Sunday, August 27, 2017

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 in 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.


SauerkrautHead said...

Thanks for posting. Your posts are always interesting and thought provoking. I find that your analyses of papers' data always give a new spin to things. I'm not quite as statistically inclined, but your explanations are helpful.

Brian Hassel said...

Thanks for the fascinating article. It certainly stood out to me that medical students (probably fairly young <30) all had TC and LDL levels that would make most doctors break out the Lipitor-branded prescription pad for a statin recommendation -- even in the 'control'.

Bill said...

psychological component of cholesterol levels were confirmed by Dwight Schrute circa 2009:

Ned Kock said...

Thanks SauerkrautHead.

Ned Kock said...

Hi Brian. When you look at country-level data, the best range of TC is somewhere between 210, where cardiovascular disease mortality is minimized; and 220, where total mortality is minimized:

Ned Kock said...

Hi Bill. Thanks, short and hilarious! I like the face that she makes at the end, when he answers her question – why would you want to raise your cholesterol?

Ned Kock said...

By the way, Bill, I used to live in Cherry Hill, near Mount Laurel. Isn’t it Laurel Acres where people take kids to tube down a hill when it snows? I think I used to take my kids there.

Bill said...

Hi Ned,
Yes, I don't have kids but that sounds about right. Small world.

Anonymous said...

great article, thank you!

raphi said...
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raphi said...
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raphi said...

Ned you always incite me to go on Pubmed safaris- thanks!

Keeping in mind the pathophysiology between infection and cholesterol, do you think that the anti-microbial properties of Coconut Oil also act via its lipid modulating effects?

And if so, is it reasonable to assume a mechanism whereby oils with a predominance of SFA and MUFA increase TC with more favourable HDL-C to LDL-C ratios than if this increase were to occur through the dietary intake of other oils? (or macronutrient variations for that matter)

Anonymous said...

Studies have shown that linoleic acid (LA) causes endothelial cell activation and dysfunction which leads to atherosclerosis. LA appears to be the most pro-inflammatory fatty acid.

It has been found that membrane cholesterol can modify and inhibit linoleic acid-mediated endothelial cell dysfunction thereby protecting the vascular endothelium from oxidative stress and polyunsaturated fatty acid-mediated inflammatory responses.

I recently rigged my computer to use it while standing. It is good to know that standing while using the computer may increase my cholesterol and thereby lower the risk of LA induced atherosclerosis.

Ned Kock said...

Hi raphi. You shouldn’t thank me for that; it is called the “HC curse”!

Ned Kock said...

Jack, soon I’m going to write a post you’ll like. It is about an interesting phenomenon, and it is not a joke. There is solid evidence that a large proportion of us are actually driven to consume foods rich in LA, which apparently increases the chances that those who do so will die early (but not because of CVD). And this idea is not only supported by empirical data, but it is also consistent with evolution. That is, this tendency has been acquired by evolution, in response to selective pressures.

Anonymous said...

Ned, I am looking forward to your post about the tendency to increase intake of linoleic acid. The great increase increase in LA intake during the past century apparently has had a great many adverse affects on many people.

Martin Brent said...

Thanks for this great article! My friend is freaking out about his sudden cholesterol increase. It is weird that he's been into sports for over a decade now...(not professionally)but still... I hope this calms him down...

lindamm99 said...

I am a 63 year old female with high cholesterol. I had my gallbladder out about 6 months ago and have been taking levothyroxine for a year due to mild hypothyroidism, probably caused by too many CAT scans. My cholesterol hovered around 220 for many years but recently spike to over 300. I'm baffled and so is my doctor. Anybody have any thoughts on why it would spike like this? I am a cancer survivor and I'm a bit nervous that a new cancer could do this.

Unknown said...

Very interesting discussion, glad that I came across such informative post. Keep up the good work friend. Glad to be part of your net community.

Unknown said...

Ned, pardon my ignorance but not quite sure on the conclusion of an increase of LDL due to either stress or sustained dieting/exercise. In these situations, are the levels "undesireable" and be dealt with as normally recommended (must be lowered)? Thanks!

Crystal said...

Wanted to add that a sudden spike in cholesterol is quite common in those of us with hypothyroidism. I experienced it myself. I've had total cholesterol in the low 140's for years (I'm 43). Last year I was diagnosed with Hashimoto's Thyroiditis. Dr. doesn't want to treat it due to fluctuations in my thyroid function. My cholesterol was at 152 at diagnoses one year ago. This year, it's at 200. A huge jump due to untreated thyroid disease.

Daniel said...

Ned, thanks for all your blogs. I followed all of this post, except for what the reasoning is for cholesterol to be on site in the endothelium. What would the purpose be under the premise of that being the firefighter?

Triathlete_303 said...

Hi Ned. Great article.
Have you ever heard of anyone who had an increase 30% - in cholesterol levels by starting to swim in chlorinated swimmingpools?
I have cycled and run all my life with a very low cholesterol level, but have taken up triathlon training and now after 12months my cholesterol doubled. The only thing that changed is that I now spend 2 go 3 hours a week in the pool.
Regards, Ed