(This post is not written to show how great cholesterol is. This post is to show that news reporting is one-sided)
The 21st century was not a good time for the cholesterol theory. Already during the 1990’s studies starting to show that low cholesterol was associated with an increase in non-cardiovascular disease (especially cancer)[i].
Since 2000, it was shown that high HDL was associated with premature death[ii], and a review of studies showed that above 60 years of age, most people showed and an inverse association with high LDL with mortality[iii]. It also showed that people with an inherited mutation resulting in higher HDL levels had a higher risk for coronary heart disease[iv], an increased risk of ischemic heart disease for specific groups[v], and in some cases does not lower myocardial infarction[vi]. Acute myocardial infarction were found to have lower LDL levels at the time of infarction than healthy controls[vii]
In 2002 it was shown that low LDL was associated with an increase in death in advanced heart failure[viii]. In Italy, it was shown that higher total cholesterol was found to be very protective for brain health[ix]. In 2008, high cholesterol was associated with better memory function[x]. In Brasil 2011, after following 800 people (65-80) for 12 years, showed results that high total cholesterol and LDL was not associated with mortality but low total cholesterol was associated with high mortality[xi]. After following 1167 with chronic hemodialysis for 10 years it was shown that hypocholesterolemia was an independent risk factor, while 200-219 mg/dl, which is seen as high, was the most protective[xii] Low LDL is associated with osteoporosis in diabetes patients[xiii] and death in patients with liver cancer[xiv]. In 2008 after examining 2500 elderly it was found that the low cholesterol group resulted in a 2 fold increase risk of dying compared to the highest cholesterol group[xv]. In 2017 it was found that men with high cholesterol had better sperm quality[xvi]. In the Czech Republic, women with the highest cholesterol were found to have the highest chance of in-hospital mortality, while those with the lowest cholesterol had the highest mortality after 78 months, suggesting an association factor instead of causative[xvii]. A systematic review for heamorrages strokes found that among 23 studies with a total of 1.4 million participants high cholesterol levels and high LDL decreased the chance of having hemorrhages strokes[xviii]. This review is further supported by the outcomes that show high cholesterol is associated with better results (less mortality) after ischemic stroke[xix].
There have been many studies that show low cholesterol is associated with high suicide attemps[xx][xxi][xxii] especially affecting the young [xxiii], many mental issues and retardation have low cholesterol levels[xxiv][xxv]
An underreported side of cholesterol is its antiinflammatory behavior and association with the immune system. Substances that stimulate the immune system, also stimulate the lipoproteins system that binds to bacteria, viruses and toxins[xxvi][xxvii][xxviii][xxix][xxx], and since cholesterol acts like an antioxidant[xxxi][xxxii][xxxiii], it seems plausible that cholesterol aids as an antioxidant to reduce inflammation[xxxiv]. This combination of inflammatory inducers, LDL, and neutrophils aggregates and can ultimately form a plaque, without cholesterol these attacks on the body may be left unchecked and cause more damage.
Statins are used to treat CVD and seem to have benefits for the heart[xxxv][xxxvi], but studies also show that statins work independently of lowering cholesterol, and contain anti-inflammatory properties[xxxvii][xxxviii], furthermore lowering LDL by way of statins showed the same improvements as when LDL levels remained unchanged[xxxix].
[i] European Heart Journal (1997) 18, 52-59. Low total cholesterol is associated with high total mortality in patients with coronary heart disease. S. Behar, E. Graff*, H. Reicher-Reiss, V. Boyko, M. Benderly, A. Shotan and D. Brunner for the Bezafibrate Infarction Prevention (BIP) Study Group*Neufeld Cardiac Research Institute, Sheba Medical Center, Tel Hashomer, and * Institute of Physiological Hygiene, Edith Wolfson Medical Center, Holon, Israel
[ii] Clin J Am Soc Nephrol. 2016 Aug 11. pii: CJN.00730116. [Epub ahead of print]High Density Lipoprotein Cholesterol and the Risk of All-Cause Mortality among U.S. Veterans.Bowe B1, Xie Y1, Xian H2, Balasubramanian S1, A Zayed M3, Al-Aly Z4.
[iii] Cardiovascular medicine Research, 2016. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. Uffe Ravnskov1, David M Diamond2, Rokura Hama3, Tomohito Hamazaki4, Björn Hammarskjöld5, Niamh Hynes6, Malcolm Kendrick7, Peter H Langsjoen8, Aseem Malhotra9, Luca Mascitelli10, Kilmer S McCully11, Yoichi Ogushi12, Harumi Okuyama13, Paul J Rosch14, Tore Schersten15, Sherif Sultan6, Ralf Sundberg
[iv]Zanoni, P. et al. Science 351, 1166–1171 (2016
[v] CLINICAL INVESTIGATION AND REPORTS Elevated HDL Cholesterol Is a Risk Factor for Ischemic Heart Disease in White Women When Caused by a Common Mutation in the Cholesteryl Ester Transfer Protein Gene. Birgit Agerholm-Larsen, Børge G. Nordestgaard, Rolf Steffensen, Gorm Jensen, Anne Tybjærg-Hansen
[vi] Lancet. 2012 Aug 11;380(9841):572-80. doi: 10.1016/S0140-6736(12)60312-2. Epub 2012 May 17. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, Hindy G, Hólm H, Ding EL, Johnson T, Schunkert H, Samani NJ, Clarke R, Hopewell JC, Thompson JF, Li M, Thorleifsson G, Newton-Cheh C, Musunuru K, Pirruccello JP, Saleheen D, Chen L, Stewart A, Schillert A, Thorsteinsdottir U, Thorgeirsson G, Anand S, Engert JC, Morgan T, Spertus J, Stoll M, Berger K, Martinelli N, Girelli D, McKeown PP, Patterson CC, Epstein SE, Devaney J, Burnett MS, Mooser V, Ripatti S, Surakka I, Nieminen MS, Sinisalo J, Lokki ML, Perola M, Havulinna A, de Faire U, Gigante B, Ingelsson E, Zeller T, Wild P, de Bakker PI, Klungel OH, Maitland-van der Zee AH, Peters BJ, de Boer A, Grobbee DE, Kamphuisen PW, Deneer VH, Elbers CC, Onland-Moret NC, Hofker MH, Wijmenga C, Verschuren WM, Boer JM, van der Schouw YT, Rasheed A, Frossard P, Demissie S, Willer C, Do R, Ordovas JM, Abecasis GR, Boehnke M, Mohlke KL, Daly MJ, Guiducci C, Burtt NP, Surti A, Gonzalez E, Purcell S, Gabriel S, Marrugat J, Peden J, Erdmann J, Diemert P, Willenborg C, König IR, Fischer M, Hengstenberg C, Ziegler A, Buysschaert I, Lambrechts D, Van de Werf F, Fox KA, El Mokhtari NE, Rubin D, Schrezenmeir J, Schreiber S, Schäfer A, Danesh J, Blankenberg S, Roberts R, McPherson R, Watkins H, Hall AS, Overvad K, Rimm E, Boerwinkle E, Tybjaerg-Hansen A, Cupples LA, Reilly MP, Melander O, Mannucci PM, Ardissino D, Siscovick D, Elosua R, Stefansson K, O’Donnell CJ, Salomaa V, Rader DJ, Peltonen L, Schwartz SM, Altshuler D, Kathiresan S.
[vii] Circ J 2008; 72: 1836 – 1843 (Received March 14, 2008; revised manuscript received June 9, 2008; accepted June 24, 2008; released online September 24, 2008) Division of Cardiovascular Medicine, Mitoyo General Hospital, Kagawa, *Department of Medical Technology, Okayama University Graduate School of Health Sciences and **Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan Mailing address: Shozo Kusachi, MD, Department of Medical Technology, Okayama University Graduate School of Health Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. E-mail: sh-ksc56@ po1.oninet.ne.jpSerum N-3 Polyunsaturated Fatty Acid Levels Correlate With the Extent of Coronary Plaques and Calcifications in Patients With Acute Myocardial Infarction Masayuki Ueeda, MD; Takenori Doumei, MD; Yoichi Takaya, MD; Ryoko Shinohata, MT*; Yusuke Katayama, MD; Nobuhiko Ohnishi, MD; Atsushi Takaishi, MD; Toru Miyoshi, MD**; Satoshi Hirohata, MD**; Shozo Kusachi, MD*
[viii] J Card Fail. 2002 Aug;8(4):216-24. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. Horwich TB1, Hamilton MA, Maclellan WR, Fonarow GC.
[ix] J Am Geriatr Soc. 2003 Jul;51(7):991-6. 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. Brescianini S1, Maggi S, Farchi G, Mariotti S, Di Carlo A, Baldereschi M, Inzitari D; ILSA Group.
[x] West R, Beeri MS, Schmeidler J, et al. Better memory functioning associated with higher total and LDL cholesterol levels in very elderly subjects without the APOE4 allele. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 2008;16(9):781-785. doi:10.1097/JGP.0b013e3181812790.
[xi] Research Article Lipids and All-Cause Mortality among Older Adults: A 12-Year Follow-Up Study Marcos Aparecido Sarria Cabrera,1 Selma Maffei de Andrade,2 and Renata Maciulis Dip1 1Discipline of Geriatrics, Postgraduate Program in Public Health, State University of Londrina (UEL), Robert Koch Avenue, 60 CEP, 86038440 Londrina, PR, Brazil 2Department of Public Health, Postgraduate Program in Public Health, State University of Londrina (UEL), Robert Koch Avenue, 60 CEP, 86038440 Londrina, PR, Brazil Correspondence should be addressed to Marcos Aparecido Sarria Cabrera, marcoscabrera@uol.com.br Received 4 October 2011; Accepted 29 November 2011
[xii] Kidney International, Volume 61, Issue 5, May 2002, Pages 1887-1893. fKidney International, Dialysis – Transplantation Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients KunitoshiIseki Masanobu Yamazato Masahiko Tozawa Shuichi Takishita
[xiii] Endocr Pract. 2007 Oct;13(6):620-8. Association of lower serum cholesterol levels with higher risk of osteoporosis in type 2 diabetes. Afshinnia F1, Chacko S, Zahedi T.
[xiv] Tohoku J Exp Med. 2013 Mar;229(3):203-11. Low serum LDL cholesterol levels are associated with elevated mortality from liver cancer in Japan: the Ibaraki Prefectural health study. Saito N1, Sairenchi T, Irie F, Iso H, Iimura K, Watanabe H, Muto T, Ota H.
[xv] Age Ageing. 2008 Mar;37(2):207-13. doi: 10.1093/ageing/afn017.Relation of plasma lipids to all-cause mortality in Caucasian, African-American and Hispanic elders. Akerblom JL1, Costa R, Luchsinger JA, Manly JJ, Tang MX, Lee JH, Mayeux R, Schupf N.
[xvi] Liu C-Y, Chou Y-C, Lin S-H, et al. Serum lipid profiles are associated with semen quality. Asian Journal of Andrology. 2017;19(6):633-638. doi:10.4103/1008-682X.195240.
[xvii] Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012 Mar; 156(1):21–28. 21 Gender differences in total cholesterol levels in patients with acute heart failure and its importance for short and long time prognosis. Lenka Spinarovaa, , Jindrich Spinarb , Jiri Vitoveca, , Ales Linhartc, , Petr Widimskyd, , Marian Fedorcoe , Filip Malekf, , Cestmir Cihalikg, , Roman Miklikb ,Ladislav Dusekh, , Klaudia Zidovaa, , Jiri Jarkovskyh, ,Simona Littnerovah, Jiri Parenica
[xviii] Wang X, Dong Y, Qi X, Huang C, Hou L. Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis. Stroke 2013; 44(7): 1833-1839.
[xix] Neurology. 2000 May 23;54(10):1944-9. Better outcome after stroke with higher serum cholesterol levels. Vauthey C1, de Freitas GR, van Melle G, Devuyst G, Bogousslavsky J.
[xx] Am J Psychiatry. 1995 Mar;152(3):419-23. Low serum cholesterol level and attempted suicide. Golier JA, Marzuk PM, Leon AC, Weiner C, Tardiff K.
[xxi] Eur Child Adolesc Psychiatry. 2010 Jul;19(7):615-9. doi: 10.1007/s00787-009-0084-x. Epub 2010 Jan 3. Total serum cholesterol levels and suicide attempts in child and adolescent psychiatric inpatients. Plana T1, Gracia R, Méndez I, Pintor L, Lazaro L, Castro-Fornieles J.
[xxii] J Affect Disord. 2001 Feb;62(3):217-9. Cholesterol and serotonin indices in depressed and suicidal patients. Sarchiapone M1, Camardese G, Roy A, Della Casa S, Satta MA, Gonzalez B, Berman J, De Risio S.
[xxiii] J Egypt Soc Parasitol. 2009 Aug;39(2):653-63. Relationship between blood cholesterol level and acute depression. Maimanee TA1, Al-Hazmi S.
[xxiv] Serum Cholesterol in Mental Retardation R. D. EASTHAM, J. JANCAR The British Journal of Psychiatry Sep 1969, 115 (526) 1013-1017; DOI: 10.1192/bjp.115.526.1013
[xxv] Postgraduate Medical Journal (March 1974) 50, 140-144. Serum cholesterol and serum triglycerides in mental retardation T. LAWLOR* M.B., B.S.(Lond.), M.R.C.(Psych.), D.P.M. F. O’HARAtPh.D. D. T. BIRTWISTLEt Ph.D. * Normansfield Hospital, Teddington, Middlesex and t Polytechnic of North London
[xxvi] Huemer HP, Menzel HJ, Potratz D, Brake B, Falke D, Utermann G, Dierich MP. Herpes simplex virus binds to human serum lipoprotein. Intervirology. 1988;29(2):68-76.
[xxvii]Netea MG, Joosten LAB, Keuter M, et al. Circulating Lipoproteins Are a Crucial Component of Host Defense against Invasive Salmonella typhimurium Infection. Ojcius DM, ed. PLoS ONE. 2009;4(1):e4237.
[xxviii]Kozarevic D, McGee D, Vojvodic N, Gordon T, Racic Z, Zukel W, Dawber T. Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia. The Journal of Experimental Medicine. 1996;184(5):1601-1608.
[xxix] Harris HW, Grunfeld C, Feingold KR, Rapp JH. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice. Journal of Clinical Investigation. 1990;86(3):696-702.
[xxx] Huemer HP, Menzel HJ, Potratz D, Brake B, Falke D, Utermann G, Dierich MP. Herpes simplex virus binds to human serum lipoprotein. Intervirology. 1988;29(2):68-76.
[xxxi] Parasassi T, Giusti AM, Raimondi M, Ravagnan G, Sapora O, Gratton E. Cholesterol protects the phospholipid bilayer from oxidative damage. Free Radic Biol Med. 1995 Oct;19(4):511-6.
[xxxii] Samuni AM, Lipman A, Barenholz Y. Damage to liposomal lipids: protection by antioxidants and cholesterol-mediated dehydration. Samuni AM, Lipman A, Barenholz Y. Chem Phys Lipids. 2000 Apr;105(2):121-34.
[xxxiii] Albert AD, Boesze-Battaglia K, Paw K, Watts A, Epand RM. Effect of cholesterol on rhodopsin stability in disk membranes. Biochimica et Biophysica Acta (BBA) – Protein Structure and Molecular Enzymology, Volume 1297, Issue 1, Pages 77-82.
[xxxiv] Pfohl M, Schreiber I, Liebich HM, Häring HU, Hoffmeister HM. Upregulation of cholesterol synthesis after acute myocardial infarction–is cholesterol a positive acute phase reactant? Atherosclerosis. 1999 Feb;142(2):389-93.
[xxxv] Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504.
[xxxvi]Knatterud GL, Rosenberg Y, Campeau L, Geller NL, Hunninghake DB, Forman SA, Forrester JS, Gobel FL, Herd JA, Hickey A, Hoogwerf BJ, Terrin ML, White C. Long-term effects on clinical outcomes of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation in the post coronary artery bypass graft trial. Circulation. 2000 Jul 11;102(2):157-65.
[xxxvii] Weis M, Pehlivanli S, Meiser BM, von Scheidt W.Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation. J Am Coll Cardiol. 2001 Sep;38(3):814-8.
[xxxviii] Vaughan CJ, Murphy MB, Buckley BM.Statins do more than just lower cholesterol. Lancet. 1996 Oct 19;348(9034):1079-82.
[xxxix] Hecht HS, Harman SM. . Relation of aggressiveness of lipid-lowering treatment to changes in calcified plaque burden by electron beam tomography. Am J Cardiol. 2003 Aug 1;92(3):334-6.