Near-iron deficiency-induced remission of gouty arthritis.

OBJECTIVES: Previous evidence supports a role for iron in the pathogenesis of gout. For example, iron, when added to media containing urate crystals, stimulated oxidative stress with subsequent complement and neutrophil activation. Conversely, iron removal inhibited these responses as well as urate-crystal-induced foot pad inflammation in rats in-vivo. The objective of the present study was to investigate whether or not iron removal may improve the outcome of gouty arthritis in humans as well. METHODS: Quantitative phlebotomy was used to remove iron in 12 hyperuricaemic patients with gouty arthritis and maintain their body iron at near-iron deficiency (NID) level (i.e. the lowest body iron store compatible with normal erythropoiesis and therefore absence of anaemia). RESULTS: During maintenance of NID for 28 months, gouty attacks markedly diminished in every patient, from a cumulative amount of 48 and 53 attacks per year before (year -2, -1), to 32, 11 and 7 during induction (year 0) and maintenance (year +1, +2) of NID, respectively. During NID, attacks were also more often of milder severity. CONCLUSIONS: During a 28-month follow-up, maintenance of NID was found to be safe and beneficial in all patients, with effects ranging from a complete remission to a marked reduction of incidence and severity of gouty attacks.

A low-iron-available, polyphenol-enriched, carbohydrate-restricted diet to slow progression of diabetic nephropathy.

Diabetic nephropathy has become the leading cause of uremia. Several lines of evidence suggest dietary factors other than protein intake have a substantial role in the progression of diabetic nephropathy to end-stage renal disease. The present investigation was initiated to evaluate whether a carbohydrate-restricted, low-iron-available, polyphenol-enriched (CR-LIPE) diet may delay and improve the outcome of diabetic nephropathy to a greater extent than standard protein restriction. To this aim, 191 diabetic patients, all with type 2 diabetes, were randomized to either CR-LIPE or standard protein restriction and the following outcomes monitored: doubling of serum creatinine, cumulative incidence of end-stage renal disease, and all cause mortality. Over a mean follow-up interval of 3.9 +/- 1.8 years, serum creatinine concentration doubled in 19 patients on CR-LIPE (21%) and in 31 control subjects (39%) (P < 0.01). Renal replacement therapy or death occurred in 18 patients on CR-LIPE (20%) and in 31 control subjects (39%) (P < 0.01). These differences were independent from follow-up interval, sex, mean arterial blood pressure, HbA(1c), initial renal dysfunction, and angiotensin system inhibitor use. In conclusion, CR-LIPE was 40-50% more effective than standard protein restriction in improving renal and overall survival rates.

Effect of iron depletion on cardiovascular risk factors: studies in carbohydrate-intolerant patients.

Controversy surrounds the role of iron (Fe) in atherosclerosis (ASCVD), mainly due to the inaccuracy of assessing body Fe stores with serum ferritin and transferrin saturation. Quantitative phlebotomy was used to test whether or not (a) Fe stores are increased in individuals at high risk for ASCVD and (b) Fe depletion to near-deficiency (NID) levels is associated with reduction of risk factors for ASCVD. Thirty-one carbohydrate-intolerant subjects completed the study. Fe stores were within normal limits (1.5 +/- 0.1 g). At NID, a significant increase of HDL-cholesterol (p < 0.001) and reductions of blood pressure (p < 0.001), total and LDL-cholesterol (p < 0.001), triglyceride (p < 0.001), fibrinogen (p < 0.001) and glucose and insulin responses to oral glucose loading (p < 0.001) were noted, while homocysteine plasma concentration remained unchanged. These effects were largely reversed by a 6-month period of Fe repletion with reinstitution of Fe sufficiency. Thus, although individuals at high risk for ASCVD are not Fe-overloaded, they seem to benefit, metabolically and hemodynamically, from lowering of body Fe to levels commonly seen in premenopausal females.

Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Increased body iron, genetic hemochromatosis (GH) mutations, and nonalcoholic fatty liver disease (NAFLD) tend to cluster in carbohydrate-intolerant patients. In an attempt to further clarify the interrelationships among these conditions, we studied 42 carbohydrate-intolerant patients who were free of the common GH mutations C282Y and H63D, and had a serum iron saturation lower than 50%. METHODS: We measured body iron stores, and induced iron depletion to a level of near-iron deficiency (NID) by quantitative phlebotomy. RESULTS: In the 17 patients with clinical evidence of NAFLD, we could not demonstrate supranormal levels of body iron (1.6 +/- 0.2 vs. 1.4 +/- 0.2 g; P = 0.06). However, at NID, there was a 40%-55% improvement (P = 0.05-0.0001) of both fasting and glucose-stimulated plasma insulin concentrations, and near-normalization of serum alanine aminotransferase activity (from 61 +/- 5 to 32 +/- 2 IU/L; P < 0.001). CONCLUSIONS: These results reflect the insulin-sparing effect of iron depletion and indicate a key role of iron and hyperinsulinemia in the pathogenesis of NAFLD.