Clarifying Ideas about Cholesterol Correlation is not proof of causation.

Most blood cholesterol comes from unburned food energy. It is a useful biomarker for indicating food energy intake has been greater than expenditure. Current American lifestyles include sleeping, eating, reading, sitting at a keyboard, standing in a line, driving a car, etc. All of these need only 200 Cals per 3 hours, and most meals have MUCH more than 200 Cal. A 1200 Cal meal leaves 1000 Cals during the next 3 postprandial hours during which the liver converts extra food energy into triglycerides and cholesterol that are released into the blood. Food energy toxicity (3:46 is now a serious health condition in the USA.

The excess energy causes transient vascular endothelial dysfunction. The transient dysfunction is amplified by omega-6 eicosanoids into harmful chronic inflammatory conditions that combine in a “metabolic syndrome” and link to a wide range of other comorbidities linked to HUFA imbalances. The transient postprandial endothelial dysfunction can be lessened by eating fewer calories per meal. Chronic inflammatory damage in atherosclerosis and acute thrombosis in heart attacks are both amplified by n-6 eicosanoids, not by the associated elevated blood cholesterol formed from food energy. Cholesterol is a most misunderstood biomarker.

Cholesterol is actually needed for cell membrane stability, and it forms important steroid hormones and bile salts. It is made especially by the liver in a complex 25-step process regulated by negative feed back signals in which circulating cholesterol actually slows formation of more cholesterol.

Food Energy Toxicity: Omega-6 Amplifies It. (3:46

Historically, high food energy density was linked with cardiovascular disease (CVD) and cholesterol Nix6 Eat3high blood cholesterol levels. This led to a broadly held (but unproved) public view that cholesterol causes CVD deaths. A 2014 review (see Figure 1 in the review) shows the association of CVD and cholesterol may occur only to the degree that people have more inflammatory n-6 HUFA than the less inflammatory n-3 HUFA.

Normal blood levels of 220mg/dL cholesterol rise 14 mg/dL with an increase of 5% food energy as saturated fat. In contrast, the level lowers about 7 mg/dL with 5% increased energy as polyunsaturated fat (PUFA). Recent work (see below) testing omega-6 actions in the diet-heart hypothesis showed that clinical trials using increased dietary omega-6 PUFA gave the expected lower cholesterol and also gave unexpected higher death rates which falsified the hypothesis that blood cholesterol levels cause death.

Testing omega-6 actions in the diet-heart hypothesis
To examine the traditional diet-heart hypothesis, previously unpublished data from the Minnesota Coronary Experiment (MCE) were recovered and analyzed and put in the context of existing diet-heart randomized controlled trials. The MCE (1968-73) is a double-blind, randomized controlled trial designed to test whether replacing saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. The intervention group had significant reduction in serum cholesterol compared with controls. However, Kaplan Meier graphs showed no mortality benefit for the intervention group. There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol with no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts. In meta-analyses, the cholesterol-lowering interventions showed no evidence of benefit on mortality from coronary heart disease or all-cause mortality. Evidence from randomized controlled trials (n=10,808) shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol, but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Ramsden CE, Zamora D, Majchrzak-Hong S, Faurot KR, Broste SK, Frantz RP, Davis JM, Ringel A, Suchindran CM, Hibbeln JR. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ. 2016 Apr 12;353:i1246. doi: 10.1136/bmj.i1246

Data were recovered and evaluated from the Sydney Diet Heart Study, a single blinded, parallel group, randomized controlled trial conducted in 1966-73. Substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis showed no evidence of cardiovascular benefit from linoleic acid intervention trials. These findings raise important questions about current worldwide dietary advice to substitute omega-6 linoleic acid (or polyunsaturated fats in general) for saturated fats. Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, Ringel A, Davis JM, Hibbeln JR. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ. 2013 Feb 4;346:e8707. doi: 10.1136/bmj.e8707.


Updated October, 2017