Cook · The American journal of clinical nutrition 2001 · Within-subject crossover dietary trial · n=12

Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet.

Cited 256 times in the scientific literature.

Level 3 - non-randomized controlled study

Within-subject sequential dietary intervention without reported randomization

PubMed 11124756 · doi:10.1093/ajcn/73.1.93 · record verified 2026-08-29

What was done

Nonheme-iron absorption from complete diets was evaluated in 12 subjects across three separate 5-day dietary periods. During each period, subjects consumed an extrinsically labeled wheat roll with every meal. The first period consisted of a freely chosen baseline diet, while the second and third periods altered intake to maximally decrease or maximally increase dietary vitamin C. Iron absorption was measured and evaluated across periods and via multiple regression pooling all periods and adjusting for individual iron status.

What was found

Mean daily vitamin C intake ranged from 51 to 247 mg/d across the three dietary periods. There was no statistically significant difference in mean nonheme-iron absorption among the three diet phases. In a pooled multiple regression adjusted for iron status, iron absorption showed a statistically significant positive correlation with ascorbic acid (P = 0.0069) and animal tissue (P = 0.0285), and an inverse correlation with dietary phosphate (P = 0.0005).

Why it matters

The strong enhancing effect of vitamin C on nonheme-iron absorption observed in single-meal fasting tests is substantially muted across complete, multi-day diets. This helps explain why long-term vitamin C supplementation often fails to meaningfully alter overall iron status.

Limits

The sample size was very small (n = 12), and the abstract does not specify participant sex, age, or baseline iron status. The dietary periods lasted only 5 days each, which may not reflect chronic nutritional adaptations. Randomization of the sequence of the altered diet periods was not reported in the abstract.

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