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Vitamin D for Vitiligo
Vitamin D or the Sunshine vitamin is synthesized in the skin following exposure to sunlight. Find out its role in the treatment of vitiligo and how its analogs are used to stop depigmentation and stimulate melanin production.
by Brad Chase
Vitamin refers to a group of 5 fat-soluble secosteroids. The important vitamers in humans are vitamin D2 and D3.
Although vitamin D is obtained from dietary sources, it can also be synthesized in the skin from cholesterol in the presence of sunlight. The body maintains the amount of vitamin D produced in this way by a negative feedback so that toxicity is prevented.
Once ingested from foods, the available forms of vitamin D are converted first to calcidiol in the liver and then to calcitriol in the kidneys. When the levels of vitamin D in the body is to be measured, calcidiol is the vitamin D metabolite that is measured.
Calcitriol is the active metabolite of the vitamin and it acts as hormone in the body.
Calcitriol is needed for bone health since it regulates the level of calcium and phosphate in the body. When produced outside the kidneys, calcitriol regulates the division, differentiation and death of cells.
The two useful forms of vitamin D in humans are called calciferol. Vitamin D2 is also known as ergocalciferol while Vitamin D3 is cholecalciferol. Vitamin D3 is found in the skin and milk of animals while vitamin D2 is produced by fungi, phytoplankton and invertebrates but not by land animals and plants.
Therefore, vitamin D3 is the form of vitamin D made in human skin.
The production of vitamin D3 requires ultraviolet radiation (UVB) and 7-dehydrocholesterol. This synthesis occurs in the innermost layer of the epidermis and the vitamin D produced is in large quantities.
Once ingested vitamin D is converted to calcitriol, the hormone is transported to target organs by binding proteins. It then binds to VDRs (vitamin D receptors) found in the nuclei of cells. These receptors can be found in the brain, heart, breast, prostate, gonads and skin.
The recommended dietary allowance for vitamin D is 15 micrograms per day. This is raised to 20 micrograms per day for people older than 70 years.
The main presentation of vitamin D deficiency is improper mineralization of bones. Therefore, the bones are softened. This leads to rickets in children and osteomalacia in adults.
Vitiligo is a skin pigmentation disorder in which white patches appear on the skin. These patches represents areas of hypopigmentation where melanin production has dropped.
Melanin is the skin pigment produced from specialized skin cells called melanocytes.
Melanin is produced in response to ultraviolet irradiation of the skin. This photosensitive compound protects the skin from damages such as sunburn. However, when the population of melanocytes fall off, the skin loses its pigment and turns white.
The usefulness of vitamin D in the treatment of vitiligo was first reported in cases of psoriasis patients receiving topical vitamin D analogs such as calcipotriol and tacalcitol.
In these patients, the vitamin D analogs caused the hyperpigmentation of the skin. Since vitiligo is hypopigmentation of the skin, it follows that these vitamin D analogs should help repigment the white patches of vitiligo.
Clinical evidences and treatment successes have since supported this view.
There are different mechanisms by which vitamin D may help treat vitiligo. Some of these are discussed below.
Calcidiol, the prohormone produced from dietary sources of vitamin D in the liver, can be converted to calcitriol by the macrophages and monocytes of the immune system. Once produced in this way, calcitriol acts like a cytokine instead of a hormone. It protects the body from microbial invasion at the local site of production.
However, vitamin D affects the immune system in more ways. For example, many immune cells include monocytes and even specialized white blood cells such as T and B cells have vitamin D receptors.
Therefore, vitamin D can suppress the activation of T cells and the release of cytokines such as TNF-alpha (tissue necrosis factor alpha). This exact effect is the reason vitamin D analogs are used in the treatment of psoriasis but it is also useful in the treatment of vitiligo.
Because vitamin D suppresses some cells of the immune system, it can protect melanocytes against autoimmune attack.
The autoimmune cause of vitiligo is believed by many researchers and clinicians to be the most important of the causes of vitiligo. When the cells of the immune system attack melanocytes, the skin can become depigmented at a very rapid rate.
However, by regulating the immune system, vitamin D can prevent the increased destruction of melanocytes, stop further depigmentation and promote the repigmentation of the skin.
Vitamin D is also known to promote the maturation of skin cells including keratinocytes, fibroblasts and melanocytes. These skin cells do have vitamin D receptors.
By promoting the differentiation and proliferation of melanocytes, vitamin D ensures that the production of new melanocytes exceeds the rate at which old melanocytes are dying.
Vitamin D is also credited with some antioxidant properties.
Unlike the antioxidant properties of vitamins A, C and E, vitamin D protects the skin from reactive oxygen species by an indirect mechanism.
Oxidative stress from reactive species interfere with calcium homeostasis in the skin. Because vitamin D restores this homeostasis, it helps reduce the levels of these reactive species in the skin. This effect protects melanocytes from being destroyed.
Calcipotriol is the most studied vitamin D analog used in the treatment of vitiligo.
Calcipotriol is also called calcipotriene. It is a synthetic compound derived from calcitriol. It is available in cream, ointment and solution forms.
Calcipotriol is indicated for the treatment of psoriasis. Its usefulness for this skin disease was due to the positive effect of vitamin D on psoriasis during an osteoporosis study. By a similar fortunate coincidence, the usefulness of calcipotriol in vitiligo treatment was discovered in psoriasis patients who also had the pigmentation disorder.
Calcipotriol is especially useful in the treatment of psoriasis and vitiligo because it has less than 1% of the activity of calcitriol on calcium metabolism while having a comparable affinity for vitamin D receptors.
This makes calcipotriol useful for treating skin disorders (since vitamin D receptors are found in the skin) without any side effects arising from interfering with calcium levels in the body.
Therefore, although 6% of calcipotriol applied topically on the skin is absorbed into systemic circulation, hypercalcemia is a very rare side effect of the drug. Most of the absorbed calcipotriol are converted to inactive metabolites soon after entering systemic circulation.
Calcipotriol is safe to use. To improve its efficacy in vitiligo treatment, it is often combined with topical glucocorticoids or UV therapy.
Calcipotriol is inactivated by acids. Therefore, it should not be combined with topical products containing salicylic acid.
In a study published in the journal, Acta Dermato-Venereologica in 2006, the association of vitamin D receptor gene in the development of vitiligo was noted in a small, inbred Romanian community.
In this community, families with vitiligo also had other autoimmune disorders such as thyroid dysfunction, diabetes mellitus and rheumatoid arthritis. The close association of vitiligo with other autoimmune diseases have also been widely reported. This strengthens the autoimmune theory of the cause of vitiligo.
However, the researchers of this study went a step further to identify the common genetic mutation in the vitiligo families. They report that the Apa-l polymorphism of gene coding for vitamin D receptor is associated with vitiligo.
It is possible that this genetic variant of the gene produces vitamin D receptors that poorly bind with natural vitamin D and its synthetic analogs. This would mean that people with this genetic mutation have lesser protection from vitamin A and may have increased risks of developing vitiligo.
A similar study was recently concluded by Chinese researchers from Fourth Medical University, Shaanxi.
In this new study, the study population was larger and more genetic variants were tested. The result showed that the Apa-I gene was definitely central to the development of vitiligo.
For example, people with the aa genotype was associated with the highest risk for vitiligo. By comparison, Aa genotype of the gene had 23% reduced risk and the AA genotype had 54% reduced risk.
Also, the Apa-I gene was identified as a significant predictor of vitamin D levels in vitiligo patients.
In a 1999 study published in the journal, Pediatric Dermatology, 21 vitiligo patients aged 5 – 17 years were given calcipotriol to apply in the evening followed by 10 – 15 minutes of exposure to sunlight the following day.
After the study, most of the children showed signs of repigmentation with 10 of them experiencing total repigmentation and only 4 with no improvements in skin color.
The study also noted that calcipotriol was well tolerated during the study and only 3 study participants complained of mild irritation.
A 1998 study published in the journal, Dermatology, compared the efficacy of PUVA with calcipotriol against only PUVA in the treatment of vitiligo.
PUVA is psoralen and UVA light therapy. It involves taking oral or topical psoralen, a photosensitive drugs a few hours before the vitiligo lesions on the skin are exposed to ultraviolet (UVA) light from special lamps.
This 18-month long study showed that the addition of calcipotriol improved the success rate of PUVA while also shortening the duration of treatment.
A 2001 study published in the British Journal of Dermatology compared the efficacy and safety of combining PUVA with calcipotriol.
The results showed that both monotherapy with calcipotriol alone and combination with PUVA were effective and that the vitamin D analog can be safely combined with the ultraviolet light treatment.
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Callumae is a Vitiligo Remedy designed to help get rid of white spots on your skin. Use in conjuction with light therapy (or natural sun light) to help get the most repigmentation to your skin.