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Open Access Review Article Epidemiology and Public Health

Diet and Vitiligo: The Story So Far

Rajoshee R. Dutta 1, Tanishq Kumar 1 , Nishikant Ingole 2

Received 08/09/2022 1. Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, IND 2.
Review began 08/13/2022 Pharmacology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, IND
Review ended 08/22/2022
Published 08/28/2022
Corresponding author: Rajoshee R. Dutta, [email protected]
© Copyright 2022
Dutta et al. This is an open access article
distributed under the terms of the Creative
Commons Attribution License CC-BY 4.0.,
which permits unrestricted use, distribution, Abstract
and reproduction in any medium, provided
Vitiligo is an acquired skin pigmentation disease with a global burden of 0.5 to 2 percent of the population.
the original author and source are credited.
Vitiligo therapy frequently poses a difficulty, which has sparked interest in alternative treatment modalities,
DOI: 10.7759/cureus.28516 including multivitamins and herbal supplementation. It has previously been established that nutrition plays
a crucial role in developing, amplifying, or rehabilitating an array of human disorders. However, the
correlation between diet diversity and immune-mediated skin diseases is still up to interpretation. Several
supplements have been studied, including vitamins, minerals, and herbal supplements. Most studies agree
that combining vitamin B12, folic acid, and sun exposure is good for inducing repigmentation.
Supplementation of zinc and phenylalanine when used in conjunction with topical steroids or UV-B
(ultraviolet B) treatment shows therapeutic effects on vitiligo due to their role in the melanin synthesis
pathway. Investigations conducted on herbal supplements have revealed that most of them contain
antioxidants, which aid in repigmentation. This narrative review's purpose is to discuss nutrition's function
in immune-mediated inflammatory skin diseases from the perspective of the most recent and reliable
information available.

Categories: Family/General Practice, Nutrition, Dermatology

Keywords: steroid treatment, herbal supplements, narrowband, puva, dietary supplementation, oxidative stress,
pigmentation, melanin, melanocytes, vitiligo

Introduction And Background

A depigmenting skin pathology, vitiligo leads to hypopigmentation in afflicted regions of the skin by a
gradual decrease in melanocytes. Current knowledge of vitiligo pathogenesis has recently advanced and is
now categorically recognized as an autoimmune disorder connected with hormonal and hereditary
influences in addition to disorders involving metabolism, oxidative stress, and cell disintegration. According
to new hypotheses, melanocytorrhagy and poor melanocyte viability are major factors. The hallmark lesion
is an amelanotic, non-scaly, chalky-white macule with clear edges [1,2]. The skin commonly affected is that
of the face, lips, hands, arms, feet, and genitalia. Additionally, affected areas typically have white hairs.
However, the underlying etiopathogenic process of vitiligo is still uncertain [3]. By repairing damaged
pigments or removing persisting pigments, vitiligo therapy aims to reduce its severity. Food supplements
and a nutrient-dense diet might be seen as essential components of treatment for vitiligo [4]. Although
vitiligo is a common condition, it was recently overlooked in dermatology and treated as an ‘orphan illness’
for therapeutic development. Patients frequently claim that doctors are not up to date regarding treatment
modalities, and most view vitiligo as a "cosmetic condition” [5]. According to physicians, the focus of future
studies should be on novel strategies such as quality of life (QOL) assessments that assess patient
satisfaction.

Review
Epidemiology
Vitiligo has a reported incidence of 0.5 to 1 percent worldwide [6]. With an estimated 8.8% incidence rate,
Gujarat, India, has by far the highest incidence worldwide [7]. Men and women both suffer from the
condition [8,9], although women have been found more likely to seek medical assistance. Young women (up
to 30 years of age) have a much higher prevalence of vitiligo than young males [8,10]. Women peak by early
adolescence, whereas males reach their peak by 45-60 [5].

Types of therapy
One of the most challenging dermatological concerns is currently treating vitiligo. Nevertheless, recent
years have seen the development of safe and efficient therapies. Therapies that may slow the condition’s
progression, transform depigmented patches, and promote repigmentation include phototherapy, systemic
and topical immunosuppressive agents, and surgical procedures [11,12]. The type of vitiligo (segmental or
non-segmental), severity, distribution, frequency, age of the patient, type of skin, and willingness to be
consistent with therapy are the factors influencing the effectiveness of the treatment. Lips, hands, and feet
are likely more resistant to treatment, whereas the head, neck, face, abdominal regions, arms, and legs
recover favorably [12]. Repigmentation first develops either at the edges of the lesions or in a specific type of

How to cite this article

Dutta R R, Kumar T, Ingole N (August 28, 2022) Diet and Vitiligo: The Story So Far. Cureus 14(8): e28516. DOI 10.7759/cureus.28516
 Published via DMIHER School of
Epidemiology and Public Health

pattern known as “perifollicular." The treatment’s efficacy must be evaluated after at least 2-3 months. The
most popular kind of treatment for vitiligo involves UV radiation and, when coupled with other therapies,
has been linked to better results [13].

Vitamin B12 and folic acid

Vitamin B12 (also known as cobalamin) constitutes one of the nine water-soluble vitamins and one of the
eight vitamin B types [14]. It is one of the most common deficiencies and, if left untreated, might result in
blood and nerve disorders [15]. A non-vegetarian diet, including meat, eggs, and dairy products, is a good
source of Vitamin B12. The normal B12 consumption is 2.4 μg per day. Only fifty to sixty percent is absorbed
[16,17]. Vitamin B12 has been shown to be useful for repigmentation in patients suffering from vitiligo. Folic
acid (or vitamin B9) has been proven to be significant for treating vitiligo. It needs to be included in the diet
as the body cannot synthesize it. According to an original study conducted in the Birmingham Medical
Center, the University of Alabama, 15 patients diagnosed with vitiligo were reported to have low levels of
Vitamin B12 and B9. After administering eight of these patients with vitamin B12 and B9 for three years,
repigmentation was observed [14]. More research is needed to identify the correct dosage of Vitamin B12
and B9 and the duration for which the skin should be exposed to the sun [18].

Vitamin C
Vitamin C constitutes one of the water-soluble vitamins. Majorly present in citrus fruits like lemon, kiwi,
oranges, and green leafy vegetables. Vitamin C should be a part of a balanced diet. It has been indicated that
vitamin C has antioxidant action and immunomodulatory characteristics [19,20]. Vitamin C is not used and
is contraindicated in treating vitiligo as it disrupts the melanin production pathways [21].

Vitamin D
Vitamin D is a fat-soluble vitamin that absorbs substances like calcium and magnesium. Vitamin D acts on
the skin receptors and disrupts the growth and development of melanocytes and keratinocytes [22,23]. 25-
hydroxyvitamin D₃ (calcifediol) acts on dihydroxy vitamin D3 receptors on the melanocytes to initiate
melanin secretion [24]. According to research, vitamin D levels impact the immune system as the immune
system has enzymes/metabolites that can metabolize vitamin D, indicating that the immune system is also
contributing to converting inactive forms of vitamin to active forms of calcitriol. This establishes a
relationship between the normal functioning of the body’s immune system and circulating vitamin D levels.
Any impairment in vitamin D levels would result in disruption of immune system physiology. It can be
assumed that dysregulation of the immune system might increase the chances of developing autoimmune
diseases. Therefore, if the proper dosage of vitamin D is administered in patients showing vitamin D
insufficiency, the outcome of treatment for autoimmune disorders can significantly increase the chances of
favoring the patient [25]. Still, insufficient medical evidence indicates that low vitamin D could result in
vitiligo. Due to this relation to the immune system, it is highly recommended to include it in the therapy for
treating vitiligo. Several studies have been conducted to understand the effect of vitamin D in vitiligo
patients. According to a pilot study by Finamor et al., which comprised 16 patients, 35000 IU (international
unit) of vitamin D3 was regularly administered every day for six months. Out of 16, 14 patients showed 25%
to 75% repigmentation, concluding that supplementation of vitamin D could decrease disease
progression [26].

Zinc
More than three thousand proteins, such as hormones, enzymes, and nuclear factors, require zinc as a
cofactor for their normal functioning. Superoxide dismutase, a skin antioxidant, uses zinc as an enzyme
cofactor [27]. Zinc also controls gene expression. Zinc may also inhibit melanocyte destruction since
apoptotic caspases are activated when intracellular zinc concentrations drop [28]. Combined with topical
steroids, zinc has been proven to be a marginal advantage in managing vitiligo. Nonetheless, this needs
additional investigation. However, treatment-related gastrointestinal adverse effects are a factor that limits
zinc supplementation [28]. In an experiment by Yaghoobi et al., 13.3% of zinc-taking
participants reported gastric discomfort [29]. Table 1 outlines the properties and impact of the supplements
mentioned above on managing vitiligo.

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Supplement Properties Impact on Management of Vitiligo

Vitamin B12 and Folic Repigmentation induced with supplementation along with sun exposure, complete repigmentation on following complete
DNA synthesis, repair, and methylation
Acid therapy

Vitamin C Antioxidant and immunomodulatory function Contraindicated as it causes disturbances in the melanin synthesis pathway

Vitamin D Immune system function Decreases disease progression when supplemented with standard therapy

Cofactor for normal functioning of hormones and enzymes inhibits melanocyte

Zinc Provides marginal advantage when combined with topical steroids
destruction

TABLE 1: Summary of Vitamin and Mineral Supplementation in Vitiligo

DNA: Deoxyribonucleic acid

Ginkgo biloba
An ancient Chinese plant, Ginkgo biloba (GB) has recently acquired considerable attention for its
contribution to the treatment of a number of ailments, particularly vitiligo, dementia, macular
degeneration, anxiety, and cardiovascular disease [30]. A decrease in cyclooxygenase activity and Tumour
Necrosis Factor alpha's role (TNF-a) in inducing the production of interleukin-8 and vascular endothelial
growth factor (VEGF) are hypothesized to be the mechanisms of anti-inflammatory effects shown by GB [31].
These qualities shown by ginkgo have been claimed as therapeutic due to the pivotal role of oxidative stress
in the pathogenesis of vitiligo. Furthermore, as emotional anxiety was found to aggravate vitiligo, ginkgo’s
anxiolytic qualities could slow down the spread of the condition. The majority of individuals consume
GB without experiencing any negative side effects, however mild gastrointestinal disturbance is the most
frequent side effect. Ginkgo is a viable alternative medicine that has been found to slow the advancement of
the illness and enhance repigmentation, according to the findings of two trials.

Polypodium leucotomos
A species of fern called Polypodium leucotomos (PL) has been investigated for its significance in the
treatment of a number of skin problems, particularly vitiligo, psoriasis, atopic dermatitis, and in preventing
UV-induced skin damage. Investigations have been done on the anti-inflammatory, antioxidant,
photoprotective, and immunomodulatory properties of PL. When used with phototherapy, ingesting PL is
used to boost the efficacy of narrowband UV-B in treating vitiligo [32,33]. It was further established that
combining PL with PUVA (psoralen plus ultraviolet-A radiation) treatment results in an increased re-
pigmentation. More participants who got >50% re-pigmentation were within the group undergoing PUVA
along with PL than the group undergoing PUVA with placebo. All subjects saw the successful treatment of
their condition following Anopsos therapy for five months, which is a hydrosoluble lipid derivative of PL
[34].

Khellin
Khellin is a crystalline extract from the plant Ammi visnaga and it has been utilized in traditional medicine
throughout the Mediterranean. Orally administered activated khellin is being studied as a promoter of
melanogenesis and proliferation of cultured normal human melanocytes and Mel-1 melanoma cells. These
have a possible role in photosensitizing vitiligo treatment when paired with UV therapy. In comparison to
no treatment, the combination of 4 percent preparation of topical khellin with monochromatic excimer laser
(MEL) treatment at 308 nm, effectively reduced depigmented lesions [35]. Although no discernible difference
has been noted in the performance of phototherapy alone and phototherapy with topical khellin, no support
substantiates the claimed advantages of topical khellin [36].

Gluten
Celiac disease (referred to as CD) is an autoimmune intestinal infection characterized by individuals who
have an adverse reaction to gluten. Damage to the intestinal mucosa, mostly in the form of diarrhea,
abdominal discomfort, and other gastrointestinal symptoms, can result from the condition. According to
several studies [37,38], people with CD had an increased prevalence of vitiligo than those without CD.
Patients who are seropositive for CD immune cells and have autoimmune skin diseases including psoriasis,
dermatitis hepatitis, and vitiligo have reportedly experienced fewer symptoms after switching to a gluten-
free diet (commonly referred to as GFD) [39-41]. Such type of knowledge is crucial for treating vitiligo
patients because the intestinal symptoms are typically vague and frequently disregarded by medical
professionals and patients. Additionally, people with vitiligo may benefit from CD screening and CD patients
with an early diagnosis of vitiligo may benefit from GFD because it may help both illnesses. To further
support these observations, large-scale, long-term follow-up investigations are necessary.

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Phenylalanine
The amino acid phenylalanine (Phe) is hypothesized to operate as a possible cure for vitiligo due to its
crucial role in the regulation of catecholamine, antibody synthesis, and most importantly, melanin
formation. These form the basis of the autoimmune and neurological pathophysiology of vitiligo.
Phenylalanine is hydroxylated to tyrosine, which is then used in the process of melanogenesis.
Phenylalanine and tyrosine are also closely involved in the production of catecholamines. According to the
neural hypothesis, the etiopathogenesis of vitiligo was associated with catecholamines released by
autonomic nerve terminals, either directly or indirectly [42]. Phenylalanine or metabolite levels that disrupt
catecholamine production may impact vitiligo onset or advancement. Each participant participated as their
own control in a clinical investigation that investigated phenylalanine’s impact on vitiligo. After four
months of UV-A treatment, the subjects received oral phenylalanine (50 mg/kg) twice a week for the first
four months. When the treatments were administered separately, no improvement was detected. Upon
administering phenylalanine along with UV-A irradiation, 94.7 percent of individuals exhibited follicular re-
pigmentation and 26.3 percent exhibited dense repigmentation [43].

Phyllanthus embelica
Phyllanthus embelica Linn., widely recognized as ‘amla fruit’ or Indian Gooseberry is extensively spread in
China, India, Indonesia, and Thailand’s tropical and subtropical areas. Research has indicated that P. emblica
has a strong antioxidant capacity owing to its high polyphenolic component and vitamin C content. P.
embelica fruit was studied further in 130 subjects in association with carotenoids and vitamin E, which are
commonly utilized in vitiligo treatments. In the research, 50 % of participants only got traditional therapies
including phototherapy and topical medications. The second section of people received traditional therapy
which included combining dietary antioxidants, vitamin E, and carotenoids thrice daily and treatment with
topical agents or phototherapy. According to these investigations, a higher percentage of patients in the
antioxidant-supplemented group saw minor re-pigmentation in the head, neck, and truck region after six
months. Antioxidants were not used in the group that had more erythema, more vitiligous patches, more
inflammation, and faster vitiligous zone expansion [44].

Piperine
In vitro studies have revealed that piperine, the main alkaloid in black pepper, stimulates melanocyte
replication and causes the development of melanocytic dendrites. According to many studies, when UV
exposure is present, piperine is recommended. Research has shown the impact of UV light on melanocytes is
stimulated by piperin. Piperine only enhanced melanocyte proliferation and dendritic production in melan-a
(mouse cell line) when it was not combined with UV-A. Mice given both piperine and UV radiation (UVR)
experienced more pronounced pigmentation than mice given either treatment alone. Studies
have pointed out that in order to prevent photoisomerization of piperine, UVR and piperine should be used
in distinct phases while treating vitiligo [45-47].

Nigella sativa
Nigella sativa is a perennial species of plant yielding black cumin, the oil isolates of which are often used to
treat a range of illnesses, especially dermatological conditions. Thymoquinone, a primary ingredient of
Nigella sativa is being carefully researched as a key element possessing a variety of benefits, particularly for
its anticancer, immunomodulating, and anti-inflammatory reactions [48-50]. Topical administration with
Nigella sativa oil has been demonstrated to considerably enhance the Vitiligo Area Scoring Index score
within four months [51]. This might be a secure and efficient supplement for conventional vitiligo therapy.

Punica granatum
One of the first fruit trees that have been planted is the pomegranate ( Punica granatum Linn.) and it is high
in polyphenolic chemicals and tannins. Thus, three to six glasses of commercially accessible pomegranate
juice per day could be sufficient to provide antioxidant benefits [52].

Green tea
The polyphenolic molecules known as catechins, which are part of the chemical class of flavonoids, are
responsible for green tea's antioxidant properties. Epigallocatechin-3-gallate (EGCG) is by far the most
common and therapeutically significant constituent of green tea. It has substantial antioxidant activity as a
ROS/RNS (reactive oxygen species/reactive nitrogen species) scavenger with regard to providing potent anti-
inflammatory characteristics which can modulate the T-cell-mediated immunological response [53]. Studies
demonstrated in two in vitro investigations that EGCG has a potent antioxidant impact on primary human
melanocytes. In fact, EGCG reduced ROS production, regenerated impaired mitochondrial function, and
lowered apoptosis influenced by hydrogen peroxide. In addition to this, EGCG also controlled oxidative
stress-triggered pathways in melanocytes exposed to this stress. Experimental investigations on mice
showed depigmentation caused by monobenzone [54]. Studies demonstrate the immune-modulating and
oxidative stress-attenuating properties of 2, 5, and 10% EGCG cream. There have not been any trials
conducted on how EGCG affects humans so far. Additionally, it was recommended to consume 5 to 16 cups

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of tea daily to achieve its antioxidant potential. The sole option appears to be EGCG extract supplementation
rather than tea infusions [55].

Curcumin
The main naturally occurring lipophilic polyphenol present in the rhizome of Curcuma longa (turmeric) and
other Curcuma species is curcumin, known as diferuloylmethane. Numerous studies revealed that curcumin
shows strong and complex antioxidant activity which enables it to influence the antioxidant system both
directly and indirectly as well as inhibiting the generation of ROS and its intracellular sources. One in vivo
investigation revealed that when narrowband UV-B (NB-UVB) and tetrahydro-curcuminoid were combined
topically on vitiligo patients' skin, the rate of skin repigmentation was marginally greater than when NB-
UVB was used alone [56]. Table 2 outlines the properties and impact of the supplements mentioned above on
managing vitiligo.

Supplement Properties Impact on Management of Vitiligo

Decrease in cyclooxygenase activity and TNF-a's role in inducing the production of Interleukin-8 and vascular endothelial growth Enhances repigmentation however mild gastrointestinal disturbances have been
Ginkgo biloba
factor (VEGF) are hypothesized to be the mechanisms of anti-inflammatory effects noted.

Polypodium
Anti-inflammatory, antioxidant, photoprotective, and immunomodulatory properties Combining Polypodium leucotomos with PUVA leads to increased repigmentation
leucotomos

Khellin Orally administered Khellin plays a role in melanogenesis by stimulating melanocytes When paired with UV therapy, contributes to a decrease in depigmented lesions

Gluten May cause inflammation which causes autoimmunity towards melanocytes Patients with vitiligo may benefit from a gluten-free diet

Phenylalanine is hydroxylated to tyrosine which is utilized in melanogenesis. Phenylalanine also causes catecholamine production Oral phenylalanine supplemented with UVA radiation contributes to increased
Phenylalanine
wherein low catecholamine levels are linked to the onset of vitiligo repigmentation

Phyllanthus When combined with traditional therapy and appropriate dietary supplementation,
Strong antioxidant property due to high polyphenolic and Vitamin C content
embelica contributed to minor repigmentation.

Contributes to patchy repigmentation when combined with UV therapy, but can

Piperine Stimulates melanocyte replication and causes the development of melanocytic dendrites
cause repigmentation when applied without UV therapy

Nigella sativa Anticancer, immunomodulating, and anti-inflammatory properties Topical administration considerably increases repigmentation

Punica
High polyphenolic content 3-5 glasses per day provide antioxidant benefits
granatum

EGCG has substantial antioxidant activity and provides potent anti-inflammatory characteristics which can modulate the T-cell-
Green tea Shows considerable repigmentation when experimented on mice
mediated immunological response. EGCG also regulates mitochondria function

Topical tetrahydro curcuminoid combined with NB-UVB leads to an increased rate

Curcumin Exhibits strong antioxidant activity and inhibits ROS production
of repigmentation than when NB-UVB is used alone

TABLE 2: Summary of Herbal Supplementation in Vitiligo

TNF-a: Tumor Necrosis Factor-alpha; PUVA: Psoralen Plus Ultraviolet-A Radiation; UV: Ultraviolet; EGCG: Epigallocatechin gallate; ROS: Reactive
oxygen species; NB-UVB: Narrowband Ultraviolet-B

Conclusions
Vitiligo is a widespread multifactorial skin condition with complicated pathophysiology. The cause and
pathogenesis of vitiligo remain unknown, despite recent significant advancements in our understanding of
the condition. In order to find novel treatment targets and medications that could arrest the evolution of the
disease or possibly cure vitiligo, it is critical to understand the biological mediators and molecular
mechanisms that result in metabolic abnormalities, melanocyte degeneration, and autoimmunity.
Numerous alternative treatments, particularly herbal products and vitamin supplements, have been
researched to support conventional therapy approaches for vitiligo. Even though several studies have
demonstrated benefits linked to these complementary therapies, more extensive and carefully monitored
trials are necessary to establish their position in the hierarchy of therapeutic approaches firmly. The most
effective treatments included oral Polypodium leucotomos with phototherapy, oral ginkgo as monotherapy,
and oral phenylalanine as an adjuvant therapy with UV-A therapy.

Additional Information
Disclosures

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Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the
following: Payment/services info: All authors have declared that no financial support was received from
any organization for the submitted work. Financial relationships: All authors have declared that they have
no financial relationships at present or within the previous three years with any organizations that might
have an interest in the submitted work. Other relationships: All authors have declared that there are no
other relationships or activities that could appear to have influenced the submitted work.

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2022 Dutta et al. Cureus 14(8): e28516. DOI 10.7759/cureus.28516 7 of 8