On the flight from London to Rome I read an article on the immune system and cancer. It got me to thinking about the immune system and a whole lot of other health problems.
It’s sunrise in The Eternal City right now. I’ve been up early watching the dawn break over St. Peters, which is a couple of miles below the hotel. I figured everyone was getting tired of travel disaster stories, so I thought this would be a good time to sketch out my views on the inflammatory basis of heart disease.
If you read enough in the medical literature you will perceive a change in outlook on the underlying cause of many of the so-called diseases of civilization, especially heart disease. Most authors – mainly, I suspect, out of desire to keep their academic positions and reputation with their peers – throw a bone to the lipid hypothesis before admitting that it probably isn’t the only cause of coronary artery disease. Over the last decade or so the progression has been thus: elevated cholesterol causes heart disease – elevated cholesterol and maybe a little inflammation cause heart disease – elevated cholesterol and inflammation cause heart disease – inflammation along with elevated cholesterol cause heart disease – and now, among the more enlightened – inflammation causes heart disease. In my opinion, it probably is inflammation by itself that is the driving force behind the development and progression of most cardiovascular disease.
When the cholesterol-causes-heart-theory was in its infancy the question became ‘what causes cholesterol levels to go up? Of course this question led to the anti-saturated-fat hysteria that pretty much still has us by the throat. But the same question needs to be asked of anyone who claims inflammation to be the cause of heart disease: What causes inflammation?
Before we address that issue, let me add that in much the same way saturated fat has been demonized as a cause of almost everything, inflammation is thought to be the catalyst for much more than simply heart disease. There has grown up a theory called the ‘common soil’ theory that implicates inflammation as the underlying problem, or the ‘common soil’ from which spring heart disease, diabetes, obesity and the other diseases common to modern man.
No one much talks about the cause of inflammation – most seem to think it is a natural part of the aging process. As we all get older, we become more inflamed. As we become more inflamed, we tend to develop heart disease, diabetes, etc., all of which are diseases that usually strike later in life.
I have a little different opinion.
Before I can argue my theory, I have to make sure we’re all on the same page about what inflammation really is.
Inflammation can’t be understood without at least a rudimentary understanding of the immune system, specifically the innate immune system, so let’s start there.
We humans along with the rest of the animal kingdom have two immune systems: an innate immune system and an adaptive immune system. The adaptive immune system is the more sophisticated of the two, and it’s the one that seems to have inspired the most research interest. The adaptive immune system is the one involved when you have hay fever, an allergic reaction, or get an immunization. It is the immune system that gives you resistance to measles or mumps once you’ve had them. It is the part of the immune system that remembers and can mobilize vast forces quickly when it discovers an invader that it has seen before, say, the measles virus. It is programmable by what it has dealt with before. The TSA would be comparable to the adaptive immune system. After we were inoculated by the events of 9/11, we grew our national immune system to protect against a threat we didn’t know existed until it hit us.
The innate immune system is a different animal. The innate immune system is a primitive, hard-wired immune system that reacts the same way to every threat. Unlike the adaptive immune system that takes a while to activate and get responsive, the innate immune system is always on the prowl and acts immediately. To carry the 9/11 metaphor further, the innate immune system was what acted immediately after 9/11: all flights canceled, all airports patrolled, no cars could stop, etc. It was an immediate, knee-jerk response to an unknown threat.
The innate immune system is pretty much the same. It lays in wait for any invasion and reacts immediately while the adaptive immune system is just getting out of bed.
If you are an animal in the wild or a Paleolithic man (or woman) and you want to survive, you’ve got to worry about two things: infection and trauma. You can get a virus, fungal or bacterial infection or you can get seriously injured. Both can do you in. The innate immune system was evolved to deal with both. (You can also starve, but that’s another matter. Starvation doesn’t happen to you in the same way infection and/or trauma do. Starvation is a prolongation of the typical feast/famine cycle, and is dealt with hormonally in ways we’ve discussed in previous posts. Plus it takes a lot longer to starve to death than it does to be killed by infection and/or trauma. The innate system deals with immediate threats.)
The innate immune system protects you against infection and trauma. It works the same for both. If you get a cut, throngs of immune cells make their way to the cut almost immediately. They begin sending signals putting out the call to other immune cells to head for the injury and join the fray. The blood clotting system is revved up to minimize blood loss. Any bacteria that enter the cut are immediately swarmed on, surrounded, and killed. The area becomes red, swollen, and painful. It is hot. All of which are the cardinal signs of inflammation known since ancient times: rubor, calor, tumor and dolor. Redness, heat, swelling and pain.
If the infection or trauma is serious enough, the cells of the innate immune system signal to the liver for help. The liver springs into action by what is called the acute-phase response, which is the production and release of even more substances to help deal with the threat.
As the injury or infection is dealt with, the innate immune system completes its work and fades into the background, lying in wait for the next exposure.
The innate immune response is something you’ve got to have to survive, but not something you want actively working all the time. You want it when you need it, but you want it to stay in the background when you don’t.
Problem is that the innate immune system can be chronically active, and when it is, you have a set up for heart disease: increased blood clotting, inflammatory cells and their products attacking blood vessel walls, the liver drifting into and out of the acute-phase response, etc. In other words, the lab picture of someone who has heart disease.
But why does the innate immune system become chronically active instead of just springing into action when needed?
What follows is my opinion and is purely speculative. But I think it makes sense.
We know the innate immune system is primitive and primed for action against infection and/or trauma. It’s the only immune system we have with first-strike capability and is primed for any immediate threat.
We now have a threat we didn’t have during our Paleolithic days. Now we have the threat of overnutrition. We are eating types of foods we didn’t eat in the past and in amounts we didn’t eat in the past. This overnutrition is a threat to our survival and it stimulates an innate immune response because that’s the only response we have. The innate immune system senses danger, reacts, but unlike the cut that heals or the bacteria that gets destroyed, the overnutrition continues. So the innate immune system remains chronically active.
Let me give you one example before I end this already overlong post. (You’ll be begging for more travelogues and tales of airline snafus after this)
When we overeat, the body has to dispose of the excess calories. (I’m talking about the typical high-carb overeating here.) The logical place to stuff them is into the fat cells, which is the first place they go. They go into the subcutaneous fat, the fat under the skin, but outside the body cavity. This is the place nature intended excess fat to go. Subcutaneous fat isn’t particularly aesthetically pleasing, but it’s also not particularly unhealthful. It’s fat where fat is supposed to be.
When the subcutaneous places to store fat are filled (or, for example, when fructose is a large component of the diet) the excess calories go looking for other storage places. The next place these calories go is into fat inside the body cavity – around and within the organs themselves. This is not a good place for fat to be.
The innate immune system regards this fat – called visceral fat – as a foreign invader and attacks. Multiple studies have shown that visceral fat is crawling with macrophages, one of the foot soldiers of the innate immune system, whereas subcutaneous fat isn’t. Once these macrophages invade the visceral fat, they begin signaling – as is their wont being on the front lines of the innate immune system – to other macrophages to join the battle. They also release toxic substances to damage and kill the foreign invaders. These substances reach the blood and are carried throughout the circulation.
Normally these macrophages and other cells of the innate immune system do their jobs, getting rid of the invaders, and mopping up. In the case of visceral fat, the fat just keeps on coming. And the innate immune system keeps on working. And the heart and blood vessels keep on getting damaged.
But it’s not just overnutrition in terms of overeating; it’s also overnutrition in terms of constant eating.
Overeating leads to the fat accumulation that stimulates the chronic inflammation, but simply eating does it as well. Eating is an inflammatory process. A number of scientific studies have shown that eating a meal, regardless of the macronutrient composition, causes acute inflammation, which makes sense when you think about it. Food coming into the body is a foreign substance that fires up the innate immune system – but it does so briefly until the food is digested and the various fats, proteins and carbohydrates are broken down into their basic units and absorbed into the blood stream. (Although it might seem strange that food that we absolutely need to live could cause inflammatory problems, it makes sense when you realize that the very oxygen we breathe and that we would be dead in about four minutes without is slowly killing us also.) When the average American noshes along throughout the day snacking on first this then that the inflammatory response becomes chronic.
Over the past couple of decades just two of dietary changes – eating more and eating more often—have led to a state of chronic inflammation. The changes in diet composition have had an additive effect as well. Numerous studies have shown that while carbohydrates in general cause more of an inflammatory response than other macronutrients, fructose specifically causes the most rapid and intense inflammatory response of all. Polyunsaturated vegetable oils of the omega-6 variety (the majority) are inflammatory, trans fats (all of which start out as vegetable oils) are the worst, and most of the fat of animal, fish and dairy origin are actually anti-inflammatory. Sadly, we’ve been busy replacing the latter with the former. We find ourselves as a nation in the situation where most of our population is overfed the wrong kinds of food all too often with resulting high rates of obesity and chronic inflammation.
This post will probably raise more questions than it answers, which is good. I’ll expand on these themes in later posts and flesh out my ideas a little more.