Allergies and hormesis

[Todd Becker]

I'm starting this thread as a follow-on to my post on Allergies and hormesis, and the discussion started by aelephant on this other forum thread.

I grew up in a home with pets, playing in the dirt and lots of outdoor exposure and never had any allergies.  The house I live is fairly relaxed about cleanliness -- we track in dirt from the garden, don't obsess about clean counter tops or slightly old food, etc. Not we that don't keep things reasonably clean.  And we don't restrict ourselves from eating any particular type of food.  But no allergies in the family.  

On the other hand, I notice that many of my kids' classmates who have allergies have grown up in spotless homes.  

This tends to confirm the 'hygiene hypothesis' that our immune systems benefit by exposure to a broad range of potential allergens in our environment and our food.  I think that the case for this is laid out pretty well in Mary Ruebush's book, "Why Dirt Is Good".

What I'm interested here is in getting a discussion going based on personal experience or observations -- either in support or against -- of the hygiene hypothesis.

[aelephant]

One thing that could have a correlation is birth number or birth order. For example in my experience "only children" (that is, without any siblings) tend to be much more sheltered than those with siblings. The parents have more energy and time to devote to earning money to afford "nicer" things that they are then motivated to keep pristine; cleaning up after one kid is much easier than cleaning up after 2 or 3; and these kids are often "micromanaged" to the point where all of their free time is scheduled. I'd be curious if there exist any data on the incidence of allergies and/or other immune disorders and birth order.

I happen to be the youngest child of three. Growing up I spent a lot of my time playing with my friends in the forest behind our house, playing in the dirt, building tree forts, etc. We always had many animals -- dogs, cats, later horses. I have no allergies or immune disorders that I'm aware of. I'd imagine that younger children are typically raised in a more "Laissez-faire" fashion than their older siblings. My parents were very hands-off in the way I was raised. Many of parents worries are shown to them to be unfounded with their first children, then they relax and give their younger kids more freedom. More freedom = more exposures to potential stressors, I imagine.

A friend of mine mentioned that sheltered or only-childs he's known that have traveled abroad have all had terrible times adjusting to local food. When I first moved to China, I was sick to my stomach for about 24 hours. Since then, no problems. I eat the local food every day. Traveling to Mexico several times, I can't recall ever getting sick.

My girlfriend, whose mother tends to be a bit of a worrier, is an only child. No doubt she was raised much more "carefully" than I was. She also has skin allergies that flare up from time to time. Merely anecdotal evidence, but an interesting observation, nonetheless.

My mother has worked for 30+ years as a nurse. Health care workers, by the nature of their job, are exposed day in and day out to immune stressors. Patients don't come to a hospital because they're healthy. She rarely has a cold, much less a severe illness like the flu. I worked for about 3 years in a pharmacy. Every other patient is sick and picking up antibiotics, while sneezing on their hands and wiping their face. I also rarely have colds, much less severe illnesses. Certainly there are multiple factors at work, but I imagine repeated exposure could only benefit one's immune function.

[aelephant]

I had to travel to Hong Kong for a visa and noticed a placard on the escalator in the subway:

"These handrails have been treated with an antibacterial agent."

I have to wonder what the hidden costs of this kind of "health initiative" are.

[thomas_seay]

Well, I was an "only" child.  I have been allergy free, except that I developed a food-allergy to avocados when I was 40, probably due to over consumption.  I was born with a penicillin allergy also, I just recalled. 

I grew up in the country, and we always kept a couple of big dogs (Great Danes, Irish Wolfhound) INSIDE the house.  On top of that, we usually had a couple of cats in the house, too.  Having a horse was not exclusively for the rich where I grew up (as it is here in the Bay Area), so I grew up riding horses and being around them a lot, including mucking their stalls.  I also played in the dirt a lot (tackle football, etc) and it wasn't a big deal if I came home dirty.  My mother expected it, and, it wasn't a big deal.  After all, it's not like she had to clean my clothes by hand.

So, if anybody got exposed to germs, it was me!!!!   

My wife has asthma (and a bunch of allergies), and I've wondered about that.  Interestingly, she grew up in China, in the city of Beijing.  Now China isn't the cleanest place in the world and she did spend a part of her youth in the countryside.  Beijing is polluted as hell, but I'm not sure that was the case during her youth.  After all, China did not begin industrializing big-time until the 1980s.

Here's one thing.  She wasn't breast-fed at all (but then again, neither was I).  She has a daughter from another relationship who grew up entirely here in the Bay area.  That daughter has asthma.  She only breast-fed her for a short while.  My two children with her were breast-fed extensively (3 years each one!!!!).  They have truly AWESOME immune systems and, of course, no asthma.  This, even though, my wife keeps things super clean (due to her own condition) and is anal about not letting the kids get dirty.

So, I don't know what conclusions to draw from the above.  You might argue that my children with her inherited something from me that did not give a predisposition to asthma and allergies.  You might argue that it was the breast-feeding that spared them of their mothers allergies.  Of course, it might be a mixture of those two things.  In their case, it certainly isn't because of super exposure to dirt, although we do keep a dog in the back yard.

[dee]

Thomas,

According to Occam's razor, the breast-feeding theory is probably the best guess.

Another interesting thing about allergies is gender: http://www.hindawi.com/journals/ja/2009/159845/

Male children have more food allergies than female, but the opposite is true for adults. Seems consistent with aelephant's views on taking care of children (girls are babied more than boys).

[Todd Becker]

My wife has asthma (and a bunch of allergies), and I've wondered about that.  Interestingly, she grew up in China, in the city of Beijing.  Now China isn't the cleanest place in the world and she did spend a part of her youth in the countryside.  Beijing is polluted as hell, but I'm not sure that was the case during her youth.  After all, China did not begin industrializing big-time until the 1980s.

The question of whether and under what conditions pollution can cause allergies or rather exert a hormetic protective effect is interesting, Thomas.  Seth Roberts, who teaches in Beijing, has written about the potential hormetic effects of pollution and smoking:
http://www.blog.sethroberts.net/2011/02/21/beijing-smog-good-or-bad/

I think that for a given individual, the effect result from a combination of many factors, including strength of the innate immune system from early childhood, initial age of exposure to pollution, level of pollution, and frequency or intermittency.  My own sense is that this latter factor -- intermittency -- may be one of the most important. Having periodic exposures to pollution, with intervening time to recover between exposures and develop immunity and resistance to allergies, may be protective, whereas chronic high level exposure may be problematic.

[Todd Becker]

Just read an interesting article "Why Are Asthma Rates Soaring?" in the April 2011 Scientific American.  The author, Veronique Greenwood, reviews recent studies suggesting that, while the hygiene hypothesis appears to account for the prevalence of allergies in general, it is at best incomplete and perhaps not predictive at all when it comes specifically to asthma. While some forms of asthma are allergy-associated, there is a type of non-allergy associated asthma that does not follow the same pattern.

According to Laura Rodrigues of the London School of Hygiene and Tropical Medicine:

We think that dirt protects against allergic asthma, as foretold by the hygiene hypothesis, but increases the risk of having the nonallergic form.

Nonallergic asthma is associated with pollutants that can irritate the airways and cause inflammation that leads to constricted breathing. So what accounts for this?  In short, there are no conclusive answers yet.  But here is one idea discussed in the Scientific American article:

A reworking of the hygiene hypothesis that focuses on changes in the normal nondisease-causing bacteria that live inside and on the body (in the intestines or the airways or on the skin) has promise. Studies by von Mutius and others have shown that children who live on farms where cows or pigs are raised and where they drink raw milk almost never have asthma, allergic or otherwise.  Presumably because the children drank unpasteurized milk and handled livestock, they have different strains of normal bacteria in their airways that are somehow more protective than those found in city kids...."There is something about westernization that means people's immune systems function in a different way."

Sounds to me that this is not a rejection of the hygiene hypothesis, but a more specific refinement of it.  It also makes a reasonable case for raw, unpasteurized milk.

[aelephant]

Well so much for me not being allergic to anything:


Friday night I noticed two bumps, one on each of my hips. They were itchy, raised and red, but I figured I was just bit by an insect. Saturday night I went out for Sichuan style hot pot (very spicy) and karaoke with some friends. Late in the night, I started to get extremely itchy, particularly on my hips and my buttocks. When I got home and took off my shirt, the above is what I saw.

We call this hives or urticaria. It can be caused by allergy to food, drugs or even to a virus.

I took a Chinese Claritin and went to bed. The next day, my skin had cleared up, but that night the hives came back, this time not on my hips, but pretty much all over my stomach, back and arms. Another Claritin & it cleared up again. The next night, it returned AGAIN. This time the hives took over my arms, neck and face. Claritin didn't help much this time and the hives were accompanied by a fever. I didn't sleep much at all last night. Now the hives have cleared up, but my hands are swollen and itchy.

A friend told me this happens to her husband about 4 times a year, typically when he is traveling abroad on business. My theory right now is that since I'm in a foreign country, my immune system is reacting strangely to a totally foreign virus. The other most probable cause would be a food allergy, but I haven't eaten anything I don't regularly eat. I have heard of people suddenly developing allergies, but I sort of doubt that is the case.

[dee]

The other most probable cause would be a food allergy, but I haven't eaten anything I don't regularly eat. I have heard of people suddenly developing allergies, but I sort of doubt that is the case.

Food preparation can make a big difference, especially in foreign countries. It may not even by how they prepared it, but what they prepared with it.

About that article Todd, it's interesting, but I wouldn't hop on the raw milk bandwagon just yet (I'm a big fan of milk, and think it's amazingly healthy, but I won't go so far to say that it's "special").

Fact of the matter is that asthma is rising, which means something is causing it. That something is unlikely to be a lack of raw milk (though that could be a cure; I've been reading up on the healing properties of raw milk diets). They even say it's linked to inflammation, and that obesity might be cause. Sounds familiar (think: heart disease). So, I'm going to channel my inner-Gary Taubes, and say that asthma is a disease of civilization (thus probably caused by modern food).

I'd even go so far as to say that gluten is probably the cause. Why? Because gluten is a lectin, lectins bind to sugar, and one of the few that gluten binds to is galactose. I wanted to make a separate post on this on "how to diffuse gluten", but I could find nothing easy, other than having sourdough (and the galactose thing, obviously) which isn't that easy in our modern gluten-full society.

So, if ever you have to have gluten grains, and you don't have ~24 hours to ferment it, having it with lactose (glucose + galactose; the sugar in milk) could definitely minimize the damage.

[JohnG]

Gotta say, I'm not a fan of the "hygiene hypothesis." The following quoted passage summarizes, very succinctly and clearly, some of the main problems I have with the idea that exposure to a less hygienic environment may be beneficial:

"In the elderly a chronic basal systemic inflammation prevails - which is evident by enhanced CRP or IL-6 plasma concentrations - and by compromised defense mechanisms against invading microbes. These alterations belong to the physiological ageing process of the immune system (immunosenescence) and are regarded as an inflammatory response towards lifelong antigen stress ("inflammatory/pathogen burden"). This lifelong antigen stress evokes an age-dependent basal inflammatory activation of innate immunity as well as a wasting of specific immunity: it is supposed that in the course of life-time due to a multitude of infectious/inflammatory events ("multiple hits") an inflammatory stress prevails or "inflammatory/pathogen burden" accumulates, which substantially contributes to an enhancement of the inflammatory parameters of natural immune response. Such enhanced inflammatory parameters characterize persons at increased risk of degenerative diseases like atherosclerosis or coronary heart disease. The risk is the higher, the higher the "pathogen burden"."

from: The Role of the "Inflammatory/ Pathogen Burden" for Cardiac Ageing (AntiCardAgeing)
http://clinicaltrials.gov/ct2/show/NCT01045512

---

In short, inflammation is one of the central weapons in the immune system's arsenal. The problem is that inflammation, as well as inflicting damage on pathogens/antigens, also appears to do damage upon the body itself. It's akin perhaps, to a country being invaded, and as the country's military is fighting off the invader, there is a lot of unavoidable self-inflicted collateral damage to their own people and infrastructure.

The immune system in humans is composed of an adaptive/specific and innate component.

The adaptive component can learn about a particular pathogen/antigen, then develop specialized specific responses to it. According to what I've read, and although it may be rather early to be certain about this, it appears that there is only a limited total number of adaptions that can be made. So, for argument's sake, 100 adaptions might be the total number, and with each new novel pathogen/antigen exposure another adaption is used up until the adaptive ability is exhausted. This may be one reason why the elderly can have a much weaker immune system, and even die from normally minor illness/infection. This may also be why immunizations becomes less effective in old age.

The innate component of the immune system, on the other hand, has a number of "stock" reactions that it uses to try to defend the body. These reaction are, at least relatively, non-specific and not specialized for the pathogen/antigen they are used against. One of these reactions is inflammation. There is evidence that with each engagement with an antigen/pathogen the basal widespread state of inflammation increases, until eventually a constant significant widescale inflammatory state arises. This inflammation has been implicated in many of the most serious and common chronic diseases of aging.

I think it's also relevant to consider that during the last 200 years(and certainly continuing during the last 20 years) there has been ever-increasing levels of hygiene(at least in the developed countries), and at the same time ever increasing levels of health and longevity. Further, there seems to be almost universal consensus(not a small thing considering we're talking about medical sciences) that increased hygiene has played one of the most important roles in increased human longevity and health during that period.

Taking these factors into account then one could, I think, reasonably hypothesize that reduced lifetime exposure to pathogens/antigens/germs(possibly with some important caveats) may generally be the most beneficial course to take.

[dee]

If you take into account exposure to unhygienic conditions is inevitable, it may be beneficial to minimize the stress it causes (this is where the hormesis:thrive on stress thing comes in).

Either way, I'm pretty sure no one is saying hygiene has caused more harm than good, though I do believe getting dirty once in a while will lower the total area under the curve for unhygienic-induced inflammation. Check out Todd's post on the opponent-process theory. Absolutely life changing in my opinion. The whole Paleo-perspective works out as well since it makes sense that humans can handle less-than-hospital-clean conditions at least sometimes.

Finally, using this statement as evidence is kind of flawed: "I think it's also relevant to consider that during the last 200 years(and certainly continuing during the last 20 years) there has been ever-increasing levels of hygiene(at least in the developed countries), and at the same time ever increasing levels of health and longevity." Since you can make the logically equivalent statement: "I think it's also relevant to consider that during the last 200 years(and certainly continuing during the last 20 years) there has been ever-increasing levels of hygiene(at least in the developed countries), and at the same time ever increasing levels of obesity and asthma." People actually use the same argument to defend grain-based diets (even if they weren't bad for you, the argument is a bad one.)

[aelephant]

http://www.sciencedaily.com/releases/2012/02/120208132549.htm

Growing up on a farm directly effects regulation of the immune system, study finds

A new study has shown, for the first time, that growing up on a farm directly affects the regulation of the immune system and causes a reduction in the immunological responses to food proteins. ...

The research, led by the University of Bristol's School of Veterinary Sciences, found that spending early life in a complex farm environment increased the number of regulatory T-lymphocytes, the cells that damp down the immune system and limit immune responses.

Dr Marie Lewis, Research Associate in Infection and Immunity at the School of Veterinary Sciences, who led the research, said: "Many large-scale epidemiological studies have suggested that growing up on a farm is linked to a reduced likelihood of developing allergic disease. However, until now, it has not been possible to demonstrate direct cause and effect: does the farm environment actively protect against allergies, or are allergy-prone families unlikely to live on farms?"

In the study, piglets were nursed by their mothers on a farm while their siblings spent their early life (from one day onwards) in an isolator unit under very hygienic conditions and were fed formula milk, therefore, reflecting the extremes of environment human babies are raised in.

The work was carried out in piglets as they are valuable translational models for humans since they share many aspects of physiology, metabolism, genetics and immunity.

The researchers demonstrated that compared to their brothers and sisters in the isolator, the farm-reared piglets had reduced overall numbers of T-lymphocytes, the immune cells which drive immune responses, in their intestinal tissues. Importantly, these dirty piglets also had significantly increased numbers of a subset of these cells, the regulatory T-lymphocytes, which pacify immune responses and limit inflammation.

This shift in the ratio of stimulatory and regulatory cells appeared to have functional effects since the farm-reared piglets also exhibited decreased antibody responses to novel food proteins when they were weaned.

Regulatory T-cells have been identified in many mammalian species, including humans, and appear to be universal regulators of immune systems and a reduction in their numbers is often associated with the development of allergies, autoimmune and inflammatory diseases.

Dr Lewis explained: "At this point it is not clear exactly what caused the increased capacity for immune regulation in our farm-reared piglets. Our previous work suggests that intestinal bacteria play a pivotal role in the development of a competent immune system and these bacteria are obtained from the environment during early life."