[Home](/) What we know Why a mechanism is not an answer [How do plant-based and animal-based diets compare for health?](/what-we-know/health-comparisons/) [1What a comparison like this can show](/what-we-know/health-comparisons/what-a-comparison-can-show/) 2Why a mechanism is not an answer [3Protein: how much, and from where](/what-we-know/health-comparisons/protein/) [4Calcium and bone: the milk question](/what-we-know/health-comparisons/calcium-and-bone/) [5Fats: which one replaces which](/what-we-know/health-comparisons/fats/) [6Heart disease and stroke](/what-we-know/health-comparisons/heart-disease-and-stroke/) [7Death from any cause](/what-we-know/health-comparisons/death-from-any-cause/) [8The reference diet, and what it projects](/what-we-know/health-comparisons/the-reference-diet-and-what-it-projects/) What we know · Part 2 of 8 # Why a mechanism is not an answer Entry checked 20 September 2026 · 8 sentences, each with its source · no person approved these sentences · [the entry's full limits](/what-we-know/health-comparisons/#limits) A mechanism is a story about how something ought to work. Calcium is what bone is made of, so more calcium ought to mean stronger bones. Antioxidants disarm the reactive molecules that damage cells, so more of them ought to mean less cancer. Saturated fat raises LDL cholesterol and LDL cholesterol causes heart disease, so less saturated fat ought to mean fewer heart attacks. Each of those three is a real finding, and each of them has been tested against what actually happened to people. Two of the three did not survive the test. Start with antioxidants, because the trial that tested them is the cleanest example in nutrition of a mechanism pointing the wrong way. In a randomised trial of 29,133 male smokers, beta carotene supplements were associated with an 18% higher incidence of lung cancer than placebo (95% confidence interval 3 to 36 percent) — the opposite of what the antioxidant mechanism predicted. [[1]](#source-1) In the same trial, total mortality was 8% higher among the men who received beta carotene (95% confidence interval 1 to 16 percent), mainly from more deaths from lung cancer and ischaemic heart disease. [[1]](#source-1) A second randomised prevention trial, in 18,314 smokers, former smokers and asbestos-exposed workers, was stopped 21 months early because the group given beta carotene and vitamin A had a relative risk of lung cancer of 1.28 (95% confidence interval 1.04 to 1.57) and a relative risk of death from any cause of 1.17 (1.03 to 1.33). [[2]](#source-2) [[2]](#source-2) [[2]](#source-2) A second large trial tested vitamin E and selenium against prostate cancer. The mechanism was well described, the doses were generous, and the follow-up was long enough to see an effect if there was one. In a trial of 35,533 men, vitamin E supplementation at 400 IU a day increased the risk of prostate cancer (hazard ratio 1.17, 99% confidence interval 1.004 to 1.36), an absolute increase of 1.6 cases per 1000 person-years. [[3]](#source-3) [[3]](#source-3) None of that says antioxidants are useless in food. It says that a mechanism strong enough to justify a supplement is not strong enough to predict what the supplement will do. The same lesson shows up in food rather than in pills, and it is easier to see there because the food is the same food. Cheese and butter contain much the same saturated fat. The mechanism predicts they should raise cholesterol alike. In a randomised crossover trial, 49 people who replaced part of their habitual fat intake with cheese had lower LDL cholesterol after six weeks than when they replaced it with butter at the same fat content. [[4]](#source-4) The same trial reports that cheese did not raise LDL cholesterol compared with the participants' habitual diet, in which total and saturated fat intakes were lower. [[4]](#source-4) Eggs are the other familiar case. Dietary cholesterol was the mechanism, and for years the advice followed from it. In three large United States cohorts followed for more than 5.5 million person-years, eating at least one egg a day was not associated with cardiovascular disease (hazard ratio 0.93, 95% confidence interval 0.82 to 1.05), and a meta-analysis of 33 risk estimates found a pooled relative risk of 0.98 (0.93 to 1.03) per additional egg a day. [[5]](#source-5) [[5]](#source-5) The third mechanism on the list above did survive its test, and the page says so plainly rather than treating every mechanism as a trap. The relevant trials replaced saturated fat with polyunsaturated fat and measured heart attacks, not cholesterol alone. The position paper that links saturated fat to cardiovascular disease through LDL cholesterol states that replacing saturated with unsaturated fats lowers LDL cholesterol, a cause of atherosclerosis, and calls that the link between the biological evidence and the disease rates measured in populations and trials. [[6]](#source-6) So the rule this page follows is not that mechanisms are wrong. It is that a mechanism is a hypothesis about people until somebody measures people, and the measurement can go either way. ## What this section does not show These are trials in people Every study on this page gave a supplement to people and counted what happened to them. None of it is a laboratory result, and none of it is a statement about how a nutrient works in a cell. The trials were in specific groups The beta carotene trials were in smokers and asbestos-exposed workers, and the vitamin E trial in men aged 50 and over. A result in those groups is not a result in everyone. Nothing here is advice This section does not say to take or to avoid any supplement. The site has no clinician and no information about any reader, and it describes published trials rather than recommending anything. What would change it A trial of the same mechanism in a different population that found the opposite, or a correction to any of the three trials, would change this section rather than a sentence in it. All twelve elements The entry's full limits block covers the dates, the study designs, who was and was not studied, the comparators, the adjustment sets, the uncertainty, the counter-signals and what we did not check. [Read it on the entry's first page.](/what-we-know/health-comparisons/#limits) This page is general information about published research. It is not medical advice, and it is not a substitute for advice from a qualified health professional. No clinician-patient relationship exists, and we do not know your diet, your medications, your test results, your medical conditions or your history. Talk to a health professional before changing your diet if you are pregnant or breastfeeding, feeding an infant or child, over 65, taking medication, living with a medical condition, or if you have been diagnosed with a nutrient deficiency or have a history of disordered eating. The evidence described is about groups and diets, not about you, and not about any product listed on this site. If you are unwell, contact a health professional; in an emergency, call 911. No clinician reviewed this entry. It is a compilation of published sources by this site. [PreviousWhat a comparison like this can show](/what-we-know/health-comparisons/what-a-comparison-can-show/) [NextProtein: how much, and from where](/what-we-know/health-comparisons/protein/) ## Sources for this section Every numbered sentence above was checked against the source with that number on the date shown. The number links to the entry in this list, and the entry's first page lists every source it cites. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The New England Journal of Medicine. randomised trial. [Open the source ↗](https://doi.org/10.1056/NEJM199404143301501) Checked 19 September 2026. Backs 2 sentences in this section. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. The New England Journal of Medicine. randomised trial. [Open the source ↗](https://doi.org/10.1056/NEJM199605023341802) Checked 19 September 2026. Backs 1 sentence in this section. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. randomised trial. [Open the source ↗](https://doi.org/10.1001/jama.2011.1437) Checked 19 September 2026. Backs 1 sentence in this section. Cheese intake in large amounts lowers LDL-cholesterol concentrations compared with butter intake of equal fat content. The American Journal of Clinical Nutrition. randomised crossover trial. [Open the source ↗](https://doi.org/10.3945/ajcn.111.022426) Checked 19 September 2026. Backs 2 sentences in this section. Egg consumption and risk of cardiovascular disease: three large prospective US cohort studies, systematic review, and updated meta-analysis. The BMJ. prospective cohort studies. [Open the source ↗](https://doi.org/10.1136/bmj.m513) Checked 19 September 2026. Backs 1 sentence in this section. Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association. Circulation. position paper. [Open the source ↗](https://doi.org/10.1161/CIR.0000000000000510) Checked 19 September 2026. Backs 1 sentence in this section. How this was written ## Method and care Every factual sentence here was checked against a retrieved copy of the source it names: one sentence, one retrieved source, one verbatim quote, one checked date. No person reviewed or approved these sentences before publication. The journal sources were retrieved as their Europe PMC records, which is the quotable text that registry serves; the EAT-Lancet material was retrieved as the text of the Commission's own summary report. The entry records, for each source, what was retrieved and what was not. Reviewed by: — no named reviewer has reviewed this entry, and no clinician has. It is a compilation of published sources by this site. Written by: Find My Next Bite's writing session, 20 September 2026, working from sources retrieved the same day. No person reviewed or approved these sentences before publication, and no clinician has read them. Funding: this section is unfunded. It takes no sponsorship, and the rule we adopted in advance says no funder may ever be a company whose products the entries or the directory describe. Corrections: if a source here has changed, moved or been retracted, tell us and we will suspend the sentence and record the change. Every change this site makes to a sentence it has published is recorded, dated, at [Corrections and revisions](/what-we-know/corrections/) — what it said before, what it says now, and which kind of change it is. Nothing here is rewritten quietly. [Read the entry from the start, with its question, its position and its full limits.](/what-we-know/health-comparisons/) Request a correction ↗ [Read our approach](/#how-it-works) [Explore the food →](/foods/)