Ferric hydroxide adipate is a ferric iron supplement containing iron hydroxide and a dietary organic acid that was developed at MRC Human Nutrition Research. We aim to determine if the ingestion of ferric hydroxide adipate with food induces a reduction in urinary phosphate concentration, compared with the administration of placebo plus the same food on a different occasion. We hypothesise that ferric hydroxide adipate binds some phosphate ions in the gastrointestinal tract, which prevents part of the phosphate load in a meal from being absorbed. On another visit, calcium will be given with the same food, as a positive control, since this element is well known to restrict dietary phosphate absorption through the formation of insoluble calcium phosphates in the gut lumen. We will compare urinary phosphate concentrations after co-ingestion of the calcium salt and food versus urinary phosphate following ferric hydroxide adipate and the same food. Additionally, the calcium data will be compared with placebo data, since a significant reduction in urinary phosphate concentrations after calcium treatment will confirm the suitability of the study design.

Finally, iron absorption from the ferric hydroxide adipate treatment will be determined by labelling this preparation with 58Fe and measuring day 14 erythrocyte 57Fe:58Fe.

The study design is: Three-way cross-over volunteer absorption study. Volunteers will not be told which treatment they receive (placebo, ferric hydroxide adipate, or supplemental calcium). Researchers co-ordinating the study on a day to day basis will be aware of treatment allocation, but analysts will not be told which samples correspond to which treatments.

Inclusion Criteria:

- Males and females, aged >18 years, who are generally healthy.

Exclusion Criteria:

• Pregnancy and lactation
• iron deficiency and iron deficiency anaemia
• weight change of +/-2kg in the past month
• dysphagia
• surgery in the past three months
• cancer in the last ten years
• diabetes
• known medical and genetic conditions interfering with calcium and phosphate metabolism: e.g. hyper/hypo-parathyroidism, Fanconi syndrome, hyper/hypothyroidism (except individuals who are taking stable doses of thyroid hormones)
• chronic infection or chronic inflammation
• cardiovascular disease
• chronic respiratory disease
• abnormal renal function (based on glomerular filtration rate)
• known renal disease
• abnormal liver function/known liver disease
• hereditary haemochromatosis or haemoglobinopathies
• gastrointestinal disease
• bone disease
• hypertension
• current use of proton pump inhibitors
• use of other medication that affects mineral homeostasis (on a case by case basis, in consultation with HNR clinician)
• Extreme muscle hypertrophy (e.g. body building)