Lipid hypothesis

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The "lipid hypothesis" was one of two hypotheses developed in the 1850s to explain the pathogenesis of atherosclerosis. It was proposed by Rudolph Virchow in 1856 and suggested that blood lipid accumulation in arterial walls causes atherosclerosis.[1] In 1913, a study by Nikolai Anitschkow showed that feeding rabbits with cholesterol induced symptoms similar to atherosclerosis, suggesting a role for cholesterol in atherogenesis.[2][3] In 1951, Duff and McMillian formulated the lipid hypothesis in its modern form in an influential review.[4] Since the emergence of cardio-vascular disease as a major cause of death in the Western world in the middle of the 20th century, the lipid hypothesis proposing that saturated fats and cholesterol in the blood are its cause has been the focus of research seeking to prove or disprove its validity. This research has culminated in the general acceptance of the "lipid hypothesis" as scientific fact by the end of the century. However, opponents still argue that the "lipid hypothesis" has not yet been fully validated, arguing amongst other things, that trans fatty acids are the determining factor in causing isquemic heart disease.

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[edit] The lipid hypothesis and cholesterol controversy of atherogenesis

During the 70s and 80s, a fair number of researchers and practitioners were questioning the lipid hypothesis due to the lack of proof that lowering blood cholesterol levels results in decreased risk for atherosclerosis. This discussion is also referred to as the "cholesterol controversy." Predictions were made that further research during the 80s and 90s would help settle this controversy.[5] The National Institute of Health held a consensus development conference on the topic in 1984 which concluded:

"It has been established beyond a reasonable doubt that lowering definitely elevated blood cholesterol levels (specifically, blood levels of low-density lipoprotein (LDL) cholesterol) will reduce the risk of heart attacks caused by coronary heart disease..."[6]

Despite this consensus, criticism persisted within the scientific community.[7] In the following years, studies with blood lipid and cholesterol-lowering drugs such as statins provided further evidence in support of the lipid hypothesis.[8][9][10] As of the end of the 1980s, this accumulated support resulted in the rejection of the "cholesterol controversy" within the scientific community.[11][12]

Further studies were designed to particularly test the validity of the "lipid hypothesis" and settle the controversy.[13][14][15] By 2002, the "lipid hypothesis" was considered to be validated as proven fact[16], or as one article stated, "universally recognized as a law."[17] Nevertheless, resistance against the acceptance of the "lipid hypothesis" as a fact still persists, arguing that it is based on false premises and misrepresented data.[18][19][20]

Nowadays, the term "lipid hypothesis" is most commonly used by the opponents of the generally accepted view concerning the role of cholesterol in causing atherosclerosis and cardiovascular disease, such as members of The International Network of Cholesterol Skeptics founded in 2003 by critic Uffe Ravnskov. Opponents use the term to stress their viewpoint that cholesterol as a causative agent of cardio-vascular disease is still an unproven conjecture.

[edit] Palm oil and blood cholesterol controversy

For many years now, it has been established that the primary cholesterol-elevating fatty acids are the saturated fatty acids with 12 (lauric acid), 14 (myristic acid) and 16 (palmitic acid) carbon atoms with a concomitant increase in the risk of coronary heart disease. Monounsaturated fatty acids such as oleic acid is as effective in reducing serum total and low-density lipoprotein (LDL) cholesterol levels as polyunsaturated fatty acids such as alpha-linoleic acid. [21] The World Health Organization in its report[22] states there is convincing evidence that palmitic oil consumption contributes to an increased risk of developing of cardiovascular diseases.

A study by a group of researchers in China comparing palm, soybean, peanut oils and lard showed that palm oil actually increased the levels of good cholesterol and reduced the levels of bad cholesterol in the blood (Zhang, et al, 1995, 1997 cited by Koh, 2006).[23]

A study by Hornstra in 1990 also showed similar results.[24]

[edit] The Alzheimer's lipid hypothesis and cholesterol controversy

A new "cholesterol controversy" is emerging out of the research of the pathogenesis of Alzheimer's disease (AD). A "lipid hypothesis of AD" has been proposed that suggests a connection between cholesterol and changes in brain lipids found in Alzheimer-type neuropathology. [25]

[edit] See also

[edit] Notes and references

  1. ^ Virchow, Rudolph (1856). Phlogose und Thrombose im Gefässystem. In: Gesammelte Abhandlungen zur wissenschaftlichen Medizin. Germany: Staatsdruckerei Frankfurt. 
  2. ^ Anitschkow NN, Chatalov S (1913). "Über experimentelle Cholesterinsteatose und ihre Bedeutung für die Entstehung einiger pathologischer Prozesse". Zentralbl Allg Pathol 24: 1-9. 
  3. ^ Anitschkow NN (1913). "Über die Veränderungen der Kaninchenaorta bei experimenteller Cholesterinsteatose". Beitr Pathol Anat 56: 379-404. 
  4. ^ Duff GL, McMillian GC (1951). "Pathology of atherosclerosis". Am J Med 11: 92-108. 
  5. ^ Gotto AM Jr (1984). "Directions of atherosclerosis research in the 1980s and 1990s". Circulation 70: III88-94. PMID 6488509. 
  6. ^ from NIH Consensus Development Conference, JAMA 1985, 253:2080
  7. ^ Steinberg D (2006). "An interpretive history of the cholesterol controversy, part IV: The 1984 coronary primary prevention trial ends it - almost". J Lipid Res 47: 1-14. PMID 16227628. 
  8. ^ Tyroler HA (1987). "Review of lipid-lowering clinical trials in relation to observational epidemiologic studies". Circulation 76: 515-522. PMID 3304704. 
  9. ^ Brown WV (1990). "Review of clinical trials: proving the lipid hypothesis". Eur Heart J 11 Suppl H: 15-20. PMID 2073909. 
  10. ^ Kroon AA, Stalenhoef AF (1997). "LDL-cholesterol lowering and atherosclerosis -- clinical benefit and possible mechanisms: an update". Neth J Med 51: 16-27. PMID 9260486. 
  11. ^ Steinberg D (1989). "The cholesterol controversy is over. Why did it take so long?". Circulation 80: 1070-1078. PMID 2676235. 
  12. ^ LaRosa JC (1998). "Cholesterol & atherosclerosis: a controversy resolved". Adv Nurse Pract 6: 36-37. PMID 9633288. 
  13. ^ Pyrola K, Steiner G (1996). "Will correction of dyslipoproteinaemia reduce coronary heart disease risk in patients with non-insulin-dependent diabetes? Need for trial evidence". Ann Med 28: 357-362. PMID 8862691. 
  14. ^ Steiner G (1996). "The Diabetes Atherosclerosis Intervention Study (DAIS): a study conducted in cooperation with the World Health Organization". Diabetologia 39: 1655-1661. PMID 9081851. 
  15. ^ Steiner G (2000). "Lipid intervention trials in diabetes". Diabetes Care 23 Suppl 2: B49-53. PMID 10860191. 
  16. ^ Steinberg D (2002). "Atherogenesis in perspective: hypercholesterolemia and inflammation as partners in crime". Nature Medicine 8: 1211-1217. PMID 12411947. 
  17. ^ Thompson GR, Packard CJ, Stone NJ (2002). "Goals of statin therapy: three viewpoints". Curr Atheroscler Rep 4: 26-33. PMID 11772419. 
  18. ^ Ravenskov, Uffe (2000). The cholesterol myths. Washington, DC: New Trends Publishing. ISBN 0-96708987-0-0. 
  19. ^ Stehbens WE (2001). "Coronary heart disease, hypercholesterolemia, and atherosclerosis I. False premises". Exp Mol Pathol 70: 103-119. PMID 11263954. 
  20. ^ Stehbens WE (2001). "Coronary heart disease, hypercholesterolemia, and atherosclerosis II. Misrepresented data". Exp Mol Pathol 70: 120-139. PMID 11263955. 
  21. ^ Vessby,B.1994. INFORM 5(2):182-185.
  22. ^ Diet, Nutrition and the Prevention of Chronic Diseases (WHO Technical Report Series 916. Geneva. 2003. pages 82, 88 &c)
  23. ^ Koh, C.S. 2006. Comments On Draft Document: Diet, Nutrition, and the Prevention of Chronic Diseases. http://www.who.int/dietphysicalactivity/media/en/gsfao_cmo_068.pdf
  24. ^ Hornstra, 1990 `Effects of dietary lipids on some aspects of the cardiovascular risk profile'. In G. Ziant [ed.], LIPIDS AND HEALTH.
  25. ^ Kivipelto M, Solomon A, Blennow K, Olsson AG, Winblad B (2006). "The new cholesterol controversy - a little bit of history repeating?". Acta Neurol Scand 114 Suppl 185: 1-2. PMID 16866903. 
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