Yearly Archives: 2011 - Page 18

Blood Lipids and Infectious Disease, Part II

Posted by on July 12, 2011 95 comments

OK, after a diversion into hunter-gatherer lipid profiles I’m back on the original goal of this series: trying to understand why serum cholesterol is protective against infections — and considering whether or under what circumstances that knowledge should affect how we eat.

In part I (Blood Lipids and Infectious Disease, Part I, Jun 21, 2011), we learned that mortality from infectious disease is essentially zero as long as serum cholesterol remains in the physiologically normal range of 200 to 240 mg/dl, and rises precipitously as serum cholesterol falls below 180 mg/dl.

Why is that? In a previous post we found that HDL has important immune functions (HDL and Immunity, April 12, 2011). Today, we’ll look at the immune functions of lipoproteins more generally.

The Logic of Evolution and the Multiple Functions of Lipoproteins

In understanding why these particles have immune functions, it may be helpful to understand the thrust of evolution.

By the time of the Cambrian explosion 530 million years ago, organisms had similar numbers of genes to organisms today, and most of these genes must have been similar in sequence to their modern descendants. We know this because their descendant genes in nearly all modern species are “homologous” and share nucleotide sequences.

So for the last 500 million years, evolution has not been adding genes or even changing genes dramatically. It’s been tweaking a fairly stable genome. And the direction of the tweaking has been toward making the genes interact in a wider and more complex number of ways with the other genes.

The effect is to give every molecule in the body a diversity of functions. Possibly serum lipoprotein particles started out merely as transporters. But they developed new functions. The most important additional functions were roles in immunity.

Because these particles circulate in the blood, and pathogens have to transit the blood in order to cause tissue infections, blood is the natural location for the strongest defenses against pathogens. For hundreds of millions of years, every blood component will have been under selective pressure to develop immune functions.

It’s commonly said that the primary function of LDL and HDL is lipid transport. But this is too narrow a view. Since pathogens are the primary cause of disease, it may be the immune functions of LDL and HDL which account for their significance as biomarkers of health and disease.

The Immune Functions of Lipoproteins

Most of the following discussion will draw from a recent review, “Plasma lipoproteins are important components of the immune system” [1]. References from this paper will be listed in parentheses, eg (1).

Lipoproteins have been shown to:

  1. Prevent bacterial, viral, and parasitic infections.
  2. Detoxify pathogen “die-off” toxins and protect against pathogen toxin-induced tissue damage.
  3. Present pathogen “die-off” toxins to the immune system to trigger antibody formation.

Detoxification and Toxin Defense

When a pathogen dies, it typically fragments and releases compounds which are toxic to humans. Such “die-off” toxins include lipopolysaccharides (LPS) and lipooligosaccharides (LOS) from Gram-negative bacteria, lipoteichoic acid (LTA) from Gram-positive bacteria, fungal cell wall components, and so on.

During infection, the number of such circulating toxins can be vastly larger than the number of pathogens. Such toxins can do a great deal of harm, and often account for most of the ill effects of disease. Medical researchers studying the often-fatal condition of sepsis commonly induce nearly all the characteristics of sepsis in animals merely by injecting LPS.

VLDL, LDL, lipoprotein(a) and HDL can all detoxify LPS and LTA; HDL is the most potent (2, 4, 5). Injecting reconstituted HDL (rHDL) into humans relieves endotoxemia (6) and LPS-induced inflammation in cirrhosis patients (7). Both LDL and HDL detoxify E. coli LPS (35).

LDL binds and inactivates some toxins, including Staphylococcus aureus ?-toxin (8), Yersinia pestis topH6-Ag (30). (Methicillin-resistant S. aureus, or MRSA, is an increasing cause of death in hospitals, and last year claimed my next-door neighbor. See The FDA Is On The Side of the Microbes, Aug 11, 2010).

LDL probably works against many other toxins too, since rats with low LDL have higher mortality when infected, but the mortality can be lessened with injections of human LDL (9). Injections of LDL prevent lethality in Vibrio vulnificus infections of mice (34).

In mice with the LDL receptor knocked out, LDL concentrations in blood are higher and there is enhanced immunity to Klebsiella pneumoniae (27) and Salmonella typhimurium (29). If the gene for apoE, a protein found in IDL which upregulates VLDL levels, is knocked out, mice become more susceptible to infection, so it appears that apoE also has immune functions (28). Mice lacking apoE are susceptible to Listeria monocytogenes (32) and Mycobacterium tuberculosis (33).

Lipoproteins may be even more important against viruses. HDL has a broad antiviral activity (18-20), and can prevent many virus species including influenza and hepatitis C from entering cells. VLDL and LDL have specific activity against certain types of virus including togaviruses and rhabdoviruses (3). Trypanosoma brucei, the parasite that causes sleeping sickness, does not always cause disease in humans because a subspecies can be destroyed by a subfraction of HDL particles which include haptoglobin-related protein and apolipoprotein L-I (10).

The role of oxLDL

Evolution has a way of turning lemons into lemonade, and fragile molecules into sensors. In the book we discuss how the body uses fragile polyunsaturated fats as signaling molecules, exploiting their proclivity to oxidize. Something similar happens with LDL.

LDL particles are fragile and easily oxidized. The body uses them as a sensor of infections, and as signaling molecules that control the response to infections.

For instance, LPS (an endotoxin) induces neutrophils to adhere to endothelial cells, promoting vascular inflammation. LPS also oxidizes LDL, creating a compound called oxPAPC which inhibits neutrophil adhesion to endothelial cells, thereby limiting the inflammatory response (12). Minimally oxidized LDL detoxifies LPS (13).

OxLDL is taken in not by the LDL receptor, but by receptors on immune cells called macrophages. When macrophages take up oxLDL they upregulate their scavenger receptors (classes A and E) by which they phagocytose (eat) bacteria and clear endotoxins (39). It has been shown that infection causes an increase in oxidation of LDL and that the resulting oxLDL promotes phagocytosis by macrophages of the specific pathogens which oxidized the LDL (42).

This may explain why atherosclerotic lesions contain large amounts of bacterial and viral DNA. Macrophages in these lesions have been stimulated by oxLDL to scavenge bacteria and viruses from the blood.

OxLDL stimulates antibody formation, including antibodies against phosphorylcholine (PC), a compound found on a wide range of pathogens including bacteria, parasites, and fungi (45-49). Anti-PC antibodies help to prevent upper airway infections (50-53).

It is thought that oxidation of LDL is an important part of the host defense to infections. OxLDL inhibits cell entry of hepatitis C (59) and Plasmodium sporozite (60).

The role of Lp(a)

Lp(a) is essentially an LDL particle with an extra apo(a) molecule bound to the apoB100 molecule by a disulfide bridge.

Some insight into the immune functions of Lp(a) developed after considering the role of plasminogen. Many pathogens recruit human plasminogen and use it to penetrate tissue barriers, enabling them to invade tissue (70, 71, 72). For instance, group A streptococcus releases an enzyme called streptokinase that activates human plasminogen and promotes invasion (73). Lp(a) has anti-fibrinolytic activity and recruits plasminogen itself, reducing availability for pathogens. For instance, Lp(a) blocks streptokinase activity (75), inhibits Staphylococcus aureus activation of plasminogen.

Moreover, Lp(a) inhibits the inflammatory response to LPS. As there is great variation in Lp(a) levels among individuals (76), this may account for variability in inflammatory response to infections.

The Exception: Candida

HDL may promote fungal infections. A recent study found that infusion of reconstituted HDL enhances the growth of Candida (25).

LDL also seems to promote fungal infections. In LDL receptor knockout mice, which have high levels of LDL, there is decreased resistance to Candida (37, 38).

OxLDL also loses its normal anti-infective role against Candida. Worse, it inhibits production of antibodies against Candida albicans (63), thus actually hurting anti-fungal immunity.

Candida is an unusual pathogen that is unusually well-adapted to living in the human body. It has learned to turn an important part of human immune defense to its own advantage.

Conclusion

High serum cholesterol protects against a host of bacterial and viral infections and some parasites, but increases risk for Candida fungal infections.

Related Posts

Other posts in this series include:

References

[1] Han R. Plasma lipoproteins are important components of the immune system. Microbiol Immunol. 2010 Apr;54(4):246-53. http://pmid.us/20377753.

Beef Tallow

Posted by on July 10, 2011 68 comments

By reader request, we’re working on Perfect Health Diet versions of classic American foods. Next week we’ll start with French fries, then maybe chocolate chip cookies.

I think I mentioned once that we’ve been cooking with beef fat a lot. This is a little healthier than plant oils, since it has more phospholipids, cholesterol, and usable nutrients, lacks plant toxins, and is low in polyunsaturated fat.

Since we’re using beef fat to good effect in a lot of recipes, it’s about time to show how we render it.

Rendering Beef Fat

We buy blocks of beef fat from our local Asian supermarket. Here’s one:

This 1.28 lb (0.6 kg) package costs less than $2 and will make about 2 cups (0.5 liter) of oil.

We normally keep the package in the freezer until a day before rendering, when we move it to the refrigerator to let the fat soften a little. The first step is to cut the fat block up into pieces with a knife, and transfer it to a suitably sized pot:

Many people add some water to the fat at this stage. The good side of this is that the water prevents the fat temperature from rising above 100ºC / 212ºF. The bad side is that it makes a mess. We prefer to do it without water.

Start heating the fat at a very low setting and use a potato masher to break up the fat into finer pieces and squeeze out oil:

Soon it will look like this:

As soon as there is a significant amount of liquid oil, pour the fat and oil through a strainer to separate the liquid and solid fats:

The brown ceramic bowl is where we’re collecting the liquid oil. The solid fat caught in the strainer gets returned to the pot for more heating.

The reason for pulling out the oil is that beef fat contains a variety of components which have different melting points. In general, triglycerides containing short-chain and polyunsaturated fats have lower melting points, triglycerides containing long saturated fats high melting temperatures. Fats with lower melting points tend to be more chemically fragile. You don’t want to overheat the fragile oils, damaging them; but you need to be able to apply more heat to render the high melting temperature fats. The solution is to separate the oil from the fat several times, and gradually turn up the cooking temperature each time.

After the solid fat has been returned to the pot, you can turn the heat up a little bit, but not too much. We’ll do maybe 4 straining cycles before we’re done.

Here’s the oil collecting in our bowl:

At the end, this is what remains:

We don’t consider these cracklings to be healthy, and discard them, but Wikipedia says that cracklings “are part of all traditional European cuisines.”

The oil can be returned to the refrigerator and used as needed as a cooking oil. It solidifies upon refrigeration, but can be cut into pieces with a knife.

The whole process takes about 30 minutes.

Conclusion

At $4/liter (quart), rendered beef fat is cheaper than olive oil or coconut oil. Since few people buy beef fat, and many butchers trim fat from meat and discard it, you may even be able to get some free from a friendly butcher.

Rendered beef fat stands up to high cooking temperatures, is more nutritious than plant oils, and tastes great. Especially, as we’ll see next week, on French fries.

Around the Web; Cancer, Infections, Cholesterol, and Nitrates Edition

Posted by on July 9, 2011 21 comments

[1] Summer Meet-up: We’ve chosen July 23 for the meet-up at Plum Island off Newburyport. We’ll be at the beach at the south end of the Island between 4:30 pm and 6:30 pm and will be happy to picnic and hang out with anyone who cares to join us.

[2] Interesting posts and news: A six year old cancer patient, Diamond Marshall, got a visit from the Kate, the Duchess of Cambridge. What struck me was that her mother had died of cancer at age 32, when Diamond was 18 months old. Coincidence? Or contagion?

Before you answer: a new paper reports that IL-8 and CRP – both markers of infection – predict future cancer.

Chris Kresser interviewed Emily Deans, a combination that is self-recommending. Among many noteworthy tidbits, Chris is working with an 83-year-old Alzheimer’s sufferer who is doing well on a Perfect Health Diet-style ketogenic diet.

Evidence that nitrate-rich foods, such as spinach and beetroot juice, are beneficial for vascular health and athleticism came out recently. Julianne Taylor has a few links. I might add that nitrates are also beneficial for immune function. Another recent study showed that exercise upregulates nitric oxide which is then stored as nitrites with long-term benefits. Nitrates also lower triglyceride levels and help cure hypertension. So, eat your spinach and exercise!

Seth Roberts reminds us of a good quote (modified from Beveridge): “Everyone believes an experiment except the experimenter; no one believes a theory except the theorist.” In another post, Seth reports that health in the US as measured by age of disease onset has not improved since the 1960s, life expectancy in the US peaked in 2007 and is now declining, medical care has stagnated, and this should be a big story.

Seth is right. Deteriorating results with exploding costs is not a good combination. We believe a focus on diet, nutrition, and antimicrobial medicine would deliver far more benefits at much lower cost than the current approach.

Pål Jåbekk notes something I’ve been meaning to blog about for quite a while:

[Y]et another study finds that overweight people have higher life expectancy than their lean counterparts, albeit with greater risk of disabilities. Perhaps our focus should be on natural foods and exercise, rather than on the significance of some extra padding. (study here)

Pål also gave us a thoughtful response to Stephan’s series on food reward. Highly recommended.

Hans Keer added starch to his diet, felt better, and decided he needs a new name for his site: Goodbye CutTheCarb.

Giardia infections account for 6.5% of cases of IBS in Italy. If you have digestive problems, it’s probably due to some kind of infection.

Via Craig Newmark, epidemiologist Tara C Smith:

As I’ve laid out this week (part 1, part 2, part 3), the realization that a fairly simple, toxin-carrying bacterium could cause a “complex” and mysterious disease like hemolytic uremic syndrome came only with 30 years’ of scientific investigation and many false starts and misleading results.

Infections should be the first suspect in any disease, not the last.

We mentioned the Flynn effect in our book: intelligence rose steadily through most of the 20th century. A group of economists offers a possible explanation: Lead poisoning caused depressed IQ in the 19th and early 20th century, and cessation of the use of lead in plumbing gradually returned IQs to normal.

Nothing to do with health, but very entertaining: Steve Sailer on Racehorse Haynes.

[2] Just to show how cultured we are, some classical music: Beethoven’s Fifth translated into sign language.

[3] The turtle doesn’t seem worried:

Via Yves Smith.

[4] It’s not so bad to be the smallest loser: If I do a blog post on why the overweight live longer, this might be a good place to start. In mice on calorie-restricted diets, those who lost weight quickly had shortened lifespans, those who lost little weight had lengthened lifespans:

[S]trains with the least reduction in fat were more likely to show life extension, and those with the greatest reduction were more likely to have shortened lifespan…. [F]actors associated with maintaining adiposity are important for survival and life extension under dietary restriction.

Having trouble losing weight? Maybe you’ll have a few extra years to figure it out.

[5] High serum cholesterol is healthy: In a paper reviewed by Dr Briffa, Japanese investigators provide further support to an idea that I believe we discussed in our book: serum cholesterol protects against stroke.

People with TC over 6.2 mmol/l (240 mg/dl) had a 77% lower risk of stroke (96% lower chance of hemorrhagic stroke) than those with TC below 4.1 mmol/l (159 mg/dl).

It looks like high serum cholesterol almost totally eliminates hemorrhage risk. Worried about stroke? Ask your doctor how you can raise your cholesterol.

[6] How do you do it? Dr. Walter Willett knows: In our book we quoted Dr. Walter Willett of the Department of Nutrition at the Harvard School of Public Health disparaging coconut oil. Dr. Willett has become friendlier toward fat in recent years, and when we saw he was re-addressing coconut oil in the Harvard Health Letter, we hoped to find an endorsement. Alas, he still favors vegetable oils. The trouble with coconut oil is that it raises serum cholesterol:

I don’t think coconut oil is as healthful as vegetable oils like olive oil and soybean oil, which are mainly unsaturated fat and therefore both lower LDL and increase HDL. (http://pmid.us/21702109)

[7] Shou-Ching’s photo art:

[8] Not the weekly video: Evidence that nurture defeats nature:

Via The Anchoress.

[9] Weekly video: Plains Milky Way from Randy Halverson:

Serum Cholesterol Among Hunter-Gatherers: Conclusion

Posted by on July 7, 2011 35 comments

So far we’ve looked at serum cholesterol among Eskimos/Inuit (Serum Cholesterol Among the Eskimos and Inuit, July 1, 2011) and !Kung San bushmen (Serum Cholesterol Among African Hunter-Gatherers, July 5, 2011). The Inuit, who live in the Arctic and eat a high-fat low-carb diet, generally had serum TC over 200 mg/dl unless parasitic diseases were common and life expectancy was short. The !Kung San, who live in sub-Saharan Africa and eat more carbs, were below 160 mg/dl and ridden with parasitic diseases and short life expectancy.

I thought I’d wrap up the hunter-gatherer cholesterol series by looking at some tropical populations outside Africa. These peoples may help us evaluate the merit of several explanations that have been put forth for variations in serum cholesterol:

  • Genetic differences. Africans tend to have lower cholesterol than non-Africans, wherever they live. Is the difference genetic? Chris Masterjohn believes genetic differences might account for up to a 30 mg/dl difference in TC. Emily Deans suggests LDL receptor variants are the most important alleles.
  • Dietary differences such as fat intake. For decades it was said that higher fat diets produce higher TC, and this was the favored explanation for variations in serum cholesterol. However, when these ideas were tested in clinical trials, diet-induced changes in TC were inconsistent.
  • Infectious disease burden. Eukaryotic pathogens such as protozoa, worms, and fungi – ie, pathogens that have mitochondria and therefore can metabolize fat and ketones – are often able to take up human lipoproteins from blood and use their fats and cholesterol for their own purposes. This tends to lead to low TC in people with a high burden of parasites. Is parasite burden the key to hunter-gatherer cholesterol levels?

We started this detour (see Did Hunter-Gatherers Have Low Serum Cholesterol?, June 28, 2011) to evaluate the claims of S. Boyd Eaton, Loren Cordain, and collaborators [1], [2], [3], [30]. Their papers tended to promote the following syllogism:

  1. Diet determines TC.
  2. Low TC is healthy.
  3. Hunter-gatherers had low TC.
  4. Therefore, hunter-gatherer diets are healthy.

So to conclude today’s post, I’ll review: Which of these four theses is supported by the data?

Australian Aborigines

There are a fairly large number of papers on cholesterol levels in Australian aborigines. Unfortunately, the vast majority are from journals, such as the Medical Journal of Australia and the Australian and New Zealand Journal of Medicine, to which I don’t have electronic access.

Therefore I’ll just cite one, a 1957 paper from Schwartz et al in the Australian Journal of Experimental Biology and Medical Science. [31]

This paper looked at aborigines from central Australia. Occupying marginal territory, they were still living a hunter-gatherer lifestyle. But there weren’t many animal foods available, nor seafoods:

The animal fat intake of the Central Australian aborigines from the Haast’s Bluff region involved in this present study is decidedly low when compared with the average intake of white Australians. This low intake of fat results both from a scarcity of fat itself, and also from demands made upon available supplies by native customs. It is likely that the males eat more animal fat than the females, because of their readier access to it after hunting, but the difference is probably small. Wichitty grubs (larvae of several species of Xyleutes moths) are an important source of fat for both women and children, however. Somewhat less than 10 p.c. of the calories in the aboriginal diet is derived from animal fat, i.e. less than one-third of the calories so derived in the white Australian diet (N. B. Tindale, personal communication). [31]

To get even 10% of calories from animal fat, they had to eat a lot of grubs.

So did this low-fat diet produce high or low cholesterol?

Serum cholesterol: … There is no significant difference between the mean values for aboriginal male (217.0 mg/dl) and aboriginal female (207.9 mg/dl). [31]

This is right in line with the levels in Eskimos and Inuit, and in the minimum mortality range of 200 to 240 mg/dl.

Australian aborigines were said to have a mean TC of 146 mg/dl (male) and 132 mg/dl (female) in Eaton et al [1]. Australian aborigines were deleted from the list of hunter-gatherers with low cholesterol in a subsequent Cordain et al paper [2]. I don’t know why this was, but I can say that at least some Australian aboriginal populations had TC over 200 mg/dl.

Kitavans

Kitavans preserved their hunter-gatherer lifestyle until recently, and Staffan Lindeberg and colleagues were able to assess cholesterol levels using modern procedures. They reported serum total cholesterol in men of 4.7 mmol/l (182 mg/dl) and in women of 6.1 mmol/l (236 mg/dl), for a male-female average of 5.4 mmol/l (209 mg/dl). [32]

Health in Kitava was generally good, although life expectancy was only 45 years [33]. Causes of death were infectious disease (notably malaria) and accidents such as drowning and falling from coconut trees.

So we have another tropical, high-carb population with normal (200 to 240 mg/dl) serum cholesterol.

New Zealand Maoris

New Zealand Maoris are probably genetically similar to Australian aborigines and Kitavans. I didn’t survey the literature on New Zealand Maoris. However, I did come across one paper [35] that led me to an interesting 1980 study of Maoris by Dr Robert Beaglehole [36].

The study was quite simple:

The relation between serum cholesterol concentration and mortality was studied prospectively over 11 years in 630 New Zealand Maoris aged 25-74. Serum cholesterol concentration was measured at initial examination in 1962-3 in 94% of the subjects and whether each was dead or alive was determined in 1974. The causes of death were divided into three categories: cancer, cardiovascular disease, and “other.” [36]

Mean serum cholesterol was 5.50 mmol/l (213 mg/dl) among women, 5.82 mmol/l (225 mg/dl) among men, for a population mean of 219 mg/dl.

Dr Beaglehole found that mortality increased as serum cholesterol decreased. Mortality was 40% to 70% higher in Maoris with TC of 160 mg/dl than in Maoris with TC of 260 mg/dl.

The association with cancer mortality was strongest: cancer mortality was 9.6% among the low-TC group (TC < 5.1 mmol/l = 197 mg/dl), 5.8% among the medium-TC group, and 3.5% among the high-TC group (TC > 5.8 mmol/l = 224 mg/dl).

West Malaysian aborigines

Just to balance the above studies I looked for a paper showing low serum cholesterol in an aboriginal population. I found a 1972 paper by Burns-Cox et al studying aborigines in West Malaysia. [37]

Like other traditional populations living active lives, these aborigines were lean and free of heart disease. They ate a high-carb diet:

Coronary heart disease has never been found in Malaysian aborigines. We report the position regarding some of the risk factors usually associated with coronary heart disease in 73 adult aborigine men.

They lived a physically active life on a diet largely of unrefined carbohydrate in the jungles of central West Malaysia. None was obese and blood pressures remained low at all ages. [37]

Their serum cholesterol levels were low – 141 to 156 mg/dl:

While the mean serum cholesterols were low, varying between 141 and 156 mg/100 ml at different ages, the mean fasting serum triglyceride levels of 135 to 164 mg/100 ml were comparable with those found in the West. This may have been due to their high carbohydrate intake. [37]

They were mostly healthy – except that they were infested with intestinal worms and malaria:

The aborigines are thin, extremely fit physically, and for many centuries have lived in the dense hilly jungles of central West Malaysia. They have a high rate of infestation with intestinal worms and malaria but appear well nourished. Their diet consists chiefly of hand-milled rice as a staple, supplemented with cassava, millet, maize, fish, and fruit, nearly all of which they grow or gather themselves. Dairy produce is taken only in very small quantities in the form of reconstituted powdered milk and it is the large volume of starchy foods which accounts for their bulky diet. [37]

Once again, we find that low serum cholesterol is associated with a high burden of eukaryotic pathogens.

Another feature that this population shares with the !Kung San is small stature. Mean averaged 5’1” (155 cm) in height and averaged 105 lb (48 kg) in weight.

Conclusion

Let’s look at the four parts of the syllogism I’ve attributed to Eaton and Cordain:

Diet determines TC. Wrong. It looks like burden of parasites is the major determinant of serum cholesterol in hunter-gatherers and human populations globally.

Low TC is healthy. Wrong. It is associated with high infectious burden, small stature, high mortality, and short lifespan.

Hunter-gatherers had low TC. Some did, some didn’t. So let’s look at a specific claim, this from the classic Cordain-Eaton paper from 2002, “The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic” (thanks, Rob!):

Over the past 64 y, anthropological research has consistently demonstrated relatively low serum cholesterol and triaglycerol levels among indigenous populations that derive the majority of their diet from animal products. [30]

Wrong. Anthropological research has not consistently demonstrated low serum cholesterol and triglycerol levels from hunter-gatherers, regardless of whether the primary dietary source was animals (Eskimo/Inuit) or plants (Kitavans, Central Australian aborigines). Rather, those with high parasite burdens had low cholesterol, regardless of diet, and healthy populations without parasites had serum cholesterol over 200 mg/dl regardless of diet.

Therefore, hunter-gatherer diets are healthy. True! Except insofar as dietary practices, such as the Eskimo practice of eating raw intestines from recently killed animals, predisposed them to picking up parasitic infections.

Overall I think the data should dispose us to look toward infectious burden, rather than genetics or diet, as the primary determinant of serum cholesterol among hunter-gatherers. If genetic differences influence mean TC among hunter-gatherer populations, it is probably because of evolutionary adaptations to local pathogens, such as the heavy parasite burden in sub-Saharan Africa.

Related Posts

The posts in this series are:

References

[1] Eaton SB, Konner M, Shostak M. Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective. Am J Med. 1988 Apr;84(4):739-49. http://pmid.us/3135745. Full text: http://www.direct-ms.org/pdf/EvolutionPaleolithic/EatonStone%20Agers%20Fast%20Lane.pdf

[2] O’Keefe JH Jr, Cordain L, Harris WH, Moe RM, Vogel R. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol. 2004 Jun 2;43(11):2142-6. http://pmid.us/15172426.

[3] Konner M, Eaton SB. Paleolithic nutrition: twenty-five years later. Nutr Clin Pract. 2010 Dec;25(6):594-602. http://pmid.us/21139123. Full text: http://ncp.sagepub.com/content/25/6/594.full.

[30] Cordain L et al. The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic. Eur J Clin Nutr. 2002 Mar;56 Suppl 1:S42-52. http://pmid.us/11965522.

[31] Schwartz CJ et al. Serum cholesterol and phospholipid levels of Australian aborigines. Aust J Exp Biol Med Sci. 1957 Oct;35(5):449-56. http://pmid.us/13499168. Full text: http://www.nature.com.ezp-prod1.hul.harvard.edu/icb/journal/v35/n5/pdf/icb195747a.pdf.

[32] Lindeberg S et al. Cardiovascular risk factors in a Melanesian population apparently free from stroke and ischaemic heart disease: the Kitava study. J Intern Med. 1994 Sep;236(3):331-40. http://pmid.us/8077891.

[33] Lindeberg S et al. Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava Study. Am J Clin Nutr. 1997 Oct;66(4):845-52. http://pmid.us/9322559.

[35] Walker AR. Cholesterol and mortality rates. Br Med J. 1980 May 31;280(6227):1320. http://pmid.us/7388525.

[36] Beaglehole R et al. Cholesterol and mortality in New Zealand Maoris. Br Med J. 1980 Feb 2;280(6210):285-7. http://pmid.us/7357343. Free full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1600122/?tool=pubmed.

[37] Burns-Cox CJ et al. Risk factors and the absence of coronary heart disease in aborigines in West Malaysia. Br Heart J. 1972 Sep;34(9):953-8. http://pmid.us/4116420.