A comprehensive scientific overview of Garcinia cambogia.

Garcinia is a plant under the family of Clusiaceae that is commonly used as a flavouring agent. Various phytochemicals including flavonoids and organic acid have been identified in this plant. Among all types of organic acids, hydroxycitric acid or more specifically (−)-hydroxycitric acid has been identified as a potential supplement for weight management and as antiobesity agent. Various in vivo studies have contributed to the understanding of the anti-obesity effects of Garcinia/hydroxycitric acid via regulation of serotonin level and glucose uptake. Besides, it also helps to enhance fat oxidation while reducing de novo lipogenesis. However, results from clinical studies showed both negative and positive antiobesity effects of Garcinia/hydroxycitric acid. This review was prepared to summarise the update of chemical constituents, significance of in vivo/clinical anti-obesity effects, and the importance of the current market potential of Garcinia/hydroxycitric acid.

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Updates on Antiobesity Effect of Garcinia Origin (−)-HCA

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. De novo lipogenesis (DNL) is vital for the maintenance of whole-body and cellular homeostasis, but aberrant upregulation of the pathway is associated with a broad range of conditions, including cardiovascular disease, metabolic disorders and cancers. Here, Steinberg and colleagues provide an overview of the physiological and pathological roles of the core DNL enzymes and assess strategies and agents currently in development to therapeutically target them. 

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Lipogenesis inhibitors: therapeutic opportunities and challenges

Obesity is associated with cardiovascular disease, diabetes and certain forms of cancer. Popular strategies on weight loss often fail to address many key factors such as fat mass, muscle density, bone density, water mass, their inter-relationships and impact on energy production, body composition, and overall health and well-being. (-)-Hydroxycitric acid (HCA), a natural plant extract from the dried fruit rind of Garcinia cambogia, has been reported to promote body fat loss in humans without stimulating the central nervous system. The level of effectiveness of G. cambogia extract is typically attributed solely to HCA. However, other components by their presence or absence may significantly contribute to its therapeutic effectiveness. Typically, HCA used in dietary weight loss supplement is bound to calcium, which results in a poorly soluble (<50%) and less bioavailable form. Conversely, the structural characteristics of a novel Ca2+/K+ bound (-)-HCA salt (HCA-SX or Super CitriMax) make it completely water soluble as well as bioavailable. An efficacious dosage of HCA-SX (4500 mg/day t.i.d.) provides a good source of Ca2+ (495 mg, 49.5% of RDI) and K+ (720 mg, 15% of RDI). Ca2+ ions are involved in weight management by increasing lipid metabolism, enhancing thermogenesis, and increasing bone density. K+, on the other hand, increases energy, reduces hypertension, increases muscle strength and regulates arrhythmias. Both Ca and K act as buffers in pH homeostasis. HCA-SX has been shown to increase serotonin availability, reduce appetite, increase fat oxidation, improve blood lipid levels, reduce body weight, and modulate a number of obesity regulatory genes without affecting the mitochondrial and nuclear proteins required for normal biochemical and physiological functions.

Bioefficacy of a novel calcium–potassium salt of (−)-hydroxycitric acid

Spices used in Indian cooking have a long history of use as medicines to prevent and treat diseases. Many studies have confirmed that spices can be useful medicines, but the major challenge is now to provide scientific evidence and plausible mechanisms for their therapeutic responses. This review focuses on the therapeutic potential of Indian spices to treat multiple symptoms of the metabolic syndrome such as insulin resistance, diabetes, obesity, altered lipid profile and hypertension. The metabolic syndrome is prevalent and has become an important financial burden to the healthcare system in both developed and developing countries. Inflammation and oxidative stress have been proposed as initiators of the metabolic syndrome, especially of insulin resistance. Natural products with anti-inflammatory and anti-oxidant properties are found in spices. Adequate doses of these compounds may be effective in treating the metabolic syndrome. Testing these potential treatments requires adequate animal models, usually rodents, so the limitations of these models are important. Furthermore, this review highlights the need for adequate legislation and regulation to ensure the safety and success of evidence-based functional foods and nutraceuticals.

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Potential health benefits of Indian spices in the symptoms of the metabolic syndrome: a review.

We examined the effects of a nondigestible disaccharide difructose anhydride III (DFAIII) on calcium absorption and retention by means of a human balance study of single-blind crossover design. Twelve healthy male subjects ingested 250 mg of shell powder as calcium carbonate (corresponding to 100 mg of calcium) with or without 1.0 g DFAIII three times a day for 13 d. In the last 4 d as a balance period, all urine and feces were collected and evaluated for calcium excretion. The apparent calcium absorption (mg/d) and rate of absorption (%) were higher, and those of retention were much higher, in the DFAIII group than in the control group. Furthermore, serum osteocalcin increased after the experimental period in the DFAIII group but not in the control group. These results indicate that DFAIII ingestion enhances intestinal calcium absorption, which might be beneficial for bone metabolism.

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Ingestion of difructose anhydride III enhances absorption and retention of calcium in healthy men.

(-)-Hydroxycitric acid (HCA) is a competitive inhibitor of the enzyme ATPcitrate-lyase, which inhibits lipogenesis in the body. Moreover, HCA increases endurance exercise performance in trained mice and athletes. However, had not been investigated in untrained animals and humans. Therefore, we investigated the effects of short-term HCA ingestion on endurance exercise performance and fat metabolism in untrained women. In two experiments designed as a double-blind crossover test, six subjects ingested 250 mg of HCA or placebo (same amount of dextrin) via capsule for 5 d and then participated in cycle ergometer exercise. They cycled at 40% VO2max for 1 h and then the exercise intensity was increased to 60% VO2max until exhaustion on day 5 of each experiment. HCA tended to decrease the respiratory exchange ratio (RER) and carbohydrate oxidation during 1 h of exercise. In addition, exercise time to exhaustion was significantly enhanced (p<0.05). These results suggest that HCA increases fat metabolism, which may be associated with a decrease in glycogen utilization during the same intensity exercise and enhanced exercise performance.

Hydroxycitric acid ingestion increases fat utilization during exercise in untrained women.

We examined how dietary melibiose affected the T-helper (Th) cell responses induced by an orally fed antigen in ovalbumin (OVA)-specific T cell receptor transgenic mice (OVA 23-3). Dietary melibiose markedly decreased the Th2 type responses as shown by a significant decrease in the interleukin (IL)-4 production and T cell proliferative response induced by sensitization from the 7-d oral administration of OVA. It was additionally observed that the Th1 type responses tended to decrease. We therefore examined the effect of melibiose feeding on the induction of immunological tolerance induced by the oral administration of an antigen (oral tolerance). The Th cell responses induced in BALB/c mice by subcutaneous immunization with OVA were suppressed by the prior oral administration of OVA. Such responses in the OVA-fed and immunized mice were further diminished by dietary melibiose. These results suggest that dietary melibiose strongly affected the Th cell responses to an ingested antigen, and further demonstrate the potential of melibiose to enhance the induction of oral tolerance.

https://www.tandfonline.com/doi/pdf/10.1271/bbb.70372

Dietary Melibiose Regulates Th Cell Response and Enhances the Induction of Oral Tolerance

We examined the effects of (-)-Hydroxycitrate (HCA) ingestion on fat oxidation during moderate intensity exercise in untrained men. Six subjects ingested 500 mg of HCA or a placebo for 5 days and did endurance exercise. Blood FFA concentrations were significantly increased and respiratory exchange ratio (RER) decreased by HCA ingestion. These results suggested short-term HCA ingestion increases fat oxidation in untrained men.

hydroxycitrate ingestion increases fat oxidation during moderate intensity exercise in untrained men.

A composition containing difructose anhydride (DFA) and use thereof. DFA is a cyclic disaccharide in which reducing ends of two fructose molecules are bonded respectively to hydroxyl groups other than the reducing ends each other. It has been clarified that DFA has effects of promoting the absorption of zinc or copper, promoting osteogenesis, promoting diuresis, improving bowel movement and preventing decay. The above-described composition is usable in drugs, foods and drinks including animal feeds. As drugs, foods and drinks for humans or animals, the composition is available for oral administration in the form of, for example, prepared powdery milk, enteral feeding products, health foods or drinks, or feed additives.

Kyoko Tomita

Papers

Ingestion of difructose anhydride III enhances absorption and retention of calcium in healthy men.

Hydroxycitric acid ingestion increases fat utilization during exercise in untrained women.

Dietary Melibiose Regulates Th Cell Response and Enhances the Induction of Oral Tolerance

hydroxycitrate ingestion increases fat oxidation during moderate intensity exercise in untrained men.

Difructose anhydride-containing composition and use thereof