Objective: To examine the effect of co-supplementation with iron and vitamin C on antioxidant status, platelet function and low density lipoprotein oxidation in normal healthy volunteers. Design: The study was carried out with two groups of 20 subjects each acting as their own control, comparing presupplemention with postsupplemention. One group was supplemented with iron and the RDA level of vitamin C and the second group with iron and 260 mgad vitamin C. Setting: The International Antioxidant Research Centre, The Guy's, King's College and St Thomas's School of Biomedical Science, Guy's Campus, London. Subjects: Forty normal healthy volunteers, recruited from the staff of the Medical School and Hospital in which two volunteers withdrew during the study. Interventions: Subjects in both studies were randomly assigned to one of two groups (5 males and 5 females group) and received supplements containing iron (14 mgad) and either 60 mgad (Group A) or 260 mgad (Group B) vitamin C for 12 wk. Blood samples were taken at 6 wk and 12 wk, and prior to supplementation and analysed for iron and antioxidant status (transferrin bound iron, vitamin C and E, and b-carotene levels) in both studies. Samples from the ®rst study were analysed for the susceptibility of LDL isolated from plasma to Cu 2 -induced oxidation and samples from the second for platelet function. Results: Transferrin-bound iron was signi®cantly increased (P`0.05) at 12 wk, in Group A subjects (from 14.9 AE 5.3 mmolal to 19.5 AE 2.3 mmolal; mean AE s.d.; n 19), whereas those in Group B showed a signi®cant increase (P`0.05) after 6 wk (from 15.8 AE 4.5 mmolal to 20.4 AE 6.6 mmolal; n 19) which decreased at 12 wk (16.3 AE 5.0 mmolal). Plasma total ascorbate signi®cantly increased from an initial level of 59.3 AE 21.3 mmolal to 87.6 AE 29.0 mmolal after 6 wk and 81.7 AE 11.4 mmolal after 12 wk following the Group B supplementation, but only after 12 wk in Group A (from 64.0 AE 24.8 mmolal to 77.2 AE 13.2 mmolal). Plasma a-tocopherol concentrations were signi®cantly increased after 6 wk and 12 wk with both levels of supplementation (from 24.2 AE 5.7 mmolal Group A and 23.4 AE 5.3 mmolal Group B to 26.3 AE 5.5 mmolal and 25.7 AE 4.7 mmolal respectively at 12 wk). The mean lag phase to oxidation of low density lipoprotein (LDL) was signi®cantly increased in subjects in Group B after 12 wk ingestion of iron and 260 mg vitamin C (from 80.0 AE 14.8 min to 97.2 AE 16.9 min; n 9). Platelet sensitivity to ADP-induced aggregation was signi®cantly decreased (P`0.05) by 12 wk in Group A (from EC 50 2.3 AE 1.3 mM to 3.7 AE 2.2 mM; n 10), whereas those receiving higher vitamin C showed a signi®cant decrease (P`0.05; from EC 50 1.9 AE 0.6 mM to 3.1 AE 1.8 mM) after 6 wk which subsequently increased towards presupplemental levels (2.6 AE 1.6 mM). Platelets from the latter subjects showed a signi®cant reduction in ADP-induced ATP secretion at both 6 wk and 12 wk. Conclusion: The results show modest bene®cial effects on LDL oxidation and platelet function following supplementatio...

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