Background

Cardiovascular diseases are disorders of the heart and blood vessels, including acute coronary and cerebrovascular events (such as myocardial infarction and stroke). Approximately 50% of disabilities resulting from cardiovascular disease are associated with a suboptimal diet. In particular, dietary gluten (a protein found in certain cereal grain) has been linked to a wide range of adverse health outcomes. For example, different gastrointestinal symptoms (such as malabsorption or diarrhoea) often occur in people affected by gluten-related diseases and the only effective treatment for these populations is an often life-long gluten-reduced or gluten-free diet. Gluten-reduced and gluten-free diets have also gained a strong popularity in the general population. The evidence on the benefits and harms of a gluten-reduced or gluten-free diet in the general population is, however, contradictory: While gluten avoidance may be associated with disease prevention, there are also concerns that a gluten-free or gluten-restricted diet may be suboptimal (due to a reduced consumption of whole-grain, a dietary key component).

Review question

We reviewed the available studies to determine the effects (i.e. health-related benefits and risks) of a gluten-reduced or gluten-free diet for the primary prevention of cardiovascular disease in the general population.

Study characteristics

The evidence is current to June 2021. We identified one randomised controlled trial (RCT) and three non-randomised studies of interventions (NRSIs) with an observational design. The RCT was conducted in Italy and included 60 healthy adults with a follow-up of six months. The NRSIs included more than 450,000 participants (either health professionals from the USA or adults (volunteers) from the general population from the UK) and reported a maximum follow-up of more than 25 years. In the NRSIs, the lowest median gluten intake was 2.6 g/day and the highest was 9.4 g/day (thereby, 1 g/day of gluten intake is equivalent to half a slice of white bread). The RCT compared a gluten-free with a usual diet.

Key results

Our results suggest that it is unclear whether gluten intake is associated with all-cause mortality. Furthermore, our findings suggest no association between gluten intake and both cardiovascular mortality and non-fatal myocardial infarction. A lower compared with a higher gluten intake may be associated with a slightly increased risk to develop type 2 diabetes — a major cardiovascular risk factor. These findings were independent of age, ethnicity, body mass index (BMI), family history of diabetes, smoking status, alcohol intake, physical activity, menopausal status and postmenopausal hormone use, oral contraceptive use, multivitamin use, total energy intake, and intakes of magnesium, folic acid and cereal fibre.

The results from the only published RCT suggested that it is unclear whether gluten intake affects systolic blood pressure. Moreover, in this RCT no differences between a gluten-free and usual diet were found for other cardiovascular risk factors including diastolic blood pressure, low-density lipoprotein levels and BMI.

No study reported data on adverse events, quality of life or on other health-relevant outcomes.

Certainty of evidence

The certainty of evidence in this review was low to very low. The studies had several methodological flaws. Taking into account that the majority of the participants from the NRSIs were health professionals, the applicability to the general population is also questionable. Given the limited findings from this review predominantly based on observational studies, no recommendations for practice can be made.