Does cholesterol play a beneficial role in immunity?

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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.


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

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