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At high pharmacological doses (used historically to lower cholesterol), niacin also affects lipid metabolism, as described in a clinical study

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Resveratrol, a sirtuin activator, has oral bioavailability below 1% due to extensive first-pass glucuronidation, rendering oral supplementation pharmacologically insignificant despite robust in vitro effects

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Many growth factors show similar patterns where optimal stimulation occurs within a narrow concentration window, and excess amounts trigger inhibitory feedback

These conditions include megaloblastic anemia, neurological disorders, cognitive decline, cardiovascular issues, and complications during pregnancy (Figure 2), among others