Introduction
Obesity is a global health crisis, with prevalence and severity on the rise. The World Health Organization estimates that the number of overweight or obese individuals could double by 2015. While pharmaceutical drugs like orlistat, lorcaserin, and sibutramine exist for obesity treatment, their side effects often outweigh the benefits. These drugs may offer short-term improvements, but rebound weight gain and serious side effects are common after discontinuing use. Therefore, there is a need for novel anti-obesity treatments that are effective and have minimal long-term side effects.
One promising approach is using nutraceuticals, which can address the nutrient-uptake imbalance that causes obesity. An effective anti-obesity nutraceutical could be fortified with nutrient ingredients that have anti-obesity effects. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) has gained recognition for its lipid-lowering function and calorie-restriction effects, positioning it as a potential anti-obesity ingredient.
What is Resveratrol?
Resveratrol is a naturally occurring compound found in foods like red grapes, peanuts, berries, cocoa, and red wine. Resveratrol might have effects in the body, including expanding blood vessels and reducing blood clotting. It may also decrease pain and swelling, reduce levels of sugar in the blood, and help the body fight against disease. While small amounts can be obtained from these sources, supplements offer higher concentrations for potentially greater health benefits.
Potential Health Benefits of Resveratrol
Resveratrol has shown promise in multiple areas of health. Research from the National Institutes of Health indicates that it can soothe inflammation and help lower cholesterol levels. University studies suggest it can protect the brain and memory. A University of Texas team discovered that resveratrol blocks enzymes that damage cells, potentially reducing the risk of heart disease and cancer.
Resveratrol and Weight Loss: What the Research Says
Excitement about resveratrol's weight loss potential began with a Harvard study demonstrating that the antioxidant helped reverse the effects of overeating in obese mice. The mice experienced increased energy expenditure, improved blood sugar and insulin levels, and extended lifespans.
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Scientists have since been investigating these findings, with recent research focusing on the role of beneficial gut bacteria. Evidence suggests that resveratrol may stimulate the growth of slimming strains of bacteria in the digestive tract, which may play a role in weight management.
Furthermore, studies indicate that resveratrol enhances the ability of muscles to absorb glucose from food, leading to more calories being directed to muscle tissue and fewer being stored as fat. Experiments at the University of Georgia found that resveratrol reduces fat cells' ability to store fat by nearly 80% and promotes their disintegration.
Resveratrol-Enriched Rice: A Novel Approach
One research effort in plant science has focused on creating transgenic cereal plants that accumulate resveratrol in their grains, offering a convenient way for dietary consumption.
In a previous study, researchers created resveratrol-enriched rice by transferring the stilbene synthase (STS) gene to Dongjin rice. One line of these plants, DJ-526, exhibited excellent agricultural characteristics and accumulated a large quantity of resveratrol in its grain.
The Resveratrol-Enriched Rice DJ-526
The parental plant of the resveratrol-enriched rice DJ-526, Oryza sativa japonica variety Dongjin rice, has grains rich in fiber and polyphenols with anti-obesity activity. Therefore, the resveratrol-enriched rice DJ-526 accumulating a large quantity of resveratrol in its grains in addition to fiber and polyphenols could be an ideal nutraceutical to treat obesity and its related diseases.
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The grains of the resveratrol-enriched rice DJ-526 contained a large amount of resveratrol. One of the current challenges in creating transgenic plants is to make a desired gene or genes functional specifically in the targeted part of the transgenic plants. It has been well known that piceid are accumulated as one of the major compounds in the plants having either natural or transgenic resveratrol biosynthetic pathways. The goal was to select a transgenic rice plant accumulating mostly resveratrol rather than piceid in its grain because the health benefits of piceid are insignificant and long-term effect on the physiology of human has not been completely understood.
After identifying the candidate T1 transgenic plants, the candidate T1 transgenic plants were transplanted into a rice paddy. By the thorough analyses of the metabolic profile of the resveratrol and its related metabolites in the every portion of the transgenic plants, a transgenic plant accumulating large quantity of resveratrol in its grain, DJ-526 was selected.
The grains of the resveratrol-enriched rice DJ-526 contained a relatively high quantity of resveratrol compared with piceid, whereas the high quantity of piceid compared with resveratrol was observed in the leaves. The resveratrol quantity in the grain of the resveratrol-enriched rice DJ-526, 1.4 μg/g, were close to the typical levels of resveratrol quantity in high-quality red wine, 0.8-5.8 μg/mL. The preferential distribution of the two related metabolites, high accumulation of resveratrol in the edible grains but low in the leaves, makes the resveratrol-enriched rice DJ-526 ideal as a resveratrol-enriched cereal plant.
Animal Studies Using Resveratrol-Enriched Rice DJ-526
Animal experiments were conducted to determine whether the resveratrol-enriched rice DJ-526 is effective for obesity and its related diseases through a synergistic combination of the innate anti-obesity property of Dongjin rice and the lipid-lowering property of transgenic resveratrol. The animal experiments showed that the resveratrol-enriched rice DJ-526 has strong anti-obesity effects and significantly improved all aspects of obesity-related diseases, suggesting its potential as an anti-obesity nutraceutical.
To investigate whether the resveratrol-enriched rice DJ-526 has an anti-obesity effect through a synergistic effect of the innate characteristics of Dongjin and the transgenic resveratrol, the efficacy of the resveratrol-enriched rice DJ-526 on obesity was examined using an in vivo mouse model. The C57BL/6 inbred mice with diet-induced obesity were fed the high fat diet (HFD) for 12 weeks in the control group or a modified HFD in the experimental group, in which the carbohydrate source was replaced with either Dongjin rice or the resveratrol-enriched rice DJ-526. The food consumption rate was the same among different mouse groups during the experimental period.
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Body weights were greatly reduced in mice fed with the resveratrol-enriched rice DJ-526 by 20.0% compared to the control, slightly greater than Dongjin rice group. The total, visceral and subcutaneous fat volumes in the resveratrol-enriched rice DJ-526 group were 17.4%, 15.2% and 2.3%, respectively, which were significantly lower than the fat volumes from the control (25.6%, 20.2% and 4.0%, respectively) and the Dongjin group (23.9%, 18.9% and 3.0%, respectively). The representative images of the micro-CT image analyses on abdominal fat deposition clearly indicated that the total, visceral and subcutaneous fat accumulation was the lowest in the resveratrol-enriched rice DJ-526 group compared with the other treatments. Based on the experimental results of the efficacy of the resveratrol-enriched rice DJ-526 on body weight and abdominal fat volumes, it was concluded that the resveratrol-enriched rice DJ-526 had an excellent anti-obesity effect.
Improvement in Lipid Profiles and Blood Glucose Levels
The consumption of the resveratrol-enriched rice DJ-526 significantly improved lipid profiles and blood glucose levels with clear anti-obesity effect in animal experiments under high-fat diet. The consumption of Dongjin rice resulted in some improvements in lipid profile and blood glucose levels compared to the control, as expected from its endogenic nature. More importantly, the consumption of the resveratrol-enriched rice DJ-526 significantly improved the lipid profiles as well as blood glucose. The consumption of the resveratrol-enriched rice DJ-526 lowered total cholesterol by 17.9% and LDL-cholesterol by 67.3%, while increasing HDL-cholesterol by 34.2% compared to the control. Also, the consumption of the resveratrol-enriched rice DJ-526 lowered blood glucose by 13.9% and triacylglycerol by 49.3% compared to the control.
Meta-Analysis of Resveratrol Supplementation and Weight Loss
A systematic review and meta-analysis of 36 randomized controlled trials (RCTs) examined the impact of resveratrol intake on weight loss. The analysis revealed that resveratrol supplementation significantly decreased body weight, body mass index (BMI), fat mass, and waist circumference. Additionally, it significantly increased lean mass.
Specifically, the meta-analysis showed that resveratrol supplementation significantly decreased body weight in obese patients compared with other diseases and type 2 diabetes mellitus.
Recommended Dosage and Considerations
Most experts recommend a daily dose of 150 to 250 mg of resveratrol, which is significantly more than can be obtained from food sources alone. Choose a supplement labeled trans-resveratrol, as it is the most potent form.
To enhance the effects of resveratrol, combine it with other antioxidants through a diet rich in plant foods or a multi-antioxidant supplement.
Potential Side Effects and Interactions
People often consume resveratrol in small amounts in foods. Resveratrol supplements are possibly safe when taken by mouth in doses up to 1500 mg daily for up to 3 months. Higher doses of up to 2000-3000 mg daily have been used safely for 2-6 months, but these higher doses are more likely to cause stomach upset. Resveratrol is possibly safe when applied to the skin for up to 30 days and when sprayed into the nose for up to 4 weeks.
Resveratrol might slow blood clotting. Taking resveratrol along with medications that also slow blood clotting might increase the risk of bruising and bleeding.
Resveratrol might change how quickly the liver breaks down some medications. This could change the effects and side effects of these medications.
Precautions
Resveratrol is likely safe when used in amounts found in some foods during pregnancy and breast-feeding. However, during pregnancy and breast-feeding, the source of resveratrol is important. Resveratrol is found in grape skins, grape juice, wine, and other food sources. Wine should not be used as a source of resveratrol when pregnant or breast-feeding.
People often consume resveratrol in small amounts in foods. But there isn't enough reliable information to know if it safe to take by mouth in larger amounts for children. Resveratrol is possibly safe in children when sprayed in the nose for up to 2 months.
Resveratrol might slow blood clotting and increase the risk of bleeding in people with bleeding disorders.
Resveratrol might act like estrogen. If you have any hormone-sensitive condition such as breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids that might be made worse by exposure to estrogen, don't use resveratrol.
Resveratrol might increase the risk of bleeding during and after surgery. Stop using resveratrol at least 2 weeks before a scheduled surgery.
Resveratrol-Rich Meal Ideas
To boost the power of resveratrol, incorporate resveratrol-rich foods into your diet alongside supplementation. Enjoy chocolate, berries, nuts, and wine with foods rich in any antioxidant (fruit, veggies, seeds, even cereal and popcorn).