Coronary Artery Disease (CAD)

Coronary Artery Disease (CAD)

Coronary artery disease accounts for more deaths than any other single condition, some 17.9 million a year worldwide, and affects 20.5 million US adults. Its classic presentation is angina pectoris, chest pressure that appears with exertion and eases with rest, reflecting a coronary supply adequate at rest but not under demand. An acute coronary syndrome is a different event: crushing chest pain radiating to the arm or jaw signals a plaque rupture and thrombus rather than progressive narrowing, and the two differ in tempo as well as in mechanism.

Four ingredients are graded against this endpoint here, and the arithmetic behind them is unlike any other page in the collection. Forty studies cover 100,350 participants, an average of more than 2,500 people per study. That ratio is the signature of hard-outcome research: when the endpoint is a myocardial infarction or a death rather than a laboratory value, trials must be large and long enough to accumulate events. The consequence is that CAD carries the best-powered supplement evidence of any cardiovascular condition here and, not coincidentally, the least flattering.

Omega-3 fatty acids hold Grade B on 20 studies and 50,000 participants. Folate and selenium are both Grade C with a mixed direction, on 40,000 and 10,000 participants respectively. Two of the four ingredients on the page are therefore recorded as inconsistent, and those two account for half the participants. An umbrella review of nutritional supplements and dietary interventions against cardiovascular outcomes mapped this pattern across the wider literature, finding that few supplement-outcome pairs are supported by high-certainty evidence once trial quality is accounted for ^[1].

Folate is the clearest illustration. Its rationale was inherited from the homocysteine hypothesis: supplementation reliably lowers homocysteine, homocysteine is associated with coronary events, therefore supplementation should reduce them. The large randomised trials did not bear out the final step, and the mixed direction recorded here is the residue of that sequence. Whether folate supplementation is warranted outside of documented deficiency has been debated on exactly these grounds ^[2].

Magnesium completes the set at Grade C on 5 studies and 350 participants, an evidence base three orders of magnitude smaller than folate's and correspondingly less able to detect or exclude an effect.

The risk factors, dyslipidaemia, hypertension, smoking, diabetes, family history of premature disease, obesity and sedentary living, are the same set that appears throughout cardiovascular medicine, and several of them are addressed by therapies whose outcome evidence is measured in tens of thousands of events. That comparison is the relevant context for any ingredient on this page: the endpoint is mortality, the trials are large, and the results have been modest.