[special post] is vitamin D the key to eczema free skin?

I’m suddenly in the groove again! Looking for science journals that interest me at the moment. My attention and memory is fleeting, so I better summarize what I found today while going keyboard crazy. If I were a bunny, I’d have done a binkie after finding all these papers. I’m excited! I told my brother “never in a million years did I expect myself to say that, considering how much I used to hate doing research when I was in school.”. This, is why passion is important – it makes things fun and enjoyable. It’s a luxury being able to enjoy what I’m doing 😀

As life is such a black box, here I am, researching about yet another hypothesis I have in mind. I’m really trying to take charge of my own health ever since the entire TSW saga – I simply can’t trust doctors anymore because I shit you not, most of them simply don’t give a damn about finding out the cause of our problems because.. it’s not their fucking problem at all! All they have to do is to fix the symptoms. For short term illness, that wouldn’t be too much of an issue. Face it, ALL DRUGS have side effects. We use drugs for a short time because the benefits outweighs the disadvantages. But in the long run, the cons most definitely trumps the pros. I was irresponsible for my own health in the past – I trusted derms blindly, and it’s crazy how I once accepted the idea of having to use topical steroids for my entire life to “control” my eczema. *shake my head*

I’m back in charge now and I’m bent on finding what’s out of balance in my body. Keep in mind that everyone is different, we may have our first onset of eczema for different reasons, so what I’m doing right now is to share possible reasons that you can look into if you’re interested. By no means am I saying that this is a one size for all solution. Don’t ever allow yourself to fall into that trap again, just like how we used to think that steroids can fix ALL problems. What works for me may not work for you, and vice versa.

For my reference, the suggested vitamin D levels in a person are summarized in the table below.

Source: The vitamin D council

After reading many different posts written by doctors as well as some health nuts, I’ve accepted the notion that a higher level of vitamin D (but still within the sufficient range) would probably be best for my optimal health, therefore my definition of a optimal vitamin D level would be somewhere between 80-100 ng/ml.

The main journal that I’m discussing today is really informative, I’ve attached the link to the full article. It talks about the role of vitamin D in atopic dermatitis, asthma, and allergic disease – it sums up pretty much all the possible aspects of being an atopic. However, I’ll only highlight the parts pertaining to atopic dermatitis right now. I don’t think I need to explain why.

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Vitamin D in Atopic Dermatitis, Asthma and Allergic Diseases
Daniel A Searing, MDa and Donald YM Leung, MD, PhDb,c,d

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A large amount of data has emerged regarding the molecular effects of vitamin D in the skin. Vitamin D Receptor (VDR) expression in the skin was first confirmed after rats injected with radio-labelled 1,25-dihydroxyvitamin D demonstrated radioactivity concentrated in the nuclei of the epidermis along with a variety of other tissues [52]. 1,25-dihydroxyvitamin D has been shown to enhance keratinocyte differentiation, as well as have either stimulatory or suppressive effects on keratinocyte growth that is concentration dependent [53]. VDR expression on keratinocytes appears to be present only in proliferating cells and consequently, the basal keratinocyte is the main VDR containing cell in the epidermis.

Basal keratinocytes, the factory of our skin cells are the only cells to contain vitamin D receptors, this suggest that vitamin D will affect the way our skin cells develop.

Variable VDR expression based on the proliferating and differentiating state of the keratinocyte, as well as local cytokine-mediated interactions may provide an explanation for vitamin D’s observed inhibitory effects in psoriatic skin and proliferative effects in normal skin [53]. Vitamin D has been shown to increase synthesis of PDGF promoting wound healing, and TNFα promoting keratinocyte differentiation [54, 55]. Decreased synthesis of IL-1α, IL-6, and RANTES secondary to vitamin D has resulted in decreased inflammation in epidermal keratinocytes [56-58].

Vitamin D seems to alleviate psoriasis and reduce the rate at which skin grows. The decreased production of interleukins resulted in decreased inflammation in epidermal skin cells.

Vitamin D has also been demonstrated to have a beneficial effect on the permeability barrier in the epidermis. Bikle and colleagues studied mice null for the expression of 25-hydroxyvitamin D-1α-hydroxylase (1OHase). Lower levels of multiple proteins necessary for formation of the stratum corneum, including filaggrin, were lower in the null mice compared to the wild-type controls [60]. Following tape disruption, null mice had a significantly delayed barrier recovery compared to wild type mice [60].

Vitamin D levels are correlated to proteins requited to sustain the formation of the stratum corneum. My understanding of proliferation and differentiation is as follows: cell proliferation is akin to skin cells being born, whereas differentiation is them growing up. If the rate of birth is higher than the rate of growing, you end up with premature scales that is commonly seen in psoriatic lesions. 25-hydroxyvitamin D-1α-hydroxylase is an enzyme that catalyze the conversion of vitamin D into its bioactive form. In mice without such an enzyme, their skin recovered slower as compared to normal mice after undergoing tape stripping, suggesting lower levels of vitamin D leads to slower growth of the epidermis.

The pathogenesis of atopic dermatitis involves both epidermal barrier and immunologic dysfunction. Atopic dermatitis patients can have defects of both the permeability barrier and the antimicrobial barrier of the stratum corneum [62]. The permeability barrier consists of hydrophobic lipids that percolate the extracellular environment of the stratum corneum and prevent water loss into the outside environment [62]. Over activity of serine proteases secondary to genetic defects, such as filaggrin and environmental stimuli, such as alkaline soaps, promotes reduction of hydration and extracellular lipids in the stratum corneum, introduction of antigens, and promotion of inflammation [62].

This is something that we should already know – the development of atopic dermatitis is both outside-in and inside-out. Our epidermal barrier may be wonky.

The physical structure consists of lipids that prevent water loss. Our skin cells are held together by little protein pieces (called corneodesmosome) which will break down by serine proteases, an enzyme that facilitates the breakdown of the corneodesmosome. It’s necessary because we have to shed off the old and aged skin cells to maintain flexible and healthy skin. However, there are many factors that may disrupt the balance of the enzyme, and/or rip the skin of its lipids, resulting in a porous barrier and inflamed skin.

An important part of the antimicrobial barrier are antimicrobial peptides (AMPs). AMPs are secreted on the surface of the skin as a first-line defence against infection. The release of AMPs can be triggered by toll-like receptors (TLRs). AMPs are secreted by many different cells in the skin, including keratinocytes and mast cells. Aside from their antimicrobial properties, they are thought to play a role in immune system signalling [65]. Cathelicidin is one of the most well known AMPs. Cathelicidin deficiency in the skin is known to be associated with atopic dermatitis. Ong et al, demonstrated significantly decreased immunostaining for cathelicidins in acute and chronic atopic dermatitis lesions compared to psoriatic skin lesions [66].

There is a second line of defence that we seldom hear of – the antimicrobial barrier. Antimicrobial peptides are proteins that protects us from none other than.. microbes. Cathelicidin deficiency has been associated with atopic dermatitis – chronic atopic lesions has a lower level of cathelicidins. HOWEVER, correlation doesn’t mean causation. We don’t know for sure if it’s the lower level of cathelicidin causing atopic dermatitis, OR the atopic dermatitis causing lower levels of cathelicidin.

This finding supports the differences in skin infections between patient with these two diseases. Amongst patients with atopic dermatitis, those with a history of herpes simplex virus (HSV) super infection have significantly lower cathelicidin levels [67]. Antiviral assays have shown that cathelicidin has activity against HSV [67]. Skin from cathelicidin deficient mice has also been shown to have reduced ability to limit vaccinia virus proliferation [68]. A multicenter study to determine phenotypes associated with eczema herpeticum (ADEH) showed that ADEH patients were more likely to experience cutaneous skin infections and have more Th2 polarized disease [69].

What caught my eyes were the lower level of cathelicidin levels in atopics who have a history of HSV. I may have interpreted it wrongly, but it just means if you’re atopic and if you have HSV, you’re more prone to skin irritations by microbial causes. It may sound a little bit more DUH because we would have already associated the HSV outbreak with a weakened immune system, so going along that line.. if you have eczema herpeticum (a manifestation of HSV), you will most likely end up getting skin infections. DUH!!!

Vitamin D has been shown to have a significant role in cathelicidin expression in the skin [65]. Wang and colleagues demonstrated that promoters of cathelicidin and beta2 defensin (another AMP) genes contain consensus vitamin D response elements and that 1,25-dihydroxyvitamin D promotes antimicrobial peptide gene expression [70].

Vitamin D promotes antimicrobial peptide gene expression. Meaning more vitamin D will increase antimicrobial peptide levels!

Given the potential for vitamin D to suppress inflammatory responses, enhance antimicrobial peptide activity, and promote the integrity of the permeability barrier, supplementation provides a possible therapeutic intervention for a variety of skin disorders, including atopic dermatitis. In a sample of 14 patients with moderate to severe atopic dermatitis who received 4,000 IU/day of vitamin D3 for 21 days, biopsied lesional skin showed a significant increase in cathelicidin expression [72].

The experiment mentioned only showed a positive relationship between supplemented Vitamin D and cathelicidin levels in the skin. No mentioning of skin condition or what! But this seems promising to me because it shows us that instead of relying on antibiotics, our body actually have their own defence system. We just need to nurture it appropriate with the right food.

A double-blind randomized controlled trial in children with winter-related atopic dermatitis (primarily mild) was performed utilizing a regimen of 1,000 IU/day of vitamin D for one month during the winter. Five subjects received supplementation versus placebo in six subjects. Baseline changes in global assessments of skin showed that the vitamin D treatment group had a significant improvement in baseline score compared to placebo [73].

This pertains ONLY to atopic dermatitis caused by winter season. It is easy to see the link between decreased amount of sunlight (and hence vitamin D) and winter season. Since they are addressing the cause of the skin issue, there is significant improvement.

So, what’s my main take away from the above paper?

1. For atopic dermatitis, it’s worth giving vitamin D supplements, or the sunlight, a shot at improving the skin condition. Dr Rap has always promoted the sun for skin issues, I believe one of the mechanism by which sunlight helps to heal skin problems is via to the vitamin D route.

2. For TSW, it’s a different story in my opinion. Our skin is over proliferating because of inflammation caused by other reasons. Our skin is inflamed because it’s been damaged and thinned out by years of steroid use. To me, the inflammation is a signal to the body to start repairing the skin. Also, there may be more than one reason leading to the red and inflamed skin during TSW, so vitamin D alone may not be enough to combat the inflammation. Imagine a dam leaking water through 10 different holes, and vitamin D is only able to plug one of those holes. It’s not gonna help much. BUT THERE’S A CATCH, once your skin has passed through the initial rebound stage, sunlight and vitamin may ease the remaining symptoms, and it may also be able to speed up your healing as mentioned by Dr Rap! But there’s a time and place for that, so be patient. Also, I am guessing that it’s highly possible that steroid damaged skin may not be able to synthesize vitamin D from sunlight exposure as efficiently. BUT THAT’S JUST A GUESS. Only god knows the extent of damage steroids have dealt on us.

3. For me, I’m clearly low on vitamin D without even testing it. Why am I so sure, you may wonder. That’s because I’m kinda stuck in a downward spiral. Problem skin -> cover them up with clothes, preference to stay in a dark room instead of being out in the sun -> lesser vitamin D produced by skin -> problem skin worsens. Even though I live near the equator, but being indoor most of the time most probably left me very poor in vitamin D. Whether or not vitamin D will help with my skin, there is no harm in bringing my levels up to a healthy level.

4. This may be a case of confirmation bias – looking for evidence that vitamin D will help with the skin after hypothesizing that vitamin D insufficiency is causing my skin problems. I can only be sure about the low level of vitamin D in my body, but I can’t say it’s the cause of my current skin issues. Only time will tell.

Speaking of looking for evidence.. I had such a fun time exploring all the relations between vitamin D and health! LOOK WHAT I FOUND, MA!

1. 9 patients with psoriasis and 16 with vitiligo received vitamin D3 35000IU (that’s a mega dose) once daily for 6 months. At the end of the trial, all of the psoriasis patients experience improvement in their conditions, while 14 of the 16 vitiligo patients had experienced some levels of repigmentation. [a] The results seem really promising, but I want to remind you that these patients were closely monitored by medical professionals, making sure that their serum vitamin D levels did not exceed a certain level. Please do not attempt this unsupervised.

2. Medium 25-OH vitamin D levels in Chinese, Malay and Indians in Singapore are all below 60 nmol/L. With males having slightly higher levels than females across the difference race. Between the race, Indians have the lowest vitamin D levels, followed by Malays, while Chinese have the highest levels. However, the highest level of 60 is still on the lower end of the vitamin D sufficiency bracket (50-125nmol/L). The 4 categories of 25-OH vitamin D levels are: at risk of deficiency (<30nmol/L), at risk of inadequacy (30-50 nmol/L), sufficiency (50-125 nmol/L), and possible harm (>125 nmol/L). If you don’t already know, the darker your skin tone, the harder it is for you to produce vitamin D. You’ll have to compensate by staying out in the sun for longer periods of time, or to take a supplement. [b]

3. 10 year old Germans showed a positive relationship between serum 25-OH vitamin D levels and eczema, and for the lifetime prevalence of eczema. Specific IgE positives for food allergens are also positively related to vitamin D levels. That means, if you’re German and you’re 10 years old, higher levels of vitamin D is associated with higher levels of eczema. Why? I don’t know. There may be other unknown factors acting in the background that led to this observation. [c]

4. Also in Germany, data drawn from children aged 1-17 showed that low serum vitamin D level is inversely associated with eczema. This study is confusing me. But just to show that there are opposing findings.[d]

5. In the other side of the world, Korean adults showed that low levels of vitamin D is associated with atopic dermatitis, but not allergic rhinitis, asthma, or IgE sensitization. There must be something in the kimchi! [e]

6. In Taiwan, children aged between 5-18 have a mean serum 25(OH)D level of 20.4 ng/mL, putting them slightly above the deficient bracket. However, 90.3% showed insufficiency – their levels are below 30ng/mL. The study showed that there are absolutely NO relations between 25(OH)D levels and asthma, rhinitis, eczema, atopy, or total serum IgE! However, they did discover independent associations between low vitamin D levels and older age, female gender, higher body mass index, winter and spring seasons, and passive smoking. [f]

7. In Hong Kong, vitamin D deficiency is associated with the diagnosis and severity of atopic dermatitis. Serum vitamin D levels are lower in atopic patients as compared to control. Atopic dermatitis severity is negative associated with vitamin D levels (the lower the level, the more severe the dermatitis) [g]

8. Vitamin D, or specifically 1,25-dihydroxyvitamin D3, regulates the expression of antimicrobial peptide cathelicidin in epidermal keratinocytes. Since cathelicidin is involved in wound healing and skin diseases, vitamin D a promising treatment to treat certain chronic wounds or atopic dermatitis. [h]

9. It may be a bad idea to supplement mothers with vitamin D supplements with the hope of raising an infant’s vitamin D levels via the mother’s milk. While vitamin D supplementation may not decrease the severity of infantile eczema at 3 months of age, it poses risk of increasing food allergy of up to 2 years of age. [i]

10. Cord blood vitamin D levels however, is inversely associated with eczema development in the first year of the infant’s life. This means that it may be a good idea to supplement vitamin D when being pregnant to reduce the chances of the infant ending up with eczema. IT’S ALL ABOUT TIMING, FOLKS. [j]

11. Vitamin D sufficiency may be a protective factor for food allergy in the first year of life. The results of this study is rather specific to Australians. Infants of Australian born parents, but not of parents born overseas, are more likely to be peanut and or egg allergic if they hare vitamin D insufficient (<50nmol/L). These infants were also more likely to have multiple food allergies rather than single food allergy.

I’m interpreting studies 3-7 as yet another reminder that our human body is really as complex as the universe. We can only try to explain the phenomena one at a time, but there can be thousands of mechanisms hidden from our sight, waiting for us to discover it after we made enough guesses. The difference in results may be attributed to the geography, culture, climate, food, just too many variables that may affect the results!

Despite the mixed results from my short review of available literature (do note that I didn’t actually read through the entire paper to analyze the design of the studies. Some of them may not be designed properly, but I’m not as meticulous! As always, please be sceptical of what they found!)

I have a plan to supplement my diet with Vitamin D capsules and then get my blood tested once my skin gets better. I just wanna make sure my levels aren’t too high, even though I’m pretty sure the dose I intend to consume is safe, considering how our body can easily manufacture 10000-15000IU of vitamin D a day. I’ll keep observing and share my findings in a few month’s time. If you’d like to experiment with vitamin D, PLEASE do your own research.

Have I sparked some hope in you? I hope I did. The thought that there may be something that I can do to improve my skin is rather empowering.

And to answer the topic question, vitamin D may be one of the puzzle to eczema free skin. If you’re suffering from atopic dermatitis/eczema because of low vitamin D levels, then this is definitely the key for you. But for most of us, chances are it’s multi factorial. As life is always going to be a black box, the only thing we can do is to keep experimenting and observing what works for us, and what doesn’t.

Sources:
[a] A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis
Danilo C Finamor, 1 Rita Sinigaglia-Coimbra, 1 Luiz C. M. Neves, 2 Marcia Gutierrez, 3 Jeferson J. Silva, 1 Lucas D. Torres, 1 Fernanda Surano, 1 Domingos J. Neto, 4 Neil F. Novo, 5 Yara Juliano, 5 Antonio C. Lopes, 6 and Cicero Galli Coimbra 1 ,*

[b] Total 25-OH Vitamin D Concentrations in Chinese, Malays and Indians
Robert Hawkins, M.D.

[c] Serum 25(OH)D concentrations and atopic diseases at age 10: results from the GINIplus and LISAplus birth cohort studies
Nina Wawro, Joachim Heinrich, Elisabeth Thiering, Jürgen Kratzsch, Beate Schaaf, Barbara Hoffmann, Irina Lehmann, Carl-Peter Bauer, Sibylle Koletzko, Andrea von Berg, Dietrich Berdel, and Jakob Linseisen

[d] Low vitamin D serum level is inversely associated with eczema in children and adolescents in Germany.
Heimbeck I1, Wjst M, Apfelbacher CJ.

[e] Low vitamin D levels are associated with atopic dermatitis, but not allergic rhinitis, asthma, or IgE sensitization, in the adult Korean population.
Cheng HM1, Kim S2, Park GH3, Chang SE4, Bang S5, Won CH4, Lee MW4, Choi JH4, Moon KC4.

[f] Suboptimal vitamin D status in a population-based study of Asian children: prevalence and relation to allergic diseases and atopy.
Yao TC1, Tu YL2, Chang SW3, Tsai HJ4, Gu PW5, Ning HC5, Hua MC6, Liao SL6, Tsai MH6, Chiu CY6, Lai SH7, Yeh KW1, Huang JL1; PATCH study group, Huang JL.

[g] Vitamin D deficiency is associated with diagnosis and severity of childhood atopic dermatitis.
Wang SS1, Hon KL, Kong AP, Pong HN, Wong GW, Leung TF.

[h] Vitamin D Regulation of Cathelicidin in the Skin: Toward a Renaissance of Vitamin D in Dermatology?
Siegfried Segaert1

[i] Increased food allergy and vitamin D: randomized, double-blind, placebo-controlled trial.
Norizoe C1, Akiyama N, Segawa T, Tachimoto H, Mezawa H, Ida H, Urashima M.

[j] Cord blood 25-hydroxyvitamin D3 and allergic disease during infancy.
Jones AP1, Palmer D, Zhang G, Prescott SL.

[k] Vitamin D insufficiency is associated with challenge-proven food allergy in infants.
Allen KJ1, Koplin JJ, Ponsonby AL, Gurrin LC, Wake M, Vuillermin P, Martin P, Matheson M, Lowe A, Robinson M, Tey D, Osborne NJ, Dang T, Tina Tan HT, Thiele L, Anderson D, Czech H, Sanjeevan J, Zurzolo G, Dwyer T, Tang ML, Hill D, Dharmage SC.