Boost Your Immune System?

My right bicep. Oily, a little sticky, and otherwise completely unlike your immune system.

This post is a wee bit of a cheat in that it is a rewrite of a Quackcast, but I have three lectures and board certification in the near future, so sometimes you have to cook the wolf.

What does that mean: boost the immune system? Most people apparently think that the immune system is like a muscle, and by working it, giving it supplements and vitamins, the immune system will become stronger. Bigger. More impressive, bulging like Mr. Universe’s bicep. That’s the body part I am thinking about. What they are boosting is vague, on par with chi/qi or innate intelligence. They never really say what is being boosted.

The other popular phrase is “support”. A product supports prostate health, or breast health or supports the immune system. It sounds like the immune system is sagging against gravity due to age and needs a lift.

The immune system, if you are otherwise healthy, cannot be boosted, and doing those things you learned in kindergarten health (reasonable diet, exercise and sleep), will provide the immune system all the boosting or support it needs.

Someone is going to write in and say Americans have a lousy diet and don’t exercise and can benefit from better food and exercise. And that’s true. If you are not taking care of yourself, your immune function can be improved to function better. But if you are at your optimal baseline, you cannot make your immune function better.

The immune system: A really, really, really, really brief primer

What is the immune system? The immune system is a mind boggling complex set of coordinated cells and proteins.

There are antibodies: IgG, IgA, IgM, IgE and IgM, further divided into 5 subtypes of IgG and 2 of IgA, each with a different affinity for different parts of pathogens.

There is complement, a series of proteins that can be activated by two separate pathways and are important in killing some kinds of bacteria and attracting white cells to infection.

There are blood components: Polymorphonuclear leukocytes, also known as white cells. And monocytes. And eosinophils and macrophages. And the lymphocytes oh my, of which there are multiple types and with different functions. Each cell line can have either a specific task or a general task in the attempt to prevent you from dying from infection. If you are infected by a virus, there is one response, a bacterium produces a different response, a parasite, yet another response, and within each response there are subsets of types of response depending on the pathogen and whether or not you have been exposed to the infectious agent in the past.

There are all the proteins and their receptors that regulate the response to infection: chemokines and interferons and interleukins, a hodgepodge of letters and numbers: IL6 and TNF and CCR5 and on and on and on.

There is the Toll system, a wing of the immune system so ancient it is found in plants.

And there all the nonspecific parts of immunity that help prevent infection: platelets and cilia that sweep potential pathogens out and iron metabolism that keeps iron away from bacteria and the list goes on and on and on. The above is the briefest of overviews of the constituents of the immune system. It is almost like saying you have described the works of Shakespeare by noting it contains the words ‘the’, ‘and’, ‘of’, ‘verily’, and ‘forsooth.’ But the purpose of this post is not to describe the immune system in detail as I would soon embarrass myself.

A call for specifics: What are you actually boosting?

So when something allegedly boosts the immune system, I have to ask what part. How? What is it strengthening/boosting/supporting? Antibodies? Complement? White cells? Are the results from test tubes (often meaningless), animal studies, or human studies? And if in human studies, what was the study population? Are the results even meaningful? Or small, barely statistically significant, outcomes in poorly-done studies?

The answer, as we shall see, is usually nothing. It is the usual making a Mt. Everest out of a molehill, and a small molehill at that. If you google the phrase “boost the immune system” you will find over 288,000 pages that give advice on how to give that old immune system a lift. Curiously, a Pubmed search with the same phase yields 1,100 references, most concerning vaccination. If you Pubmed ‘enhanced immune system’ you get 41,000 references mostly concerning immunology. None of the references concern taking a normal person and making the immune system work better than its baseline to prevent or treat infection. I have yet to see a quality clinical study that demonstrates that, in normal, not nutritionally- or otherwise-compromised people, that some intervention can lead to a meaningful increase in immune function and as a result have fewer infections. Maybe such a study exists. I can’t find it. Send me the reference. I suppose the comment section will soon flood me with examples.

If you are normal and in good health, there is nothing you can do to make your baseline better.

Random advice fail

Randomly reading some of the advice on boosting the immune system yields Dr. Phil-level inanities that are trivial yet true. Get a good night’s sleep. Duh. Exercise regularly. Double duh. Avoid being a fat ass couch potato American whose idea of exercise is driving to Burger King for a triple Whopper with extra-large fries. What a concept. Don’t smoke or drink. These sites often intermix common, well-known beneficial lifestyle changes with all sorts of nonsense.

By the way, I need a lifestyle. Best as I can tell, I just have a life. I live it, and someday I won’t. But I need style. That is the problem of being from Portland: no style. It’s the old joke: what’s the difference between yogurt and Portland, Oregon? Yogurt has culture. Sigh.

There are numerous quack nostrums that allegedly boost your immune system. Exactly what is boosted and how is a mystery. Perhaps you are filled with toxins, then any number of detoxification regimens can improve your immune function. How precisely? Another mystery.

All the classic quack interventions: chiropractic, homeopathy, acupuncture, can also boost your immune system by, you know, changing some energy vibration or unblocking something or other. In fact one of the amazing things is that as best I can tell, there is no quack practice that someone, somewhere, will not say boosts your immune system.

People who receive regular chiropractic adjustments have immune system competency that is 200% greater than those who don’t.

Homeopathic remedies stimulate the immune system to assist the body in repairing any imbalances that may have occurred.

The following acupressure points are effective for dealing with a condition that may be caused by a weak immune system. Elegant Mansion (K 27) reinforces immune system functioning by strengthening the respiratory system. Steady, firm pressure on the Sea Of Vitality points (B 23 and B 47) fortifies the immune system, rejuvenates the internal organs, and relieves pain associated with lower back problems. The Sea of Energy (CV 6) tones the abdominal muscles and intestines, and helps fortify the immune, urinary, and reproductive systems. Firm pressure on the Three Mile Point (St 36) immediately boosts the immune system with renewed energy. It helps tone and strengthen the major muscle groups, providing greater endurance. Bigger Stream (K 3) on the inside of the ankle helps balance the kidney meridian and strengthen the immune system. Bigger Rushing (Lv 3) and Crooked Pond (LI 11),ire important points for relieving pain and strengthening the immune system. The Outer Gate point (TW 5) helps to balance the immune system and strengthen the whole body. Hoku (LI 4) is a famous decongestant and anti-inflammatory point; it relieves arthritic pain and strengthens the immune system Last, and most important of all, the Sea of Tranquility (CV 17) governs the body’s resistance to illness and decreases anxiety by regulating the thymus gland. Each of these important points benefits the immune system by enabling the internal organs to function at optimal levels.

I suspect that if one were to do all these interventions as once, your immune system would be raised to such a high level of activation that you would probably spontaneously combust. You heard it here first: the reason for spontaneous combustion is multiple, simultaneous boostings of the immune system.

This kind of nonsense is successful in part because that we all are aware that chance of illness increases with the number of stressors in your life, and the worse your life or lifestyle, the worse you are likely to feel and the more likely you are to have an illness. This phenomenon is real for groups of people. The more stressors, the higher the likelihood something will bad will happen with your life. This effect is harder to quantify for an individual. If you don’t sleep well, eat poorly, don’t exercise, get a divorce and a parent dies, in the next year you are more likely to have a medical problem. I remember toting up my stress score in medical school and based on my number I should have been dead three months earlier.

I would bet that when people turn to these quack nostrums, they do feel better, but not because of the nostrums, but because, for however short a period of time, they are no longer participating in the less than optimal habits that define standard American diet and activity. What they are probably doing is getting back towards a baseline of optimal health, not improving their health past what it is capable of.

I would bet 6 million years of evolution have more or less tuned our immune system to be running optimally, as long as we do the basics of eating well, exercising etc. All the stuff we failed to learn in kindergarten. You can be deficient in vitamins or sleep, etc., which will make you prone to illness, but if you are at baseline, you can’t improve your immune system in any meaningful way.

The sources of boostering

When reading the literature on the immune boosting properties of various products you find there are several kinds of results that they use to justify their claims, all with a thick coating of exaggeration and hyperbole.

The first is just made up. Somebody somewhere decided that this product enhanced immune function. Often the claim is based on ancient wisdom. You know, ancient wisdom, the same ancient wisdom that gave us the flat Earth and slavery and women as inferior, that ancient wisdom. Always a reliable indicator. Most of the time there is no data to support the claims of immune boosting.

Then there are test tube tests for boosting immune system,

The immune system is always looking to distinguish between self and not self. All the cells of your body are labeled with proteins, the major histocompatabilty complex for those of you keeping score, that are, in part, signals to the immune system. This protein on my cell surface identifies me as me to me. And no I am not preparing to sing opera. It tells the immune system, don’t shoot, I’m one of you. Other people’s tissue don’t have the same labels. Bacteria and other pathogens not only lack these signals, they have constituents in their cells that the body has evolved very specific responses against.

For example, E. coli has a toxin, called lipopolysaccaride in its cell walls that the body very specifically recognizes with a wing of the immune system, called the Toll-like receptor. If you incubate immune cells in a test tube with chemicals or non-self life (bacteria, virus, etc.) the cells react. That is what they are supposed to do. In medicine we call it the inflammatory response.

Oh look: Virus. Fungus. New chemical. Is it part of us? Nope. Respond. Kill kill kill. Here is a point I have made in the past. If you take a cell from the immune system and expose it to some chemicals or bacteria, you activate it, you get an inflammatory response. It’s primed. And if you then challenge that activated cell with another pathogen, it will kill that pathogen better than if the cell was not primed. It only works with some pathogens, usually those that are killed by nonspecific cell-medicated immunity.

Listeria and Candida are always popular pathogens that the immune system responds with a nonspecific (i.e. cellular) rather than a specific (i.e. humoral or antibody) response, probably because they are unusual enough pathogens that it made no sense evolutionarily to develop a specific response like we see to more common pathogens.

Some organisms, often unusual ones, are killed with a nonspecific response of the immune system, whereas others, such as viruses, which are killed by very specific antibody, or meningococcus, which really needs complement for optimal killing. This response is used to suggest that the immune system is being boosted and they imply that this boosting is to your benefit. Other test tube studies may show that mediators of inflammation, such as TNF or Il-1 are increased, which is what one would expect if you expose the immune system to a pathogen or a probiotic organism.

The mmmmmeat of the post

Those who say that that their product, for example probiotics, boost the immune system, point to studies such as these that show that in response to bacteria, cells of the immune system are activated, they are exhibiting the expected inflammatory response to a foreign invader. They call it boosting. I call it the inflammatory response. What could be better than priming your immune system so that it is better able to respond to a pathogen? This preamble leads us to the meat of this post: Is it good to have the immune system activated? Is it good to have your immune system primed? Or boosted? Maybe not. It does explain why taking a probiotic helps increase the antibody response to influenza vaccine in the elderly and decreases the duration of respiratory infections. A short term inflammatory response may be of benefit, but it may not be an effect you want to have persist.

But here is some recent, interesting literature, about the effects of having an inflammatory response to acute and chronic infections. Chronic inflammation of all types is associated with atherosclerosis i.e. hardening of the arteries, nicely reviewed in Libby et al.’s Circulation article, “Inflammation and Atherosclerosis” from 2002. An inflammatory state can occur from many things, not just infections.

First up: the NEJM, “Treatment of periodontitis and endothelial function” from 2007.

Periodontitis is gum infection and endothelial cells are them what line the arteries of the body. So they took a 120 people in England with bad periodontal disease (insert your own English dentition joke here, I don’t stoop to those kind of cheap shots) to either aggressive treatment of their disease or standard treatment. Aggressive treatment consisted of scenes from the movie Marathon Man:

Patients in the intensive-treatment group underwent the adjunctive full-mouth intensive removal of subgingival dental plaque biofilms with the use of scaling and root planing after the administration of local anesthesia; teeth that could not be saved were extracted, and microspheres of minocycline were delivered locally into the periodontal pocket.

What they looked at in this study, however, were markers of inflammation and endothelial function. Initially, when they were really reefing and scraping the teeth, which is going to cause bacteremia and bleeding, the aggressively treated group had a big spike in signs of inflammation, but long term, as their gums healed, they had a decrease markers of inflammation and better measured arterial flow. Those in the standard group did not get the same long term response; they continued to have signs of inflammation and endothelial cell activation. And this means?

Chronic exposure to bacteria leads to an inflammatory state and has detrimental effects on arteries. Taking lots of probiotics, or other substances that cause an inflammatory response, or boosting the immune system in the parlance of the quacks, should act like chronic periodontitis with chronic sustained signs of inflammation.

Who cares?

Maybe you, if you are taking immune boosters that could really activate the immune system; that should lead to chronic inflammation, which is associated with hardening of the arteries.

Thrombosis, the boostering bonus prize

But wait. There’s more. The inflammatory state is a prothombotic state. Infected people make blood clots, and they can make these clots for a long time. Clots can manifest in several common ways: heart attacks, strokes, and pulmonary emboli (i.e. blood clot to the lung). There are now several studies out there demonstrate an epidemiological link between a recent infection and a thrombotic event. For example, from “Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting,” Lancet, 2006:

7278 deep vein thrombosis patients and 3755 pulmonary embolism patients who were registered in a UK general practice database from 1987 to 2004. In the 2 weeks after a urinary tract infection, the risks of deep vein thrombosis and pulmonary embolism increased by 2.1-fold each, the report indicates. It took longer than 1 year for these elevated risks to return to baseline values.

Urinary tract infections increase your risk of blood clots and pulmonary embolism for up to a year.

How about heart attacks? Well, in Clinical Infectious Diseases 2007; 45:158-65 they looked at acute myocardial infarction and acute pneumococcal pneumonia and found an association, which had been noted since early last century. Acute pneumonia leads to heart attack.

Stroke? In European Heart Journal they looked at a database of strokes and heart attacks and found that:

There was strong evidence of an increased risk of both events in the seven days following infection — for MI, the adjusted odds ratio (OR) was 2.10, and for stroke, the OR was 1.92. The risk was highest in the three days following infection (OR 3.75 for MI and 4.07 for stroke). The risk of events was reduced over time, so there was little excess risk beyond one month after infection.

And a simple community-acquired pneumonia decreases 5 year life expectancy in a VA population from 84 months to 34 months:

Although the cause of the decreased long-term survival is not yet clear, it may be that the systemic inflammatory response produced by CAP accelerates the natural course of medical comorbidities such as atherosclerosis, Dr. Peyrani suggested. This hypothesis, she said, is bolstered by a recent study that showed reduced long-term survival in CAP+ patients who were clinically cured but had increased interleukin 6 and interleukin 10 levels at the time of hospital discharge.

So chronic inflammation and acute inflammation both increase your risk of thrombosis and vascular events. What would probiotics and immune boosters do if they really worked? They would cause acute and chronic inflammation. For those who may think I am talking about vaccines, not here. Vaccines cause the development of a specific antibody against whatever you are immunizing against, but it does not cause a generalized inflammatory response.

Correlation is not causation…but

Now I am well aware that association is not causality, and I am also well aware of the issues with epidemiological data to prove causality. But I submit for your consideration that if some product is really boosting your immune system, it is really activating your inflammatory response, and perhaps it may not be such a good idea.

Whenever I listen to skeptics talk about ID, they always complain how ID cannot make any predictions. Now I have been practicing ID for 23 years, and it is a science and I can make predictions. To suggest that ID is somehow inferior is. Huh? What? ID is intelligent design? Not infectious diseases? Oh. That’s different. Never mind.

But I will make a prediction: people who use probiotics or other substances that can measurably lead to an inflammatory response, or, have their immune system boosted, will have more strokes, heart attacks and pulmonary embolisms. So when you read that some product or other boosts the immune system, ask:

1. Says who?
2. What part of the immune system?
3. Are they calling an inflammatory response a boosting of the immune system?

If the answer to number three is a big yes, perhaps you should avoid the product. When it comes to your immune system, if you are normal, leaving good enough alone is probably the way to go.