Does cholesterol play a beneficial role in immunity?

In general terms, the body likes to keep its physiological and biochemical parameters within a certain range – not too high and not too low. This applies to an endless stream of factors including blood sugar levels, temperature, blood pH, blood pressure and sodium levels. However, there are some doctors and researchers who believe that the normal rules do not apply to cholesterol, and specifically ‘low density lipoprotein’-cholesterol (LDL-cholesterol).

There is a general belief that LDL-cholesterol is ‘bad’ and is largely responsible for the narrowing of the vessels and heart disease and cerebrovascular disease (the precursors of heart attack and stroke respectively). Using this line of thinking, then the lower we get cholesterol levels, the better.

Regular readers of this blog may know that cholesterol is an essential element in the body. It’s in all cell membranes, and a major constituent of key components including several hormones and vitamin D (actually, vitamin D is a hormone, despite it being branded a ‘vitamin’).

I was recently reading that cholesterol may have a role in the body’s ability to resist infection too. Some evidence for a protective role here comes from studies which link higher cholesterol levels with reduced risk of infection. In one study, for instance, over a 15-year period, those with higher initial levels of total cholesterol were found to be less likely to be admitted to a hospital with an infectious disease [1].

Now, studies of this nature (epidemiological studies) do not tell us that cholesterol protects against infection, only that these two factors are associated with each other. However, other evidence for the beneficial role of cholesterol in immunity comes from studies in which toxins made by bacteria have been shown to bind to cholesterol, which effectively inactivates them. In one study, mice with genetically high cholesterol were found to be significantly less prone to death after injection with bacteria compared to mice with lower cholesterol levels [2].

This evidence is interesting, but it tells us little about the role of cholesterol in human immunity. However, while I was researching this post I came across an interesting human study in which some attempt was made to assess the role of cholesterol in immunity in humans [3].

This study took 21 individuals who had confirmed infection with tuberculosis (TB). All of the individuals were treated with standard TB medication (four antibiotics taken in combination) over a period of 8 weeks.

Of the 21 participants, 10 were given a cholesterol-rich diet (800 mg of cholesterol a day – about the amount of cholesterol found in 5 medium-sized eggs). The rest of the study participants were to eat a diet which contained 250 mg of cholesterol each day.

After two weeks of treatment, 80 per cent of those eating a high-cholesterol diet were free of TB infection, compared to only 9 per cent of the others. This difference was statistically significant. The authors of the study concluded that:

“A cholesterol-rich diet accelerated the sterilization rate of sputum cultures in pulmonary tuberculosis patients, suggesting that cholesterol should be used as a complementary measure in antitubercular treatment.”

The findings support this conclusion, but it should be borne in mind that the benefits from the diet may not have come from additional dietary cholesterol per se. The cholesterol came via enrichment of the diet with foods such as butter, beef liver and egg yolk. It’s possible, therefore, that the benefits came from other nutritional elements found in these foods, say. The authors of this study acknowledge this possibility.

Cholesterol levels were monitored in this study and did not increase significantly more in the cholesterol-rich diet eaters compared to the others. In a way, this is to be expected, as we know that blood cholesterol levels usually do not change much in response to dietary change (most of the cholesterol in the bloodstream is manufactured in the liver, and it seems that the body tries to keep relatively tight control over cholesterol levels).

The authors of the study suggest that the higher cholesterol diet may have benefitted individuals not through a rise in blood cholesterol levels, but by “[replenishing] metabolic pools (e.g. cell membranes), transformed into other products such as hormones and vitamins A and D, or catabolized through bile salts. Thus, it is reasonable to speculate that the replenishment of metabolic pools occurred faster in those patients eating a cholesterol-rich diet than in control subjects, even when no differences in serum cholesterol levels were observed between the groups due to the catabolism of cholesterol into bile acids.”

Interestingly, the authors of this research quote a study which found that when mouse immune cells (macrophages) are depleted of cholesterol, their ability to ‘eat’ (phagocytose) TB organisms declines by more than 85 per cent [4].

Taken as a whole, the evidence I think supports the idea that cholesterol plays a role in immunity, and it’s another reason to be wary about driving cholesterol levels down to ever-lower levels.

References:

1. Iribarren C, et al. Cohort study of serum total cholesterol and in-hospital incidence of infectious diseases. Epidemiol Infect 1998;121:335–47.

2. Netera MG, et al. Low-density lipoprotein receptor-deficient mice are protected against lethal endotoxemia and severe Gram-negative infections. J Clin Invest 1996;97:1366–72.

3. Perez-Guzman C, et al. A Cholesterol-Rich Diet Accelerates Bacteriologic Sterilization in Pulmonary Tuberculosis. Chest 2005;127(2):643-51

4. Gatfield J, et al. J Essential role for cholesterol in entry of mycobacteria into macrophages. Science 2000; 288, 1647-1650

18 Responses to Does cholesterol play a beneficial role in immunity?

  1. Christopher Palmer 25 April 2013 at 10:56 am #

    The cholesterol cycle supplies cholesterol rich bile to the GI tract for digestion, and then transports cholesterol and lipids (in a chylomicron – the larger of the lipoproteins) back over the GI divide for metabolic and physiologic purpose. For me as a patient this has the look of a natural and virtuous cycle – as opposed to one that could be vicious by virtue (?) of being maladaptive.

    I was writing to friend the other day. In the letter I was explaining how the thinking of Dr Ancel Keys was confounded by an unnoticed factor or error. 100 years ago some Russians in white coats added isolated cholesterol and added some to the chow fed to some rabbits. The Russians induced atherosclerosis in those rabbits. But in the 1970s a team in the US did the same. They chose a range of mammals including dogs, and they took care too isolate pure cholesterol and to keep it pure.

    Cholesterol is highly reactive, and readily oxidises in air. So this team purposefully created the three variations of oxy-cholesterol in addition to pure cholesterol. Pure cholesterol did no harm, while one of the variations upon oxy-cholesterol did a lot of harm and induced atherosclerosis. Sadly the cholesterol bandwagon had gathered enough momentum to be undaunted by this revelation.

    You regularly say cholesterol is the foundation molecule for a great many physiological important biochemicals, including the steroidal hormones. The sex hormones are steroidal. Not only does the sterol that is chole-sterol distinguish plants from creatures, it distinguishes the sexuality of plants and creatures, determines the difference of the sexes in many creatures and clearly in mammals, and explains how rabbits can be so, erm, ‘productive’, whilst they themselves ingest only plant sterols in the wild.

    hence in the letter I worked my way around to pointing to the irony in the diet-heart hypothesis and the misfortune of its principle founder, Dr Ancel Keys. In not being alerted to the possibility that the cholesterol those Russians fed to those bunnies could have become oxidised to several oxy-cholesterols Keys attached life threatening properties to something that not only makes creatures possible, but accounts for the sexes, and oils the process of reproduction, as is especially the case, it is commonly agreed, with rabbits.

    How ironic is that, Dr Briffa?

    The proponents and adherents of the diet-heart hypothesis, or cholesterol hypothesis, are the ones with egg on their faces, surely!?

  2. George @ the High Fat Hep C Diet 26 April 2013 at 3:33 am #

    If you read the biographies of famous people who died of consumption, their restricted diets, amounting in some cases to anorexia, are obvious. Either poverty, crazy ideas about diet, or poor medical advice played a role; diet and sunlight were important elements producing cures in TB sanitoriums.
    It’s no co-incidence that Franz Kafka wrote “The Hunger Artist” about an anorexic, was painfully thin himself, and died young of consumption.

  3. Stipetic 26 April 2013 at 6:54 am #

    Facinating post. I knew about LDL and HDL’s antimicrobial properties, but wasn’t aware of the effect of cholesterol on TB. Truly amazing results. We need more Perez-Guzman et al investigators. Putting patient health ahead of dogma. Kudos to them.

  4. JEYoung 26 April 2013 at 11:36 am #

    Interesting post, thank you for these studies on adults. In the new edition of Perfect Health Diet page 366-67, the Jaminets suggest that optimal LDL cholesterol is above 100mg/dl, and total above 200mg. They cited three infant lipid studies to illustrate that lower numbers would indicate impaired immune function. There are more detailed posts on their blog about “Blood Lipids and Infectious Disease” and possible reasons for cholesterol’s immune function. So if your doctor suggests that LDL should be below 100mg, aiming to be above that number seems the better advice.

  5. Galina L. 26 April 2013 at 12:05 pm #

    Right after the end of World War II my mom’s aunt’s new husband was diagnosed with TB. There were a shortage of food then and that family sold all material things they had in order to buy on a black market eggs, butter and salted pork fat for the man because it was a common knowledge that TB patients needed the diet high in nutrition, and back then people didn’t think fruits and vegetables were very nutritious, but butter , meat and eggs. His illness was cured.

  6. Sue Bedford RGN 26 April 2013 at 4:26 pm #

    A film called “Statin Nation: The Great Cholesterol Cover Up” has recently been produced and is currently available to view for free on YouTube – http://www.youtube.com/watch?v=iZctVYxiW2w. If anyone believes cholesterol is the cause of heart disease by the end of that film, their brains must be starved of cholesterol!

  7. Susan Wallace 26 April 2013 at 6:05 pm #

    Thank you yet another fascinating blog, Dr Briffa.

    I would like to support Galina’s account of how TB used to be treated. My mother was diagnosed with TB in the 1930s and was sent away for country air and a “rich” diet of eggs, butter, cream, cheese, meat etc. (no antibiotics then!) She was quickly and completely cured.

    When I was at school in the 50s, a classmate contracted TB and was away for a while. When she returned she looked very healthy, although she was a bit plumper (she lost this extra weight over time) which she told us was because she was given “lots of fatty foods”. She too remained completely free of TB from then on.

  8. Shirley Bright 27 April 2013 at 3:54 pm #

    Many thanks to Sue Bedford for bringing the film to my attention. I would urge EVERYONE to watch it. It lasts for over an hour, so be prepared to spend the time, but it is so WORTH EVERY MINUTE.

  9. Martin 28 April 2013 at 4:41 am #

    Just an observation: during a period of excessive cholesterol numbers (over 300) I experienced zero flu the whole autumn/winter/spring season. As soon as I managed to reduced the number I got sick.

  10. William L. Wilson, M.D. 28 April 2013 at 12:06 pm #

    I tend to eat a low carb, moderate protein, high fat (healthy fats) diet. I recently had my lab done and my total cholesterol is well over 200 and my LDL is in the mid-100′s, much higher than recommended. My HDL cholesterol was in the 30′s before I changed my diet but it is now 70. My triglycerides are also low. My CRP is low and in my 60′s I have no obvious health problems.

    My PCP keeps wanting to put me on a statin. No thanks! I haven’t had a cold or flu in decades despite the fact that I am exposed to these diseases every day. It’s unfortunate that many in the medical profession look at cholesterol numbers totally out of context.

  11. Colin williams 29 April 2013 at 8:15 am #

    Antoher great article, informative and thought provoking. Just as a thought, rembering I’m not a clinician I just have to manage GPs for my sins!, but with the evidence from the TB trial you quote being so significant, I was wondering could its principles be beneficial in the fight against Chest infection with Cystis Fibrosis patients? I have an interest in this area as I lost my beloved daughter to CF 5 years ago at 22 yrs old.

  12. Maureen Goodin 30 April 2013 at 9:37 am #

    Were found to be significantly less prone to death after injection with bacteria compared to mice with lower cholesterol levels

  13. Tony Mach 5 May 2013 at 6:41 pm #

    Surely an interesting result in this TB study. Eat animal products, help your immune system!

    And I would not be the slightest bit surprised if cholesterol in the human body plays some sort of role in the immune system – I harbor some suspicion about that myself. And I think accepted wisdom now is that *dietary* cholesterol is a bogey man from the last century…

    But in this TB study it could have been the animal protein, it could have been the fatty acid composition (e.g. the eicosanoids DHA+DPA+AA), it could have been the immunoglobulins (in butter and eggs), …

    Based on the TB study anything beyond “consumption of animal products is beneficial for you immune system” is speculative, I fear – so nothing to see here about cholesterol, dietary or otherwise.

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