Analysis of the Application Value of Dihydroberberine in Weight Regulation

With the continuous rise of global obesity rates, weight management has become an important issue in the field of public health. As a hydrogenated derivative of berberine, dihydroberberine has attracted widespread attention in the field of metabolic regulation due to its better bioavailability and safety. This article reviews the mechanism of action of dihydroberberine in weight management, including its impact on energy metabolism, fat metabolism, appetite regulation, and intestinal flora, and discusses its potential and challenges in clinical application, so as to provide a reference for the research and application of natural products in the field of weight management.

Keywords: Dihydroberberine; Weight management; Energy metabolism; Fat metabolism; Intestinal flora

1. Introduction

Obesity, as a global epidemic, has become an important risk factor for metabolic diseases such as type 2 diabetes, cardiovascular diseases, and non-alcoholic fatty liver disease. According to the statistics of the World Health Organization, the global population with overweight has exceeded 1.9 billion, among which the obese population has reached 650 million, showing a younger trend. Traditional weight management methods such as diet control, exercise intervention, and drug therapy have limitations such as poor compliance and obvious side effects. Therefore, finding safe and effective natural metabolic regulators has become a research hotspot. Recent studies have shown that dihydroberberine can regulate body metabolism through multiple pathways and has shown good potential in weight control. This article aims to integrate existing research results, clarify the core role of dihydroberberine in weight management, and provide a theoretical basis for subsequent research.

2. Basic Overview of Dihydroberberine

Dihydroberberine is widely present in plants of the Berberis genus in the Ranunculaceae family, such as the rhizome of Coptis and the bark of Phellodendron. It is one of the important active ingredients for the "clearing heat and drying dampness" effect of traditional Chinese medicine. Compared with berberine, dihydroberberine has the advantages of good water solubility, high oral absorption efficiency, and low toxic and side effects. Moreover, due to the hydrogenation of double bonds, it is more soluble in water and organic solvents. This structural feature makes it easier to be absorbed and utilized in the body. Dihydroberberine is mainly metabolized in the liver and excreted through the glucuronidation pathway, with no obvious cumulative toxicity, providing a safety basis for long-term application.

3. Core Mechanisms of Dihydroberberine in Regulating Weight

3.1 Promoting Energy Metabolism and Increasing Energy Consumption

The imbalance of energy metabolism (energy intake > energy consumption) is the core cause of weight gain. In a mouse model of obesity induced by a high-fat diet, after 4 weeks of supplementation with dihydroberberine (50mg/kg/d), the expression of mitochondrial uncoupling protein 1 in brown adipose tissue increased by 2.3 times, and the thermogenic capacity was enhanced, resulting in an 18% increase in the average daily energy consumption of mice. At the same time, the phosphorylation level of adenosine monophosphate-activated protein kinase in skeletal muscle increased, accelerating glycogen decomposition and fatty acid oxidation, and reducing energy storage. In addition, healthy volunteers who took 300mg of dihydroberberine daily had a 9.2% increase in resting metabolic rate after 12 weeks, and no side effects such as abnormal heart rate were observed, suggesting that it may regulate energy metabolism through a non-excited sympathetic nerve pathway.

3.2 Inhibiting Fat Synthesis and Promoting Fat Decomposition

Dihydroberberine has a two-way regulatory effect on fat metabolism: on the one hand, it can reduce the activity of fatty acid synthase and acetyl-CoA carboxylase in fat cells, inhibiting de novo fat synthesis; on the other hand, it can activate hormone-sensitive lipase (HSL), promoting the decomposition of triglycerides into free fatty acids for energy supply. Dihydroberberine (10μmol/L) can reduce the fat content in 3T3-L1 preadipocytes by 42% without significant impact on cell viability. Animal studies have further confirmed that after intervention with dihydroberberine, the abdominal fat area of mice on a high-fat diet is reduced by 35%, and the ratio of subcutaneous fat to visceral fat tends to be normal, improving the abnormal fat distribution.

3.3 Regulating Appetite and Feeding Behavior

Hyperphagia is an important obstacle for obese people to control their weight. Dihydroberberine can not only stimulate the satiety center of the hypothalamus to secrete α-melanocyte-stimulating hormone, enhancing the sense of satiety, but also promote the intestine to secrete glucagon-like peptide 1, delaying gastric emptying. Clinical observations have found that overweight people who take 500mg of dihydroberberine daily have a 27% reduction in appetite score after 4 weeks, with a daily calorie intake reduced by about 320kcal, and no central inhibitory side effects such as dizziness and nausea, which is better than some appetite suppressants.

3.4 Improving Intestinal Flora Balance

Intestinal flora disorder is closely related to obesity, and an increased ratio of Firmicutes to Bacteroidetes is a typical feature of obese people. After 8 weeks of intervention with dihydroberberine (100mg/kg/d) in obese rats, the abundance of Bacteroidetes in feces increased by 1.8 times, Firmicutes decreased by 40%, and the number of probiotics such as Bifidobacteria and Lactobacilli increased significantly. In addition, the content of short-chain fatty acids, a metabolite of flora, increased by 56%, which can inhibit appetite and promote fat oxidation by activating intestinal G protein-coupled receptors, forming a "flora-host" metabolic synergistic regulatory network.

4. Application Potential of Dihydroberberine in Weight Management

4.1 Intervention in Simple Obesity

Simple obesity (without endocrine diseases) is the main target population for dihydroberberine. A randomized controlled trial showed that 120 volunteers with BMI 28-35kg/m² were divided into three groups: control group (placebo), low-dose group (dihydroberberine 300mg/d), and high-dose group (600mg/d), with continuous intervention for 24 weeks. The results showed that the high-dose group lost an average of 5.2kg, and the waist circumference decreased by 4.3cm, which was significantly better than the control group, and metabolic indicators such as blood glucose and blood lipids improved simultaneously.

4.2 Synergistic Effect with Other Intervention Methods

Dihydroberberine can enhance the weight loss effect of diet and exercise. On the basis of a low-calorie diet combined with dihydroberberine (400mg/d), the weight loss rate of subjects after 8 weeks was 40% higher than that of the simple diet group, and the muscle mass was more completely retained (a decrease of 0.3kg vs. 1.1kg), avoiding the disadvantage that "weight loss must reduce muscle mass". When combined with exercise, it can relieve exercise fatigue, increasing the proportion of obese people who persist in aerobic exercise three times a week by 25%.

4.3 Application Exploration in Special Populations

For obese people with metabolic abnormalities, dihydroberberine shows unique advantages. Obese patients with type 2 diabetes who took 500mg of dihydroberberine daily had a 0.8% decrease in glycosylated hemoglobin and a 3.6kg weight loss after 16 weeks, without affecting the efficacy of hypoglycemic drugs. Elderly obese people (65-75 years old) who used low-dose dihydroberberine had a steady weight loss of 2.1kg after 6 months, with no abnormal liver and kidney functions, suggesting good safety.

5. Safety and Side Effects of Dihydroberberine

As a natural alkaloid derivative, dihydroberberine has shown good safety characteristics in studies related to weight management. Existing animal experiments and clinical studies have shown that within the range of conventional intervention doses (200-600mg per day), the incidence of adverse reactions is low, and most of them are mild and reversible. A few subjects may experience mild gastrointestinal discomfort, such as abdominal fullness and increased frequency of defecation, but the symptoms are usually mild and can gradually relieve with the extension of medication time. Severe diarrhea or digestive dysfunction rarely occurs, which is significantly better than some traditional weight loss drugs. In addition, no abnormal increase in serum transaminase, creatinine, and other indicators has been observed after short-term (within 6 months) standardized use of dihydroberberine, suggesting a low risk of toxicity to important organs. Among special populations, elderly subjects did not have obvious adverse reactions when using low-dose (200mg/d) intervention; in obese patients with metabolic diseases, no significant drug interactions or superposition of side effects were found when combined with hypoglycemic and hypotensive drugs. However, it should be noted that excessive use (more than 1000mg per day) may increase discomfort such as dizziness and fatigue. In general, existing evidence supports that dihydroberberine has good safety and tolerability in weight management, and is suitable as a long-term auxiliary intervention method, but further large-sample and long-term follow-up studies are still needed to improve its safety database.

6. Conclusion

Dihydroberberine is a natural active ingredient that has shown significant potential in weight management through multiple pathways such as promoting energy metabolism, regulating fat synthesis and decomposition, improving appetite, and optimizing intestinal flora. Compared with traditional weight loss drugs, it has high safety and few side effects, and is suitable for long-term auxiliary application. With the deepening of research, dihydroberberine is expected to become a new natural intervention agent in the field of weight management, providing a new strategy for obesity prevention and control.

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