Naturopathic and Adjunctive Treatment Approaches for Vitiligo

Vitiligo is a skin condition characterized by an acquired loss of functioning melanocytes, leading to the absence of pigmentation. It is believed to affect approximately 1–4% of populations in South Asia, the United States, and Europe.¹, ² It is primarily classified as nonsegmental and segmental, with the nonsegmental form being the most common (comprising up to 90% of cases). The nonsegmental form is also characterized by an onset typically in adulthood, a progressive course with lifelong duration, lesion occurrence at sites of pressure or friction, and a relation to autoimmunity.

A genetic predisposition may be contributory, as up to 40% of patients report a family history of vitiligo.³ Among possible triggering factors, emotional stress, sunburn, and mechanical factors (such as friction from clothing or footwear, chronic pressure, scratching, wounds, and presence of other skin disease) have all been reported.⁴ The pathogenesis underlying vitiligo has yet to be fully elucidated; however, the theorized mechanisms at play give insight into the ways in which potential natural therapeutics may hold influence. Table 1 provides an overview of such mechanisms.

Table 1. Possible Mechanisms of Vitiligo Pathogenesis

Conventional treatment approaches are typically tailored according to the type of vitiligo diagnosed, clinical severity, and the patients’ comfort level of lesion appearance. For all cases, prevention of triggering factors is key. This can include support for emotional stress, if present, as well as patient education regarding the avoidance/limitation of both mechanical irritation (such as tight-fitting footwear or clothing-based friction) and sunburn.

Education toward sunscreen use and other sun-protection strategies is key, since unprotected skin can lead to a darkening of unaffected skin (amplifying the contrast with areas affected by vitiligo). Additionally, the lack of melanin over affected skin may increase susceptibility to sunburn and skin damage in those areas.⁶ In general, treatments can include cosmetic camouflage, such as cosmetic stains, dyes, or creams; topical corticosteroids (e.g., clobetasol propionate or betamethasone valerate); topical calcineurin inhibitors (e.g., pimecrolimus or tacrolimus); phototherapy approaches, such as narrow-band UVB (NB‑UVB) and psoralen plus UVA (PUVA). There currently is no known cure for vitiligo. Early intervention is warranted however, given how recently developed lesions seem to respond more efficiently to treatment than older ones.⁷ Another facet of management is to assess for any impact the presence of vitiligo has had on a patients’ mental health and feelings of self-esteem. This is in light of research suggesting the experience of various psychosocial effects for some individuals with vitiligo, including depression, anxiety, poor body image, and difficulties with sexual relationships. Management using naturopathic approaches and/or referral to a mental-health specialist can help address these concerns, if present.^8,9,10,11

A Sample of Naturopathic and Adjunctive Treatment Considerations

The bulk of the natural-based therapies we will review have been studied for use only in conjunction with conventional treatments, and in particular, phototherapy. As such, this offers an opportunity for both a naturopathic doctor and one’s treating dermatologist to coordinate a treatment approach. The adjunctive integration of dietary adjustments as well as herbal and nutritional oral supplementation may provide a variety of benefits. These include antioxidant, immunomodulatory, and photoprotective effects which target some of the contributing factors seen in vitiligo, such as oxidative stress and the autoimmune destruction of melanocytes.¹² Additionally, research we will explore suggests how they may act synergistically with conventional treatments while also improving the tolerability of phototherapy.¹³

Dietary Intake of Essential Fatty Acids

Some research has suggested that the types of fats consumed in the diet may modulate the risk of vitiligo development. In a recent case-control study, compared to those without vitiligo, subjects with vitiligo were found to consume both a higher amount of saturated fatty acids (p = 0.008) and a lower amount of essential fatty acids, specifically the omega‑3 fatty acids eicosapentaenoic acid (EPA) (p = 0.001) and docosahexaenoic acid (DHA) (p = 0.004).¹⁴ Although these findings may represent the anti-inflammatory benefits derived from such fat-intake profile, the authors did report how the association between the anti-inflammatory omega‑3 and vitiligo were lost once adjusting for confounding variables such as age, gender, and body mass index. What was not affected by such confounders, however, was the association between total fat intake and vitiligo, which showcased an adjusted odds ratio of 2.84 (95% CI: 1.63–5.44, p = 0.01).¹⁵ In this context, the risk of vitiligo is nearly three times higher in those consuming the highest amounts of total fat. Further research should help elucidate the protective or damaging effects various subtypes of dietary fats may have in this regard.

Antioxidant - Combination Supplement

Much interest has centered around antioxidants, such as alpha-lipoic acid, owing to its properties as an antioxidant, cell-membrane protector, and vitamin C recycler, as well as to its positive impact on oxidative stress and inflammation.¹⁶ One clinical trial has demonstrated the ability of an antioxidant combination to aid in the repigmentation process when combined with NB‑UVB treatment. In a randomized, double-blind, placebo-controlled multicenter pilot trial, 28 subjects with nonsegmental vitiligo were analysed for the effects of supplementing with an antioxidant-combination supplement for two months prior to, and six months during, NB‑UVB therapy.¹⁷ The antioxidant supplement contained alpha-lipoic acid (50 mg), vitamin C (50 mg), vitamin E (20 mg), polyunsaturated fatty acids (12%), and cysteine monohydrate (50 mg), with two tablets taken daily. By the study’s end, a noted clinical finding reaching significance was that 47% of the test group achieved a grade‑3 level of repigmentation (> 75% repigmentation; p < 0.05 v. placebo), and just under 24% attained a grade‑1 (< 50% repigmentation) or grade‑2 (50–75%) level of repigmentation. This contrasts with 18% of the placebo group obtaining a grade‑2 or ‑3 level of improvement. In addition, biochemical analysis demonstrated a reduction in intracellular ROS production for the test group (by 57% and 60% of baseline values at 2 and 6 months, respectively; p < 0.02), compared to the absence of such findings for the placebo group. The authors concluded that this intervention helped augment the effectiveness of the NB‑UVB therapy, while seemingly accounting for the oxidative stress occurring in individuals with vitiligo.¹⁸

Polypodium leucotomos

Polypodium leucotomos (PL) is a tropical fern sourced from South and Central America. Noted constituents of PL include polyphenolic compounds, such as vanillic acid, caffeic acid, p‑coumaric acid, and ferulic acid, along with monosaccharides. These are believed to contribute toward its photoprotective, antioxidant, and chemoprotective effects, among others.^19,20 The primary use of oral PL-extract supplementation is as an adjunctive form of photoprotection. Its use in this way, alongside the use of other sun-protective measures including sunscreen, may provide an additional layer of protection against the development of sunburn. Other research is emerging regarding a possible benefit for use in cutaneous pigment concerns such as melasma and vitiligo, managing photosensitive skin concerns, and photoaging.^21,22,23

Specific to vitiligo, PL may offer numerous benefits owing to its immunomodulatory, anti-inflammatory and antioxidant properties. In addition to these, its photoprotective effects are believed to limit adverse effects inherent to PUVA therapy, which can include sunburn reaction, blistering, dark repigmentation, and an increased risk of skin cancer.²⁴ By contrast, NB‑UVB therapy is generally better tolerated, and is considered a first-line treatment for many forms of vitiligo. To date, PL has only been studied for use as an adjunctive oral therapy for either PUVA or NB‑UVB. In these human trials, this combination with phototherapy has demonstrated increased repigmentation effects over areas treated.^25,26,27 For example, a team studied the effects of twice-weekly NB‑UVB therapy in combination with either 250 mg PL three times per day or placebo in 50 subjects with vitiligo vulgaris, a form of generalized vitiligo exhibiting a scattering of lesions with extensive dissemination.^28,29 After 26 weeks, a significant increase in repigmentation was observed in the PL group (44% increase) over areas of the head and neck as compared to placebo group (27% increase) (p = 0.006]. Slightly increased, but nonsignificant, differences were found for other body areas, including the trunk (6% increase in PL v. placebo), hands and feet (5% increase v. placebo), and extremities (4% increase v. placebo).³⁰

The mechanism of PL’s capacity for repigmentation include antioxidation and inhibition of cell-mediated immune responses, such as a reduction in interleukin‑2, interferon‑gamma, and tumour necrosis factor‑alpha; and an increase in interleukin‑10.³¹

Black Cumin (Nigella sativa) Seed Oil

Richly growing across areas like Eastern Europe, the Middle East, and parts of Asia,³² the flowering plant of Nigella sativa produces black seeds whose oil is extracted for use in a variety of skin concerns.³³ Its primary component, thymoquinone, is believed to underpin many of its medicinal properties, including anti-inflammatory, immunomodulating, and antimicrobial effects.^34 35 In a six-month human clinical trial, a team studied subjects with either generalized or localized vitiligo, having been diagnosed within the last five years.³⁶ Twenty-six of the subjects applied black cumin seed oil topically over the areas of vitiligo daily, and assessment was made in relation to changes seen in the Vitiligo Area Scoring Index (VASI), whereby a score of 0 indicates the absence of depigmentation and that of 5 represents absence of pigmentation.³⁷ At the end of the six months, the average VASI score reduced from its baseline score of 4.98 (± 4.81) to 3.75 (± 3.91) (p = 0.02), with the greatest percentage of improvement being noted over the lower extremities, trunk, head, and neck.³⁸ Although further research is needed to elucidate its mechanism(s) of action, one theory purports that Black cumin seed oil enhances the ability of melanin to disperse within the skin.³⁹ This relates to animal research in lizards suggesting that thymoquinone may simulate acetylcholine activity, causing the release of melanin via the stimulation of cholinergic receptors.⁴⁰ Thymoquinone is also believed to work by protecting cells from oxidative stress and damage.⁴¹

Conclusion

Numerous natural agents are being explored for their use and applicability in the management of vitiligo, especially in combination with current conventional treatments such as phototherapy. Although this emerging research is exciting, additional high-quality human trials are needed to answer key questions, including which approaches offer the highest degree of efficacy, length of use needed before benefits are seen, optimal oral or topical dosage, and details surrounding safety.