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Showing posts with label Filaggrin. Show all posts
Showing posts with label Filaggrin. Show all posts

Tuesday 16 January 2018

How much Histidine? Dermatitis and FLG mutations


Today’s post is not about autism, it is about allergy and atopic dermatitis in particular.
Many people are affected by atopic dermatitis (AD), also known as eczema; it is particularly common in those with autism. Children who develop asthma have often first developed atopic dermatitis (AD).
Atopic Dermatitis is another of those auto-immune conditions and the sooner you stabilize such conditions the better the prognosis.




Skin therapies from a company
spun-off from Manchester University


Histidine
A while back on this blog I was looking at the various amino acids and came across the observation that histidine, a precursor of histamine, appears to be a mast cell stabilizer. Mast cells are the ones that release histamine and IL-6 into your blood. Histamine then does on the trigger yet more IL-6 to be produced.  IL-6 is a particularly troublesome pro-inflammatory cytokine.
At first sight giving a precursor of histamine to people who want less histamine seems a crazy thing to do, but plenty of people report their allergies improving after taking histidine. As we have discovered, feedback loops are very important in human biology and these can be used sometimes to trick the body into doing what you want it to do. Having a higher level of histidine in your blood might make histamine production easier but it might also be telling the body not to bother, or just to delay mast cells from degranulating.  Whatever the mechanism, it does seem to work for many people. 

How Much Histidine?
Most histidine pills are 0.5g and it appears people use about 1g to minimize their allergy. 1g is the dose Monty, aged 14 with ASD, has been using during the pollen allergy season.
My sister recently highlighted a new "high tech" OTC product for skin conditions, Curapella/Pellamex, its main ingredient is histidine and it is a lot of histidine, 4g.




The company that produces the supplement have teamed up with the Universities of Edinburgh and Manchester to make a clinical trial, which is featured below.
They are considering the interaction between histidine and filaggrine (produced by the FLG gene). 

Mutations in the FLG gene are associated with atopic dermatitis and indeed with asthma, hay fever, food allergies, and, rather bizarrely, skin sensitivity to nickel.
In effect it is suggested that histidine makes filaggrine work better and thus atopic dermatitis and some other skin conditions will improve.  



Atopic dermatitis (AD), also known as eczema, is one of the most common chronic skin conditions worldwide, affecting up to 16% of children and 10% of adults. It is incurable and has significant psychosocial and economic impacts on the affected individuals. AD etiology has been linked to deficiencies in the skin barrier protein, filaggrin. In mammalian skin, l-histidine is rapidly incorporated into filaggrin. Subsequent filaggrin proteolysis releases l-histidine as an important natural moisturizing factor (NMF). In vitro studies were conducted to investigate the influence of l-histidine on filaggrin processing and barrier function in human skin-equivalent models. Our further aim was to examine the effects of daily oral l-histidine supplementation on disease severity in adult AD patients. We conducted a randomized, double-blind, placebo-controlled, crossover, nutritional supplementation pilot study to explore the effects of oral l-histidine in adult AD patients (n=24). In vitro studies demonstrated that l-histidine significantly increased both filaggrin formation and skin barrier function (P<0 .01="" respectively="" span="" style="background: yellow; margin: 0px;">Data from the clinical study indicated that once daily oral l-histidine significantly reduced (P<0 .003="" 34="" 39="" 4="" ad="" after="" and="" assessment="" by="" disease="" eczema="" measure="" of="" oriented="" patient="" physician="" scoringad="" self-assessment="" severity="" span="" the="" tool="" treatment="" using="" weeks="">. No improvement was noted with the placebo (P>0.32). The clinical effect of oral l-histidine in AD was similar to that of mid-potency topical corticosteroids and combined with its safety profile suggests that it may be a safe, nonsteroidal approach suitable for long-term use in skin conditions that are associated with filaggrin deficits such as AD. 
In this paper, we suggest that a simpler, nutritional supplementation of l-histidine may have a beneficial potential in AD.

l-histidine is a proteinogenic amino acid that is not synthesized by mammals. In human infants, it is considered “essential” due to low levels of histidine-synthesizing gut microflora and minimal carnosinase activity, which helps in releasing free l-histidine from carnosine.24 Our interest in the use of l-histidine in AD was stimulated by several observations. Firstly, in both infants and adults, a histidine-deficient diet results in an eczematous rash.25 In rodents, 3H-histidine is rapidly (1–2 hours) incorporated into profilaggrin within keratohyalin granules after intraperitoneal or intradermal injection14,26 and within 1–7 days is released as a free NMF amino acid in the upper stratum corneum.14 Furthermore, reduced stratum corneum levels of free NMF amino acids, including histidine and its acidifying metabolite urocanic acid (UCA), are associated with AD disease severity and FLG genotype.27,28

Given this evidence for the dependence of filaggrin processing and NMF formation on suitable levels of l-histidine, we hypothesized that l-histidine would both enhance filaggrin processing in an in vitro, organotypic, human skin model and have beneficial effects as a nutritional supplement in subjects with atopic dermatitis. 

After a 2-week wash-out period in which subjects were asked not to use any medicinal product for their AD, the same measures were repeated and patients were provided with identical sachets containing either 4 g l-histidine (Group A) or 4 g placebo (erythritol); Group B) which was taken once a day, dissolved in a morning fruit drink.  





Conclusion

It looks like 4g of histidine has the same potency as mild topical steroid creams, when treating atopic dermatitis.
The big problem with topical steroids is that you can only use them for a week or two. It you use them for longer, you end up with a bigger problem than the one you were trying to treat.
The 4g a day of histidine is put forward as a safe long term therapy.
Is the mode of action related to mast cells or filaggrin (FLG)? Or perhaps both?
If 1g of histidine does improve your allergies, perhaps you should feel free to try a little more.
You can buy histidine as a bulk powder. Pellamex is quite expensive, particularly if more than one family member is affected, as you would expect to find in a genetic condition.