Should you drink your coffee filtered?

Coffee is one of the most widely consumed beverages in the world. Arguably a key reason for this is that coffee has psychoactive properties that we may be hardwired to value, even if subconsciously. For example, it increases alertness; possibly a fitness-enhancing effect in our evolutionary past. Here the term “fitness” in “fitness-enhancing effect” means “reproductive success”, and does not mean having great athletic ability or having shredded abs.

The two most common sources of coffee beans, which are roasted and ground prior to brewing, are the widely favored Coffea arabica, and the "robusta" form Coffea canephora. The arabica form accounts for 80 percent or so of world consumption. The graph below, from a study by Bonita and colleagues (), shows the per capita consumption of coffee in various countries. As you can see, Scandinavian countries are big consumers.



Most people probably drink filtered coffee. However, there are many unfiltered coffee preparation methods that are also widely used. Greek coffee, Turkish coffee, coffee prepared with a French press, and “cowboy coffee” are all unfiltered.

In the photo below (from: Goldenstate.wordpress.com), illustrating cowboy coffee, note that the coffee pot is placed near but not over the fire.



What is “cowboy coffee”? This method of preparation has many variations. A simple one involves mixing ground coffee with hot water, and then keeping the coffee simmering on very low fire for a while. It is called cowboy coffee due to its association with coffee drank by cowboys around a campfire.

After brewed, coffee tends to rise and spill out of the pot if heated at a high temperature. To avoid this, one should turn off the fire just prior to the coffee boiling, heat the coffee in a pot on very low fire, or heat the coffee by placing the pot near but not too close to a campfire. The same is generally true for tea.

With cowboy coffee you need significantly less coffee per measure of water, and the coffee ends up with a stronger flavor – if prepared properly. You also keep two key oily components of the coffee, namely the diterpenes known as kahweol and cafestol; its polyphenols, most notably chlorogenic acid; and some of the coffee particles.

Both kahweol and cafestol seem to be associated with reduction in certain types of cancer in humans, and show strong anti-cancer effects in rats (). The same seems to be generally true for chlorogenic acid (). The coffee particles, if ingested, would probably be treated as indigestible fiber and promote colon health. This is usually the fate of indigestible and partially digestible plant matter.

Why is filtered coffee often recommended? Well, unfiltered coffee is believed to promote heart disease. But that is not primarily due to any strong association having been found between unfiltered coffee consumption and heart disease. In fact, the absence of evidence in favor of this hypothesis in long-term studies is rather conspicuous ().

The belief that unfiltered coffee can promote heart disease is due to evidence showing that consumption of 4 cups per day of unfiltered coffee raises total cholesterol by up to 10 mg/dl ().

Only diehard proponents of the lipid hypothesis would look at total cholesterol increase as a marker of heart disease, in part because total cholesterol may increase due to an increase in HDL cholesterol – a much more reliable marker, but of protection against heart disease, particularly within certain ranges. And yes, unfiltered coffee consumption is associated with an increase in HDL cholesterol ().

Moreover, some of the metabolites of caffeine, 1-methyxanthine and 1-methyluric acid, appear to help prevent LDL oxidation; caffeine metabolites also seem to have potent anti-inflammatory properties ().

Some research provides evidence of the importance of moderation in coffee consumption as an important factor in its relationship with health. In this respect, coffee is like almost anything that can be ingested, including water – the dose makes the poison. In a study of 40,000 post-menopausal women in the US reviewed by Bonita and colleagues (), the hazard ratio of death attributed to heart disease was 0.76 for consumption of 1–3 cups/day, 0.81 for 4–5 cups/day, and 0.87 for ≥6 cups/day. Interestingly, the same study reported that the hazard ratio for death from other inflammatory diseases was 0.72 for consumption of 1–3 cups/day, 0.67 for 4–5 cups/day, and 0.68 for ≥6 cups/day.

Frequently you hear about the possible connection between coffee consumption and gastritis. The most widely cited study I could find that looked into this link found no association between coffee consumption and reflux-associated gastritis ().

By the way, if you have gastritis, you should consider getting tested for Helicobacter pylori (), especially if you like eating raw fish.

Stress and coffee consumption may have similar effects in those who test positive for Helicobacter pylori (see, e.g., ). In those individuals, past research has found a link between: (a) stress, coffee consumption, and other purported “stomach irritants”; and (b) exacerbation of gastritis symptoms, stomach ulcers, and stomach cancer.

This discussion on gastritis is largely unrelated to the issue of drinking unfiltered coffee. It is unclear based on the past studies that I reviewed whether coffee filtration has anything to do with any possible connection between coffee consumption and exacerbation of gastritis symptoms caused by other factors.

As a side note, it is important to keep in mind that the acidity of coffee is nowhere near the acidic of gastric acid, which the stomach is uniquely designed to handle.

I may be wrong, but from what I can see, if you drink coffee regularly and it causes no problems for you, drinking unfiltered coffee is not a bad idea at all.

The PCSK9 enzyme, LDL cholesterol, and cardiovascular diseases

Cardiovascular diseases are currently the leading cause of death in most developed countries. They are particularly common among seniors; i.e., those aged 65 and older. Part of the reason for this is that infectious diseases do not kill as many people as they used to.

Given the trend toward population aging, with seniors making up an increasingly larger percentage of the population, the market for drugs against cardiovascular diseases is growing. A new class of such drugs is making the news lately; they target the PCSK9 enzyme ().

Enzymes are (usually) proteins that speed up chemical reactions, and are needed in virtually all metabolic processes that occur in cells. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme that degrades LDL cholesterol receptors on the surface of liver cells. Fewer LDL cholesterol receptors mean reduced uptake of the particles that carry LDL cholesterol, and thus more LDL particles in circulation. This may be problematic if these are small-dense LDL particles ().

Small-dense LDL particles include particles that are significantly smaller than the gaps in the endothelium (). The endothelium is a thin layer of cells that line the interior of arteries. Those gaps are about 25-26 nanometers (nm) in diameter. Small-dense LDL particles can contribute a lot more to the formation of atheromas (atherosclerotic plaques) in predisposed individuals than large-buoyant LDL particles.

There is evidence of the natural occurrence of low LDL cholesterol in individuals of African descent due to genetic mutations influencing PCSK9 levels (). This leads us to a very important question. By reducing PCSK9 in circulation, can we also reduce the incidence of cardiovascular disease?

The answer to this question depends on whether LDL cholesterol is a causative factor in cardiovascular disease. If it is, then reducing PCSK9 in circulation can indeed reduce the incidence of cardiovascular disease. The problem is that, most of the evidence so far suggests that LDL cholesterol is NOT a causative factor in cardiovascular disease.

Yes, there are studies that show that LDL cholesterol is correlated with cardiovascular disease, but the problem is that LDL cholesterol is a marker of other factors that are better candidates for causes of cardiovascular disease – hence the correlation. For example, LDL cholesterol goes up with mental stress (), and chronic mental stress seems to be a good candidate for a cause of cardiovascular disease.

LDL cholesterol is also a marker of a diet with more saturated fat in it (). In many contexts, a diet with more saturated fat in it is a more nutritious diet, which leads to a negative association between LDL cholesterol and mortality.

The graph below shows the shape of the association between total cholesterol (TOTCHOL) and mortality from all cardiovascular diseases (MVASC), based on an analysis of the China Study II dataset (). LDL cholesterol is the main component of total cholesterol in most people. The values are provided in standardized format; e.g., 0 is the average, 1 is one standard deviation above the mean, and so on. The best-fitting curve was obtained with the software WarpPLS ().

In fact, when we combine the totality of the evidence linking LDL cholesterol and cardiovascular diseases, LDL cholesterol seems to come out as a marker of protective factors. A reflection of this is a widely cited study by Weverling-Rijnsburger and colleagues, of LDL and HDL cholesterol as factors in cardiovascular diseases among people aged 85 and older (). The conclusions of the study were that:

- There was no association between LDL cholesterol level and risk of fatal cardiovascular disease.

- A low HDL cholesterol level was associated with a two-fold higher risk of fatal cardiovascular disease.

- Both low LDL cholesterol and low HDL cholesterol levels were associated with an increased mortality risk from infections.

The results above are particularly interesting because the study participants, given their ages, were at a high risk of mortality from cardiovascular diseases. It seems that the best scenario for these folks would have been a concomitant increase in both LDL and HDL cholesterol levels, which seems to be exactly what happens when one increases his or her intake of foods rich in saturated fat and dietary cholesterol ()!

Should you take a drug that targets the PCSK9 enzyme, to reduce your LDL cholesterol? Maybe you should ask Peter ().

Large LDL and small HDL particles: The best combination

High-density lipoprotein (HDL) is one of the five main types of lipoproteins found in circulation, together with very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and chylomicrons.

After a fatty meal, the blood is filled with chylomicrons, which carry triglycerides (TGAs). The TGAs are transferred to cells from chylomicrons via the activity of enzymes, in the form of free fatty acids (FFAs), which are used by those cells as sources of energy.

After delivering FFAs to the cells, the chylomicrons progressively lose their TGA content and “shrink”, eventually being absorbed and recycled by the liver. The liver exports part of the TGAs that it gets from chylomicrons back to cells for use as energy as well, now in the form of VLDL. As VLDL particles deliver TGAs to the cells they shrink in size, similarly to chylomicrons. As they shrink, VLDL particles first become IDL and then LDL particles.

The figure below (click on it to enlarge), from Elliott & Elliott (2009; reference at the end of this post), shows, on the same scale: (a) VLDL particles, (b) chylomicrons, (c) LDL particles, and (d) HDL particles. The dark bar at the bottom of each shot is 1000 A in length, or 100 nm (A = angstrom; nm = nanometer; 1 nm = 10 A).

As you can see from the figure, most of the LDL particles shown are about 1/4 of the length of the dark bar in diameter, often slightly more, or about 25-27 nm in size. They come in different sizes, with sizes in this range  being the most common. The smaller and denser they are, the more likely they are to contribute to the formation of atherosclerotic plaque in the presence of other factors, such as chronic inflammation. The larger they become, which usually happens in diets high in saturated fat, the less likely they are to form plaque.

Note that the HDL particles are rather small compared to the LDL particles. Shouldn’t they cause plaque then? Not really. Apparently they have to be small, compared to LDL particles, to do their job effectively.

HDL is a completely different animal from VLDL, IDL and LDL. HDL particles are produced by the liver as dense disk-like particles, known as nascent HDL particles. These nascent HDL particles progressively pick up cholesterol from cells, as well as performing a number of other functions, and “fatten up” with cholesterol in the process.

This process also involves HDL particles picking up cholesterol from plaque in the artery walls, which is one of the reasons why HDL cholesterol is informally called “good” cholesterol. In fact, neither HDL nor LDL are really cholesterol; HDL and LDL are particles that carry cholesterol, protein and fat.

As far as particle size is concerned, LDL and HDL are opposites. Large LDL particles are the least likely to cause plaque formation, because LDL particles have to be approximately 25 nm in diameter or smaller to penetrate the artery walls. With HDL the opposite seems to be true, as HDL particles need to be small (compared with LDL particles) to easily penetrate the artery walls in order to pick up cholesterol, leave the artery walls with their cargo, and have it returned back to the liver.

Interestingly, some research suggests HDL particles that are larger in size, when compared with other HDL particles (not with LDL particles), seem to do a better job than very small HDL particles in terms of reducing risk of cardiovascular disease. It is also possible that a high number of larger HDL particles in the blood is indicative of elevated levels of "effective" HDL particles; i.e., particles that are effective at picking up cholesterol from the artery walls in the first place.

Another interesting aspect of this cycle is that the return to the liver of cholesterol picked up by HDL appears to be done largely via IDL and LDL particles (Elliott & Elliott, 2009), which get the cholesterol directly from HDL particles! Life is not that simple.

Reference:

William H. Elliott & Daphne C. Elliott (2009). Biochemistry and Molecular Biology. 4th Edition. New York: NY: Oxford University Press.

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.

The anatomy of a VAP test report

The vertical auto profile (VAP) test is an enhanced lipid profile test. It has been proposed, chiefly by the company Atherotech (), as a more complete test that relies on direct measurement of previously calculated lipid measures. The VAP test is particularly known for providing direct measurements of LDL cholesterol, instead of calculating them through equations ().

At the time of this writing, a typical VAP test report would provide direct measures of the cholesterol content of LDL, Lp(a), IDL, HDL, and VLDL particles. It would also provide additional measures referred to as secondary risk factors, notably particle density patterns and apolipoprotein concentrations. Finally, it would provide a customized risk summary and some basic recommendations for treatment. Below is the top part of a typical VAP test report (from Atherotech), showing measures of the cholesterol content of various particles. LDL cholesterol is combined for four particle subtypes, the small-dense subtypes 4 and 3, and the large-buoyant subtypes 2 and 1. A breakdown by LDL particle subtype is provided later in the VAP report.

In the table above, HDL cholesterol is categorized in two subtypes, the small-dense subtype 2, and the large-buoyant subtype 3. Interestingly, most of the HDL cholesterol in the table is supposedly of the least protective subtype, which seems to be a common finding in the general population. VLDL cholesterol is categorized in a similar way. IDL stands for intermediate-density lipoprotein; this is essentially a VLDL particle that has given off some of its content, particularly its triglyceride (or fat) cargo, but still remains in circulation.

Lp(a) is a special subtype of the LDL particle that is purported to be associated with markedly atherogenic factors. Mainstream medicine generally considers Lp(a) particles themselves to be atherogenic, which is highly debatable. Among other things, cardiovascular disease (CVD) risk and Lp(a) concentration follow a J-curve pattern, and Lp(a)’s range of variation in humans is very large. A blog post by Peter (Hyperlipid) has a figure right at the top that illustrates the former J-curve assertion (). The latter fact, related to range of variation, generally leads to a rather wide normal distribution of Lp(a) concentrations in most populations; meaning that a large number of individuals tend to fall outside Lp(a)’s optimal range and still have a low risk of developing CVD.

Below is the middle part of a typical VAP report, showing secondary risk factors, such as particle density patterns and apolipoprotein concentrations. LDL particle pattern A is considered to be the most protective, supposedly because large-buoyant LDL particles are less likely to penetrate the endothelial gaps, which are about 25 nm in diameter. Apolipoproteins are proteins that bind to fats for their transport in lipoproteins, to be used by various tissues for energy; free fatty acids also need to bind to proteins, notably albumin, to be transported to tissues for use as energy. Redundant particles and processes are everywhere in the human body!

Below is the bottom part of a typical VAP report, providing a risk summary and some basic recommendations. One of the recommendations is “to lower” the LDL target from 130mg/dL to 100mg/dL due to the presence of the checked emerging risk factors on the right, under “Considerations”. What that usually means in practice is a recommendation to take drugs, especially statins, to reduce LDL cholesterol levels. A recent post here and the discussion under it suggest that this would be a highly questionable recommendation in the vast majority of cases ().

What do I think about VAP tests? I think that they are useful in that they provide a lot more information about one’s lipids than standard lipid profiles, and more information is better than less. On the other hand, I think that people should be very careful about what they do with that information. There are even more direct tests that I would recommend before a decision to take drugs is made (, ), if that decision is ever made at all.

Familial hypercholesteromia: Why rely on cholesterol levels when more direct measures are available?

There are two forms of familial hypercholesteromia (FH), namely heterozygous and homozygous FH. In heterozygous FH only one copy of the gene that causes it is present, inherited either from the father or the mother. In homozygous FH, which is the most lethal form, two copies of the gene are present. FH is associated with early-onset cardiovascular disease (CVD).

Homozygous FH may happen if both the father and mother have heterozygous or homozygous FH. If both the father and mother have heterozygous FH, the likelihood that at least one in four children will have homozygous FH will be high. If both parents have homozygous FH the likelihood that all children will have homozygous FH will be high.

In fact, in the latter case, homozygous FH in the children is almost certain. One case in which it won’t occur is if the combining FH gene from the father or mother mutates into a non-FH gene before it is used in the assembly of the genome of the child. A gene mutation in a specific locus, only for the father or mother, is an unlikely event, and would lead to heterozygous FH. Two gene mutations at once in the same locus, for the father and mother, is a very unlikely event.

By the way, despite what many are led to believe based on fictional characters in movies and series like the X-Men and Hulk, mutations in functional genes usually lead to harmful traits. In our evolutionary past, those traits would have been largely removed from the gene pool by selection, making them rare or nonexistent in modern humans. Today we have modern medicine; a double-edged sword.

Mutations leading to super-human traits are very, very unlikely. The myostatin gene, for example, suppresses muscle growth. And yet the mutations that lead to little or no secretion of the related myostatin protein are very uncommon. Obviously they have not been favored by selection, even though their holders are very muscular – e.g., Germany’s “Incredible Hulky” ().

Okay, back to FH. Xanthelasmas are relatively common among those who suffer from FH (see photo below, from Globalskinatlas.com). They are skin deposits of cholesterol, have a genetic basis, and are NOT always associated with FH. This is important – several people have xanthelasmas but not FH.

FH is a fairly rare disease, even in its heterozygous form, with an overall incidence of approximately 0.2 percent. That is, about 1 in 500 people in the general population will have it. Genetically related groups will see a much higher or lower rate of incidence, as the disease is strongly influenced by a genetic mutation. This genetic mutation is apparently in the LDL receptor gene, located on the short arm of chromosome 19.

The table below, from a study by Miltiadous and colleagues (), paints a broad picture of the differences one would typically see between heterozygous FH sufferers and non-FH controls.

The main difference is in total cholesterol and in the relatively large contribution of LDL to total cholesterol. A large difference is also seen in Apolipoprotein B (indicated as "Apo B"), which acts as a LDL transporter (not to be confused with a LDL receptor). The LDL cholesterol shown on the table is calculated through the Friedewald equation, which is notoriously imprecise at low triglyceride levels ().

Looking at the total cholesterol row on the table, and assuming that the numbers after the plus/minus signs are standard deviations, we can conclude that: (a) a little more than two-thirds of the heterozygous FH sufferers had total cholesterol levels falling in between 280 and 446; and (b) a little more than two-thirds of the non-FH controls had total cholesterol levels falling in between 135 and 225.

Keep in mind that about 13.5 percent {calculated as: (95-68)/2} of the non-FH controls had total cholesterol levels between 225 and 270. This is a nontrivial percentage; i.e., these may be a minority but are not rare individuals. Heterozygous FH sufferers are rare, at 0.2 percent of the general population. Moreover, about 2 percent of the non-FH controls had non-pathological total cholesterol levels between 270 and 315. That is not so rare either, amounting to an “incidence” 10 times higher than heterozygous FH.

What would happen if people with heterozygous FH were to replace refined carbohydrates and sugars with saturated fat and cholesterol in their diets? Very likely their already high total cholesterol would go up higher, in part because their HDL cholesterol would go up (). Still, how could they be sure that CVD progression would accelerate if they did that?

According to some studies, the higher HDL cholesterol would either be generally protective or associated with protective factors, even among those with FH (). One of those protective factors may be a more nutrient-dense diet, as many foods rich in cholesterol are very nutrient-dense – e.g., eggs, organ meats, and seafood.

This brings me to my main point in this post. It is mainstream practice to diagnose people with FH based on total and/or LDL cholesterol levels. But the main problem with FH is that it leads to early onset of CVD, which can be measured more directly through simple tests, such as intima-media thickness and related ultrasound plaque tests (). These are noninvasive tests, done in 5 minutes or so, and often covered by insurance.

Even if simple direct tests are not perfect, it seems utterly nonsensical to rely on cholesterol measures to diagnose and treat FH, given the possible overlap between pathological and non-pathological high total cholesterol levels.