A review of topical and systemic nutrients in the management of melasma

Dr Laurena Law 
BMED (Newcastle)
DFM (HKCFP)
Dip in Practical Dermatology (cardiff)
P Dip ComPsychMed (Hong Kong)

Melasma is a complex pigmentary condition 

Melasma is a complex pigmentary condition with a higher prevalence of around 90% occurs in females and dark skin types. Multiple etiologies including light exposure, hormonal influences (such as pregnancy or oral contraceptive pill use), family history and oxidative stress have been implicated in the pathogenesis of this disorder. When melasma occurs during pregnancy, it is called chloasma or ‘mask of pregnancy.’ It often fades gradually after delivert, but may remain for years or permanently.

Histology shows increased melanosomes, solar elastosis, dermal blood vessels and perivascular lymphohistiocytic infiltrates. Various treatment modalities including, chemical peels, topical lightening agents, lasers/ light-based devices and oral/ systemic therapies are employed in treating this chronic recurring skin condition. In recent times oral therapies for melasma has been showing some promise. These include tranexamic acid, glutathione, polypodium leucotomos extract, beta-carotenoid and procyanidin.

Avoidance of sunlight and application of a broad-spectrum sunscreen are important components of treatment with the most frequent topical medication being hydroquinone. However, adverse effects of hydroquinone include skin irritation, phototoxic reactions with secondary post-inflammatory hyperpigmentation and onchronosis.

Topical vitamin C has been shown to inhibit melanin synthesis.

A small study with 16 women suffering from idiopathic melasma were assigned to a split face application of 5% ascorbic acid cream and 4% hydroquinone at night for 16 weeks. Subjective ratings of good or excellent were reported in 92% using hydroquinone and 62.5% using ascorbic acid. According to colorimetric measurements, the treatments were of similar efficacy. Skin irritation occurred in 69% of hydroquinone and 6% of patients treated with ascorbic acid.

Topical azelaic acid is a naturally occurring compound present in some foods such as whole grains, rye and barley. It has been reported to reduce the hyperactive melanocytes and to inhibit tyrosinase (enzyme involved in melanin synthesis). Topical 20% azelaic cream has been used to treat various hyperpigmentary disorders.

155 patients with melasma in a double blind RCT was given 20% azelaic acid and 2% hydroquinone for 24 weeks. 73% of those receiving azelaic acid and 19% of those receiving hydroquinone had good or excellent results according to measurement of pigment intensity and lesion size. Mild to moderate skin irritation occurred initially with both treatments.

Another larger study of 329 women compared 20% azelaic cream with 4% hydroquinone cream twice a day for 24 weeks. Good or excellent results were seen in 64.8% of patients using azelaic acid and 72.5% using hydroquinone. The difference was not significant.

In dark skinned Indian women with melasma, topical 20% azelaic acid cream twice per day for 24 weeks produced good or excellent results in 90% of cases.

All the studies used broad-spectrum sunscreen in addition to topical bleaching agents.

Topical niacinamide is thought to inhibit melanosome transfer from melanocytes to keratinocytes. 2 studies suggest that it is useful.

18 Japanese women with hyperpigmentation were randomly assigned to 5% niacinamide to one side of the face and placebo moisturiser on the other side twice per day for 8 weeks. Results showed reduction of 26% with niacinamide vs 15% placebo.

27 Mexican women with melasma was randomly assigned to 4% niacinamide cream on one side and 4% hydroquinone cream on the other. The Melasma Area and Severity Index score was 62% with niacinamide and 70% with hydroquinone.

Oral Treatments:

The acceptance of nutritional supplementation in the general population is growing. In Hong Kong from 2008 to 2014, the number of adults taking health supplements increased from 2 million to 2.7 million with 1.6% comprising beauty supplements with an average monthly expenditure of $48USD to $84USD. Oral natural compounds that have demonstrated safety and efficacy in melasma and photoprotection in human studies are also inexpensive with an average monthly cost of $20USD to $40USD per month.

PycnogenolÒ is an extract prepared from French marine pine bark is a widely used nutritional supplement which contains antioxidants such as bioflavonoids, catechins, procyanidins and phenolic acids.

Studies show that doses between 75-100 mg per day for up to 12 weeks and 40 mg daily for 24 weeks improves appearance of photodamaged skin and has good safety profile after measuring cholesterol, liver function, renal function, iron and electrolyte markers. PycnogenolÒ downregulates the expression of genes in human skin involved in melanin synthesis and improved skin elasticity and hydration by upregulation of mRNA hyaluronic acid synthase-1.

PycnogenolÒ is an extract prepared from French marine pine bark is a widely used nutritional supplement

Vitamin C 300mg/day, Vitamin E 150 IU/ day and pine bark extract 25mg 3 times per day in uncontrolled trials reduce the severity of melasma.

60 women with melasma were randomly assigned to receive 24mg or procyanidins, 6mg of beta-carotene, 60mg of vitamin C and Vitamin E 15IU twice per day or placebo for 8 weeks. The degree of improvement determined by MASI was significantly greater in the active treatment group (30% vs 7%)

A systemic review suggests the efficacy and safety of oral and topical tranexamic acid with minor side effects such as hypomenorrhea, mild abdominal discomfort and transient skin irritation. In addition, a retrospective analysis of 561 predominantly female patients treated with oral tranexamic acid for 4 months showed that 89.7% improved, 10% had no improvement and 0.4% worsened. Better response rates occurred in those with a family history. There is a relapse rate of 27.2% and one patient had a developed deep vein thrombosis. She was subsequently found to have familial protein S deficiency. Therefore, assessment for familial and personal history of thromboembolic disease is indicated prior to starting treatment.

Oral glutathione at a dose of 500mg per day for 4 weeks in an RCT of 60 students decreased melanin indices with good tolerability. However, long-terms safety has not been established. Intravenous glutathione for skin lightening is not recommended due to inadequate data on long term safety.

But systemic review on intravenous glutathione for chemo-induced toxicity and Parkinson’s disease reported minimal adverse effects over 4-12 weeks.

Polypodium leucotomos extract (PLE) is a naturally derived compound from a native South American fern. A systemic review sponsored by the manufacturer of FernblockÒ(Heliocare, Ferndale Healthcare) showed beneficial photoprotective effects and safety of their product compared to other products using different extraction methods. Other studies have independently shown photoprotective effects. There are several mechanisms by which this occurs. The inhibition of mitochondrial DNA damage by UV photons, anti-inflammatory action via COX-2 inhibition, prevents immune suppression and blocks lipid peroxidation.

Polypodium leucotomos extract (PLE) is a naturally derived compound from a native South American fern 

An RCT of 60 women with Fitzpatrick skin type III-IV was given an 8 weeks course of oral procyanidin 48 mg, Vitamins A (beta carotene 6mg), Vitamin C 60 mg, Vitamin E 15 IU (D-alpha tocopherol) showed safety and tolerability with significant improvement in malar regions. Mexameter results demonstrated a significant decrease in the degree of pigmentation in the left malar (165.85 ± 70.909) and right malar (161.33 ± 61.824) regions (P < 0.0001). MASI scores showed a significant improvement in the left malar (2.4862 ± 1.67816) and right malar (1.8889 ± 1.67110) regions (P 1⁄4 0.001).

Topical and systemic modalities generally result in better outcomes than monotherapy. Systemic melasma and photoprotection therapies are showing to be a safe, effective and a potentially economical tool in a physician’s armamentarium for this complex and recurrent pigmentary disorder.

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