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Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight loss
Diabetes, Obesity and Metabolism
Abstract
The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels.
A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30-60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking.
At the end of 8 weeks, body weight and BMI decreased by 5-6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C.
The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.
... It also decreased blood fat and "bad" LDL cholesterol levels (Kumar et al., 2013) [13] . In addition, a study in moderately obese people showed that Gymnema extract decreased triglycerides and bad "LDL" cholesterol by 20.2% and 19%, respectively and interestingly it increased "good" HDL cholesterol levels by 22% (Preuss, 2004) [20] . High levels of "bad" LDL cholesterol and triglycerides are risk factors for heart disease. ...
... It also decreased blood fat and "bad" LDL cholesterol levels (Kumar et al., 2013) [13] . In addition, a study in moderately obese people showed that Gymnema extract decreased triglycerides and bad "LDL" cholesterol by 20.2% and 19%, respectively and interestingly it increased "good" HDL cholesterol levels by 22% (Preuss, 2004) [20] . High levels of "bad" LDL cholesterol and triglycerides are risk factors for heart disease. ...
... In another study, rats on a high fat diet that were fed a Gymnema extract gained less weight (Luo 2007, Kumar et al., 2013 [5,13] . Moreover, a study in 60 moderatelyobese people taking a Gymnema extract found a 5-6% decrease in body weight, as well as reduced food intake (Preuss 2004) [20] . By blocking sweet receptors on human taste buds, Madhunasini may cause human to eat fewer sweet foods and consume fewer calories. ...
Diabetes mellitus (DM) results from the inability of the pancreas to produce sufficient insulin or weakened cellular response to the insulin produced, which leads to hyperglycemia. Current treatments of DM focus on the use of oral hypoglycemic drugs such as acarbose, alphaglucose inhibitors, sulphonylureas, thiazolidinediones, and biguanides to control blood glucose levels. However, these medications are known to have various side effects in addition to their bioavailability, efficacy, and safety concerns. These drawbacks have increased interest in the anti-diabetic potential of plant-derived bioactive compounds. Madhunasini (Gymnema sylvestre, Asclepiadaceae) is regarded as one of the plants with potent anti diabetic properties. This plant is also used for controlling obesity in the form of Gymnema leaf powder. The active compound of the plant is a group of acids termed as gymnemic acids. It has been observed that there could be a possible link between obesity, Gymnemic acids and diabetes. Gymnema is most often consumed in Western medicine in the form of pills or tablets, making dosage easier to control and monitor. It can also come in the form of leaf powder or extract.
... In recent years, it has been reported in anti-obesity studies that melatonin or niacin applications limit obesity and regulate physiological and metabolic damage due to obesity (Preuss et al., 2004;Cantó et al., 2012;Mostafavi et al., 2017;Heo et al., 2018;Yin et al., 2018;Ye et al., 2019;Xiang et al., 2020;Mendes et al., 2021). However, there is no study evaluating and comparing niacin and melatonin administration on anti-obesity. ...
... In addition, Xiang et al. (2020) concluded that niacin supplementation could improve lipid profiles for patients with T2DM without affecting glycemic levels (Xiang et al., 2020). In addition, Preuss et al. (2004) state that the combination of niacin-bound chromium can be used as a safe weight loss formula (Preuss et al., 2004). Similarly, weight loss was observed in the two groups in which niacin supplement was applied together with exercise in our study. ...
... In addition, Xiang et al. (2020) concluded that niacin supplementation could improve lipid profiles for patients with T2DM without affecting glycemic levels (Xiang et al., 2020). In addition, Preuss et al. (2004) state that the combination of niacin-bound chromium can be used as a safe weight loss formula (Preuss et al., 2004). Similarly, weight loss was observed in the two groups in which niacin supplement was applied together with exercise in our study. ...
In recent years, the increase in obesity in the world has led to the development of new strategies in combating obesity. In the present study, it was aimed to investigate the effect of niacin and melatonin supplements to combat obesity in rats as a model organism. Treadmill exercise was performed on rats after niacin and melatonin supplementation for 10 days. In each group, weight loss was observed at the end of the 10 days exercise. In this study, it was observed that niacin supplementation leading to weight loss in rats that had treadmill exercise when compared to the control group. In addition, it was found that the weight loss observed in melatonin+niacin supplement was higher than niacin supplement only. It was found that the weight loss observed in the group given melatonin+niacin supplement was higher than the weight loss observed in niacin supplement only. As a result, niacin and melatonin supplementation can be recommended before exercise to combat obesity.
... Rats fed the highest amount of extract, and therefore receiving the highest dose of HCA (154 mmol HCA/kg diet), significantly decreased epididymal fat accumulation, compared to the other groups. Table 1 presents a summary of the results obtained in 20 reported intervention studies in humans [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. In 12 studies, statistically significant reductions in body weight were observed [14,15,[18][19][20][21][22][26][27][28]30,31]. ...
... Table 1 presents a summary of the results obtained in 20 reported intervention studies in humans [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. In 12 studies, statistically significant reductions in body weight were observed [14,15,[18][19][20][21][22][26][27][28]30,31]. Conversely, the supplementation turned out to be ineffective in the remaining studies [13,16,17,[23][24][25]29,32]. ...
... In the studies where significant weight loss was observed, the average value was between 2 and 6 kg in 2-4 months, with the exception of one where a loss of 14 kg was induced in 6 months [31]. Interestingly, in 11 studies [19][20][21]23,24,26,27,[29][30][31][32], significant reductions in other parameters, such as waist and hip circumference, triglycerides, cholesterol and glucose were also observed regardless of body weight loss. It was specified in the vast majority of the studies that the supplement should be consumed approximately half an hour before meals. ...
Nowadays, obesity is one of the great nutritional problems facing public health. The prevalence of this pathology has increased in a worrying way over recent years, currently reaching epidemic proportions. In this context, nutritional supplements are presented as a therapeutic alternative to which more and more people are turning to. Nutritional supplements to lose weight based on the Garcinia plant, specifically on Garcinia cambogia, are commonly used. The active principle of this plant to which these properties have been attributed, is hydroxycitric acid (HCA). The aim of the present review is to gather reported data concerning the effectiveness of nutritional supplements based on Garcinia extracts on weight loss and their possible negative effects. Contradictory results have been observed regarding the effectiveness of the supplements. While statistically significant weight loss was observed in some studies, no changes were found in others. Regarding safety, although Garcinia supplements have been revealed as safe in the vast majority of the studies carried out in animal models and humans, some cases of hepatotoxicity, serotonin toxicity and mania have been reported. In conclusion, the results suggest that Garcinia-based supplements could be effective in short-term weight loss, although the data are not conclusive. In addition, the safety of the complement should be further studied.
... Every week, a digital weighing scale was used to record the animals' body weight. Researchers measured the weights of the pancreas, liver, and kidneys after the rats were euthanized so they could evaluate the efficacy of therapies and the damage that diabetes had caused to these organs [13][14][15]. ...
... After that, they were embedded in paraffin, sectioned at a thickness of 5 µm, and stained with hematoxylin. Under a light microscope, the stained sections were checked for histopathological changes, such as β-cell destruction, inflammatory changes, and tissue regeneration [15][16][17]. ...
Introduction: Hyperglycemia due to insulin resistance or decreased insulin production characterizes diabetes mellitus, a chronic metabolic condition. Due to its promise in managing diabetes with fewer adverse effects, herbal treatments have received interest. The anti-diabetic effects of Gymnema sylvestre and Momordica charantia have long made them popular medicinal herbs. Their effectiveness in rats with diabetes caused by streptozotocin (STZ) is the focus of this investigation. Materials and Methods: The use of streptozotocin (50 mg/kg, intraperitoneally) was used to produce diabetes in Wistar rats. Rats were randomly assigned to one of five groups: normal control, diabetic control, G. sylvestre (250 mg/kg), M. charantia (250 mg/kg), or combination (250 mg/kg each extract). In this four-week trial, researchers looked at participants' oxidative stress markers, body weight, lipid profiles, and fasting blood glucose (FBG) levels. Additionally, pancreatic tissue was examined histopathologically. Results: G. sylvestre and M. charantia both considerably decreased FBG levels when contrasted with the diabetic control group (p < 0.05). The hypoglycemic impact was particularly noticeable in the combo treatment. Lipid profile indicators, such as total cholesterol and triglycerides, improved in the treated groups. The levels of antioxidant enzymes (SOD, CAT, and GSH) were found to be significantly higher, and histological analysis showed that the treated groups had regenerated pancreatic β-cells. Conclusion: According to the results, both Momordica charantia and Gymnema sylvestre have strong anti-diabetic effects, but the combination is even more effective. Possible supplementary use of these herbal extracts in the treatment of diabetes is being considered. To confirm their medicinal efficacy, additional clinical trials are necessary.
... This process is purported to support fat metabolism and energy production, particularly during exercise, which may potentially enhance endurance and facilitate fat loss. While some preliminary research suggests the use of maca and gymnema sylvestre leaf extract, common ingredients in thermogenic supplements, potentially benefitting endurance and weight management, more research is needed to clarify their specific roles and effectiveness in enhancing physical performance and body composition [32][33][34]. ...
... Green tea catechins and L-carnitine have been shown to further enhance fatty acid transport into mitochondria, optimizing their use as an energy source [24,28,31]. Additionally, maca and gymnema sylvestre leaf extract may contribute metabolic or hormonal regulatory effects that support these processes [32][33][34]. Together, these mechanisms sustain elevated energy expenditure and fat utilization, which could explain the greater reductions in fat mass and body fat percentage observed in the TS group compared to the placebo group. In contrast, the placebo group relied solely on the effects of resistance training to improve body composition, lacking the metabolic enhancements provided by thermogenic supplement ingredients. ...
Featured Application
This study demonstrates that chronic ingestion of a thermogenic supplement in conjunction with a resistance training program can significantly enhance fat loss while maintaining strength gains in trained individuals. These findings may inform the development of targeted supplementation strategies for individuals seeking to optimize fat loss while engaging in resistance training.
Abstract
As interest in weight management and metabolic health grows, thermogenic supplements have gained attention for their potential to enhance caloric expenditure and fat loss. This study aimed to investigate the effects of chronic thermogenic supplement ingestion on body composition and strength outcomes during an 8-week periodized resistance training program. Thirty-four resistance-trained males were randomized into thermogenic supplementation (TS) (n = 18) or placebo (n = 16) groups in a double-blind, placebo-controlled design. Participants consumed thermogenic or placebo capsules daily, with dosage adjusted midway through the intervention. Body composition was assessed using ultrasound-based body fat analysis, and strength was measured via bench press and back squat one-repetition maximum (1-RM) tests. Results indicated that TS experienced significantly greater reductions in fat mass (−0.65 kg vs. 0.12 kg, p = 0.029) and body fat percentage (−0.89% vs. −0.08%, p = 0.039) compared to the placebo. Both groups demonstrated significant and comparable improvements in squat (TS: 16.87 kg, placebo: 18.47 kg) and bench press strength (TS: 7.80 kg, placebo: 7.13 kg). These findings suggest that thermogenic supplement ingestion can enhance fat loss without impeding strength adaptations. Future research should explore the dose–response effects and applicability of thermogenics in different populations and over extended durations.
... The anti-obesity effect of HCA can also be addressed through serotonin regulation [45]. In human therapeutic trials, Preuss et al. [54] stated that HCA reduced hunger, In an in vivo study, the composition of water extract of G. atroviridis fruit and 50% ethanol extract of K. angustifolia, in a ratio of 2:1, effectively reduced the body weight of fattened mice by approximately 12.6%, at a dose of 13.44 mg/20 g BW [52]. In another study, Achmadi [53] applied G. atroviridis in an in vivo investigation on rats. ...
... The anti-obesity effect of HCA can also be addressed through serotonin regulation [45]. In human therapeutic trials, Preuss et al. [54] stated that HCA reduced hunger, weight loss, and plasma leptin levels, while increasing serum serotonin levels and improving lipid profile. In addition, Kim et al. [55] indicated that the potential of HCA to reduce body weight increase was possibly related to its combined effects on the metabolic and serotonin pathways. ...
Obesity is characterized by the accumulation of excessive fat, potentially leading to degenerative diseases. Pancreatic lipase, an enzyme responsible for converting 50–70% of dietary fat into monoglycerides, free fatty acids, and various other smaller molecules, plays a crucial role in fat metabolism. Therefore, this study aimed to review selected Indonesian medicinal plants with the potential to inhibit the activity of the pancreatic lipase enzyme. The results showed that kunci pepet (Kaempferiae angustifolia Rosc.), asam gelugur (Garcinia atroviridis), temulawak (Curcuma xanthorrhiza), jombang (Taraxacum officinale F. H. Wigg), pegagan (Centella asiatica), and pala (Myristica fragrans) had strong inhibitory effects, exceeding 50% for both in vitro and in vivo studies. Therefore, further studies are needed to explore the potential of these medicinal plants as anti-obesity treatments.
... HCA is widely utilized in supplements designed for weight loss and weight management. Several studies on HCA, either alone or in combination with other natural ingredients, have demonstrated its beneficial effects for weight loss (Preuss et al. 2004;Roy et al. 2004;Kim et al. 2008;Leonhardt and Langhans 2002). Most of the supplements contain about 60% of HCA. ...
... Gymnema extract has also been used in combination with other plant extracts especially HCA-SX extract from Garcinia to serve as an effective weight-loss formula. A daily dose of G. sylvestre extract (400 mg) in combination with HCA-SX (4667 mg) and niacinbound chromium (4 mg), over a period of eight weeks, resulted in significantly reduced food intake and serum leptin levels, and a concomitant reduction in cholesterol, low-density lipoproteins, triglycerides compared to the control (Preuss et al. 2004). ...
Overweight and obesity are global health challenges associated with an increased risk of life-threatening comorbidities. Whereas a healthy diet and a lifestyle with a sufficient amount of exercise is the first recommendation to avert complications arising from overweight, a variety of prescription medicines is recognised as potential aids in weight loss. However, concerns about adverse effects of many prescription weight-loss agents has made that may drugs are now prohibited in some countries, though not in all countries. This has given rise to a clandestine market which has made proper monitoring of safety of products on sale increasingly complex. In addition to pharmaceutical products, a wide range of food substitutes or food supplements that are marketed as aids in weight loss is available. Regulation of food ingredients is considerably less stringent than regulation for pharmaceutical products; whereas pharmaceutical companies need to provide evidence of safety and efficacy before they are allowed marketing of any products, manufacturers of herbal and dietary supplements are just expected to ensure safety of their products. A sustainable reduction in food intake can be a major challenge, and people on weight-loss programmes have to fight cravings and hunger pangs. Appetite suppression-based therapies are the novel and promising treatments to control obesity. Recently, the peptide Semaglutide (Wegovy®, Ozempic®) has emerged as a very popular appetite suppressing prescription drug, which is administered by injection, though oral formulations have been developed too. Appetite suppressing herbal supplements have often been used traditionally since ages and are therefore generally regarded as safe. The aim of present review is to reflect on the most popular herbal supplements that are currently marketed as appetite suppressants, and that are widely promoted as aids in weight loss exercises. Notably, members of the family Apocynaceae, e.g. Caralluma spp. and Hoodia spp. contain pregnane glycosides that have been shown to restore sensitivity to the appetite suppressant hormone leptin in obese mice. The anti-obesity effect of Garcinia spp. (Clusiaceae) has been attributed to the presence of hydroxycitric acid (HCA), which inhibits fatty acid and triglyceride biosynthesis. In addition, HCA administration has been shown to increase serotonin levels, which in turn results in reduced appetite. A similar mechanism of action is seen with extracts of Griffonia simplicifolia (Fabaceae) that are particularly rich in the serotonin precursor 5-hydroxytryptophan. A third mechanism of action is seen in Gymnema sylvestre (Apocynaceae) which contains gymnemic acids that selectively inhibit oral sweet taste sensation in humans, thus lessening the appeal of sweets and pastries.
... According to Lewis and Neelekantan (1965) [14] , hydroxycitric acid (HCA) is a key organic acid that predominates in the fruit rinds of G. gummi-gutta. HCA helps to reduce obesity by suppressing appetite (Preuss et al., 2004;Kovacs et al., 2006) [19,12] and enhancing energy outlay (Leonhardt & Langhans, 2002) [13] . The fleshy fruit rind of the tree is the richest natural source of potential anti-obesity plant metabolite (-)-Hydroxycitric acid (HCA) along with minute quantity of citric, tartaric, and malic acids (Lewis & Neelekantan, 1965;Jayaprakash & Sakaraiah, 2000) [14,8] . ...
... According to Lewis and Neelekantan (1965) [14] , hydroxycitric acid (HCA) is a key organic acid that predominates in the fruit rinds of G. gummi-gutta. HCA helps to reduce obesity by suppressing appetite (Preuss et al., 2004;Kovacs et al., 2006) [19,12] and enhancing energy outlay (Leonhardt & Langhans, 2002) [13] . The fleshy fruit rind of the tree is the richest natural source of potential anti-obesity plant metabolite (-)-Hydroxycitric acid (HCA) along with minute quantity of citric, tartaric, and malic acids (Lewis & Neelekantan, 1965;Jayaprakash & Sakaraiah, 2000) [14,8] . ...
Forests are a rich reserve of compounds that can be used as pharmaceuticals and nutraceuticals. The genus Garcinia, which belongs to the Clusiaceae family, has about 200 species that are found throughout the world's tropics, mostly in Asia, Africa, and Polynesia Garcinia gummi-gutta (L) Rob. is the most commercially exploited for organic acids with its vast economic importance worldwide. Hydroxycitric acid (HCA) is known to have excellent anti-obesity property. Field study was conducted to determine the effect of different locations and its site factors on organic acid content of G. gummi-gutta fruits in 9 different sites of Uttara Kannada, Karnataka. A statistically significant influence of sites conditions on the organic acid content. The Organic acids were found higher in site S1(with altitude 646.3 m MSL, high precipitation and average temperature of 24 ℃), the highest of 7.85±0.23% (-)-Hydroxycitric acid lactone (HCA-L) with the average 7.15±0.57% and 21.52±1.28% of HCA with the average of 18.47±1.50% was found respectively. The HCA and HCA-L had very strong positive correlation (r = 0.84 to 0.98) with site factors (except mean annual temperature).
... Random sequence generation and selective reporting of participants were mentioned in all included trials, and all of them had a low risk of bias. Furthermore, in the case of allocation concealment four trials had unclear risk of bias 6,9,18,19 , and the others had a low risk of bias 10,16,17,20 . Moreover, one study had a high risk of bias regarding incomplete outcome data 6 , and two studies 16,18 had a high risk of bias for another source of bias. ...
... Furthermore, the improving effect of GC increased in the study population ≥ 50. When 2800 mg/day HCA was administered to participants, a 17.1 % reduction in serum leptin level was found after 4 weeks which doubled following 8 weeks 17 . Similar findings were reported by Preuss et al. 16 . ...
... The phenolic compounds present in grape seed could inhibit hypertrophy and adipogenesis in the process of visceral white adipose tissue lipolysis activation [21], and can also elevate fat oxidation in the liver [22]. Moreover, they can slow down fat absorption and food digestion [23,24], while decreasing appetite and food ingestion at the same time [24,25]. ...
... Moreover, grape seed extract could delay the rate of absorption and decrease food digestion, both of which can decrease weight gain [23,24]. Also, it is hypothesized that grape seed extract could reduce appetite and food consumption [24,25]. It was reported in a study on obese individuals that grape seed extract could decrease neuropeptide Y (NPY), which is an important brain-derived peptide that can increase food consumption and fat storage [12]. ...
Introduction:
There is a growing interest in the considerable benefits of grape products intake, as some studies have indicated that they may improve cardiometabolic risk factors. However, the widespread impact of grape products on the anthropometric indices is not fully resolved.
Method:
The purpose of this systematic review and meta-analysis was to examine the effects of grape products intake on anthropometric indices in adults. Randomized controlled trials (RCT) examining the effects of grape products intake on anthropometric indices, published up to December 2021, were identified through PubMed, SCOPUS, and ISI Web of Science databases. 30 studies with 35 effect sizes, including 1284 participants (708 cases and 576 controls), were included and analyzed using a random-effects model to calculate weighted mean differences (WMDs) with 95% confidence interval (CI).
Result:
The outcomes have revealed grape products intake to significantly decrease body weight (p = 0.001) and body mass index (p = 0.004) in obese participants, and also, a greater effect was observed when grape seed extract was used.
Conclusion:
Our study suggests that grape products intake may help to decrease body weight in obese participants. Future large RCTs with longer duration and obese populations are needed to expand our findings.
... The hydroalcoholic extract from G. cambogia zone of inhibition on various bacterial strains ranged in size from 10 mm to 17 mm. The concentrations with the highest antibacterial activity against IC 50 53.88 g/mL is the value of the G. cambogia fruit extract. It is common knowledge that tissue protein denaturation results in inflammatory situations. ...
... cambogia supplement's ability to fight obesity. 50 Despite the fact that G. cambogia and supplements containing G. cambogia are most well-known for its ability to help people lose weight, numerous studies have shown that G. cambogia also has anti-inflammatory, anti-diabetic, antioxidant, antimicrobial, anti-ulcer, and hepatoprotective properties. ...
Background: Natural substances that were initially obtained from plants were once regarded as a beneficial source of possible medicinal agents and were recognized as crucial in the development of human diseases. The current study sought to determine whether hydroalcoholic extracts of Garcinia cambogia plant fruits included any bioactive substances. Materials and Methods: The plant fruits were collected, shade-dried, ground into a fine powder, and then extracted using Soxhlet extractors and organic solvents. After that, the extracts were examined for the presence of phytochemicals using GC-MS/HPTLC, antioxidant, anti-inflammatory, and antibacterial techniques. According to the GC-MS studies, the hydroalcoholic extracts of G. cambogia contained 25 bioactive components. Results: The secondary metabolites identified in the plant, discovered by GCMS/HPTLC, are what give the plant extracts their powerful medicinal qualities. The results of the antimicrobial activity demonstrated outstanding antioxidant and anti-inflammatory properties as well as effective dose-dependent inhibitory activity against all of the tested species. Conclusion: The current study provided early data on the bioactive components present in G. cambogia fruit extracts, which have outstanding antimicrobial, antioxidant, and anti-inflammatory action, which could provide a significant platform for pharmaceutical companies to create different Garcinia species-based medications.
... Ramkumar et al. (2009) were also reported weight reduction in rodents by gymnema dietary application. Clinical data suggests that a mixture of G. sylvestre, fenugreek, vitamin C, chitosan and niacin-chromium complex as dietary supplement reduced the body weight (Preuss, 2004;Woodgate and Conquer, 2003). also reported the reduced weight and diabetes Millets with administration of G. sylvestre extract. ...
... Combination of G. sylvestre extract plus hydroxycitric acid treatment resulted in reduced weight, BMI, markers of urinary fatty acid oxidation, and lipid content (Pothuraju, 2014). Joffe (2001), Preuss (2004), and Shanmugasundaram (1990a) investigated the antidiabetic role of gymnemic acid with an extract concentration of 200 to 400 mg. Low HbA1c, FBG, insulin resistance, kidney function, and apolipoprotein B were reported in the patients medicated with G. sylvestre . ...
... Ramkumar et al. (2009) were also reported weight reduction in rodents by gymnema dietary application. Clinical data suggests that a mixture of G. sylvestre, fenugreek, vitamin C, chitosan and niacin-chromium complex as dietary supplement reduced the body weight (Preuss, 2004;Woodgate and Conquer, 2003). also reported the reduced weight and diabetes Millets with administration of G. sylvestre extract. ...
... Combination of G. sylvestre extract plus hydroxycitric acid treatment resulted in reduced weight, BMI, markers of urinary fatty acid oxidation, and lipid content (Pothuraju, 2014). Joffe (2001), Preuss (2004), and Shanmugasundaram (1990a) investigated the antidiabetic role of gymnemic acid with an extract concentration of 200 to 400 mg. Low HbA1c, FBG, insulin resistance, kidney function, and apolipoprotein B were reported in the patients medicated with G. sylvestre . ...
Diabetes mellitus is one of the world's significant wellness issues, affecting the urban population more than the rural areas. The prevalence of this disease is increasing speedily day by day. Effective regulation of blood glucose levels is the most critical factor in decreasing the dangers of diabetic complexities. Chemically synthesized anti-diabetic drugs available in the market have many side effects; therefore, plant-derived substances may provide a better alternative medicine to combat diabetes. These natural molecules are presumed to be effective, economical as well as with no side effects. Among different accessible plants, garlic (Allium sativum), a typical cooking flavor, and a long history as a people cure have anti-diabetic potential. According to several reports, garlic's antiglycation, antioxidative, and anti-inflammatory properties have been related to its function in preventing diabetes. Notwithstanding, there is no standard concession to utilizing garlic for anti-diabetic purposes, principally due to less logical proof from human examinations and discrepant information from animal studies.
A promising approach to cure this disease by garlic plant molecules focuses throughout this chapter. In this book chapter, the authors collected the scientific evidence available throughout the various experimental platforms and literature related to the garlic plant's functional role in improving the blood sugar level of diabetic patients. This book chapter focuses on the pharmacology, secondary metabolite profiling, ingredients of garlic plant with insulin-mimetic activity, and its health benefits. Garlic supplements are useful in treating diabetic patients, and this chapter content may disclose a path for the researchers to combat this disease in the future.
Keywords: Anti-diabetic; diabetes mellitus; insulin; Allium sativum; insulin secretagogue; metabolic syndrome
... Serum leptin levels were reduced by 44.3% and 39.2%, respectively, in these two groups. It is unclear whether the greater weight loss observed was due to the presence of the combination of G. sylvestre, niacin-bound chromium, or the effectiveness of the combination of these elements [122]. An acute and subacute toxicity study in rats using crude extracts and fractions of the plant showed that subacute doses of 300 and 600 mg/kg body weight may be harmful to the liver and kidneys. ...
... For six months, six to fifteen drops of Gymnema sylvestre "Q" were taken twice or four times a day with 1/4 cup of water [18]. •Weight loss: extract (GSE; 400 mg) has been investigated in conjunction with niacin-bound chromium (NBC; 4 mg) and a water-soluble, calcium-potassium salt of (−)-hydroxycitric acid (HCA-SX) (4,667 mg) [19]. An overview of Gymnema sylvestre and its claims in different regions of India is provided in the following Table 1 [20]. ...
Abstract: Gymnema sylvestre, commonly known as Gudmar and belonging to
the Asclepiadaceae family, has a rich history in Ayurvedic medicine. It is
traditionally used to address various health issues such as kapha, pitta
imbalances, ulcers, eye conditions, diabetes, and phlegm-related disorders
when combined with flowers and bark. The herb is utilized in different dosing
forms for managing diabetes and weight loss. Its phytochemical composition
includes compounds like stigmasterol, triterpenoid saponins, Gymnemic acids,
and gymnema saponins. Gymnemic acid, a key component, demonstrates anti�diabetic properties through diverse mechanisms. It showcases a range of
functional and pharmacological properties, including anti-diabetic, anti�microbial, anti-inflammatory, dental care, anti-fungal, and anti-obesity activities.
It also shows potential in addressing the link between obesity, diabetes, and
Gymnemic acid, along with benefits for the gastrointestinal tract and as a snake
venom antidote. The herb holds promise for future applications and research in
various health-related areas.
... The use of a water-soluble extract of GS leaves (400 mg/day) in patients with T2DM resulted in lower levels of glycosylated hemoglobin and glycosylated plasma protein than in controls, suggesting that GS increases endogenous insulin, possibly by regenerating the remaining β-cells in T2DM [80]. Another study showed that GS (400 mg for 8 weeks) combined with bioavailable (-)-hydroxycitric acid and niacin-bound chromium (4 mg for 8 weeks) lowered body weight, BMI, food intake, total cholesterol, LDL, triglycerides, and serum leptin levels [81]. GS has also been proposed as a nutraceutical therapy for metabolic syndrome [82]. ...
Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. Methodology: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. Results: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. Conclusion: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.
... Similar studies carried out on rats showed that aqueous extract of G. sylvestre resulted in decreased body weight of rats while methanolic extract resulted in increased body weight of rats (Pothuraju et al., 2014). Another study carried out on obese people showed that G. sylvestre extract treatment for 8 weeks resulted in a significant decrease in body weight (Preuss et al., 2004). Our study results are also consistent with the findings of another study carried out on alloxan-induced diabetic rats (Kumar et al., 2012). ...
The current study aimed to explore the anti‐diabetic effect of aqueous extracts of Gymnema sylvestre , Trigonella foenum‐graecum and mixture of both the plants in alloxan‐induced diabetic rabbits. A total of 30 rabbits were grouped into six equal groups as: normal control, diabetic control, diabetic treated with 300 mg/kg body weight (bw) G. sylvestre , diabetic treated with 300 mg/kg bw T. foenum‐graecum , diabetic treated with 300 mg/kg bw mixture of both the plants and diabetic treated with 500 mg/kg bw metformin for 4 weeks. Diabetes was induced to all the study group animals except normal control by intravenous administration of alloxan monohydrate (80 mg/kg bw). Blood glucose was measured by glucometer and other biochemical parameters were determined through various kit methods. Serum insulin was measured through ELISA kit method. Results showed that both the plants and metformin significantly ( p < .05) decreased the fasting blood glucose. Hypoglycemic activity of aqueous extract of G. sylvestre and metformin was found slightly higher than aqueous extract of T. foenum‐graecum and the mixture of both the plants. However, a significant ( p < .05) rise in insulin secretion was observed in studied plants extract treated rabbits. Serum urea, creatinine, and liver enzymes were found reduced significantly ( p < .05) in treated rabbits whereas packed cell volume was also returned to normal in treated animals as compared to control group. The study concluded that G. sylvestre and T. foenum‐graecum extracts have comparable effects with metformin in normalizing the blood glucose level and have more pronounced effect than metformin in restoring the serum biochemical parameters to normal levels. Hence, these plants may be the good alternative medicine in managing the diabetes mellitus.
... Other parameters viz., food intake, total cholesterol, LDL and triglycerides amount were significantly reduced. On the other hand, increased levels of HDL and excretion of urinary fat metabolites was also observed (Preuss et al. 2004). The study shows that GSE + HCA-SX is a good formulation that can lead to obesity control and reduced blood lipid levels. ...
Gymnema sylvestre R.Br. (Family: Apocynaceae), commonly called ‘gurmar’, is a commercially important medicinal plant. It is traditionally used as an antidiabetic agent, which is mainly due to the presence of gymnemic acids (triterpenoid glycosides). The plant is also a good source of oleanane-type triterpenoid saponins, flavonoids, steroidal glycosides, sterols, etc. Gurmarin, a protein, is known to suppress sweet taste. Its bioactive compounds have shown diverse therapeutic potentials viz., anticancer, anti-inflammatory, antidiabetic, radioprotective, antimicrobial, hypolipidaemic. Some of these medicinal properties have been validated through clinical trials. The present review focuses on the traditional phytochemical, medicinal properties, pharmacological and clinical trials undertaken on G. sylvestre.
... Citric acid and glyceric acid, the two most important organic acids, reached their maximum concentrations after 48 h of fermentation. Preuss et al. (2004) reported that hydroxycitric acid (HCA) reduced body weight growth and fat deposition in obese people, while improving their anthropometric and metabolic state. A heat map analysis was used to cluster onion samples based on their organic acid concentration in different ROE and FOE samples (Fig. 2). ...
The bioconversion of onion extracts with P. acidilactici MNL5 enhances the metabolites and has a synergistic lipid-reduction impact that is beneficial for anti-obesity studies. The 48 h fermented onion extracts (FOE) demonstrated an enhanced inhibitory activity against pancreatic lipase (89.5 ± 1.25%) as compared to the raw onion extract (ROE) (33.4 ± 0.86%). The antioxidant properties of FOE significantly increased compared to the ROE inhibitory effect on DPPH (99.5 ± 2.40 mg vitamin C equiv. /mg, DW FOE), and ABTS (104.5 ± 2.32 mg vitamin C equiv./mg, DW FOE). Based on FOE's higher antioxidant activity, UHPLC-Q-TOF-MS/MS demonstrated dramatic changes in the untargeted metabolite profile as compared to ROE. Moreover, C. elegans supplemented with FOE and quercetin exhibited an enhanced lifespan activity, lipid reduction, and decreased triglycerides. FOE can lower cholesterol and enhance quercetin to promote pancreatic lipase activity for synergistic anti-obesity effects.
... The major metabolic disorder associated with diabetes is dyslipidemia 30 . The diabetic untreated rats in this study showed the main features of diabetic dyslipidemia: elevated triglycerides (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and a decrease in the high density lipoprotein-cholesterol (HDL-C). ...
Background: Medicinal plants are used as alternative therapy for diabetes. This study investigated comparative effects of methanolic extracts of Anacardium occidentale (linn) nut, leaf and stem bark on hyperglycemia and associated abnormalities in streptozotocin-induced diabetic rats. Methods: Ninety male Wistar albino rats weighing (200±20g) were used and diabetes was induced by single intraperitoneal injection of streptozotocin (50mg/kgb.wt). The rats were allotted into 9 groups, 10rats/group. Group I: (non-diabetic); Group II: (diabetic untreated); Groups: III & IV: diabetic rats received 100mg/kgb.wt& 200mg/kgb.wt nut extract; Groups: V & VI: diabetic rats received 100mg/kgb.wt& 200mg/kgb.wt leaves extract; VII & VIII were diabetic rats received 100mg/kgb.wt& 200mg/kgb.wt stem bark extract and Group IX: diabetic rats received 2mg/kgb.wt p.o glimepirides for 4weeks. Daily food and water intakes were recorded; weekly body weight and blood glucose levels were measured throughout the experiment. The animals were sacrificed on the last day and fasting plasma blood glucose was withdrawn for biochemical parameters estimation. Results: Fasting plasma blood glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase, alkaline (ALT), aminotransferase (ALP), urea, uric acid, creatinine, malondialdehydes (MDA) and water intake levels were significantly (p<0.01, 0.05) reduced in the extracts treated groups. However, High density lipoprotein- cholesterol (HDL-C), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), body weight and food intake levels were significantly (p<0.01, 0.05) increased in the extracts treated groups. Conclusion: Anacardium occidentale parts posses anti-diabetic properties. The nut has extreme therapeutic efficacy and could be used as alternative therapy for diabetes. Keywords: Anacardium occidentale, Hyperglycemia, Lipid profiles, Antioxidants, Kidney function.
... Obesity: Rodent preclinical studies observed HCA reducing body mass via a mode associated with calorie limitation 93 an action not seen in humans. 94 Further corroboration of association amongst weight reduction and ACLY by 2 more advantageous ACLY hampering agents withproperties well studied-Bempedoic acid besides BMS-303141 werecausing body weight accrual reduction besides adiposity independent of food consumption alterations, in preclinical models. 85,91,95 Proofs from pooled evaluation of clinical trials showed Bempedoic acid stimulated modest weight reduction in humans. ...
For survival fatty acids are necessary, working as substrates for bioenergy generation, structural constitutents along with signaling molecules. With their key part, evolutionary modes bycells for fatty acids formation from alternative carbon resources via a event labelled as de novo’’ lipogenesis ( DNL). In spite of the knowledge of significance regarding its up regulation abnormalities being correlatedwith numerous types of pathological conditions. Attempt at hampering core DNL enzymes inclusive ofcitrate/iso citratecarrier(CIC), ATP citrate lyase ( ACLY), acetyl CoA carboxylase(ACC) along with fatty acid synthase( FAS) apparently should turn out to be a good therapeutic approach. Although numeroushurdles anticipated regarding effectiveness, selectiveness besides safety variable newer classes of synthetic DNL hampering agents have reached clinical stage generation besides becoming the basis for a newer class of treatment substances. Having earlier reviewed numerous articles regarding obesity along with its co-morbidities type2 Diabetes mellitus (T2DM) NAFLD /NASH here we have presented a narrative review regarding the evolutionary generation of DNL hampering agents as potential treatment agents. For this we review utilizing search engine pubmed, google scholar; web of science; embase; Cochrane review library for which we have extracted data from earliest data with the recognition of significance of various enzymes besides their allosteric, covalent, transcriptional control of fatty acids generation & the problems encountered for their generation till date. Apart from obesity associated therapeutics their utility extends to acne vulgaris, various cancer thrapies besides treating neurod generational diseases.
Keywords: de novo’’ lipogenesis ( DNL), FAS hampering agents, evolutionary generation
... Obesity. Preclinical studies in rodents found that HCA reduces body mass through a mechanism related to caloric restriction 168,169 , but this effect is not observed in humans 170,171 (Supplementary Fig. 1). Bempedoic acid and BMS-303141, two of the better-characterized ACLY inhibitors, have strengthened a potential connection between weight loss and ACLY, with both reducing body weight gain and adiposity independently of changes in food intake in preclinical models 160,166,167,172 . ...
Fatty acids are essential for survival, acting as bioenergetic substrates, structural components and signalling molecules. Given their vital role, cells have evolved mechanisms to generate fatty acids from alternative carbon sources, through a process known as de novo lipogenesis (DNL). Despite the importance of DNL, aberrant upregulation is associated with a wide variety of pathologies. Inhibiting core enzymes of DNL, including citrate/isocitrate carrier (CIC), ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), represents an attractive therapeutic strategy. Despite challenges related to efficacy, selectivity and safety, several new classes of synthetic DNL inhibitors have entered clinical-stage development and may become the foundation for a new class of therapeutics.
... Triglycerides, cholesterol level, lipoproteins with a low density, as well as serum leptin levels all fell, whereas high density lipoprotein concentrations as urinary fatty metabolites excretion rose. This research found that combining Gymnema extract with HCA-SX, NBC may be used as a safe and effective weight loss solution that can help people lose weight and improve their BMI while also supporting healthy blood lipid levels [45,46]. ...
In this paper explored the pharmacognostical profile of gymnema sylvestre and its anti-hyperglycemic activity has been documented well with references. The importance of the species in Ayurveda has been highlighted. The bioactive components like gymnema sylvestre has a variety of secondary metabolites, including oleanane, gymnemic acid, gymnemasides (A-F), gymnemic acid (IXVIII) homologue, gymnemic acid A1 and its derivatives, triterpenoidsaponin, al has been clearly includedin the review kaloid (Conduritol-A), polypeptide (Gurmarin), and gymnemasaponins. This study has provided the groundwork for developing a pharmacognostical profile of medicinal plant growers and collectors. The goal of this review study is to provide a regional profile of the indigenous knowledge system for medicinal plant usage and cultural behaviors related to healing. This study aids in the identification of novel ethnomedicinal plant species in the study region, which may lead to the development of new medicines. The plant toxicity test results indicated that it may be used as an alternative to diabetes therapy with no or little adverse effects. This study confirms the conventional use of indigenous plant-derived natural medicine for treating diabetes mellitus. The study also highlighted the efficacy of "Ayurveda" which is an ancient tradition, used in some parts of India. This ancient concept should be carefully evaluated in the light of modern medical science and can be utilized partially if found suitable. I hope that this kind of research will be useful to future researchers as per their needs.
... A number of herbs and spices have been shown to be effective in managing key risk factors of MetS, including obesity/abdominal obesity, lipid profiles, hypertension, FBG, and insulin sensitivity [48,50,54]. Furthermore, an efficient decrease in the waist-to-hip ratio and waist circumference were reported in studies that used one or more herbal/spice extracts, including the use of Zingiber officinale [55,56], and others have reported decreased appetite in obese individuals after regular consumption of some herbs leading to weight loss [57,58]. Illustrating the clinical use of some herbs and spices, Table 1 contains 13 studies conducted in humans, and the effects of herbs and spices on MetS risk factors are noted. ...
Metabolic syndrome (MetS) is a combination of physiologically dysregulated parameters that can include elevated fasting blood glucose, high blood pressure, central obesity, increased triglyceride levels, insulin resistance, diabetes, elevated low density lipoprotein levels, and reduced high density lipoprotein levels in the blood. Effective clinical management of MetS is critical as it is strongly associated with long lasting and fatal complications in patients. Alongside standard care of lifestyle changes and medication, dietary supplements derived from herbal resources could be an alternative therapeutic strategy that is safe, efficient, culturally acceptable, and has few side effects. Of the dietary supplements, spicy foods have always been considered a great source of functional bioactive compounds. Herbal therapy is broadly used in many countries as a treatment or as a preventive measure in the management of MetS risk factors, including blood glucose, blood pressure, and blood lipid levels. Herein, an attempt is made to evaluate the recent studies in the management of MetS with herbal alternatives, and to explore the possibility of their use as therapeutic treatments or supplements.
... One of the associated metabolic disorders of diabetes is dyslipidemia which is one of the risk factors of diabetes [37]. Hypercholesterolemia and hypertriglyceridemia have been reported to occur in alloxan treated rats [38,39]. ...
Aim: The study investigated the anti-hyperglycemic and anti-hyperlipidemic potentials of methanol extracts of Piper guineense and Aframomum melegueta leaves with a view to utilizing the plants in the treatment and management of cardiovascular disorders. Methodology: Twenty-eight healthy albino rats were randomly divided into seven equal groups: Group I received normal saline (2 ml/kg bwt); Group II received a single dose of alloxan(150 mg/kg bwt) intraperitoneally; Group III received alloxan (150 mg/kg bwt) + glibenclamide (5 mg/kg Original Research Article Morakinyo et al.; EJMP, 27(1): 1-8, 2019; Article no.EJMP.45970 2 bwt);Group IV received alloxan (150 mg/kg bwt) +PG (200 mg/kg bwt); Group V received alloxan (150 mg/kg bwt) + PG (400 mg/kg bwt); Group VI received alloxan (150 mg/kg bwt) + AM 200 (mg/kg bwt); Group VII received alloxan (150 mg/kg bwt) + AM (400 mg/kg bwt). The blood glucose level was determined before and after treatment with the extracts. The lipid: (total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were estimated using the Randox diagnostic kits. Results: The results revealed that alloxan was able to induce hyperglycemia at 150 mg/kg bwt and post-treatment with P. guineense and A. melegueta at 200 mg/kg and 400 mg/ kg bwt were able to significantly lower the blood glucose level which was quite apparent in AM treated groups. Also, the extracts at 200 mg/kg and 400 mg/kg were able to bring a significant (p < 0.05) reduction in TC, TG and LDL concentrations when compared to the alloxan treated group with the highest reduction in AM treated groups. Conclusion: These results revealed that the methanol extract of P. guineense and A. melegueta elicited anti-hyperglycemic and anti-hyperlipidemic potentials of the extracts with the highest effect observed in A. melegueta treated rats.
... Gymnemic acids exhibit antidiabetic and antiinflammatory activities (Liu, Kiuchi, & Tsuda, 1992, Manni & Sinsheimer, 1965. The components isolated from Gymnema sylvestre like betaine, choline, gurmarin, gymnemic acid IV, trimethylamine, gymnemic acid, and gymnemosides activate the restoration of pancreatic β-cells and the insulin secretion (Preuss et al., 2004;Sugihara et al., 2000). In rodents, it showed increased insulin secretion and restoration of pancreatic β-cells (Al-Romaiyan, King, Persaud, & Jones, 2013;Ramkumar et al., 2009). ...
Global diabetes epidemic is the major cause of fatality and lethality. As per IDF 2019 report, diabetes caused 4.2 million deaths, approximately 463 million people are living with diabetes and by 2045, this will rise to 700 million. Nowadays, the physicians and common people in both developed and developing countries are using medicinal plants and their formulations to treat diseases with the postulation that organic commodities are safe for consumption. These plants may act as inhibitors or inducers of the Cytochrome P450 or transport and efflux proteins or both and may alter gastrointestinal, renal functions leading to Herb‐Drug Interactions. This review intends to focus on the frequently employed medicinal plants, their traditional uses, their Cytochrome P450 inhibition or induction activity, phytochemical, and pharmacological effects, established HDI with the help of in vitro tools, in vivo pharmacokinetics and pharmacodynamics studies to understand the impact of herbs on ADME of the drug and whether it is beneficial, harmful or has no effect respectively. This review will help the physicians and other health care professionals as a reference guide to update their knowledge and expertise about HDI. However, more quality research in this area is needed to evaluate the efficacy of many herbal medicines, thereby reducing side effects and improving the safety of patients.
... These findings supported by a clinical trial of Preuss et al. (2004) who studied Gymnema sylvestre extract at a dose of 400mg/day along with hydroxyl citric acid and niacin bound chromium given to moderately obese individuals for eight weeks which decreased TC, LDL-C and TG contents significantly, with increased serum HDL-C. Furthermore, Suparna and Santanu (2019) reported that Gymnema sylvestre biocomponents possess both antidiabetic and antioxidant activities with their antidiabetic features also. ...
This investigation aimed to study the effect of gymnema (Gymnema sylvestre) and sea grape (Coccoloba uvifera L.) on carbon tetrachloride (CcL4) induced hepatotoxicity in rats. Thirty male albino rats weighing 150±5g were divided into 6 equal groups (n=5 rats); one group kept as control negative, while the other 5 groups injected s/c by CcL4 in parrafin oil 50% V/V (2ml / kg b.wt.) twice a week for two weeks for liver intoxication incidence, one of them left as (C +ve) while the rest four groups orally administered using two doses 5 & 10% of gymnema and sea grape each. At the end of experimental period (45 days), blood samples were collected for serum separation to determine serum liver enzymes, total cholesterol, triglycerides, atherosclerosis index, lipoprotein fractions and kidney functions. The obtained results demonstrated that gymnema and sea grape at two doses 5 &10%, especially at high dose for each herb caused significant improvement in liver enzymes, lipid profiles, serum glucose and kidney functions in hepatotoxic rats. According to the results, gymnema and sea grape could improve the levels of liver enzymes, lipid profiles, glucose and kidney functions in CcL4 induced hepatotoxicity in rats.
... This action is mediated through the inhibition of the ATP-citrate liase, an enzyme that is required for the first step in the lipogenesis process (Ohia et al., 2002). AHC also seems to act on serotonin levels reducing food intake (Preuss et al., 2004). Besides, other metabolic actions of AHC on lipid metabolism have been reported such as increase of fatty acid oxidation and regulation of genes involved in lipid metabolism (Han et al., 2016;Hayamizu et al., 2003;Kovacs and Westerterp-Plantenga, 2006;Roy et al., 2007). ...
Background
Nowadays, overweight and obesity are worldwide epidemics associated with the development of diseases such as diabetes, dyslipidemias, hypertension and even cancer. Treatments for these conditions are not very successful and therefore looking for new strategies is imperative. Garcinia cambogia (GC) is used in Asia and Africa for hypolipidemic, antidiabetic and anti-obesity purposes while Glucomannan (GNN) is a diet supplement used to control weight in Japan and China. Here, the efficacy of GC and GNN in weight reduction and the impact on metabolic status of obese/overweight patients for 3 and 6 months was tested.
Material and Methods
This study was a pre-post test study. Adults> 18 years old (n = 136) with a body mass indexin excess of 25 were recruited for this study. These patients also suffered from diabetes mellitus type 2, dyslipidemias, hypertension and their combinations. They were treated with 1 g/day of both GC and GNN for 3 and 6 months
Results
The treatment reduced weight, visceral fat, fat mass, increased metabolic basal rate and was also effective reducing levels of triglycerides, glucose and cholesterol compared to baseline. There were not any adverse effects reported. Reduction in weight were independent of sex, age and previously reported condition.
Conclusions
It was concluded that treatment with GC and GNN is useful in the long term to reduce weight and improve the metabolic status of overweight/obese patients.
... Its leaves contain gurmarin, flavonoids, triterpenoid and saponins. The most bioactive compound of this plant are gymnemic acids, a class of tri-terpenoidsaponins, which have the effect of put down the taste of sweetness on the tongue from sucrose, xylitol, stevia and made up sweeteners such as aspartame (Liu et al., 2004 andDi-Fabio et al., 2015). In Japan, there were 50 tons of GSL are consumed every year for weight loss. ...
The genus Garcinia is composed of around 200 species distributed in the tropics and subtropics. Out of 36 species from India, Garcinia gummi-gutta (L.) Roxb. is an important non-timber forest product (NTFP) from the southwestern ghats of India. It is a small- or medium-sized fruit tree valued for its fruits as a condiment. Moreover, the plant is a better source of phytochemicals such as xanthones, benzophenones, organic acids, and amino acids. Among these phytochemicals, hydroxycitric acid (HCA), an important organic acid enriched in fruit rinds, has the mechanism for regulation of lipid metabolism and obesity control. HCA helps to regulate serotonin synthesis and thereby suppresses food intake in our body. Also, it competitively inhibits the ATP-citrate lyase meant for the conversion of citrate to oxaloacetate and acetyl coenzyme A, a building block of fatty acid synthesis. Furthermore, an array of pharmacological effects such as antioxidant, antitumor, anti-allergic, anti-inflammatory, antibacterial, antifungal, antiviral, neuroprotective, anti-HIV, enzyme inhibition, and hypoglycemic effects has been well elucidated based on in vitro as well as in vivo experimental models. A generous portion of phytoconstituents with therapeutic potentialities has been contributed by the fruits, followed by leaf and bark. An array of health, wellness, and nutraceutical supplements are being produced from the plant by reputed pharma companies all over the world. To fulfil the needs of pharmaceutical industries, breeding approaches could be enhanced to improve the genome of G. gummi-gutta. Thus, underutilized plants, in turn, may contribute significantly to plant-based industry, thus benefiting the rural people who engage in the collection, processing, and marketing of such resources.
Intracellular levels of NAD+ regulate metabolism, among other ways, through enzymes that use NAD+ as a substrate, capable of inducing catabolic processes, such as lipid oxidation, glucose uptake, and mitochondrial activity. In several model organisms, administering precursor compounds for NAD+ synthesis increases its levels, improves lipid and glucose homeostasis, and reduces weight gain. However, evidence of the effects of these precursors on human patients needs to be better evaluated. Therefore, we carried out a systematic review and meta-analysis of randomized clinical trials that assessed the effects of NAD+ precursors on Metabolic Syndrome parameters in humans. We based our methods on PRISMA 2020. Our search retrieved 429 articles, and 19 randomized controlled trials were included in the meta-analysis. We assessed the risk of bias with the Rob 2 algorithm and summarized the quality of evidence with the GRADE algorithm. Supplementation with NAD precursors reduced plasma levels of total cholesterol and triglycerides in volunteers, but the intervention did not significantly affect the other outcomes analyzed. Three of the included articles presented a high risk of bias. The quality of evidence varied between very low and low due to the risk of bias, imprecision, and indirectness. The number of participants in outcomes other than lipidemia is still generally tiny; therefore, more clinical trials evaluating these parameters will increase the quality of the evidence. On the other hand, quality randomized studies are essential to assess better the effects of NAD+ precursors on lipidemia.
Garcinia cambogia (GC) has antioxidant, anticancer, antihistamine, and antimicrobial properties. To determine the effect of GC on lipid profiles, a systematic review and meta‐analysis was carried out. Up to February 9, 2023, six electronic databases (Web of Science, Cochrane Library, Embase, PubMed, Scopus, and Google Scholar) were searched at any time without limitations. Trials examining the impact of GC on serum levels of total cholesterol (TC), triglycerides (TG), low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol (HDL‐C) in adults were included. The total effect was shown as a weighted mean difference (WMD) and 95% confidence interval (CI) in a random‐effects meta‐analysis approach. This systematic review and meta‐analysis included 14 trials involving 623 subjects. Plasma levels of TC (WMD: −6.76 mg/dL; CI: −12.39 to −0.59, p‐value = 0.032), and TG (WMD: −24.21 mg/dL; CI: −37.84 to −10.58, p < 0.001) were significantly reduced after GC use, and plasma HDL‐C (WMD: 2.95 mg/dL; CI: 2.01 to 3.89, p < 0.001) levels increased. low‐density lipoprotein cholesterol levels (WMD: −1.15 mg/dL; CI: −16.08 to 13.78, p‐value = 0.880) were not significantly affected. The effects of lowering TC and TG were more pronounced for periods longer than 8 weeks. Consuming GC has a positive impact on TC, TG, and HDL‐C concentrations. The limitations of this study include the short duration of analyzed interventions and significant heterogeneity. Nevertheless, it is imperative to conduct well‐structured, and high‐quality long‐term trials to comprehensively evaluate the clinical effectiveness of GC on lipid profile, and validate these findings.
Lipid metabolism disorder is closely related to metabolic diseases, inflammation, and cancer. The concentration of citrate in the cytosol has a significant impact on lipid synthesis. The expression of citrate transporters (SLC13A5 and SLC25A1) and metabolic enzymes (ACLY) proves to be substantially raised in various diseases related to disorders of lipid metabolism, such as hyperlipemia, nonalcoholic fatty liver disease, and prostate cancer. Targeting key proteins in the citrate transport and metabolic pathways is considered an effective strategy for treating various metabolic diseases. However, there is currently only one ACLY inhibitor approved for marketing, and no SLC13A5 inhibitor has entered clinical research. Further development of drugs targeting citrate transport and metabolism is needed for the treatment of metabolic diseases. This perspective summarizes the biological role, therapeutic potential, and research progress of citrate transport and metabolism and then discusses the achievements and prospects of modulators targeting citrate transport and metabolism for therapeutic applications.
Purpose:
Despite the introduction of various pharmaceutical therapies for treating obesity, selecting the optimal treatment remains challenging for both patients and physicians. Therefore, in this network meta-analysis (NMA), we aim to simultaneously compare the available drugs for treating obesity to determine the most effective treatment options.
Methods:
International databases, including PubMed, Web of Science, Scopus, Cochrane Library, and Embase, were searched for studies published from database inception to April 2023. The consistency assumption was evaluated using by the loop-specific and design × treatment interaction approaches. The effects of treatment in the NMA were summarized using mean differences based on a change score analysis. The random-effects model was used to report the results. Results were reported with 95% CIs.
Findings:
Of 9519 retrieved references, 96 randomized controlled trials, including 68 with both men and women, 23 with women only, and 5 with men only, met the eligibility criteria for this study. There were 4 treatment networks in the trials of both men and women, 4 in the trials of women only, and 1 in the trials of men only. The best-ranked treatments in the network in the trials of both men and women were (1) semaglutide, 2.4 mg (P-score = 0.99); (2) hydroxycitric acid, 4667 mg 3 times daily, supervised walking, and 2000-kcal/d diet (P-score = 0.92); (3) phentermine hydrochloride and behavioral therapy (P-score = 0.92); and (4) liraglutide plus advice to diet and exercise (P-score = 1.00). In women, the best-ranked treatments were beloranib (P-score = 0.98) and sibutramine, metformin, and hypocaloric diet (P-score = 0.90). In men, there was no significant difference among treatments.
Implications:
According to the results of this NMA, semaglutide seems to be an effective treatment option for both men and women, whereas beloranib appears to be particularly effective for women with obesity and overweight, but its production has been stopped since 2016 and is not available. (Clin Ther. 2023;XX:XXX-XXX) © 2023 Elsevier HS Journals, Inc.
The mechanism of the drying process is the process of heat transfer and mass transfer that takes place simultaneously. The pressure of the water vapor in the acid gelugur is higher than that on the surface interface of the gums and air acids. Intensity solar radiation averages around 300-590w / m2 and Ambient Temperature 28,830C. The hot air condition in the drying box averages 320C. The content of total citric acid gelugur acid was 1.2787% with 3mm slice thickness and 1.3981% with a 5mm slice thickness. Drying is done from 08.00-17.00 am with a hot air flow rate of 1.5m/s.
There are some vegetal principles which modify the taste to sour, cause reduction in sweetness, induction of sweetness and flavor in the non sweet food. Few among those, induce sweetness in drinking water i.e. water and beverages taste sweet during drinking after their consumption. These chemicals are important because they substitute sugre (calorie rich) and zero calorie super sweet principle as they are calorie free and help in providing different tastes and rectifying different ailments e. g. diabetes and cardiovascular, kidney and liver disorders, high calories sugar consumption is restricted. Some of such natural organic acid like gymnemic acid not only reduce sweetness in mouth but also interact with sugar in intestine and reduce their calories. These taste modifiers are protein, triterpenoid, polysaccharides, polyphenol, ester of quinic acid etc. in nature. They are found in different plants as mentioned in Table 15.1.
Food supplements of plant origin for weight control are increasingly being demanded by consumers as a way to promote good health. Among them, those based on Garcinia cambogia (GCFS) are widely commercialized considering their bioactive properties, mainly due to (-)-hydroxycitric acid ((-)-HCA). However, recently, controversy has arisen over their safety; thus, further research and continuous monitoring of their composition is required. Hence, in this work, a multi-analytical approach was followed to determine not only (-)-HCA but also other constituents of 18 GCFS, which could be used as quality markers to detect fraudulent practices in these samples. Discrepancies between the declared (-)-HCA content and that experimentally determined were detected by LC-UV in 33% of the samples. Moreover, GC-MS analyses of GCFS allowed the detection of different compounds not present in G. cambogia fruits and not declared on supplement labels, probably related to heat exposure or to the addition of excipients or other extracts. This multi-analytical methodology is shown to be advantageous to address different fraudulent practices affecting the quality of these supplements.
The medicinal properties of Carex baccans Nees. (Cyperaceae) has widely been exploited in traditional healing practices for the treatment of various ailments. Though, this is a widely used herb, not much is known about the adverse implications it may have. Therefore to shed some light into this aspect, acute and sub-acute toxicity study of the plant’s crude extract and fractions were carried out in Swiss albino mice following Organization for Economic Co-operation and Development 423 and 407 guidelines respectively. Additionally, the phytochemical composition of the crude extract was also determined. Effect of the extract and the fraction was analyzed taking into consideration the body weight, organs weight, blood physiology, key markers of liver and kidney functions, and microscopic analysis of liver, kidney and intestine structural composition using scanning and transmission electron microscopy. The results showed that the crude extract exert no observable signs of acute toxicity even at a dose of 5000 mg/kg body weight of mice, however, the butanol fraction proved to be toxic with a mean lethal dose of 4677.35 ± 103.38 mg/kg. Repeated oral sub-acute test of the mice with crude extract and fraction of the crude extract was also found to exert adverse effects on the animals at high doses (500 mg/kg body weight and above) when compared to control group. These adverse implications were manifested in the body weight, hematology, biochemistry, and the structural and ultrastructural composition of some important organs. Therefore, it may be concluded that the plant C. baccans, if taken in its crude native form has a high safety margin at a single dose but not the butanol fraction. Furthermore, repeated exposure to the plant, both in its crude and fractionated (butanol fraction) form at high doses should be discouraged as it may have severe implications. © 2021 Informatics Publishing Limited and The Society of Toxicology. All rights reserved.
The uses of herbal biomolecules as phytomedicines in healthcare have been practiced from the early stage of human civilization to the modern age. Plethora of plants with significant value are available worldwide. According to World Health Organization (WHO), about 80% of world population receives phytomedicine for their primary healthcare. Herbal biomolecules are chemicals that have definite biological activities including alkaloids, glycosides, coumarins, flavonoids, terpenoids, carbohydrates, oils, etc. Active biomolecules from herbal resources have been popularly used for the treatment of various diseased conditions, such as cancers, diabetes, malaria, mental illness, microbial infections, cardiovascular disorders, etc., and have also been extensively used as antioxidants, immunomodulators, neutraceuticals, anticancer agents, antidiabetics, etc. In addition, many herbal biomolecules have been exploited as functional biomaterials in different biomedical applications like drug delivery, antimicrobial applications, tissue engineering, wound healing, etc. To attain the optimal health benefits with the uses of herbal biomolecules, standardization of phytoconstituents with the application of modern analytical techniques as well as uses of sophisticated analytical equipments are very much essential. The global market for herbal biomolecules as phytomedicines is increasing day by day. Strict regulation and systematic scientific research will definitely brighten the future prospects of herbal biomolecules.
This systematic review and meta‐analysis aims to find the effect of Gymnema sylvestre (GS) supplementation on glycemic control in type‐2 diabetes mellitus (T2DM). PubMed, Cochrane library, Google Scholar, and Science Direct were searched from inception to June 2020 to identify the studies that reported GS supplementation on glycemic parameters. Standardized mean difference (SMD) was calculated by comparing the post‐intervention data with baseline data. SMDs with 95% confidence intervals (CIs) were pooled using a random‐effects model. Our meta‐analysis consisting of 10 studies with a total of 419 participants showed that GS supplementation significantly reduces fasting blood glucose (FBG) (SMD 1.57 mg/dl, 95% CI 2.22 to −0.93, p < .0001, I² 90%), postprandial blood glucose (PPBG) (SMD 1.04 mg/dl, 95% CI 1.53 to −0.54, p < .0001, I² 80%), and glycated haemoglobin (HbA1c) (SMD 3.91, 95% CI 7.35 to −0.16%, p < .0001, I² 99%) compared to baseline. Further, our study also found that GS significantly reduces triglycerides (SMD 1.81 mg/dl, 95% CI 2.95 to −0.66, p < .0001, I²: 96%), and total cholesterol (SMD 4.10 mg/dl, 95% CI 7.21 to −0.99, p < .0001, I²: 98%) compared to baseline. Our study shows that GS supplementation is effective in improving glycemic control and reducing lipid levels in T2DM patients and suggests that such supplementation might be used as an effective therapy for the management of T2DM and its associated complications to an extent.
Objective
Dietary supplements and alternative therapies are commercialized as a panacea for obesity/weight gain as a result of the minimal regulatory requirements in demonstrating efficacy. These products may indirectly undermine the value of guideline‐driven obesity treatments. Included in this study is a systematic review of the literature of purported dietary supplements and alternative therapies for weight loss.
Methods
A systematic review was conducted to evaluate the efficacy of dietary supplements and alternative therapies for weight loss in participants aged ≥18 years. Searches of Medline (PubMed), Cochrane Library, Web of Science, CINAHL, and Embase (Ovid) were conducted. Risk of bias and results were summarized qualitatively.
Results
Of the 20,504 citations retrieved in the database search, 1,743 full‐text articles were reviewed, 315 of which were randomized controlled trials evaluating the efficacy of 14 purported dietary supplements, therapies, or a combination thereof. Risk of bias and sufficiency of data varied widely. Few studies (n = 52 [16.5%]) were classified as low risk and sufficient to support efficacy. Of these, only 16 (31%) noted significant pre/post intergroup differences in weight (range: 0.3‐4.93 kg).
Conclusions
Dietary supplements and alternative therapies for weight loss have a limited high‐quality evidence base of efficacy. Practitioners and patients should be aware of the scientific evidence of claims before recommending use.
Ten new polyisoprenylated benzophenone derivatives, 4,8-epi-uralione F (1), 4,8-epi-uralione G (2), uralione S (3), coccinone J (4), 6-epi-coccinone C (5), coccinone I (6), 36-hydroxy-guttiferone J (7), multiflorone I (8), garciniagifolone F (9) and 36-hydroxy-garciniagifolone F (10), were isolated from the fruits of Garcinia cambogia, along with seven known analogues. The structures of the new compounds were established based on the detailed analysis of 1D and 2D nuclear magnetic resonance (NMR) spectra and high resolution electrospray ionization mass spectrometra (HRESIMS), and their absolute configurations were determined from the electronic circular dichroism (ECD) spectra. All the isolates were tested for their inhibitory effects against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The results indicated that compound 1 displayed a potent NO inhibitory effect with an IC50 value of 41.60 ± 0.17 μM. Furthermore, compound 1 suppressed inducible NO synthase (iNOS) expression in a dose-dependent manner through inhibiting the activation of nuclear factor-κB (NF-κB).
Garcinia cambogia, with its active component hydroxycitric acid (HCA), is widely used for weight loss due to its anorexigenic effect, increased fat oxidation, and regulation of endogenous lipid biosynthesis. The potential effectiveness of G. cambogia in reducing body weight and fat has been concluded in several studies in both experimental animals and humans. However, the results of some randomized placebo-controlled human clinical trials have either not reported the same outcome or there has been a marginal reduction in body weight on a short-term basis, not beyond 12 weeks. Other beneficial effects of Garcinia in experimental studies include antiinflammatory, antiulcerogenic, antioxidant, hepatoprotective, cytotoxic, erythropoietic, and miscellaneous other effects. Studies with G. cambogia conducted in experimental animals have not reported mortality or significant toxicity. Further, at doses usually recommended for humans no side effects have been reported. However, G. cambogia should not be concurrently used with other drugs to circumvent drug interactions. Currently, a large number of G. cambogia/HCA-containing dietary supplements are being marketed, although the reports of toxicity associated with the regular use of these supplements have raised concerns. In most cases complaints have been related to formulations containing multiple ingredients including G. cambogia. Another reason for adverse effects of G. cambogia/HCA can be related to idiosyncratic reactions by individual patients or other drugs used concurrently with these supplements resulting into in a drug/herb-induced toxic interaction.
A review of 144 published studies of the relationship between socioeconomic status (SES) and obesity reveals a strong inverse relationship among women in developed societies. The relationship is inconsistent for men and children in developed societies. In developing societies, however, a strong direct relationship exists between SES and obesity among men, women, and children. A review of social attitudes toward obesity and thinness reveals values congruent with the distribution of obesity by SES in different societies. Several variables may mediate the influence of attitudes toward obesity and thinness among women in developed societies that result in the inverse relationship between SES and obesity. They include dietary restraint, physical activity, social mobility, and inheritance.
Incorporation of ³H from ³H2O was used to measure the rate of fatty acid synthesis in rat liver. (—)-Hydroxycitrate strongly inhibits fatty acid synthesis in vivo.
To develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, the reference population, and the age and sex specific cut off points.
International survey of six large nationally representative cross sectional growth studies.
Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States.
97 876 males and 94 851 females from birth to 25 years of age.
Body mass index (weight/height(2)).
For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut off points of 25 and 30 kg/m(2) for adult overweight and obesity. The resulting curves were averaged to provide age and sex specific cut off points from 2-18 years.
The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.
The adipocyte hormone leptin is thought to serve as a signal to the central nervous system reflecting the status of fat stores. Serum leptin levels and adipocyte leptin messenger RNA levels are clearly increased in obesity. Nevertheless, the factors regulating leptin production are not fully understood. The aim of this study was to determine the effects of in vivo administration of the synthetic glucocorticoid dexamethasone and weight loss on serum leptin levels in two independent protocols. Twenty-five obese subjects were studied (18 women and 7 men, mean age 26.6 +/- 6 years, BMI 31.1 +/- 2.5 kg/m(2), %fat 40.3 +/- 8.3) and compared at baseline to 22 healthy individuals. Serum levels of leptin, insulin, proinsulin and glucose were assessed at baseline and after ingestion of dexamethasone, 4 mg per day (2 mg, twice daily) for two consecutive days. To study the effects of weight loss on serum leptin, 17 of the obese subjects were submitted to a low-calorie dietary intervention trial for 8 weeks and again blood samples were collected. Serum leptin levels were significantly higher in the obese group compared to the control group and a high positive correlation between leptinemia and the magnitude of fat mass was found (r = 0.88, P<0.0001). After dexamethasone, there was a significant increase in serum leptin levels (22.9 +/- 12.3 vs 51.4 +/- 23.3 ng/ml, P<0.05). Weight loss (86.1 +/- 15.1 vs 80.6 +/- 14.2 kg, P<0.05) led to a reduction in leptin levels (25.13 +/- 12.8 vs 15.9 +/- 9.1 ng/ml, P<0.05). We conclude that serum leptin levels are primordially dependent on fat mass magnitude. Glucocorticoids at supraphysiologic levels are potent secretagogues of leptin in obese subjects and a mild fat mass reduction leads to a disproportionate decrease in serum leptin levels. This suggests that, in addition to the changes in fat mass, complex nutritional and hormonal interactions may also play an important role in the regulation of leptin levels.
Hypercholesterolemia, a significant cardiovascular risk factor, is prevalent in the American population. Many drugs lower circulating cholesterol levels, but they are not infrequently associated with severe side effects. Accordingly, natural means to lower cholesterol levels safely would be welcomed. We examined 40 hypercholesterolemic subjects (total cholesterol 210-300 mg/dL) in a randomized, double-blind, placebo-controlled study. The four groups of ten subjects received either placebo bid, chromium polynicotinate (Cr) 200 microg bid, grape seed extract (GSE) 100 mg bid, or a combination of Cr and GSE at the same dosage bid. Over two months, the average percent change +/- SEM in the total cholesterol from baseline among groups was: placebo -3.5% +/- 4, GSE -2.5% +/- 2, Cr -10% +/- 5, and combination -16.5% +/- 3. The decrease in the last group was significantly different from placebo (p < 0.01). The major decrease in cholesterol concentration was in the LDL levels: placebo -3.0% +/- 4, GSE -1.0% +/- 2.0, Cr -14% +/- 4.0, and the combination -20% +/- 6.0. Again, the combination of Cr and GSE significantly decreased LDL when compared to placebo (p<0.01). HDL levels essentially did not change among the groups. Also, there was no significant difference in the triglyceride concentrations among the groups; and no statistically significant differences were seen in the levels of autoantibodies to oxidized LDL (Ox-LDL). However, the trend was for the two groups receiving GSE to have greater decreases in the latter parameter, i.e., -30.7% and -44.0% in the GSE and combined groups in contrast to -17.3% and -10.4% in the placebo and chromium groups. We determined the number of subjects in each group who decreased autoantibodies to oxidized LDL greater than 50% over eight weeks and found these ratios among groups: placebo = 2/9, Cr = 1/10, GSE = 6/10, and combined = 3/8. Thus, 50% of subjects (9/18) receiving GSE had a greater than 50% decrease in autoantibodies compared to 16% (3/19) in the two groups not receiving GSE. No significant changes occurred in the levels of circulating homocysteine and blood pressure among the four groups. We conclude that a combination of Cr and GSE can decrease total cholesterol and LDL levels significantly. Furthermore, there was a trend to decrease the circulating autoantibodies to oxidized LDL in the two groups receiving GSE.
There is evidence that hydroxycitric acid (HCA), an extract of dried fruit rind of South Asian trees of the genus Garcinia cambogia, can reduce food intake in experimental animals. In the present study, we investigated the effect of HCA on basal and potassium-depolarization evoked increase in radiolabeled serotonin ([3H]-5-HT) release from rat brain cortex slices in vitro. HCA (10 microM-1 mM) altered the baseline of spontaneous tritium efflux but had no significant effect on potassium-evoked release of [3H]-5-HT. When applied on its own, HCA (10 microM-1 mM) elicited a concentration-dependent increase in efflux of [3H]-5-HT reaching a maximum at 300 microM. We conclude that HCA can increase the release of radiolabeled 5-HT from the isolated rat brain cortex.
Assessment of a possible relationship between habitual as well as manipulated meal frequency, blood glucose pattern, macronutrient- and energy intake (EI), and energy intake regulation in partially temporally isolated men.
A partially temporally isolated within-subject design assessing energy intake regulation in spite of intervention. Intervention consisted of manipulating meal frequency by offering iso-energetic (1 MJ) preloads high in fat or carbohydrate (CHO), with the same energy density. We have previously shown that after a high-CHO preload, inter-meal-interval was 1 h, while after a high-fat preload intermeal-interval was 2 h.
Twenty healthy young (18-31 y) normal weight (body mass index (BMI): 22.8+/-1.9 kg/m(2)) men.
On two separate days, each after a different preload: subsequent subjects' responses to the preload, eg manipulated meal frequency; continuous blood glucose levels and blood glucose patterns: macronutrient composition of food intake; EI; appetite ratings; and taste perception. From controlled 3-day food intake diaries: habitual meal frequency; EI; and macronutrient-intake.
Accuracy of energy intake regulation is expressed as minimizing the difference in energy intake, despite intervention. The difference in 24 h EI on the two test days after the preloads (r(2)=0.56; P<0.001) was a function of habitual meal frequency. Variation in energy intake was primarily explained by habitual meal frequency (r(2)=0.76; P<0.0001). Adding macronutrient composition and number of blood glucose declines to this increased the explained variation to 86 and 96%, respectively. Percentage energy from CHO or from fat explained the variation in habitual meal frequency (r(2)=0.84; P<0.0001). Adding the total number of blood-glucose declines to this increased the explained variation to 88%, and adding average baseline blood glucose levels, sweetness perception and hunger suppression during preload consumption increased the explained variation to 91%. Manipulated meal frequency was related to habitual meal frequency (r(2)=0.86; P<0.0001) and was a function of the number of transient and dynamic blood glucose declines (r(2)=0.74; P<0.0001).
Habitual meal frequency is of greater significance in energy intake regulation in healthy young men than manipulated meal frequency. Healthy young men with a high habitual meal frequency showed lower 24 h EI, and a smaller difference in EI after macronutrient specific preloads, compared to those with a low habitual meal frequency, thus showing a more accurate energy intake regulation. Habitual meal frequency is based upon a cluster of related factors including macronutrient composition of the food, sweetness perception, hunger suppression, blood glucose declines and average baseline blood glucose levels.
A growing body of evidence demonstrates the efficacy of Garcinia cambogia-derived natural (-)-hydroxycitric acid (HCA) in weight management by curbing appetite and inhibiting body fat biosynthesis. However, the exact mechanism of action of this novel phytopharmaceutical has yet to be fully understood. In a previous study, we showed that in the rat brain cortex a novel HCA extract (HCA-SX, Super CitriMax) increases the release/availability of radiolabeled 5-hydroxytryptamine or serotonin ([3H]-5-HT), a neurotransmitter implicated in the regulation of eating behavior and appetite control. The aim of the present study was 2-fold: (a) to determine the effect of HCA-SX on 5-HT uptake in rat brain cortex in vitro; and (b) to evaluate the safety of HCA-SX in vivo. Isolated rat brain cortex slices were incubated in oxygenated Krebs solution for 20 min and transferred to buffer solutions containing [3H]-5-HT for different time intervals. In some experiments, tissues were exposed to HCA-SX (10 microM - 1 mM) and the serotonin receptor reuptake inhibitors (SRRI) fluoxetine (100 microM) plus clomipramine (10 microM). Uptake of [3H]-5-HT was expressed as d.p.m./mg wet weight. A time-dependent uptake of [3H]-5-HT occurred in cortical slices reaching a maximum at 60 min. HCA-SX, and fluoxetine plus clomipramine inhibited the time-dependent uptake of [3H]-5-HT. At 90 min, HCA-SX (300 microM) caused a 20% decrease, whereas fluoxetine plus clomipramine inhibited [3H]-5-HT uptake by 30%. In safety studies, acute oral toxicity, acute dermal toxicity, primary dermal irritation and primary eye irritation, were conducted in animals using various doses of HCA-SX. Results indicate that the LD50 of HCA-SX is greater than 5,000 mg/kg when administered once orally via gastric intubation to fasted male and female Albino rats. No gross toxicological findings were observed under the experimental conditions. Taken together, these in vivo toxicological studies demonstrate that HCA-SX is a safe, natural supplement under the conditions it was tested. Furthermore, HCA-SX can inhibit [3H]-5-HT uptake (and also increase 5-HT availability) in isolated rat brain cortical slices in a manner similar to that of SRRIs, and thus may prove beneficial in controlling appetite, as well as treatment of depression, insomnia, migraine headaches and other serotonin-deficient conditions.
To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes.
We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale.
A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported.
There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.
Objective: The main objective of this study was to evaluate blood leptin as a marker of obesity and correlate it with anthropometric measurements.Patients and Methods: There were 70 healthy obese and 35 lean individuals. Fasting plasma leptin was determined by radioimmunoassay in both study groups. The vital signs, body weight and height were taken, and the skinfold thickness was measured over the triceps muscle and in the subscapular region.Results: The median leptin level in the obese was significantly higher than that of the lean controls (38 Vs 5.6 ng/ml, p < 0.0001). The females had a higher median leptin level than the males (41.3 Vs 22 ng/ml, p < 0.0001). Twenty-three of the seventy patients studied (32.8%) had normal leptin levels. The median systolic blood pressure and the fasting blood glucose in the obese were significantly higher than in lean controls (130 vs 120 mm Hg, p < 0.05 and 5.3 vs 5.0 mmol/l, p < 0.01 respectively). Leptin correlated well with the grades of obesity (Rs = 0.4, p < 0.01), BMI (Rs = 0.4, p < 0.001), triceps (Rs = 0.4, p < 0.01) and subscapular SFTs (Rs = 0.4, p < 0.001), but not with fasting blood glucose (Rs = 0.2, p = 0.2).Conclusions: The systolic blood pressure, fasting blood leptin and sugar are higher in obese than lean individuals. Leptin is also higher in females than males and it correlates well with anthropometric measurements. However, it is not a perfect estimate of obesity, as 23 out of the 70 patients studied had normal leptin levels.
Progressive insulin resistance may contribute to both enhanced glycosylation of proteins and nucleic acids and augmented free radical damage commonly associated with aging. Accordingly, ingestion of chromium and antioxidants which improve insulin sensitivity and/or lessen free radical formation could theoretically ameliorate these basic disorders and lessen signs and symptoms of chronic age-related disorders. However, this supposition is based primarily upon acute rather than chronic data. Therefore, we divided 104 F344/BN rats into 2 groups: a control group receiving a basic diet and a test group receiving the same diet with added chromium polynicotinate (5 ppm), zinc monomethionine (18 ppm elemental zinc), and a grape seed extract high in flavonoids (250 ppm). Initial mean systolic blood pressures (SBP) of both control and test groups were 122 mm Hg. Over the first 7 months, the SBP of the control animals steadily increased to 140 mm Hg and remained at this level for the next 7–8 months. In contrast, the SBP of the test animals initially decreased over the first 4 months to as low as 110–114 mm Hg. The SBP then increased over the following months, essentially reaching the starting value of 120 mm Hg. This was still significantly lower than control (p
Objective
To develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, the reference population, and the age and sex specific cut off points.
Design
International survey of six large nationally representative cross sectional growth studies.
Setting
Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States
Subjects
97 876 males and 94 851 females from birth to 25 years of age
Main outcome measure
Body mass index (weight/height2).
Results
For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut off points of 25 and 30 kg/m2 for adult overweight and obesity. The resulting curves were averaged to provide age and sex specific cut off points from 2-18 years.
Conclusions
The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.
Hydroxycitrate (HCA), a popular dietary supplement for weight loss, is a competitive inhibitor of ATP-citrate lyase, an extramitochondrial enzyme involved in the initial steps of de novo lipogenesis (DNL). Although animal studies have shown that HCA effectively inhibits DNL and induces weight loss, these findings have not been consistent in humans. This raises the possibility that the bioavailability of HCA may differ among species. We developed a new GC/MS method to measure HCA levels in blood, using [U-13C]citrate (CA*) as internal standard to account for losses associated with the isolation, derivatization, and measurement of HCA. HCA and CA* were derivatized with BSTFA + 10% TMCS and analyzed using PCI/GC/MS (CA*, m/z 471; and HCA, m/z 553). The plasma HCA concentration was measured over a 3.5-h period in four subjects having ingested 2 g of HCA. Their plasma HCA concentration ranged from 0.8 to 8.4 μg/ml 30 min and 2 h after ingestion, respectively. These results demonstrate that when taken acutely, HCA is absorbed, yet present in small quantities in human plasma. This simple method requiring minimal sample preparation is able to measure trace amounts of HCA with accuracy and precision.
We examined whether dietary supplementation of hydroxycitrate (HCA), a competitive inhibitor of the extramitochondrial enzyme ATP–citrate–lyase, which inhibits lipogenesis, reduces food intake and body weight regain in rats after 10–15% weight loss. In four experiments, 24 male rats were fed restrictively (10 g/day) for 10 days and then given ad lib access to one of four different diets (HI-Suc=high sucrose; HI-Glu=high glucose; Chow=grounded standard rat chow; HI-Glu+Fat=high glucose+fat) varying in the content of fat and low molecular carbohydrates for the following 10 days. For half of the rats (n=12), the ad lib diet was supplemented with 3% (w/w) HCA. HCA reduced body weight regain with all diets except Chow. HCA also reduced food intake temporarily with three of the four tested diets. The suppressive effect of HCA on food intake was particularly strong with the HI-Glu+Fat diet (fat=24% of energy). With Diet HI-Glu and HI-Glu+Fat HCA reduced the feed conversion efficiency (cumulative body weight regain (g)/cumulative food intake (MJ)) during the 10 ad lib days, suggesting that it also increased energy expenditure. This effect seemed to be positively related to the glucose content of the diet. All in all, HCA reduced body weight regain after substantial body weight loss, and the effects are presumably linked to its inhibiting effect on lipogenesis, but the exact mechanism still has to be determined.
Effects on systolic blood pressure (SBP) of ingesting three agents reported to influence insulin metabolism, i.e., chromium polynicotinate, bis(maltolato)oxovanadium (BMOV), and the herb, Gymnema sylvestre, were assessed simultaneously in spontaneously hypertensive rats (SHR).
In the first study, SHR were fed either a starch, sugar, or sugar diet containing chromium polynicotinate, bis(maltolato)oxovanadium (BMOV), or G. sylvestre. Tail SBP was estimated indirectly and various blood chemistries were measured. TBARS formation was determined in hepatic and renal tissue. In a second study, tail SBP was measured in SHR ingesting diets containing different concentrations of BMOV.
Compared to starch, SHR consuming sucrose showed a significant elevation of SBP within days that was maintained for the duration of study. Addition of chromium polynicotinate to the sucrose diet at the beginning of study prevented the sucrose-induced elevation of SBP for 2 weeks, but SBP rose significantly after that. BMOV at high concentrations overcame the sucrose-induced rise in SBP and even decreased SBP below values seen in SHR eating the starch diet, but marked weight loss was noted. A second study examined different concentrations of BMOV. At 0.01% w/w concentration of BMOV, SBP was still significantly decreased, even though SHR did not lose body weight (BW) early on. SHR consuming G. sylvestre showed no change or even elevated SBP. Hepatic thiobarbituric acid reacting substances (TBARS) formation, an estimate of lipid peroxidation, was decreased by chromium polynicotinate and BMOV, and renal TBARS by chromium polynicotinate. Circulating cholesterol concentrations were decreased in the SHR consuming G. sylvestre.
Chromium decreases the portion of SBP elevated by high sucrose intake as shown previously, but high levels of sucrose ingestion can eventually overcome this. BMOV overcame sucrose-induced elevation of SBP as well as some of the "genetic hypertension." Different from chromium, this decrease was not overcome by high levels of dietary sucrose. The significant lowering of cholesterol with G. sylvestre ingestion indicates some effect on metabolism, but G. sylvestre did not lower and even raised SBP.
Formaldehyde (FA), acetaldehyde (ACT), malondialdehyde (MDA) and acetone (ACON) were simultaneously identified in urine, and their excretion quantitated in response to chemically induced oxidative stress. Urine samples of female Sprague-Dawley rats were collected over dry ice and derivatized with 2,4-dinitrophenylhydrazine. The hydrazones of the four lipid metabolic products were quantitated by high-performance liquid chromatography on a Waters 10-microns mu-Bondapak C18 column. The identities of FA, ACT, MDA and ACON in urine were confirmed by gas chromatography-mass spectrometry. An oxidative stress was induced by orally administering 100 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin, 75 mg/kg paraquat, 6 mg/kg endrin or 2.5 ml/kg carbon tetrachloride to rats. Urinary excretion of FA, ACT, MDA and ACON increased relative to control animals 24 h after treatment with all xenobiotics. The system has wide-spread applicability to the investigation of altered lipid metabolism in disease states and exposure to environmental pollutants.
GS4, a water-soluble extract of the leaves of Gymnema sylvestre, was administered (400 mg/day) to 27 patients with insulin-dependent diabetes mellitus (IDDM) on insulin therapy. Insulin requirements came down together with fasting blood glucose and glycosylated haemoglobin (HbA1c) and glycosylated plasma protein levels. While serum lipids returned to near normal levels with GS4 therapy, glycosylated haemoglobin and glycosylated plasma protein levels remained higher than controls. IDDM patients on insulin therapy only showed no significant reduction in serum lipids, HbA1c or glycosylated plasma proteins when followed up after 10-12 months. GS4 therapy appears to enhance endogenous insulin, possibly by regeneration/revitalisation of the residual beta cells in insulin-dependent diabetes mellitus.
Glycerol was shown recently to be metabolized to formaldehyde by microsomes from chowfed control rats (Winters et al., Biochem Biophys Res Commun 153: 612-617, 1988). In the present study, experiments were carried out to evaluate the oxidation of glycerol by microsomes isolated from rats treated with inducers of different isozymes of cytochrome P-450. The oxidation of glycerol to formaldehyde was increased in microsomes from rats treated with pyrazole, ethanol or acetone relative to their respective controls, but not after treatment with phenobarbital or 3-methylcholanthrene. This reaction was sensitive to inhibition by carbon monoxide and was inhibited by compounds known to be effective substrates for P-450j, e.g. aniline, ethanol, pyrazole and 4-methylpyrazole. Treatment with pyrazole caused an increase in Vmax for glycerol oxidation but did not affect affect the Km (about 15 mM) for glycerol, as compared to saline controls. Evidence that the product of glycerol metabolism is formaldehyde was provided by the observation that this product served as a substrate for the glutathione-dependent formaldehyde dehydrogenase, and the amount of formaldehyde detected was identical to that detected by the Nash reaction. By utilizing [14C]glycerol, and coupling the formaldehyde dehydrogenase reaction to the formate dehydrogenase reaction, 14CO2 could be detected, indicating that the formaldehyde produced was derived from the added glycerol. These results suggest that that glycerol is not metabolically inert when added to microsomes but serves as an effective substrate for the cytochrome P-450j isozyme, extending the alcohol substrate specificity of this enzyme to poly-ols. The production of formaldehyde from glycerol may require caution since glycerol is often present in microsomal or reconstituted systems.
Daily metabolizable energy intake (ME) and total daily energy expenditure (TEE) were measured in 28 nonobese and 27 obese adolescents over a 2-wk period. Reported ME was significantly (p less than 0.001) lower than measured TEE in both the nonobese and the obese groups (2193 +/- 618 vs 2755 +/- 600 kcal/d and 1935 +/- 722 vs 3390 +/- 612 kcal/d, respectively). Reported ME as a percentage of TEE was significantly lower in the obese than the nonobese group (58.7 +/- 23.6% vs 80.6 +/- 18.7%, respectively). When reported ME was adjusted to account for changes in body energy stores, reported ME still remained significantly lower than TEE in both groups. ME was highly reproducible over the 2-wk period. Intraclass correlation coefficients among days for subjects with complete 14-d diaries were 0.87 and 0.89 for nonobese and obese groups, respectively. In both groups, interindividual variability in ME was significantly greater than intraindividual variability. Our data suggest that reported ME in nonobese and obese adolescents is not representative of TEE or energy requirements.
A review of 144 published studies of the relationship between socioeconomic status (SES) and obesity reveals a strong inverse relationship among women in developed societies. The relationship is inconsistent for men and children in developed societies. In developing societies, however, a strong direct relationship exists between SES and obesity among men, women, and children. A review of social attitudes toward obesity and thinness reveals values congruent with the distribution of obesity by SES in different societies. Several variables may mediate the influence of attitudes toward obesity and thinness among women in developed societies that result in the inverse relationship between SES and obesity. They include dietary restraint, physical activity, social mobility, and inheritance.
Malondialdehyde (MDA) derivatives occur as normal constituents of rat and human urine. In a previous study, it was found that MDA excretion in rats is responsive to MDA intake and to certain factors that increase lipid peroxidation in vivo: vitamin E deficiency, iron administration and a high concentration of cod liver oil (CLO) fatty acids in the tissues. In the present study, the effect on MDA excretion of several additional dietary and endogeneous factors was evaluated.
The composition of dietary fatty acids had a major influence on MDA excretion in fed animals, being highest for animals fed n−3 fatty acids (20∶5 and 22∶6) from CLO, intermediate for those fed n−6 (18∶2) acids from corn oil (CO) and lowest for those fed saturated acids from hydrogenated coconut oil (HCO). Diet was the main source of urinary MDA in all groups. Fasting produced a marked increase in urinary MDA, which tended to be higher in rats previously fed CLO. Fasting MDA excretion was not affected by the level of CO in the diet (5, 10 or 15%), indicating that feeding n−6 acids does not increase lipid peroxidation in vivo. Adrenocorticotropic hormone and epinephrine administration increased urinary MDA, further indicating that lipolysis either releases fatty acid peroxides from the tissues or increases the susceptibility of mobilized fatty acids to peroxidation. A decrease in fasting MDA excretion was observed in rats previously fed a high level of antioxidants (vitamin E+BHT+vitamin C) vs a normal level of vitamin E. MDA excretion increased following adriamycin and CCl4 administration. No increase was observed following short-term feeding of a choline-methionine-deficient diet, which has been reported to increase peroxidation of rat liver nuclear lipids.
This study provides further evidience that urinary MDA can serve as a useful indicator of lipid peroxidation in vivo when peroxidation of dietary lipids is precluded.
Discussion of a natural food, namely the Malabar Tamarind, that may be effective in the treatment of obesity.
IN THE last decade, the explosive increase in our knowledge of neuropeptides has demonstrated that the release of peptides from the gastrointestinal tract can modulate behavior; and, contrariwise, gastrointestinal peptides have been shown to be synthesized and released in the central nervous system and act as neurotransmitters. This review will concentrate on the role of peptides as modulators of feeding behavior and weight regulation. The complexities of the neurochemical regulation of food intake are not surprising when one considers the varied inputs involved in the determination of feeding behavior. With depletion of an organism's energy stores, a series of signals arise which force the animal to hunt for food. When the food source is found, the animal needs to do a cost-benefit analysis, i.e. a determination of whether the potential danger and the energy expenditure involved are justified in terms of the calories to be gained and secondarily, to decide whether or not the food is suitable for consumption.
Rat liver microsomes catalyzed the oxidation of glycerol to a Nash-reactive material in a time- and protein-dependent manner. Omission of the glycerol or the microsomes or any of the components of the NADPH-generating system resulted in almost a complete loss of product formation. Apparent Km and Vmax values for glycerol oxidation were about 18 mM and 2.5 nmol formaldehyde per min per mg microsomal protein. Carbon monoxide inhibited glycerol oxidation indicating a requirement for cytochrome P-450. That the Nash-reactive material was formaldehyde was validated by a glutathione-dependent formaldehyde dehydrogenase positive reaction. These studies indicate that glycerol is not inert when utilized with microsomes or reconstituted mixed function oxidase systems, and that the production of formaldehyde from glycerol may interfere with assays of other substrates which generate formaldehyde as product.
The feeding of powdered leaves of Gymnema sylvestre in the diet of rats for 10 days prior and 15 days after i.v. beryllium nitrate significantly protected the animals from the full fall of blood glucose seen in rats receiving beryllium nitrate alone. The feeding of the leaves for 25 days to normal rats did not alter blood glucose significantly. The leaves may contain a principle that could be useful as a prophylactic against beryllium toxicity.
These studies were designed to determine the effect of (−)-hydroxycitrate upon the accumulation of lipid in the rat by examining appetite, wt gain, and total body lipid profiles. The chronic oral administration of a nontoxic dose of (−)-hydroxycitrate to growing rats for 11–30 days caused a significant reduction in body wt gain, food consumption, and total body lipid. The administration of equimolar amounts of citrate did not alter wt gain, appetite, or body lipid. No increase in liver size or liver lipid content occurred with either treatment. Pair feeding studies demonstrated that the reduction in food intake accounted for the decrease in wt gain and body lipid observed with (−)-hydroxycitrate treatment.
The purpose of these investigations was to ascertain the effect of (−)-hydroxycitrate on the accumulation of lipid in the
meal fed rat by examining the rates of lipogenesis after acute and chronic treatment. Oral administration of (−)-hydroxycitrate
depressed significantly the in vivo lipogenic rates in a dose-dependent manner in the liver, adipose tissue, and small intestine.
The hepatic inhibition was significant for the 8 hr period, when control animals demonstrated elevated rates of lipid synthesis.
The kinetics of this reduction of in vivo hepatic lipogenesis were identical after acute or chronic administration of (−)-hydroxycitrate.
However, in vitro rates of lipogenesis were elevated after chronic administration of (−)-hydroxycitrate for 30 days. Rats
receiving (−)-hydroxycitrate consumed less food than the untreated controls; however, this decreased caloric intake was not
responsible for the drug induced depression of hepatic lipogenesis, as shown by studies using pair fed rats.
A novel anti-obesity agent which inhibits fatty acid synthesis and stimulates fatty acid oxidation is described. The hydrochloride salt of Ro 22-0654 (4-amino-5-ethyl-3-thiophenecarboxylic acid methyl ester) is a potent inhibitor of fatty acid and cholesterol synthesis in rat-isolated hepatocytes. Hepatic fatty acid synthesis was inhibited in vivo in a dose-dependent fashion with a duration of action of approximately 8 h. Adipose tissue fatty acid synthesis was also inhibited in vivo. Inhibition of fatty acid synthesis occurs without any apparent effect on several lipogenic enzymes, the tricarboxylic acid cycle, and the pentose phosphate shunt. Ro 22-0654 also stimulated fatty acid oxidation (in vitro) and lipolysis (in vivo). In long-term studies (2 months), Ro 22-0654 decreased body weight gain in Sprague Dawley and genetically-obese Zucker rats. Food intake was decreased following a single dose and for several days during chronic treatment. However, while food intake quickly returned to normal, body weight gain remained lower in treated rats. The effect on body weight gain can be ascribed to decreased total body lipid content in the absence of an effect on lean body mass. It is suggested that Ro 22-0654 may have utility in the treatment of human obesity.
The regulation of body weight and composition involves input from genes and the environment, demonstrated, for example, by the variable susceptibility of inbred strains of mice to obesity when offered a high-fat diet. The identification of the gene responsible for obesity in the ob/ob mouse provides a new approach to defining links between diet and genetics in the regulation of body weight. The ob gene protein product, leptin, is an adipocyte-derived circulating protein. Administration of recombinant leptin reduces food intake and increases energy expenditure in ob/ob mice, suggesting that it signals to the brain the magnitude of fat stores. Information on the regulation of this protein is limited. In several rodent models of obesity including db/db, fa/fa, yellow (Ay/a) VMH-lesioned, and those induced by gold thioglucose, monosodium glutamate, and transgenic ablation of brown adipose tissue, leptin mRNA expression and the level of circulating leptin are increased, suggesting resistance to one or more of its actions. We have assessed the impact of increased dietary fat on circulating leptin levels in normal FVB mice and FVB mice with transgene-induced ablation of brown adipose tissue. We find that high-fat diet evokes a sustained increase in circulating leptin in both normal and transgenic mice, with leptin levels accurately reflecting the amount of body lipid across a broad range of body fat. However, despite increased leptin levels, animals fed a high-fat diet became obese without decreasing their caloric intake, suggesting that a high content of dietary fat changes the 'set point' for body weight, at least in part by limiting the action of leptin.
The inhibitory effects of gurmarin (a peptide isolated from the leaves of Gymnema sylvestre) on sweet taste responses were studied by examining the chorda tympani nerve responses to various taste substances before and after lingual treatment with gurmarin in C57BL and BALB mice. Treatment with gurmarin at 3 micrograms/ml or more selectively suppressed responses to sucrose without affecting responses to NaCl, HCl, and quinine in C57BL mice, whereas gurmarin at 100 micrograms/ml did not significantly suppress sucrose responses in BALB mice. Responses to various sweet substances in C57BL mice decreased to approximately 45-75% of control after gurmarin, and the suppressive effect of gurmarin was reversible. The profile of the residual responses of C57BL mice to various sweeteners after gurmarin was almost identical to that of BALB mice, which was hardly affected by gurmarin. These results strongly suggest that there are at least two types of sweet taste receptors in mice, gurmarin-sensitive and -insensitive. Probably, C57BL and BALB mice share an identical gurmarin-insensitive receptor, and C57BL mice also have a gurmarin-sensitive receptor.
The sweetness-suppressing polypeptide gurmarin has been isolated from the leaves of Gymnema sylvestre and consists of 35 amino acid residues including three intramolecular disulfide bonds. The primary structure has already been determined. The positions of the disulfide bonds were located, by a combination of mass spectrometric analysis and sequencing of cystine-containing peptides obtained by thermolysin-catalyzed hydrolysis of gurmarin, to be at Cys3-Cys18, Cys10-Cys23, and Cys17-Cys33.
The relationships between dietary and environmental factors and obesity are reviewed. Findings from selected population studies of diet and body weight are presented. In general, the results from population studies of diet and obesity have been inconsistent and marked with methodological weaknesses, especially the use of cross-sectional study design. Apart from the diet, several social and economic factors appear to be important correlates of obesity in the population. However, most studies have focused on the socioeconomic status as a broad, composite measure. The relationships between income, education, occupation, place of residence, and obesity are reviewed here, with emphasis on the developing countries. In many developing countries, the changing dietary pattern, along with rising life expectancy and changing socioeconomic environment, has contributed to the increasing problems of obesity and other diet-related chronic diseases that will have an enormous impact on the health and health care resource of these countries in the near future.
Although the disorders associated with obesity have been extensively studied, little attention has been paid to the fact that obesity is itself a chronic disease. This misunderstanding of the nature of obesity has contributed to the stigmatization of obese persons and to the use of inappropriate or inadequate treatment regimens. Although the etiology of obesity is still unclear, genetic, metabolic, and social factors are all believed to play a role in its development and progression. Behavioral therapy, exercise, very-low-calorie diets, drug therapy, and surgery affect the treatment of obesity of differing levels of severity. The regaining of weight following treatments other than surgery is very frequent, in part because periods of weight loss are rarely followed by maintenance programs. An increasing awareness of the chronic, multifactorial nature of obesity will ideally lead to the development of new long-term treatment programs that are safe and effective. Such programs are urgently needed in light of new data that show that the prevalence of obesity is increasing in the United States, as much as 30% in the last decade.
Chromium supplementation may affect various risk factors for coronary artery disease (CAD) and non-insulin-dependent diabetes mellitus (NIDDM), including body weight and composition, basal plasma hormone and substrate levels, and response to an oral glucose load. This study examined the effects of chromium supplementation (400 micrograms.d-1), with or without exercise training, on these risk factors in young, obese women. Chromium picolinate supplementation resulted in significant weight gain in this population, while exercise training combined with chromium nicotinate supplementation resulted in significant weight loss and lowered the insulin response to an oral glucose load. We conclude that high levels of chromium picolinate supplementation are contraindicated for weight loss in young, obese women. Moreover, our results suggest that exercise training combined with chromium nicotinate supplementation may be more beneficial than exercise training alone for modification of certain CAD and NIDDM risk factors.
Serotonin (5-HT) has been implicated in the control of eating behavior and body weight. Stimulants of this monoamine reduce food intake and weight gain and increase energy expenditure, both in animals and in humans. This article reviews evidence that supports a role for hypothalamic serotonergic receptor mechanisms in the mediation of these effects. A variety of studies in rodents indicate that, at low doses, 5-HT or drugs that enhance the release of this neurotransmitter preferentially inhibit the ingestion of carbohydrate, more than fat or protein. This phenomenon is mediated, in part, by 5-HT receptors located in various medial hypothalamic nuclei. A negative feedback loop exists between the consumption of this macronutrient and the turnover of 5-HT in the hypothalamus. That is, carbohydrate ingestion enhances the synthesis and release of hypothalamic 5-HT, which in turn serves to control the size of carbohydrate-rich meals. A model is described that proposes the involvement of circulating hormones and glucose in this feedback process. These hormones, including insulin, corticosterone, and the adipose tissue-derived hormone, leptin, have impact on serotonergic function as well as satiety. This model further suggests that 5-HT exerts its strongest effect on appetite at the start of the natural feeding cycle, when carbohydrate is normally preferred. Clinical studies provide evidence that is consistent with the proposed model and that implicates 5-HT in disturbances of eating and body weight disorders.
Hydroxycitric acid, the active ingredient in the herbal compound Garcinia cambogia, competitively inhibits the extramitochondrial enzyme adenosine triphosphate-citrate (pro-3S)-lyase. As a citrate cleavage enzyme that may play an essential role in de novo lipogenesis inhibition, G cambogia is claimed to lower body weight and reduce fat mass in humans.
To evaluate the efficacy of G cambogia for body weight and fat mass loss in overweight human subjects.
Twelve-week randomized, double-blind, placebo-controlled trial.
Outpatient weight control research unit.
Overweight men and women subjects (mean body mass index [weight in kilograms divided by the square of height in meters], approximately 32 kg/m2).
Subjects were randomized to receive either active herbal compound (1500 mg of hydroxycitric acid per day) or placebo, and both groups were prescribed a high-fiber, low-energy diet. The treatment period was 12 weeks. Body weight was evaluated every other week and fat mass was measured at weeks 0 and 12.
Body weight change and fat mass change.
A total of 135 subjects were randomized to either active hydroxycitric acid (n = 66) or placebo (n = 69); 42 (64%) in the active hydroxycitric acid group and 42 (61%) in the placebo group completed 12 weeks of treatment (P = .74). Patients in both groups lost a significant amount of weight during the 12-week treatment period (P<.001); however, between-group weight loss differences were not statistically significant (mean [SD], 3.2 [3.3] kg vs 4.1 [3.9] kg; P = .14). There were no significant differences in estimated percentage of body fat mass loss between treatment groups, and the fraction of subject weight loss as fat was not influenced by treatment group.
Garcinia cambogia failed to produce significant weight loss and fat mass loss beyond that observed with placebo.
Dietary supplements that contain ephedra alkaloids (sometimes called ma huang) are widely promoted and used in the United States as a means of losing weight and increasing energy. In the light of recently reported adverse events related to use of these products, the Food and Drug Administration (FDA) has proposed limits on the dose and duration of use of such supplements. The FDA requested an independent review of reports of adverse events related to the use of supplements that contained ephedra alkaloids to assess causation and to estimate the level of risk the use of these supplements poses to consumers.
We reviewed 140 reports of adverse events related to the use of dietary supplements containing ephedra alkaloids that were submitted to the FDA between June 1, 1997, and March 31, 1999. A standardized rating system for assessing causation was applied to each adverse event.
Thirty-one percent of cases were considered to be definitely or probably related to the use of supplements containing ephedra alkaloids, and 31 percent were deemed to be possibly related. Among the adverse events that were deemed definitely, probably, or possibly related to the use of supplements containing ephedra alkaloids, 47 percent involved cardiovascular symptoms and 18 percent involved the central nervous system. Hypertension was the single most frequent adverse effect (17 reports), followed by palpitations, tachycardia, or both (13); stroke (10); and seizures (7). Ten events resulted in death, and 13 events produced permanent disability, representing 26 percent of the definite, probable, and possible cases.
The use of dietary supplements that contain ephedra alkaloids may pose a health risk to some persons. These findings indicate the need for a better understanding of individual susceptibility to the adverse effects of such dietary supplements.
(-)-Hydroxycitric acid (HCA) reportedly promotes weight loss, in part, through suppression of hunger. However, this mechanism has never been evaluated in humans in a controlled study. Eighty-nine mildly overweight females were prescribed 5020-kJ diets for 12 weeks as part of a double-blind, placebo-controlled parallel group study. Forty-two participants ingested 400-mg caplets of Garcinia cambogia 30-60 min prior to meals for a total dose of 2.4 g/day (1.2 g/day HCA). Forty-seven participants ingested matched placebos. Weight and body composition were assessed at baseline and every other week for 12 weeks. Food intake and appetitive variables were assessed at baseline and monthly for 12 weeks. Both groups lost body weight with the active group achieving a significantly greater reduction (3. 7+/-3.1 kg versus 2.4+/-2.9 kg). No effects of the HCA were observed on appetitive variables. The active treatment group did not exhibit better dietary compliance or significant correlations between appetitive variables and energy intake or weight change. This study does not support a satiety effect of HCA.
This pilot study was designed to determine whether 600 microg niacin-bound chromium ingested daily over 2 months by African-American women undergoing a modest dietary and exercise regimen influences weight loss and body composition.
Twenty overweight African-American women, engaged in a modest diet-exercise regimen, participated in a randomized, double-blinded, placebo-controlled, crossover study. They received placebo three times a day (t.i.d.) during the control period and niacin-bound chromium, 200 microg t.i.d., during the verum period. Control and verum periods were each 2 months in duration. One-half received placebo first (group 1), the other half received chromium first (group 2). Body weights (b.w.) and blood chemistries were measured by routine clinical methodology. Fat and nonfat body masses were estimated using bioelectrical impedance (electrolipography).
In the first group of 10 women receiving niacin-bound chromium after the placebo period (group 1), b.w. loss was essentially the same, but fat loss was significantly greater and non-fat body mass loss significantly less with chromium intake. In contrast to the previous findings, there was a significantly greater loss of fat in the placebo compared to the verum period in the second group of eight women who received chromium first (group 2). Blood chemistries were not affected by intake of chromium for 2 months.
Niacin-bound chromium given to modestly dieting-exercising African-American women caused a significant loss of fat and sparing of muscle compared to placebo. Once chromium was given at these dose levels, there was a 'carry-over' effect. Blood chemistries revealed no significant adverse effects from the ingestion of 600 microg of niacin-bound chromium daily over 2 months.
In rodents leptin inhibits food intake, stimulates energy expenditure, reverses obesity, ameliorates insulin resistance, and accelerates sexual maturation. These potent and diverse effects have stimulated interest in exploring a role for leptin in the treatment of human metabolic disorders. However, the significance of leptin in human (patho)physiology is still being investigated. The present review summarizes current knowledge of leptin regulation, provides a critical assessment of initial experience with leptin therapy, and discusses potential targets for recombinant leptin therapy in humans. The results of numerous studies indicate that leptin is indeed a regulated human hormone: The physiological factors that influence leptin secretion include gender, adiposity, physical exercise, feeding, and caloric restriction. Several hormones, including insulin, glucocorticoids, estradiol, growth hormone, testosterone, somatostatin, and insulin-like growth factor-I also modulate leptin secretion. The results of initial trials of leptin therapy in humans have become available. Treatment with recombinant human leptin (0.028 mg/kg) induced a progressive weight loss (without evidence of tachyphylaxis) in a morbidly obese patient with congenital leptin deficiency. The weight loss averaged 1-2 kg/month, was associated with preservation of lean muscle mass, and was almost exclusively accounted for by depletion of body fat. Administration ofrecombinant leptin (0.01-0.3 mg/kg) also resultedin a dose-dependentweight loss among lean and obese humans with presumably normal leptin genotype. Thus leptin may have a therapeutic role in humans, but its physiological functions and regulation first need to be fully unravelled.
(-)-Hydroxycitric acid [(-)-HCA] is the principal acid of fruit rinds of Garcinia cambogia, Garcinia indica, and Garcinia atroviridis. (-)-HCA was shown to be a potent inhibitor of ATP citrate lyase (EC 4.1.3.8), which catalyzes the extramitochondrial cleavage of citrate to oxaloacetate and acetyl-CoA: citrate + ATP + CoA --> acetyl-CoA + ADP + P(i) + oxaloacetate. The inhibition of this reaction limits the availability of acetyl-CoA units required for fatty acid synthesis and lipogenesis during a lipogenic diet, that is, a diet high in carbohydrates. Extensive animal studies indicated that (-)-HCA suppresses the fatty acid synthesis, lipogenesis, food intake, and induced weight loss. In vitro studies revealed the inhibitions of fatty acid synthesis and lipogenesis from various precursors. However, a few clinical studies have shown controversial findings. This review explores the literature on a number of topics: the source of (-)-HCA; the discovery of (-)-HCA; the isolation, stereochemistry, properties, methods of estimation, and derivatives of (-)-HCA; and its biochemistry, which includes inhibition of the citrate cleavage enzyme, effects on fatty acid synthesis and lipogenesis, effects on ketogenesis, other biological effects, possible modes of action on the reduction of food intake, promotion of glycogenesis, gluconeogenesis, and lipid oxidation, (-)-HCA as weight-controlling agent, and some possible concerns about (-)-HCA, which provides a coherent presentation of scattered literature on (-)-HCA and its plausible mechanism of action and is provocative of further research.
We review evidence regarding the influence of dietary fat, fiber, the glycemic index and sugar on energy intake and body weight. Although data from comprehensive long-term studies are lacking, published investigations suggest that the previous focus on lowering dietary fat as a means for promoting negative energy balance has led to an underestimation of the potential role of dietary composition in promoting reductions in energy intake and weight loss. More randomized clinical trials are needed to examine the relative utility of different putative dietary factors in the treatment of obesity.
Assessment of the effects of 2 weeks of daily administration of HCA on energy intake and satiety in overweight men and women.
A 6-week randomized placebo-controlled single-blinded cross-over trial.
consumed three times daily for 2 weeks 100 ml tomato juice (placebo) and, separated by a 2 week wash-out period, 100 ml tomato juice with 300 mg HCA.Subjects: Twelve males and 12 females (body mass index 27.5+/-2.0 kg/m(2); age 37+/-10 y).
After 2 weeks, 24 h energy intake (EI), appetite profile, hedonics, mood and possible change in dietary restraint were assessed in the laboratory restaurant. Prevention of degradation and bio-availability was documented.
Twenty-four-hour EI was decreased by 15-30% (P<0.05) with HCA treatment compared to placebo, without changes in the appetite profile, dietary restraint, mood, taste perception and hedonics, while body weight tended to decrease (P=0.1).
HCA treatment reduced 24 h EI in humans while satiety was sustained.
The prevalence of obesity is increasing worldwide, which indicates that the primary cause of obesity lies in environmental and behavioural changes rather than in genetic modifications. Among the environmental influences, the percentage of fat energy of the everyday diet and the lack of physical activity are two important factors, which contribute to explain the rising prevalence of obesity. In this review, several lines of evidence are presented to illustrate why dietary fat does affect obesity development. There are four factors which support a link between dietary fat and obesity development:The thermic effect of nutrients, expressed as percentage of their energy content, is 2-3% for lipids, 6-8% for carbohydrates and 25-30% for proteins. This means that the efficiency of nutrient utilization (calculated as 100%-the thermic effect of the nutrient) is higher for fat than for carbohydrate or protein.Postingestive fuel selection favours the oxidation of dietary proteins and carbohydrates, whereas dietary fats are preferentially stored as triacylglycerol in adipose tissue. Alcohol, by inhibiting lipid oxidation, indirectly favours the storage of dietary fats.High-fat diet promotes excessive energy intake by passive overconsumption; the fat-induced appetite control signals are too weak or too delayed to prevent excessive energy intake from a fatty meal. The only proof that dietary fats contribute to weight gain is to test the long-term effect of ad libitum low-fat diets. Most studies on low-fat diets show that they induce a modest weight loss in obese individuals, but their long-term effect from a public health perspective is limited, probably due to a low compliance to the dietary advice.