As both rosacea and autism affect my family, I was wondering if a link between the two conditions existed. Chronic inflammation is one of the hallmarks of both rosacea and autism and research has suggested that processes triggered by our innate immunity are to blame for such inflammation.
Innate immunity is how our body reacts to foreign microorganisms by activating specialized “killer” cells such as macrophages without the involvement of antibodies, which are part of our adaptive immune system.
Besides the inflammatory processes that play a role in the etiology of autism and rosacea, both conditions appear to have key trigger factors such as environmental factors, dietary factors and stress.
With the discovery in 2007 of a link between rosacea and antimicrobial peptides (specifically cathelicidins) that are aberrantly processed and overly abundant in rosacea skin, I wanted to find out if there were any studies done that looked at antimicrobial peptides such as cathelicidins and autism.
Cathelicidins
Cathelicidins belong to a group of antimicrobial peptides that are found in the skin and in certain white blood cells (neutrophils) and contribute to the body’s early host defense against infection.
Cathelicidins are produced as inactive precursor proteins and when cleaved into activated antimicrobial peptides, destroy bacteria by disrupting the integrity of their membranes (just as most antibiotics do).
Cathelicidins are not just activated by skin injuries and invading microorganisms. The cathelicidin response is also dependent on the steroid hormone vitamin D.
In addition to its effect on calcium homeostasis and bone formation, vitamin D is an important regulator of the innate immune response.
Studies have shown that the cathelicidin genes are controlled by a vitamin D response element (a molecular switch if you will): when activated vitamin D levels are low (such as in the winter), in theory there will be less production of cathelicidins.
How Does Vitamin D work?
We get some of our vitamin D through our food, but the majority of active vitamin D is produced in the skin: UVB radiation from the sun is required to produce pre-vitamin D3 (calciol) from 7-hydroxycholesterol. Pre-vitamin D3 needs to be modified by 2 additional enzymes (found in skin, liver and kidneys) to generate active vitamin D3 (calcitriol).
So how does vitamin D fit in with autism?
Some people believe that since vitamin D plays such an important role in innate immunity and early brain development, that vitamin D deficiency during gestation or early childhood may contribute to the development of autism.
The theory behind this is, that the increase in the number of autism cases over the last 20 years does not follow classic Mendelian inheritance. While autism has a strong genetic basis with many different genes playing a role, it is fair to say that the role these genes play in the etiology of autism could not have changed much over the last 20 years.
It may be possible that environmentally responsive genes play a much larger role in the development of conditions such as autism and that something in the environment, before or after birth, is influencing the outcome of our genotype.
The rise in autism incidence over the last 20 years corresponds with increasing medical advice to stay out of the sun and use high SPF sunscreens, which may have resulted in a severe vitamin D deficiency in many people (especially during the winter months).
In addition, a strikingly high male-to-female ratio in autism can be explained by the stimulating effect estrogen has on vitamin D levels in the brain: estrogen protects female brains from calcitriol deficiencies whereas testosterone does not. Note that in rosacea there seems to be a high female-to-male ratio.
If vitamin D deficiency plays any role in autism, then symptoms should improve during the summer. Also, autism prevalence would be higher in (more) Northern latitudes. Some studies (see Cannell 2008) found an association between prevalence of autism and latitude, including recent CDC data that looked at autism prevalence in 14 states.
How can sun avoidance in the summer lead to vitamin D deficiency?
When a fair skinned adult stays in the sun for 20 minutes (full body), approximately 20,000 units of vitamin D enters their circulation. You would have to drink 200 glasses of milk or take 50 multivitamins to receive a similar amount of vitamin D.
Patients suffering from Rickets, a condition in which vitamin D deficiency is caused by a genetically defective production of the enzyme that activates vitamin D, share some of the symptoms of autism such as hypotonia and developmental delay.
Children with Williams’s Syndrome, who have very high levels of vitamin D in early infancy, often show signs that are the complete opposite of autism such as overfriendliness, empathy and increased sociability.
A number of drugs can interfere with vitamin D metabolism. One of them is sodium valproate (a.k.a. Depakote), a drug that is frequently used to treat epilepsy, seizures and convulsions.
Numerous animal studies have shown that sodium valproate (or valproic acid) given during pregnancy can lead to abnormal brain development and symptoms of autism in offspring. It has been shown that sodium valproate interferes with vitamin D’s actions. Sodium valproate or valproic acid is often used to generate mice that show the classic symptoms of autism.
Vitamin D and rosacea
While the available data from studies suggests a possible risk factor for autism and vitamin D deficiency, it is unclear at the present time whether vitamin D has a positive or negative effect on the outcome of rosacea.
Based on the findings of Yamasaki and colleagues, vitamin D would increase cathelicidin production, which in rosacea would lead to a higher level of (disease causing) antimicrobial peptides.
However, some studies have looked at the seasonal effect of rosacea and reported that for the majority of rosacea patients, symptoms did improve during the summer months.
Also, other studies have found that vitamin D deficiency is associated with increased levels of the matrix metalloproteinases (MMP 2 and 9), which are related to the serine proteases involved in rosacea.
If higher levels of vitamin D could lower the levels of the serine proteases in the skin that are causing the inflammation-causing splicing of cathelicidin, then higher levels of circulating vitamin D could therefore be beneficial to the management of rosacea symptoms.
Additional Reading
Zanetti, M. (2005) The role of cathelicidins in the innate host defenses of mammals. Curr. Issues Mol. Biol. 7: 179-196.
Schauber, J. and Gallo, R.L. (2008) The vitamin D pathway: a new target for control of the skin’s immune response? Exp. Dermatol. 17: 633-39.
Cannell, J.J. (2008) Autism and vitamin D. Med. Hypotheses 70: 750-59.
Yamasaki, K. et al. (2007) Increased serine protease activity and cathelicidin promote skin inflammation in rosacea. Nat. Med. 13: 975-80.
This article appeared originally on Reverta’s blog. You can read it here.
Marian Webster
There is increasing concern about the resistance of microorganisms to various drugs and the perspective of continuous use of antibiotics is not yet well defined. Therefore, many measures to solve this problem need to be adopted, e.g., the controlled use of antibiotics, expansion of research for the better understanding of the resistance mechanisms, and continuing attempts to develop new synthetic and natural drugs. Peptides, we believe, constitute a novel potential therapeutic agent against diseases caused by pathogenic organisms.
wormgirl1
Very interesting!
I beleive that the gut somehow plays a role in both rosacea and autism possibly through inappropriate permeability.
I agree that demodex mites play a role in rosacea. Do the mites influence this, or does the “leaky gut” create a friendly environment for the mites in which they flourish?
Here is an exact quote from an article in a reputable medical journal:
“It is possible that Demodex influences the expression levels and the processing of cathelicidin.” Bevins CL, Fu-Tong L. Rosacea: skin innate immunity gone awry? Nature Medicine 13, 904 – 906 (2007).
It’s possiible that people are allergic to certain commensal pathogens carried by demodex, or to the demodex exoskeleton.
I am a researcher who suffers terribly from rosacea, and the only thing I have found that appears to have some good possibilities for demodex eradication backed by reasonable science is tea tree oil (TTO)as outlined in an article:
Gao Y-Y, Di Pascuale MA, Li W, Baradaran-Rafii A, Elizondo A, Raju VK, Tseng SCG. In vitro and in vivo killing of ocular demodex by tea tree oil. Br J Ophthalmol 2005;89:1468-1473.
Dr. Tseng has gone on to patent products, but this technique could be followed through by any motivated patient. Although it is uncomfortable, it is not unbearable, as I can attest. At week 1, I have not had any reduction in redness, but my acne is clearing, and my skin is less itchy.
dr prem raj pushpakaran
Regulation of cathelicidin genes are controlled by their upstream elements, of which calciferol response elements (CRE) plays a crucial role in combination with retinoid x receptor (RXR). Electrophoretic mobility assays may be performed to study the DNA-Protein interactions.
dave
I have borderline vit. D levels. Everytime i increase supplementation of vitamin D my rosacea flares big time, and I even develop cysts (which I normally never have). I can go out in the sun (sun hits my back only, not my face). The rosacea flare from this vitamin D is not as severe. I think there is a link between vitamin D and rosacea, and have always suspected this due to my reaction to it. I took antibiotics for years. This is not a permanent solution as your gut bacteria will be messed up (perhaps leading to Leaky Gut and aggravating your rosacea in the long run). As rosey indicated, laser treatment is the only effective treatment for rosacea, in my particular case. I think expanding on your blog about the relation of gut health to rosacea relative to Leaky Gut Syndrome would be very informative.
rosey
I found that cabbage juice helped for a period of time with rosacea. I think it helped with leaky gut, which many people have as a result of stress, food allergies, and dysbiosis. Eventually it stopped working for me, and now the only thing that I have found to work for the reddness is laser, and antibiotics for the white heads. Although I hate going that route, and know that the antibiotics are not the answer, and the laser is probably doing long term damage.
Vitamin D Deficiency
Vitamin D can be tricky, milk, where it is readily available, is a good source of it but can be near poisonous for adults as they mature out of childhood. A healthy dose of sun on the other hand, can provide the requisite vitamin D but puts a large strain on the skin where one can develop growths from too much ultraviolet radiation. Vitamin D pills are probably the safest middle ground.
Gene
Antibiotics and chemicals are responsible for destoying the immune system of the skin. As we – rosaceans, often listen to wrong advices to use the antibiotics as only possible rosacea treatment, we suffer in the long run. Candida is not only one. How about the demodicosis (demodex)?? Read some interesting facts here http://skinimprovements.com/blog/ about the link between the use of chemicals and antibiotics and development of demodex.
ANG
I was diagnosed with rosacea approx 2 years ago, I tried many treatments to get rid of it and nothing worked.
Anyway since I have always been prone to Thrush I decided to do a little research last week on the pooter and educated myself on the whole candida thrush and tinea thing as they are apparently all related.
Well lets just say that I self diagnosed myself as having TINEA FACIEI and went out and bought Ego Tinea cream which I have been applying for 3 days now.
AND GUESS WHAT it’s actually clearing up. My face almost looks normal only after 3 days.
I think that just maybe this could be what some ppl out there have without even realising it.
Good Luck !!!!
inquiry7
I just did a quick Google search.. appears Autism and Candida both implicated with shortage of Vitamin D. I tell you.. Candida. Improve the immune system, avoid antibiotics, get on the ‘candida’ diet.
inquiry7
Please add to your research the possibly of a Candida link. I had chronic sinus problems caused by candida. Eliminating the Candida practically eliminated my Allergy problems also. Allergies, of course, are a hypersensitive response to allergens. As candida invade the body it modifies its environment (your body and immune system). There is also a Candida – Autism link. I am becoming convinced that Candida may cause many of the health problems people have. Antibiotics may make the problem worse or even cause the problem of Candida overgrowth. thanks.
Paula Harris
I’m not sure what to make of this! I’ve had plenty of vitamin D my entire life, & too much sun(when younger). My symptoms worsen in heat/humidity…yet, cold & wind make it bad, too. I just hope they find a “cure” for both conditions.