|Year : 2022 | Volume
| Issue : 3 | Page : 147-150
Nutraceuticals in vitiligo: not just “designer” foods
Pooja Arora MBBS,MD, DNB
Professor, Department of Dermatology, DrRam Manohar Lohia Hospital & Post Graduate Institute of Medical Education & Research, New Delhi, India
|Date of Submission||22-Nov-2022|
|Date of Acceptance||22-Nov-2022|
|Date of Web Publication||30-Nov-2022|
Dr. Pooja Arora
Department of Dermatology, 9547, Sector C 9, Vasant Kunj, New Delhi 110070
Source of Support: None, Conflict of Interest: None
Keywords: nutraceuticals, vitiligo, vitamins, minerals, botanicals
|How to cite this article:|
Arora P. Nutraceuticals in vitiligo: not just “designer” foods. Pigment Int 2022;9:147-50
“Let food be thy medicine” was a philosophy given by Hippocrates 2500 years ago. While the concept of “food as medicine” was largely abandoned except for the adage “an apple a day keeps the doctor away”, the concept has resurfaced with the COVID-19 pandemic. People nowadays have realized the importance of healthy nutrition to build immunity and fight diseases. As we usher into the era of preventive medicine, several classes of products that focus on natural ingredients are being developed. Popular amongst these are nutraceuticals and nutricosmetics.
The word “nutraceutical” is a hybrid of “nutrition” and “pharmaceutical” and was coined by Stephen DeFelice in 1989. It was originally defined as ‘a food (or part of food) that provides medical or health benefits, including the prevention and/or treatment of a disease. Nutraceuticals are being increasingly utilized to promote health and well-being apart from their use in various chronic diseases. The global nutraceutical market is expected to grow at a compound annual growth rate (CAGR) of 9.07% and reach USD 446.35 billion in the year 2027. This exponential growth can be attributed to various factors like growing prevalence of lifestyle diseases (obesity, diabetes, cardiovascular diseases), increasing awareness among people of the importance of preventive healthcare and the growing demand for personalized nutrition. There is indeed a “nutraceutical revolution” with a myriad of products being developed for a wide range of diseases like Alzheimer’s disease, Parkinson’s disease as well as for prevention of ageing.
Nutraceuticals can be classified based on the mechanism of action, food source, chemical nature and the specific health benefit provided. In essence, all nutraceuticals are natural and can be categorized into traditional and non-traditional types. Traditional nutraceuticals include chemical constituents (vitamins, minerals, amino acids, phytochemicals), probiotics and nutraceutical enzymes whereas nontraditional ones include fortified (added nutrients and ingredients) and recombinant nutraceuticals (food made through biotechnology and genetic engineering). The most popular amongst these are vitamins and minerals being used as supplements and herbal products.
The use of nutraceuticals has widened with application in pigmentary disorders like melasma, vitiligo and prevention of photoageing. In this article, we will provide a brief insight into the role of this class of pharmaceuticals in vitiligo.
The pathogenesis of vitiligo is multifactorial with oxidative stress being postulated as a trigger for immune dysregulation in patients with genetic predisposition. This has given rise to various vitamins, minerals and botanical extracts being investigated for their antioxidant and immunomodulatory properties. As normal diet may not provide nutrients in sufficient quantities to counter the oxidative stress, these are being supplemented as nutraceuticals.
| Vitamins and minerals as nutraceuticals|| |
Vitamin B12 & folic acid
Role of vitamin B12 and folic acid was explored due to the decreased blood levels observed in various studies in patients with vitiligo. Montes and colleagues found reduced levels of B12, folic acid and vitamin C in patients and reported cessation of disease progression with repigmentation upon prolonged supplementation. Juhlin et al treated 100 patients of vitiligo with 1mg of vitamin B12 and 5 mg of folic acid twice daily along with sun exposure (in summer) and UVB radiation (in winter) for 3-6 months. The authors found cessation of disease activity in 64% of patients along with repigmentation in 52%. However, lack of a control group precludes role of vitamin B12 and folic acid in treatment. On the contrary the only randomized controlled trial done by Tijoe et al did not show any benefit of vitamin supplementation in patients treated with narrow band ultraviolet-B (NBUVB). It has been hypothesized that these two vitamins decrease the levels of homocysteine that have been found to be elevated in vitiligo.
Vitamin C has a skin lightening effect and theoretically suggested to be avoided in vitiligo. However, Yoon and colleagues suggested that antioxidant effects override the risk and vitamin C should be supplemented in a dose of 0.5 to 2 gram per day.
Vitamin D binds to vitamin D receptors in skin and affects growth and differentiation of melanocytes and keratinocytes. It also exerts an immunomodulatory action by inhibiting pro-inflammatory cytokines. It can stimulate melanogenesis and inhibit T cell action.
Given the role of vitamin D in pathogenesis of vitiligo, supplementation may be useful.
However, the effect of vitamin D supplementation has not been studied much. Study done by Finamor et al in 16 patients with vitiligo found arrest of disease activity with prolonged high dose supplementation with Vitamin D, but the study lacked a control group.
Ramadan et al found low tissue and serum levels of vitamin E in patients with vitiligo compared to controls. Beneficial effects of supplementation was seen in one study where 400 IU of vitamin E per day resulted in greater repigmentation along with NB-UVB compared to NB-UVB alone. There was also significant reduction in plasma malondialdehyde (MDA) compared to light monotherapy. Hence, Vitamin E can be beneficial in vitiligo due to its antioxidant effects and its ability to augment UVB treatment efficacy.
Zinc acts as a cofactor for antioxidant enzyme superoxide dismutase and plays a key role in melanogenesis. An Indian study found significant difference in serum zinc levels in patients with generalized vitiligo and controls. Serum zinc levels have been found to be negatively correlated with levels of inflammatory cytokines (IL-6, IL-4 and IL-17) and disease activity and severity., Supplementation showed greater improvement in patients compared to those treated with steroids alone.
| Herbal supplements as nutraceuticals|| |
Many botanicals are used in vitiligo for their antioxidant, anti-inflammatory and immune modulating properties.
Green tea contains numerous catechins that have diverse biological effects. Epigallocatechin-3 (EGCG) is the most abundant and biologically active compound in green tea. EGCG has strong antioxidant and anti-inflammatory effects. Two in vitro studies have demonstrated antioxidant effects of EGCG in human melanocytes triggered by chemical induced oxidative stress. However, the strength of green tea in nutraceuticals to obtain the beneficial anti-oxidant effect has not been studied. EGCG extract supplementation is better than consumption of green tea.
Ginkgo biloba (GB)
Pharmacological actions of Ginkgo biloba are due to the presence of two major fractions: the terpene thialactones (TTL) and flavonoids. These exert a strong antioxidant action, along with anti-inflammatory due to inhibition of cyclooxygenase & vascular endothelial growth factor (VEGF). It also has an anxiolytic action which can be beneficial in stress induced vitiligo. Study conducted by Parsad et al in 2003 found cessation of vitiligo activity in patients taking GB extract (40 mg three times daily for 6 months) compared to placebo group along with repigmentation in few patients. The exact dose has not been studied but benefits can be experienced after 240 mg per day. In another study, GB extract was given 60 mg twice a day and resulted in improvement in vitiligo area severity index (VASI), Vitiligo European Task Force (VETF) score in 11 out of 12 subjects. Authors concluded that GB significantly stopped the progression of disease.
Polypodium leucotomos (PL)
Polypodium leucotomos is a tropical fern with antioxidant and photoprotective properties. It also has immunomodulatory effects. Various studies have shown that PL given orally in a dose of 750 mg per day along with psoralen ultraviolet A (PUVA) or UVB therapy causes repigmentation in lesions of vitiligo especially in the head and neck area after 3-6 months of treatment. One of these studies also found decrease in percentage of CD+25, HLADR+ and CD8+ CD45RO+ lymphocytes compared to baseline. There was better response in patients with light skin, suggesting an immunomodulatory effect of adjuvant use of PL with PUVA. Side effects are mild and include mild itching and gastrointestinal upset.
Khellin is an extract from the seeds of Ammi visnaga that is a medicinal plant found in Mediterranean region. Khellin has structural similarity to psoralens hence utilized in treatment of vitiligo. It does not create DNA cross links after UVA exposure hence it’s not mutagenic.
It has been used in a dose of 100 mg followed by sunexposure or UVA radiation for 3-4 months with good response in the form of significant repigmentation., Side effects include nausea, elevation of transaminases and orthostatic hypotension. Due to these, topical khellin is being used preferred.
It is a polyphenol found in Curcuma long (turmeric) with strong antioxidant properties that have demonstrated in in vitro studies. In an in vitro study done by Asawanonda et al, topical tetrahydrocurcuminoid caused significant repigmentation when used along with NB-UVB than the latter alone.
Phyllanthus emblica L
Phyllanthus emblica L, also known as gooseberry or amla, has high level of antioxidant effects due to high content polyphenols and vitamin C. The daily recommended intake of vitamin C can be fulfilled with 2 to 3 portions of amla fruit per day. P. emblica L has not been studied as monotherapy in vitiligo but one study found the beneficial effect of supplementation with fruit extract mixed with vitamin E and carotenoids along with phototherapy.
| Amino acids as nutraceuticals|| |
Phenylalanine (L-Phe) is an essential amino acid that is taken up by melanocytes and converted to tyrosine by enzyme phenylalanine hydroxylase (PAH). Thus, it is an important precursor in the melanin synthesis pathway. Studies have shown that metabolism and uptake of phenylalanine is impaired in vitiligo. Also, Phe interferes with production of antibodies against melanocytes by saturating AA transported and hence limiting available pool of AA for antibody synthesis. Hence, it may limit progression of disease. Several studies have shown that oral L-Phe (100mg/kg for 3-6 months) when used with UVA/sunlight resulted in significant repigmentation in lesions of vitiligo.,
The above evidence indicates the antioxidant, immunomodulatory and photoprotective properties of various ingredients being used commonly in nutraceuticals. Controlled studies are lacking, however, few chemicals like phenylalanine, Ginkgo biloba and Polypodium leucotomos have shown promising results in preliminary trials and may be used as adjunctive therapy. Further studies are needed to determine the appropriate dose needed to exert beneficial actions. Also, the efficacy in various subgroups of vitiligo like active and stable, localized and generalized and segmental and non-segmental, needs to be determined in proper trials. Batch variation, purity and sourcing of these supplements are further issues that need to be addressed while planning such studies. Though generally regard as safe, side effects need to be monitored especially regarding minerals that can cause toxicity. Before choosing a nutraceutical, the above factors should be taken into consideration so that maximum benefit can be gained without adverse effects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Brower V. Nutraceuticals: poised for a healthy slice of the healthcare market? Nat Biotechnol. 1998;16:728-731.
Montes LF, Diaz ML, Lajous J, Garcia NJ. Folic acid and vitamin B12 in vitiligo: a nutritional approach. Cutis. 1992;50:39-42.
Juhlin L, Olsson MJ. Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure. Acta Derm Venereol. 1997;77:460-2.
Tjioe M, Gerritsen MJ, Juhlin L, van de Kerkhof PC. Treatment of vitiligo vulgaris with narrow band UVB (311 nm) for one year and the effect of addition of folic acid and vitamin B12. Acta Derm Venereol 2002;82:369-72.
Yoon J, Kim TH, Sun YW. Complementary and alternative medicine for vitiligo. In: Park KK, Murase JE, editors. Vitiligo: management and therapy. INTECH Open Access Publisher; 2011
Finamor DC, Sinigaglia-Coimbra R, Neves LC, Gutierrez M, Silva JJ, Torres LD et al.
A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis. Dermatoendocrinol. 2013;5:222-34.
Ramadan R, Tawdy A, Abdel Hay R, Rashed L, Tawfik D et al.
The antioxidant role of paraoxonase 1 and vitamin E in three autoimmune diseases. Skin Pharmacol Physiol 2013;26:2-7.
Balci DD, Yonden Z, Yenin JZ, Okumus N. Serum homocysteine, folic acid, and vitamin B12 levels in vitiligo. Eur J Dermatol 2009;19:382.
Shameer P, Prasad PV, Kaviarasan PK. Serum zinc level in vitiligo: a case control study. Indian J Dermatol Venereol Leprol 2005;71:206.
] [Full text]
Sanad EM, El-Fallah AA, Al-Doori AR, Salem RM. Serum Zinc and Inflammatory Cytokines in Vitiligo. J Clin Aesthet Dermatol. 2020;13:S29-S33.
Zaki AM, Nada AS, Elshahed AR, Abdelgawad NH, Jafferany M, Elsaie ML. Therapeutic implications of assessment of serum zinc levels in patients with vitiligo: A patient controlled prospective study. Dermatol Ther. 2020;33:e13998.
Bagherani N, Yaghoobi R, Omidian M. Hypothesis: zinc can be effective in treatment of vitiligo. Indian J Dermatol 2011;56:480.
] [Full text]
Zhu Y, Wang S, Lin F, Li Q, Xu A. The therapeutic effects of EGCG on vitiligo. Fitoterapia 2014;99:243-51.
Cohen BE, Elbuluk N, Mu EW, Orlow SJ. Alternative Systemic Treatments for Vitiligo: A Review. Am J Clin Dermatol. 2015;16:463-74.
Parsad D, Pandhi R, Juneja A. Effectiveness of oral Ginkgo biloba in treating limited, slowly spreading vitiligo. Clin Exp Dermatol 2003;28:285-7.
Szczurko O, Shear N, Taddio A, Boon H. Ginkgo biloba for the treatment of vitiligo vulgaris: an open label pilot clinical trial. BMC Complement Altern Med 2011;11:21.
Reyes E, Jaén P, de las Heras E, Carrión F, Alvarez-Mon M, de Eusebio E et al.
Systemic immunomodulatory effects of Polypodium leucotomos as an adjuvant to PUVA therapy in generalized vitiligo: A pilot study. J Dermatol Sci. 2006;41:213-6.
Ortel B, Tanew A, Hönigsmann H. Treatment of vitiligo with khellin and ultraviolet A. J Am Acad Dermatol. 1988;18:693-701.
Hofer A, Kerl H, Wolf P. Long-term results in the treatment of vitiligo with oral khellin plus UVA. Eur J Dermatol. 2001;11:225-9.
Asawanonda P, Klahan SO. Tetrahydrocurcuminoid cream plus targeted narrowband UVB phototherapy for vitiligo: a preliminary randomized controlled study. Photomed Laser Surg. 2010;28:679-84.
Colucci R, Dragoni F, Conti R, Pisaneschi L, Lazzeri L, Moretti S. Evaluation of an oral supplement containing Phyllanthus emblica fruit extracts, vitamin E, and carotenoids in vitiligo treatment. Dermatol Ther 2015;28:17-21.
Antoniou C, Schulpis H, Michas T, Katsambas A, Frajis N, Tsagaraki S et al.
Vitiligo therapy with oral and topical phenylalanine with UVA exposure. Int J Dermatol. 1989;28:545-7.
Cormane RH, Siddiqui AH, Westerhof W, Schutgens RB. Phenylalanine and UVA light for the treatment of vitiligo. Arch Dermatol Res. 1985;277:126-30.