Comparison of the Effects of Vitamins and/or Mineral Supplementation on Glomerular and Tubular Dysfunction in Type 2 Diabetes

Response to Farvid et al.

Recently, Farvid et al. (1) reported on the effects of dietary supplementation of physiologic doses of vitamins and/or minerals on urinary albumin excretion rate (UAER)/urinary protein excretion rate (UPER), blood pressure, and lipid profile. Although not mentioned in the article, data on blood pressure and lipids have previously been reported elsewhere (2,3).

The main finding is a significant reduction in UAER of ∼66% in the group receiving both minerals and vitamins. Although Farvid et al. claimed this to be the primary end point, it was only measured once as albumin-to-creatinine ratio in morning spot urine at baseline and after 3 months. Repeated measurements (usually at least three) are always required to obtain valid data and correct diagnosis of persistent micro- and macroalbuminuria due to a coefficient of variation of 30–50%. There is a marked discrepancy between the level of UAER (30 mg/g creatinine), suggesting microalbuminuria, and the level of UPER (1–2 g/g creatinine; equal to overt nephropathy). An inconsistent effect of mineral and vitamin supplementation on UAER and UPER was reported, suggesting a chance finding.

Furthermore, mean diastolic blood pressure in the minerals and vitamins group before treatment dropped from 94 (Table 1 in Farvid et al.) to 83 (Table 6) mmHg after exclusion of 2 of the 19 patients; this indicates an error in one of the tables, as it would only be possible if the two excluded patients had a mean diastolic blood pressure of 187 mmHg. The technique for blood pressure measurement was not stated. The conditions for the power calculation were not stated, but according to their previous reports, it was powered to detect changes in HDL cholesterol (2) and blood pressure (3).

It is claimed that the UAER findings are in accordance with the literature (refs. 14–16 in Farvid et al.). However, pharmacological doses of vitamins C and E had no or minimal effect (19%) on UAER (refs. 14,15). In contrast, a 50% reduction in UAER was reported in nine patients, applying pharmacological doses of vitamin C (ref. 16).

In conclusion, the study was not powered for realistic changes in UAER/UPER, insufficient methods for valid characterization of UAER/UPER were applied, and the effect of minerals and vitamins on UAER/UPER was not consistent, clearly suggesting a type 1 error or chance finding.