Micronutrients and diabetic retinopathy: A systematic review

Methodological quality of the review: Medium confidence

Author: Lee CTC, Gayton EL, Beulens JWJ, Flanagan DW, Adler AI.

Region: Details not provided

Sector: Diabetic retinopathy, micronutrients

Sub-sector: None specified

Equity focus: None specified

Review Type: Effectiveness review

Quantitative synthesis method: Narrative analysis

Qualitative synthesis methods: Not applicable

Background

Micronutrients may potentially alter the risk of diabetic retinopathy (DR) by interfering with pathological mechanisms. Vitamin C, vitamin E and magnesium have been studied in relation to their association with DR. However, evidence relating to these micronutrients and their effect on DR is limited and offers conflicting results.

Research objectives

To ‘evaluate the evidence for the association between intake and blood levels of micronutrients and diabetic retinopathy.’

Main findings

The authors identified 15 studies for inclusion in the systematic review: 12studies contained cross-sectional analysis only, one included cross-sectional and longitudinal analysis and two were prospective cohort studies. Four studies examined the association between DR and vitamin C and vitamin E, four studies included vitamin C only, two studies included vitamin E only and five studies included magnesium only. For the overall quality of the evidence gathered for this review, 10 studies were graded II (medium) and two studies received a rating of I (low). None of the included studies were graded III (high) quality.

Authors noted that the review included studies with marked variation between the quality of the studies and major differences in study design, the measurement of micronutrients and incomplete ascertainment of retinopathy.

For vitamin C, hospital-based studies ‘reported an inverse association between plasma levels with retinopathy, whereas population-based studies showed no association between dietary intake and retinopathy’. For vitamin E, there was no association with dietary intake or plasma levels and retinopathy. For magnesium the results were inconsistent; with a single prospective analysis showing an association between low levels in plasma and progression of retinopathy but cross-sectional studies reporting inconsistent results.

Evidence suggested that dietary intake of or plasma levels of vitamin C and E and magnesium did not seem to be associated with diabetic retinopathy.

As evidence from included studies was inconclusive, authors recommended further prospective studies to establish the nature of the associations between micronutrients and DR. They suggested that these studies should repeatedly measure dietary and supplement intake and biomarkers.

Methodology

Authors conducted a search in PUBMED and EMBASE from 1998 to May 2008 and included observational studies with cross-sectional, case-control or prospective designs with participants with diabetes. The exposures were micronutrients, including dietary intake or serum/plasma levels of vitamin C, vitamin E and magnesium. The authors included studies that measured these micronutrients using dietary methods or biomarkers. Studies were restricted to articles written in English only. The outcome measure used was DR, including the presence or absence of non-proliferative or proliferative retinopathy.  The authors used the Newcastle-Ottawa Scale to assess the quality of the evidence, which uses a 0- to 4-star rating for categories of selection and exposure/outcome measurement and 0- to 3-star rating for comparability.

Applicability/external validity

The review included studies with marked variation between the quality of the studies and major differences in study design, the measurement of micronutrients and incomplete ascertainment of retinopathy. Therefore results may not be generalizable.

Geographic focus

The authors did not report on the geographical location of studies included in the review.

Quality assessment

The systematic review is based on a search of two relevant electronic databases, and on reference lists in included studies. Grey literature search and studies in other languages other than English were not considered for this review, which may have potentially affected the overall summary or quality of this review.

Authors acknowledged limitations of the review and also noted that as cross-sectional analyses were included in the review, this ‘limits the ability to establish a temporal relationship, and does not preclude the possibility of reverse causation, namely, that the diagnosis of diabetic retinopathy leads an individual to increase his or her intake of micronutrients’. Therefore, overall there is medium confidence in conclusions about the effects of this study.