Welcome new subscribers! Please poke around, if you are interested in our chronic health epidemic and what is causing it, I think you will find some interesting ideas here.
Here are the first few paragraphs of the piece as published on Dr. Malone’s Substack, and all of the references.
Heart disease is the leading cause of death in the United States and industrial countries around the world. This is hardly news, but what is not widely understood is that this has not always been the case.
Even as recently as the early 20th Century in the United States and United Kingdom, what we now call atherosclerotic cardiovascular disease (ASCVD) was unusual. If you find this hard to believe, consider that while a comprehensive list of causes of death was first commenced in 1836 in the U.K., and an International Causes of Death list (building upon the previous work from several nations) was created in 1893, it wasn’t until 1930 that coronary disease was included as a cause (Strong, 1936), 18 years after it was first described (Herrick, 1912). Heart disease previously had been ‘rheumatic’, or caused by damage from infection.
And lest you think that this was a result of incompetence, lack of attention, or increasing lifespan, the foremost cardiologist of the 20th Century, Dr. Paul Dudley White, goes through all these possibilities in his 1971 “Perspectives” (60 years after graduating from medical school) and dismissed them all; ultimately noting that it must be some change in the lifestyle, as children dying before their parents of this novel disease became common.
“The automobile, richer food, more tobacco, a faster life, and more pollution of everything have become available to all of us in the United States.” (White, 1971)
“What has been most disturbing is the fact that the children appear to be afflicted with coronary disease at a much earlier age than were their parents.” (Levine, 1963)
References
Ahrens, E. H. (1976). The Management of Hyperlipidemia: Whether, Rather Than How. Annals of Internal Medicine, 85(1), 87–93. https://doi.org/10.7326/0003-4819-85-1-87
Borén, J., Chapman, M. J., Krauss, R. M., Packard, C. J., Bentzon, J. F., Binder, C. J., Daemen, M. J., Demer, L. L., Hegele, R. A., Nicholls, S. J., Nordestgaard, B. G., Watts, G. F., Bruckert, E., Fazio, S., Ference, B. A., Graham, I., Horton, J. D., Landmesser, U., Laufs, U., … Ginsberg, H. N. (2020). Low-Density Lipoproteins Cause Atherosclerotic Cardiovascular Disease: Pathophysiological, Genetic, and Therapeutic Insights: A Consensus Statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal, 41(24), 2313–2330. https://doi.org/10.1093/eurheartj/ehz962
Brown, M. S., & Goldstein, J. L. (1990). Scavenging for Receptors. Nature, 343(6258), 508–509. https://doi.org/10.1038/343508a0
Campos, H., Khoo, C., & Sacks, F. M. (2005). Diurnal and acute patterns of postprandial apolipoprotein B-48 in VLDL, IDL, and LDL from normolipidemic humans. Atherosclerosis, 181(2), 345–351. https://doi.org/10.1016/j.atherosclerosis.2004.12.045
Christakis, G., Rinzler, S. H., Archer, M., & Kraus, A. (1966). Effect of the Anti-Coronary Club Program on Coronary Heart Disease Risk-Factor Status. JAMA, 198(6), 597–604. https://doi.org/10.1001/jama.1966.03110190079022
de Lorgeril, M., Renaud, S., Mamelle, N., Salen, P., Martin, J. L., Monjaud, I., Guidollet, J., Touboul, P., & Delaye, J. (1994). Mediterranean Alpha-Linolenic Acid-Rich Diet in Secondary Prevention of Coronary Heart Disease. Lancet (London, England), 343(8911), 1454–1459. https://doi.org/10.1016/s0140-6736(94)92580-1
Enig, M. G., & Fallon, S. (1998, December). The Oiling of America. Nexus Magazine, Dec ’98-Jan ’99.
Felton, C. V., Crook, D., Davies, M. J., & Oliver, M. F. (1994). Dietary Polyunsaturated Fatty Acids and Composition of Human Aortic Plaques. The Lancet, 344(8931), 1195–1196. https://doi.org/10.1016/S0140-6736(94)90511-8
Goldstein, L. J., & Brown, S. M. (1977). The Low-Density Lipoprotein Pathway and its Relation to Atherosclerosis. Annual Review of Biochemistry, 46(1), 897–930. https://doi.org/10.1146/annurev.bi.46.070177.004341
Goldstein, J. L., Ho, Y. K., Basu, S. K., & Brown, M. S. (1979). Binding Site on Macrophages That Mediates Uptake and Degradation of Acetylated Low Density Lipoprotein, Producing Massive Cholesterol Deposition. Proceedings of the National Academy of Sciences of the United States of America, 76(1), 333–337. https://doi.org/10.1073/pnas.76.1.3
Gresham, G. A., & Howard, A. N. (1961). The Effect of Dietary Fats and Synthetic Glycerides on the Production of Atherosclerosis and Thrombosis in the Rat. British Journal of Experimental Pathology, 42(2), 166–170.
Herrick, J. B. (1912). Clinical Features of Sudden Obstruction of the Coronary Arteries. Journal of the American Medical Association, LIX(23), 2015–2022. https://doi.org/10.1001/jama.1912.04270120001001
Keys, A. (1952). Human Atherosclerosis and the Diet. Circulation. https://doi.org/10.1161/01.CIR.5.1.115
Kris-Etherton, P. M., Eckel, R. H., Howard, B. V., Jeor, S. C. S., & Bazzarre, T. L. (2001). AHA Science Advisory: Lyon Diet Heart Study. Benefits of a Mediterranean-style, National Cholesterol Education Program/American Heart Association Step I Dietary Pattern on Cardiovascular Disease. Circulation, 103(13), 1823–1825. https://doi.org/10.1161/01.CIR.103.13.1823
Lee, J. H., Duster, M., Roberts, T., & Devinsky, O. (2022). United States Dietary Trends Since 1800: Lack of Association Between Saturated Fatty Acid Consumption and Non-communicable Diseases. Frontiers in Nutrition, 8. https://doi.org/10.3389/fnut.2021.748847
Newport, M. T., & Dayrit, F. M. (2024). The Lipid–Heart Hypothesis and the Keys Equation Defined the Dietary Guidelines but Ignored the Impact of Trans-Fat and High Linoleic Acid Consumption. Nutrients, 16(10), Article 10. https://doi.org/10.3390/nu16101447
Ramsden, C. E., Hibbeln, J. R., & Lands, W. E. (2009). Letter to the Editor re: Linoleic acid and coronary heart disease. Prostaglandins Leukot. Essent. Fatty Acids (2008), by W.S. Harris. Prostaglandins, Leukotrienes and Essential Fatty Acids, 80(1), 77. https://doi.org/10.1016/j.plefa.2008.12.002
Ramsden, C. E., Zamora, D., Majchrzak-Hong, S., Faurot, K. R., Broste, S. K., Frantz, R. P., Davis, J. M., Ringel, A., Suchindran, C. M., & Hibbeln, J. R. (2016). Re-Evaluation of the Traditional Diet-Heart Hypothesis: Analysis of Recovered Data from Minnesota Coronary Experiment (1968-73). BMJ, 353. https://doi.org/10.1136/bmj.i1246
Rose, G. A., Thomson, W. B., & Williams, R. T. (1965). Corn Oil in Treatment of Ischaemic Heart Disease. British Medical Journal, 1(5449), 1531–1533. https://doi.org/10.1136/bmj.1.5449.1531
Page, I. H., Allen, E. V., Chamberlain, F. L., Keys, A., Stamler, J., & Stare, F. J. (1961). Dietary Fat and Its Relation to Heart Attacks and Strokes. Circulation, 23(1), 133–136. https://doi.org/10.1161/01.CIR.23.1.133
Singman, H. S., Berman, S. N., Cowell, C., Maslansky, E., & Archer, M. (1980). The Anti-Coronary Club: 1957 to 1972. The American Journal of Clinical Nutrition, 33(6), 1183–1191. https://doi.org/10.1093/ajcn/33.6.1183
Steinberg, D., Parthasarathy, S., Carew, T. E., Khoo, J. C., & Witztum, J. L. (1989). Beyond Cholesterol. Modifications of Low-Density Lipoprotein That Increase Its Atherogenicity. The New England Journal of Medicine, 320(14), 915–924. https://doi.org/10.1056/NEJM198904063201407
Strong, G. F. (1936). The Prognosis of Coronary Thrombosis. Canadian Medical Association Journal, 35(3), 274–277.
Taubes, G. (2008). Good Calories, Bad Calories: Fats, Carbs, and the Controversial Science of Diet and Health. Penguin RandomHouse. https://amzn.to/3ZdNHVB
Witztum, J. L., & Steinberg, D. (1991). Role of Oxidized Low Density Lipoprotein in Atherogenesis. Journal of Clinical Investigation, 88(6), 1785–1792. https://doi.org/10.1172/JCI115499
White, P. D. (1971). Perspectives. Progress in Cardiovascular Diseases, 14(3), 250–255. https://doi.org/10.1016/0033-0620(71)90022-3
““We need only find drugs or dietary treatments that slow the conversion of native LDL to the relevant modified form” (Steinberg, 1989)”
Instead, we got statins, which, unless I'm mistaken, reduce overall LDL cholesterol. Not just the bad kind. Is that right?
It's a very helpful overview.