
27
Saw palmetto (Serenoa
repens)
X
29,30
X
29
Ashwagandha X
33
X
31
X
31
Curcumin (Turmeric) X
33
Piperine (Black Seed
Pepper)
X (curcumin)
34
Capsaicin X
37
X
35
Horsetail X
39
Other
Methylsulfonylmethane
(MSM)
Nutraceutical
AminoMar

X
45,46,47,48
Synergen Complex

X
49
Nourkrin

X
50
ª2020 the International Society of Dermatology International Journal of Dermatology 2020
Adelman, Bedford, and Potts Oral hair growth supplement ingredients Review 9

supporting their use in hair loss conditions, with larger clinical
trials needed to fully investigate their mechanism, safety, and
efficacy.
Ashwagandha, curcumin, and capsaicin have no clinical evi-
dence supporting their use as oral supplements in hair loss con-
ditions. There are small studies giving evidence supporting the
use of PSO and saw palmetto as complementary or alternative
treatment in androgenetic alopecia. Horsetail and methylsul-
fonylmethane have mild evidence supporting their use as com-
plementary treatments to promote skin and hair health.
Marine complexes, specifically AminoMar

, have demon-
strated a positive impact on hair health. The Synergen Com-
plex

and Nourkrin

both have mild evidence supporting their
use in hair loss conditions, with further trials necessary to vali-
date clinical efficacy. Again, these complexes are all unique and
administered with diverse cocktails of ingredients. More
research and investigation are needed to fully understand the
role of marine complexes in hair loss conditions.
Questions (answers after references)
1Which of the following can be obtained through consumption
of meat?
a Beta-carotene
b Preformed vitamin A
c Vitamin C
d Selenium
2Low serum levels of which of the following have been associ-
ated with androgenetic alopecia?
a Vitamin A
b Biotin
c Zinc
d Iron
3Low serum levels of which of the following have been associ-
ated with telogen effluvium?
a Biotin
b Zinc
c Iron
d Vitamin E
4Consumption of which of the following enhances iron absorp-
tion?
a Vitamin C
b Biotin
c Zinc
d Selenium
5Deficiency of which of the following is NOT associated with
hair loss?
a Vitamin C
b Niacin
c Biotin
d Selenium
6Which of the following has antiandrogenic properties?
a Horsetail
b Pumpkin seed oil
c Curcumin
d Capsaicin
7Which of the following has stress-modulating properties?
a Ashwagandha
b Saw palmetto
c Horsetail
d Curcumin
8Piperine (black pepper seed) enhances the absorption of:
a Saw palmetto
b Capsaicin
c Horsetail
d Curcumin
9True or false: Nutraceutical refers to food or food-derived
nutrients with medicinal, health-promoting, disease-preventing
properties.
10 True or false: There is no evidence that oral nutraceuticals
promote hair growth.
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Answers to Questions
1Answer: B. Preformed vitamin A is available in the human
diet through consumption of meat.
2Answer: C. Low levels of serum zinc have been associated
with androgenetic alopecia.
3Answer: C. Low levels of serum iron have been associated
with telogen effluvium.
4Answer: A. Consumption of vitamin C enhances intestinal
iron absorption.
5Answer: A. Although vitamin C deficiency results in abnormal
hair morphology, it does not result in hair loss.
6Answer: B. Pumpkin seed oil is able to block 5-alpha reduc-
tase, an enzyme that converts testosterone to the more
potent dihydrotestosterone, making it antiandrogenic.
7Answer: A. Ashwagandha has stress-modulating properties.
8Answer: D. Co-administration of piperine with curcumin can
increase curcumin bioavailability by over 100% compared to
curcumin alone.
9Answer: True. Nutraceuticals are natural, bioactive com-
pounds derived from food with both nutritional and medicinal
properties.
10 Answer: False. There is evidence from multiple clinical trials that
oral nutraceuticals have a beneficial effect on hair growth.
International Journal of Dermatology 2020 ª2020 the International Society of Dermatology
Review Oral hair growth supplement ingredients Adelman, Bedford, and Potts
12