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Mein Konto
Relation
Axelsson AS, Tubbs E, Mecham B, et al. Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes.Scientific Transl. Med. 2017;9(394):eaah4477.
Objective
To find new drugs that can help address an important pathological mechanism of type 2 diabetes mellitus - the liver's ability to produce glucose through gluconeogenesis.
Study design
Randomized, double-blind, placebo-controlled trial
Participant
Investigators recruited 103 Scandinavian patients with type 2 diabetes mellitus (T2D) diagnosed within 10 years before study entry. Participants had either well-controlled or poorly controlled T2D; Poorly controlled T2D was defined as a glycated hemoglobin (HbA1c) level above 50 mmol/mol. For reference: 48 mmol/mol or more corresponds to an HbA1c of 6.5%; 42 to 47 mmol/mol corresponds to an HbA1c of 6.0% to 6.4% (prediabetes); and an HbA1c of less than 42 mmol/mol represents normal blood sugar. Ninety-seven patients completed the study; 60 had well-controlled and 37 had poorly controlled T2D. Seventeen of the patients with poorly controlled disease were obese. All but 3 participants (who were well controlled) were taking metformin.
Participants with poorly controlled disease were divided into 2 groups – non-obese and obese (BMI > 30 kg/m2) – as hepatic glucose production is more impaired in obese patients.
Study parameters assessed
Blood levels of fasting glucose (a representation of hepatic glucose production) and hemoglobin A1c were measured at the start and end of the study. After initial blood tests (fasting glucose, HbA1c, and an oral glucose tolerance test), participants received 1 daily dose of broccoli sprout extract (BSE) or placebo. The BSE contained 150 mmol sulforaphane (SFN) per dose. At the end of the 12-week period, blood tests were repeated.
Primary outcome measures
Change from Baseline in Fasting Glucose and Hemoglobin A1c Levels at 12 Weeks.
Key insights
Sulforaphane administered as concentrated BSE improved fasting blood glucose levels and reduced HbA1c levels in obese patients with T2D. The magnitude of HbA1c reduction was greater in participants with higher baseline HbA1c (−0.2 mmol/mol per 1 mmol/mol higher baseline HbA1c;P=0.004). The association between baseline HbA1c levels and magnitude of change was not significant in the placebo group (P=0.5). There was also an association between BMI and change in HbA1c in the BSE treatment group, with the magnitude of reduction being greater in overweight participants (−0.4 mmol/mol per 1 kg/m2 or higher BMI;P=0.015). The association between BMI and change in HbA1c was not significant in obese participants in the placebo group.
These results are remarkable considering that more than 400 million people worldwide have diabetes and an even larger number have prediabetes.
There were no safety concerns with the use of SFN and it was well tolerated.
Practice implications
In this study, the authors report the benefits of SFN as BSE in regulating blood sugar levels in diabetics.
Preclinical experiments
The clinical study described here was preceded by extensive research to identify a novel drug for the treatment of diabetes. The researchers generated a disease signature based on diabetes-associated gene networks in liver tissue, the site of glucose overproduction in T2D, and then compared it to drug signatures from a large database. After searching the extensive database, they found that SFN had the most overlap with diabetes-relevant gene signatures related to hepatic glucose production.
They first tested the effect of SFN on glucose production using a rat hepatoma cell line. Incubation of these cells with SFN showed a dose-dependent decrease in blood glucose production. This mechanism can be partially explained by the nuclear translocation of the nuclear factor erythroid 2-related factor 2 (NRF2) and the associated downregulation of key enzymes for gluconeogenesis.
They then tested SFN on various animal models in vivo. They examined glucose intolerance in rats fed high-fat and high-fructose diets. Both diets had a benefit, and in fact the magnitude of the benefit was quite similar to using metformin. Additionally, the rats administered SFN had reduced hepatic glucose production, which in turn had similar benefits to metformin. Additionally, there was an advantage in glucose tolerance for mice suffering from diet-induced diabetes.
Clinical study
After both in vitro and in vivo studies supported SFN's potential to treat diabetes, researchers moved on to test its effects on glucose control in people with T2D, the clinical trial described in this review. The results showed that SFN in the form of concentrated BSE improved fasting blood glucose levels and reduced HbA1c levels in obese patients with T2D.
These results are remarkable considering that more than 400 million people worldwide have diabetes and an even larger number have prediabetes.1Poorly controlled blood sugar also increases the risk of cancer, particularly breast cancer.2.3
The SFN in this study was administered as a dried powder of an aqueous extract of broccoli sprouts. The choice of BSE was influenced by other clinical studies that used BSE as a source of SFN, including studies on cancer,4chronic obstructive pulmonary disease,5inflammatory diseases and autism. In this study, SFN reduced HbA1c levels in diabetic patients with a daily BSE dose containing 150 mmol of SFN. A number of human studies have shown that the dose of SFN should be 40 to 60 mg for its many health benefits.6
Clinically, we would probably have better results with a whole plant, such as: B. germinated broccoli seeds, as the chewing process and microbial enzymes in our mouth (myrosinase) contribute to the activation of SFN. This can be achieved by consuming around 100g of broccoli sprouts.