​ Research Progress on the Anti-Obesity Effect of Glucoraphanin

1. Introduction 

Obesity has become a major global public health challenge. According to the prediction of theWorld Obesity Atlas 2025, the global adult obese population will increase from 524 million in 2010 to 113 million in 2030, and the overweight/obesity rate of Chinese adults is expected to reach 41%. Metabolic diseases caused by obesity, such as insulin resistance and non-alcoholic fatty liver disease, pose a serious threat to health. Glucoraphanin (GLR), a thioglucoside found in cruciferous vegetables, whose hydrolyzed product is sulforaphane (SFN), regulates metabolism through multiple targets and provides a new direction for obesity intervention.

2. Metabolism of Glucoraphanin 

The metabolism of glucoraphanin consists of two stages: enzymatic hydrolysis and absorption. First, during chewing or digestion, plant-derived myrosinase hydrolyzes approximately 30% of GLR into SFN, and the remaining part enters the intestine and is further converted by intestinal flora such asEscherichia coli andEnterococcus faecalis. After being absorbed in the small intestine, SFN binds to glutathione through a thioether linkage reaction to form a metabolite, N-acetylcysteine derivative, which is eventually excreted in urine. However, high temperature can inactivate myrosinase, leading to reduced SFN production. Broccoli seed extract, with stable myrosinase activity, serves as an efficient supplementary source.

3. Anti-Obesity Mechanisms of Glucoraphanin 

3.1 Regulation of Oxidative Stress and Inflammation 

By activating the nuclear transcription factor Nrf2, SFN induces the expression of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), scavenges reactive oxygen species (ROS), and alleviates oxidative damage to adipose tissue. Meanwhile, SFN inhibits the NF-κB pathway, reduces the release of pro-inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and improves obesity-related chronic inflammation.

3.2 Remodeling of Lipid Metabolism 

SFN promotes fat decomposition through two pathways: Browning of white adipose tissue: It activates uncoupling protein-1 (UCP-1), increases mitochondrial thermogenesis, converts white adipose tissue into brown adipose tissue, and accelerates energy consumption. Activation of lipophagy: It induces adipocyte autophagy via the AMPK-mTOR-ULK1 signaling pathway, degrades lipid droplets, and releases free fatty acids. In addition, SFN inhibits the activity of lipogenic enzymes such as sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS), thereby reducing lipid accumulation.

3.3 Regulation of Intestinal Flora 

SFN alters the composition of intestinal flora, decreases the abundance of endotoxin-producing bacteria such asDesulfobivrionaceae, and reduces metabolic endotoxemia caused by the entry of lipopolysaccharide (LPS) into the bloodstream. At the same time, it promotes the proliferation of beneficial bacteria such asAkkermansia, enhances intestinal barrier function, and improves insulin sensitivity.

4. Pharmacological Research on the Anti-Obesity Effect of Glucoraphanin 

4.1 Evidence from Animal Experiments 

High-fat diet model: After supplementing SFN, the weight gain of mice decreased by 15%, visceral fat reduced by 20%, and hepatic steatosis was significantly alleviated. Mechanistically, SFN activates insulin signaling by inhibiting the JNK pathway, promotes hepatic glycogen synthesis, and inhibits gluconeogenesis. 

Metabolic syndrome model: After 8 weeks of intervention with glucoraphanin extract (RSG), the levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in obese mice decreased, hepatic lipid deposition reduced, and the diversity of intestinal flora significantly increased.

4.2 Human Clinical Exploration 

Short-term intervention: Fifty volunteers in Qidong, China, took 350 mg GLR/day or 25 mg SFN/day in a crossover manner. After 2 weeks, the metabolic excretion rate of pollutants such as benzene and acrolein increased by 20%-50%, indicating that it enhances detoxification capacity. 

Long-term effect: Two hundred and eighty-seven subjects drank SFN-containing beverages continuously for 12 weeks. The metabolic levels of benzene and acrolein in their blood increased significantly. Moreover, by activating the Nrf2 pathway, SFN maintained the antioxidant effect for 72 hours, which was significantly better than that of vitamin C.

5. Safety Evaluation of Glucoraphanin 

5.1 Toxicity and Side Effects 

Animal experiments showed that the median lethal dose (LD50) of glucoraphanin exceeded 5 g/kg, which was much higher than the clinically applied dose. In human studies, no serious adverse reactions were observed when 9-36 mg SFN was ingested daily, and only a small number of people experienced mild gastrointestinal discomfort such as abdominal distension and diarrhea. It should be noted that long-term high-dose intake may affect thyroid iodine uptake, so people with abnormal thyroid function should use it with caution.

5.2 Dosage Recommendation 

The daily recommended intake of water extract of broccoli seeds (containing 13%-20% GLR) is ≤1.8 g, corresponding to approximately 234-360 mg of GLR. When used as a food additive, the recommended addition amount is 0.1%-1%.

6. Conclusion and Prospect 

Glucoraphanin exerts anti-obesity effects by activating Nrf2, regulating the AMPK-mTOR pathway, and remodeling intestinal flora. Animal experiments have confirmed that it can reduce fat accumulation and improve metabolic parameters, while human studies have initially verified its safety and efficacy. However, existing studies have limitations: human trials have small sample sizes and short durations, the dosage differences among different populations (e.g., diabetic patients) and the interaction mechanism with other anti-obesity drugs remain unclear. Future research can focus on precise dosage optimization, combined intervention strategies, and dosage form development. Although glucoraphanin shows potential, more high-quality studies are needed to consolidate its clinical application foundation.

References 

[1] Bankole T, Ma T, Arora I, Lei Z, Raju M, Li Z, Li Y. The Effect of Broccoli Glucoraphanin Supplementation on Ameliorating High-Fat-Diet-Induced Obesity through the Gut Microbiome and Metabolome Interface.Mol Nutr Food Res. 2024 May;68(9):e2300856. 

[2] Nagata N, Xu L, Kohno S, Ushida Y, Aoki Y, Umeda R, Fuke N, Zhuge F, Ni Y, Nagashimada M, Takahashi C, Suganuma H, Kaneko S, Ota T. Glucoraphanin Ameliorates Obesity and Insulin Resistance Through Adipose Tissue Browning and Reduction of Metabolic Endotoxemia in Mice.Diabetes. 2017 May;66(5):1222-1236. 

[3] Xu L, Nagata N, Ota T. Impact of Glucoraphanin-Mediated Activation of Nrf2 on Non-Alcoholic Fatty Liver Disease with a Focus on Mitochondrial Dysfunction.Int J Mol Sci. 2019 Nov 25;20(23):5920.