How Low Can You Go?

A common dogma of the medical community is that it is best to reduce your levels of cholesterol as low as possible or at least what is determined low density lipoprotein cholesterol (bad cholesterol). This is simply a fallacy as that cholesterol places such an important part of several biochemical pathways in the body and as transport mechanism. A recent journal article from Journal of the American College of Cardiology (JACC) and mentioned in Science Daily a couple of days ago suggests that low levels of LDL may increase the the likelihood of cancers. The primary aim of statins (drugs that lower cholesterol) and the way they work impacts the formation of LDL in the liver. There are drawbacks to this study which the authors clearly address.

Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer: Insights From Large Randomized Statin Trials

Alawi A. Alsheikh-Ali, Prasad V. Maddukuri, Hui Han, Richard H. Karas

In large randomized statin trials, we found no significant relationship between magnitude of low-density lipoprotein cholesterol (LDL-C) lowering and rates of elevated liver enzymes or rhabdomyolysis. For any 10% LDL-C reduction, rates of elevated liver enzymes increased significantly with higher statin doses. Additional analyses demonstrated a significant inverse association between cancer incidence and achieved LDL-C levels, but no such association with percent or absolute LDL-C reduction. Hence, drug and dose-specific effects are likely more important determinants of liver and muscle toxicity than magnitude of LDL-C lowering. Furthermore, the cardiovascular benefits of low LDL-C may in part be offset by an increased cancer risk.

There is growing evidence (Karlamangla et al., 2004, Brescianini et al., 2003; Iribarren et al., 1995; Schatz et al., 2001; Schupf et al., 2005; Volpato et al., 2001; Weverling-Rijnsburger et al., 1997, Melton et al. 2006) that there may be a threshold for cholesterol in the body, so if you have too little cholesterol you can die from cancer and if it is too high you kick off from heart disease. As heart disease continues to be the leading cause of mortality in the US and a growing problem in the rest of the word it will become increasingly important to understand the underlying complex genetic interactions that characterize cholesterol levels in humans.

References

Brescianini S, Maggi S, Farchi G, Mariotti S, Di Carlo A, Baldereschi M, Inzitari D. 2003. Low total cholesterol and increased risk of dying: are low levels clinical warning signs in the elderly? Results from the Italian Longitudinal Study on Aging. J Am Geriatr Soc 51: 991–996.

Iribarren C, Reed DM, Chen R, Yano K, Dwyer JH. 1995. Low serum cholesterol and mortality. Which is the cause and which is the effect? Circulation 92:2396–2403.

Karlamangla AS, Singer BH, Reuben DB, Seeman TE. 2004. Increases in serum non-high-density lipoprotein cholesterol may be beneficial in some high-functioning older adults: MacArthur Studies of Successful Aging. J Am Geriatr Soc 52:487–494.

Melton PE, M. Zlojutro, K Kimminau, MH Crawford (2006) "Biological Aging and Cox hazard analysis of mortality trends in a Mennonite community from south-central Kansas" American Journal of Human Biology 18(3):387-401.

Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD. 2001. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet 358:351–255.

Schupf N, Costa R, Luchsinger J, Tang MX, Lee JH, Mayeux R. 2005. Relationship between plasma lipids and all-cause mortality in nondemented elderly. J Am Geriatr Soc 53:219–226.

Volpato S, Leveille SG, Corti MC, Harris TB, Guralnik JM. 2001. The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterol. J Am Geriatr Soc 49: 1142–1147.

Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RG. 1997. Total cholesterol and risk of mortality in the oldest old. Lancet 350: 1119–1123.