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Immunity to Infection
Part 3: Low Blood Cholesterol Compromises Immune Function
There is a substantial amount of evidence that relatively low cholesterol levels in apparently healthy individuals is associated with increased subsequent mortality from cancer. It is also associated with other, non-heart related deaths. A group at the Center for Clinical Pharmacology, University of Pittsburgh, Pennsylvania, tested whether the effectiveness of their immune systems differed in individuals with high and low levels of blood cholesterol.[i] The low cholesterol group's cholesterol averaged 3.9 mmol/L (151 mg/dL); the high cholesterol group averaged 6.8 mmol/L (261 mg/dL). The immune systems of the men in the low cholesterol group were significantly less effective than those of the high cholesterol group. This finding was not surprising as several studies have shown that cholesterol is necessary for the proper functioning of blood cells — macrophages and lymphocytes — that form part of our immune systems. For this reason low blood cholesterol undoubtedly adversely affects our bodies' ability to fight infection. This could well be another reason why infectious diseases are becoming more prevalent in our society.
Tuberculosis (TB), a disease thought to have been conquered decades ago, is returning. It has been noticed that low levels of cholesterol are common in patients suffering from TB. TB patients with low cholesterol also have higher death rates, particularly those cases with small (military) nodules. A hospital for respiratory diseases tested whether giving TB patients high-cholesterol meals would be effective in treating their condition.[ii] They split patients into two groups. One had meals containing 800 mg of cholesterol per day; the other had 250 mg of cholesterol per day. The trial was a success. By the second week, the numbers of TB bacteria in sputum was reduced 80% in the high-cholesterol group; it was only reduced by 9% in the low-cholesterol group. High-cholesterol diets now form part of the treatment for TB.
Infections and deaths in surgical patients
Low cholesterol is also linked to increased susceptibility to infection, including development of postoperative infection,[iii] and it predicts death and adverse outcomes in hospitalised patients.[iv] While some of this could be due to illness causing lower cholesterol, it may also be that low cholesterol contributes to illness; indeed, animal studies suggest lipoproteins may serve to protect against bacterial infection-induced death.[v]
It has been suggested in cases of critical surgical illness that a low cholesterol level is more likely to lead to the development of organ failure and death.
A study of patients undergoing surgery for gastrointestinal diseases at the Universita di L'Aquila in Italy, found that 'Hypocholesterolemia [low blood cholesterol] seems to represent a significant predictive factor of morbidity and mortality in critically ill patients.'[vi] Of the patients studied, 35.1% contracted a postoperative infection. The highest incidence of postoperative septic complications (72.7%) was encountered in patients with cholesterol levels below 2.73 mmol/L (105 mg/dl). The authors say 'The results of this study seem to indicate a significant relationship between preoperative hypocholesterolemia and the incidence of septic complications after surgery. Moreover, evaluation of blood cholesterol levels before major surgery might represent a predictive factor of septic risk in the postoperative period.'
Low cholesterol levels have also been associated clinically with the development of hospital infections. A study conducted at the Department of Surgery, Weill Medical College of Cornell University, New York, set out to verify this. They found that lower levels of total cholesterol, and of LDL and HDL occurred early in the course of critical illness; this led to the development of a hospital infection; and with or without the infection, lower cholesterol was independently associated with a higher death rate.[vii] The authors conclude: 'Decreased serum cholesterol concentration is an independent predictor of mortality in critically ill surgical patients. Repletion of serum lipids is a feasible therapeutic approach for the management of critical illness.'
Many patients in hospitals have or acquire infections during or after major abdominal surgery. The Department of Surgery at the Catholic University, Rome, Italy, conducted a study to identify factors that influenced mortality in patients who are affected by such infections.[viii] The hospital records of patients who had had a variety of abdominal operations and who had acquired an infection such as peritonitis were reviewed. Checking deaths against a battery of blood measurements, the authors of the study found that low cholesterol levels and low protein levels were both 'strongly and independently associated with the outcome'.
Professor Uffe Ravnskov would not be at all surprised. He found that: 'There is much evidence that blood lipids play a key role in the immune defence system. Bacterial endotoxin and Staphylococcus aureus a-toxin bind rapidly to and become inactivated by low-density-lipoprotein (LDL).'[ix] (Staphylococcus aureus is what the 'SA' in MRSA stands for.) Ravnskov also pointed out that 'Total cholesterol is inversely associated with mortality caused by respiratory and digestive disease, the aetiologies of which are mostly infectious. Total cholesterol is also inversely associated with the risk of being admitted to hospital because of an infectious disease.' In other words, if you have low cholesterol, you are more likely to end up in hospital and more likely to contract an infection while there.
References
[i]. Muldoon MF, Marsland A, Flory JD, et al. Immune system differences in men with hypo- or hypercholesterolemia. Clin Immunol Immunopathol 1997; 84: 145-9.
[ii]. Perez-Guzman C, Vargas, MH, Quinonez, F, et al. A Cholesterol-Rich Diet Accelerates Bacteriologic Sterilization in Pulmonary Tuberculosis. Chest 2005; 127: 643-651.
[iii]. Leardi S, Altilia F, Delmonaco S, et al. Blood levels of cholesterol and postoperative septic complications. Ann Ital Chir 2001; 71: 233-237.
[iv]. Crook MA, Velauthar U, Moran L, Griffiths W. Hypocholesterolaemia in a hospital population. Ann Clin Biochem 1999; 36: 613-616.
[v]. Read TE, Harris HW, Grunfeld C, et al. The protective effect of serum lipoproteins against bacterial lipopolysaccharide. Eur Heart J 1993; 14(suppl K): 125-129.
[vi]. Leardi S, Altilia F, Delmonaco S, et al. Op cit.
[vii]. Bonville DA, Parker TS, Levine DM, et al. The relationships of hypocholesterolemia to cytokine concentrations and mortality in critically ill patients with systemic inflammatory response syndrome. Surg Infect (Larchmt). 2004; 5: 39-49.
[viii]. Pacelli F, Doglietto GB, Alfieri S, et al. Prognosis in intra-abdominal infections. Multivariate analysis on 604 patients. Arch Surg 1996; 131: 641-5.
[ix]. Uffe Ravnskov. High Cholesterol May Protect Against Infections and Atherosclerosis. Quart J Med 2003; 96: 927-34.
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