Sulforaphane, a naturally occurring compound found in cruciferous vegetables, has exhibited therapeutic potential to support the management of type 2 diabetes (T2D) via attenuating exaggerated glucose production and glucose intolerance.
Interdisciplinary research led by investigators from the University of Gothenburg (Göteborg, Sweden) first analyzed the pattern of gene expression associated with T2D and identified a key network of 50 genes strongly linked to the pathophysiology of T2D (they called it the T2D signature). Then, they screened the gene signatures of more than 3800 drug candidates in order to identify compounds that exhibited the highest overlap with the T2D signature and therefore the ones most likely to counteract the effects of T2D. Through this process, they identified sulforaphane as the top candidate that might reverse the T2D disease signature. Subsequently, the researchers conducted a series of in vitro and in vivo experiments as well as a human clinical trial to validate this prediction.
The in vitro experiments confirmed the premise that sulforaphane decreased glucose production in rat liver cells under diabetogenic conditions, and down-regulated the expression of genes involved in glucose production. The animal study demonstrated that sulforaphane prevented the development of glucose intolerance despite intake of high-fat diet or high-fructose diets. Sulforaphane was also effective in treating animals that had already developed glucose intolerance, and the efficacy was similar to that of metformin. Further, in diabetic mice, sulforaphane improved glucose tolerance via reduced gluconeogenetic rate.
The researchers also investigated the effect of sulforaphane-containing broccoli sprout extracts (BSE) in patients with T2D. A total of 103 patients with T2D, and on metformin, were randomized to receive placebo or BSE (containing 150 μmol/day sulforaphane) for 12 weeks. The results indicated BSE was most effective in improving fasting glucose and HbA1c in patients with BMI > 30 and with dysregulated T2D; HbA1c was reduced from 57.1 mmol/mol (or 7.38%) at baseline to 53.4 mmol/mol (or 7.04%) at 12 weeks. However, BSE exhibited no effects in those with well-regulated T2D. As importantly, BSE was well tolerated and no serious adverse events were reported during the trial.
The study results were published in the journal Science Translational Medicine (June 2017).
Why is this Clinically Relevant?
- Although metformin is currently the treatment of choice for T2D, approximately 15% of T2D patients cannot take metformin due to reduced kidney glomerular filtration rate (GFR)
- Up to 30% of metformin users develop side effects such as abdominal pain or diarrhea. As a result, many patients are unable to continue with metformin and need alternative treatment options
- Broccoli sprouts extracts (BSE) contain high concentration of glucoraphanin which is converted to sulforaphane by the release of intrinsic enzyme myrosinase during the breakdown of cell walls such as from chewing or chopping
- Not all BSEs are created equal. For example, heat exposed BSEs (such as heat from cooking) have no efficacy because there is no longer active myrosinase to convert glucoraphanin to sulforaphane
- Clinicians should consider a BSE supplement that contains active myrosinase for reliable sulforaphane conversion in their patients of dysregulated T2D and as a nutritional adjunct to diet and lifestyle education
 Axelsson, A.S., et al., Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. Sci Transl Med, 2017. 9(394).