Riboflavin supplements for blood pressure lowering in adults

Higher blood pressure is strongly related to an increased risk of cardiovascular disease. There has been interest in riboflavin (vitamin B₂) as a potential intervention to lower blood pressure, particularly for those with a common genetic polymorphism in the methylene tetrahydrofolate reductase enzyme (MTHFR).

To assess the benefits and harms of riboflavin supplements compared to placebo or no additional treatment for lowering systolic and diastolic blood pressure.

We searched the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase, Clarivate Web of Science, Clarivate Food Science & Technology Abstracts and two clinical trials registries. There were no restrictions on language, publication year, or publication status. The latest search date was 24 October 2024. We also handsearched the reference lists of included studies.

We included randomised controlled trials (RCTs) conducted in adults that evaluated oral riboflavin supplements compared with an inactive control (e.g. placebo or no additional treatment) and measured at least one of the critical outcomes. We did not include trials that evaluated multivitamins containing riboflavin. Participants in both the intervention and control groups were able to receive standard medical therapy for hypertension prior to and during the trial.

The critical outcomes were systolic blood pressure and diastolic blood pressure. The important outcomes were antihypertensive medication, adverse events and biomarkers of riboflavin status.

We used the Cochrane RoB 2 tool to assess the risk of bias in included studies for the following outcomes: systolic blood pressure, diastolic blood pressure, antihypertensive medication and adverse events.

We used standard Cochrane methods. For the critical outcomes, which were continuous, we calculated mean differences (MD) and 95% confidence intervals (CIs). We used a fixed-effect meta-analysis to pool data for each outcome where possible. We conducted subgroup analyses, including by MTHFR C677T genotype.

We included four RCTs, which contributed 374 total participants for quantitative synthesis, although the number of participants included for each outcome varied. Most included studies for most outcomes had an overall high risk of bias.

The evidence is very uncertain about the effect of riboflavin on systolic blood pressure (MD -1.94 mmHg, 95% CI -5.74 to 1.86 mmHg; P = 0.32; 3 studies, 320 participants; very low-certainty evidence) and diastolic blood pressure (MD -3.03 mmHg, 95% CI -5.97 to -0.09 mmHg; P = 0.04; 2 studies, 271 participants; very low-certainty evidence). No RCTs reported data on changes in dose or number of antihypertensive medications. One RCT (54 participants) reported data on adverse events by intervention group; there were two adverse events in the riboflavin group and one in the control group. Low-certainty evidence suggests that riboflavin may result in little to no difference in adverse events.

The evidence for the effect of oral riboflavin supplements on systolic and diastolic blood pressure is very uncertain. The evidence comes from four RCTs, three of which had an overall high risk of bias. Large, well-conducted trials are needed for high-certainty evidence of the effect of riboflavin for blood pressure lowering.

KEB was supported by a Sir Charles Hercus Health Research Fellowship from the Health Research Council (Grant number: 19/110) and a Senior Heart Foundation fellowship from the Heart Foundation of New Zealand, supported in part by the GR Winn Trust (Grant number: 3728679).

Protocol (2023): DOI: 10.1002/14651858.CD015464.