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.