Sudden cholesterol increase? It may be psychological

There are many published studies with evidence that cholesterol levels are positively associated with heart disease. In multivariate analyses the effects are usually small, but they are still there. On the other hand, there is also plenty of evidence that cholesterol is beneficial in terms of health. Here of course I am referring to the health of humans, not of the many parasites that benefit from disease.

For example, there is evidence () that cholesterol levels are negatively associated with mortality (i.e., higher cholesterol leading to lower mortality), and are positively associated with vitamin D production from skin exposure to sunlight ().

Most of the debris accumulated in atheromas are made up of macrophages, which are specialized cells that “eat” cell debris (ironically) and some pathogens. The drug market is still hot for cholesterol-lowering drugs, often presented in TV and Internet ads as effective tools to prevent formation of atheromas.

But what about macrophages? What about calcium, another big component of atheromas? If drugs were to target macrophages for atheroma prevention, drug users may experience major muscle wasting and problems with adaptive immunity, as macrophages play a key role in muscle repair and antibody formation. If drugs were to target calcium, users may experience osteoporosis.

So cholesterol is the target, because there is a “link” between cholesterol and atheroma formation. There is also a link between the number of house fires in a city and the amount of firefighting activity in the city, but we don’t see mayors announcing initiatives to reduce the number of firefighters in their cities to prevent house fires.

When we talk about variations in cholesterol, we usually mean variations in cholesterol carried by LDL particles. That is because LDL cholesterol seems to be very “sensitive” to a number of factors, including diet and disease, presenting quite a lot of sudden variation in response to changes in those factors.

LDL particles seem to be intimately involved with disease, but do not be so quick to conclude that they cause disease. Something so widespread and with so many functions in the human body could not be primarily an agent of disease that needs to be countered with statins. That makes no sense.

Looking at the totally of evidence linking cholesterol with health, it seems that cholesterol is extremely important for the human body, particularly when it is under attack. So the increases in LDL cholesterol associated with various diseases, notably heart disease, may not be because cholesterol is causing disease, but rather because cholesterol is being used to cope with disease.

LDL particles, and their content (including cholesterol), may be used by the body to cope with conditions that themselves cause heart disease, and end up being blamed in the process. The lipid hypothesis may be a classic case of reverse causation. A case in point is that of cholesterol responses to stress, particularly mental stress.

Grundy and Griffin () studied the effects of academic final examinations on serum cholesterol levels in 2 groups of medical students in the winter and spring semesters (see table below). During control periods, average cholesterol levels in the two groups were approximately 213 and 216 mg/dl. During the final examination periods, average cholesterol levels were 248 and 240 mg/dl. These measures were for winter and spring, respectively.



One could say that even the bigger increase from 213 to 248 is not that impressive in percentage terms, approximately 16 percent. However, HDL cholesterol does not go up significantly response to sustained (e.g., multi-day) stress, it actually goes down, so the increases reported can be safely assumed to be chiefly due to LDL cholesterol. For most people, LDL particles are the main carriers of cholesterol in the human body. Thus, in percentage terms, the increases in LDL cholesterol are about twice those reported for total cholesterol.

A 32-percent increase (16 x 2) in LDL cholesterol would not go unnoticed today. If one’s LDL cholesterol were to be normally 140 mg/dl, it would jump to 185 mg/dl with a 32-percent increase. It looks like the standard deviations were more than 30 in the study. (This is based on the standard errors reported, and assuming that the standard deviation equals the standard error multiplied by the square root of the sample size.) So we can guess that several people might go from 140 to 215 or more (this is LDL cholesterol, in mg/dl) in response to the stress from exams.

And the effects above were observed with young medical students, in response to the stress from exams. What about a middle-aged man or woman trying to cope with chronic mental stress for months or years, due to losing his or her job, while still having to provide for a family? Or someone who has just been promoted, and finds himself or herself overwhelmed with the new responsibilities?

Keep in mind that sustained dieting can be a major stressor for some people, particular when one gets to that point in the dieting process where he or she gets regularly into negative nitrogen balance (muscle loss). So you may have heard from people saying that, after months or years of successful dieting, their cholesterol levels are inexplicably going up. Well, this post provides one of many possible explanations for that.

The finding that cholesterol goes up with stress has been replicated many times. It has been known for a long time, with studies dating back to the 1950s. Wertlake and colleagues () observed an increase in average cholesterol levels from 214 to 238 (in mg/dl); also among medical students, in response to the mental and emotional stress of an examination week. A similar study to the one above.

Those enamored with the idea of standing up the whole day, thinking that this will make them healthy, should know that performing cognitively demanding tasks while standing up is a known stressor. It is often used in research where stress must be induced to create an experimental condition. Muldoon and colleagues () found that people performing a mental task while standing experienced an increase in serum cholesterol of approximately 22 points (in mg/dl).

What we are not adapted for is sitting down for long hours in very comfortable furniture (, ). But our anatomy clearly suggests adaptations for sitting down, particularly when engaging in activities that resemble tool-making, a hallmark of the human species. Among modern hunter-gatherers, tool-making is part of daily life, and typically it is much easier to accomplish sitting down than standing up.

Modern urbanites could be seen as engaging in activities that resemble tool-making when they produce things at work for internal or external customers, whether those things are tangible or intangible.

So, stress is associated with cholesterol levels, and particularly with LDL cholesterol levels. Diehard lipid hypothesis proponents may argue that this is how stress is associated with heart disease: stress increases cholesterol which increases heart disease. Others may argue that one of the reasons why LDL cholesterol levels are sometimes found to be associated with heart disease-related conditions, such as chronic stress, and other health conditions is that the body is using LDL cholesterol to cope with those conditions.

Specifically regarding mental stress, a third argument has been put forth by Patterson and colleagues, who claimed that stress-mediated variations in blood lipid concentrations are a secondary result of decreased plasma volume. The cause, in their interpretation, was unspecified – “vascular fluid shifts”. However, when you look at the numbers reported in their study, you still see a marked increase in LDL cholesterol, even controlling for plasma volume. And this is all in response to “10 minutes of mental arithmetic with harassment” ().

I tend to think that the view that cholesterol increases with stress because cholesterol is used by the body to cope with stress is the closest to the truth. Among other things, stress increases the body’s overall protein demand, and cholesterol is used in the synthesis of many proteins. This includes proteins used for signaling, also known as hormones.

Cholesterol also seems to be a diet marker, tending to go up in high fat diets. This is easier to explain. High fat diets increase the demand for bile production, as bile is used in the digestion of fat. Most of the cholesterol produced by the human body is used to make bile.

Cabeza de Vaca: Supernaturalism and psychosomatic disorders

Andrew Weil, a major proponent of the idea of self-healing (), has repeatedly acknowledged the influence of osteopaths such as Robert C. Fulford () on him, particularly regarding his philosophy of health management. Self-healing is not about completely autonomous healing; it is about healing by stimulation of the body's self-repair processes, which in some cases can be achieved by simply reducing stress.

Interestingly, there are many reported cases of osteopaths curing people from various diseases by doing things like cranial manipulation and other forms of touching. We also have much evidence of health improvement through prescription of drugs that don’t appear to have any health benefits, which is arguably a similar phenomenon.

The number of such reported cases highlights what seems to be a reality about diseases in general, which is that they often have a psychosomatic basis. Their “cure” involves making the person affected believe that someone can cure him, a healer, with or without drugs. The healer then cures the person essentially by her power of suggestion.

Paleoanthropological evidence suggests that this healer-induced phenomenon has always been widespread among hunter-gatherer cultures, so much so that it may well have been the result of evolutionary pressures. If this is correct, how does it relate to health in our modern world?

I am very interested in hunter-gatherer cultures, and I have also been living in Texas for almost 10 years now. So it is only natural for me to try to learn more about the former hunter-gatherer groups in Texas, particularly those who lived in the area prior to the introduction of horses by the Europeans.

There are parks, museums, and other resources on the topic in various parts of Texas, which are at driving distance. Unfortunately much has been lost, as the Plains Indians of Texas (e.g., Comanches and Kiowas) who succeeded those pre-horse native groups have largely been forcibly relocated to reservations in Oklahoma.

Anthropological evidence suggests that the earliest migrations to America have occurred via the Bering Strait, initially from Siberia into Alaska, and then gradually spreading southward to most of the Americas between 13,000 and 10,000 years ago.

Much of what is known about the early Texas Indians is due to Álvar Núñez Cabeza de Vaca, a Spanish explorer who survived a shipwreck and lived among the Amerindians in and around Texas between 1528 and 1536. He later wrote a widely cited report about his experiences ().


(Cabeza de Vaca and his companions; source: Biography.com)

In Spanish, “cabeza de vaca” means, literally, “cow’s head”. This odd surname, Cabeza de Vaca, clearly had a flavor of nobility to it in Spain at the time.

You may have heard that early American Indians were uniformly of short stature, not unlike most people at the time, but certainly shorter than the average American today. Cabeza de Vaca dispels this idea with his description of the now extinct Karankawas, a description that has been born out by anthropological evidence. The male members “towered above the Spaniards”, often 6 ft or taller in height, in addition to being muscular.

The Karankawas were a distinct indigenous group that shared the same environment and similar food sources with other early groups of much lower stature. This strongly suggests a genetic basis for their high stature and muscular built, probably due to the “founder effect”, well known among population geneticists.

Cabeza de Vaca and three companions, two Spaniards and one Moroccan slave, were believed by the Amerindians to be powerful healers. This enabled them to survive among early Texas Indians for several years. Cabeza de Vaca and his colleagues at times acknowledged that they were probably curing people through what we would refer today as a powerful placebo effect.

Having said that, Cabeza de Vaca has also come to believe, at least to a certain extent, that he was indeed able to perform miraculous cures. He repeatedly stated his conviction that those cures were primarily through divine intervention, as he was a devout Christian, although there are many contradictory statements in this respect in his reports (possibly due to fear from the Spanish Inquisition). He also performed simple surgeries.

Much has been written about Cabeza de Vaca’s life among the early Indians of Texas and surrounding areas, including the report by Cabeza de Vaca himself. One of my favorites is the superb book “A Land So Strange” () by Andrés Reséndez, a professor of history at the University of California at Davis ().

The Spanish explorer’s experiences have been portrayed in the film “Cabeza de Vaca” (), which focuses primarily on the supernatural angle, with a lot of artistic license. I must admit that I was a bit disappointed with this film, as I expected it to show more about the early Indians’ culture and lifestyle. Juan Diego, the Spanish actor portraying Cabeza de Vaca, was razor thin in this film - a fairly realistic aspect of the portrayal.

It is quite possible that modern humans have an innate tendency to believe in and rely on the supernatural, a tendency that is the product of evolution. We know from early and more recent evidence from hunter-gatherer societies that supernatural beliefs help maintain group cohesion and, perhaps quite importantly, mitigate the impact that the knowledge of certain death has on the mental health of hunter-gatherers.

Homo sapiens is unique among animals in its awareness of its own mortality, which may be a byproduct of its also unique ability to make causal inferences. Supernatural beliefs among hunter-gatherers almost universally address this issue, by framing death as a threshold between this existence and the afterlife, essentially implying immortality.

Yet, supernatural beliefs seem to also have a history of exploitation, where they are used to manipulate others. Cabeza de Vaca himself implies that, at points, he and his companions took personal advantage of the beliefs in their healing powers by the various indigenous groups with which they came into contact.

Modern humans who are convinced that they have no supernatural beliefs often perceive that to be a major advantage. But there could be disadvantages. One is that they may have more difficulty dealing with psychosomatic disorders. The conscious knowledge that they are psychosomatic could possibly pale in comparison with the belief in supernatural healing, in terms of curative power. Another potential disadvantage is a greater likelihood of suffering from mental disorders.

Finally, those who are sure that they have no supernatural beliefs; are they really correct? Well, subconsciously things may be different. Perhaps a good test would be to go to a “convincing” movie (i.e., not a laughable “B-level” one; for lack of a better word) about supernatural things, such as possession or infestation by evil spirits, and see if it has any effect on you.

If the experience does have an effect on you, even a small one, couldn't this suggest that your subconscious belief in the supernatural may not be so easy to control in a conscious way? I suspect that having no supernatural beliefs is unnatural and unhealthy. In most cases it probably creates a conscious-subconscious conflict, and a fairly pessimist view of the world.

My guess is that it is better to have those beliefs, in some form or another, and be on guard against exploitation.