L-arginine, an endogenous amino acid, is a safe substance that can be found in food. The compound is involved in synthesis of various products responsible for regulatory functions in the body. Particularly noteworthy is, among others, nitric oxide, a signaling molecule regulating carbohydrate and lipid metabolism. The increasing experimental and clinical data indicate that L-arginine supplementation may be helpful in managing disturbed metabolism in obesity, regulate arterial blood pressure or alleviate type 2 diabetes symptoms, but the mechanisms underlying these effects have not been sufficiently elucidated. This review aims to present the up-to-date information regarding the current uses and health-promoting potential of L-arginine, its effects on nitric oxide, carbohydrate and lipid metabolisms, based on the results of in vivo, in vitro studies, and clinical human trials. Available literature suggests that L-arginine may have beneficial effects on human health. However, some studies found that higher dietary L-arginine is associated with worsening of an existing disease or may be potential risk factor for development of some diseases. The mechanisms of regulatory effects of L-arginine on carbohydrate and lipid metabolism have not been fully understood and are currently under investigation.

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A number of health-promoting properties of Stevia rebaudiana Bertoni and its glycosides, including the antihyperglycemic activity, have been found. The mechanisms of the antidiabetic action of stevia have not been fully understood. The aim of this study was to evaluate the effects of supplementary steviol glycosides on high-fat fed streptozotocin-induced diabetic rats with particular attention to lipid metabolism. The experiment was conducted on 70 male Wistar rats, of which 60 were fed a high-fat diet for 8 weeks followed by intraperitoneal injection of streptozotocin, to induce type 2 diabetes. Afterwards, rats were divided into six groups and fed a high-fat diet supplemented with pure stevioside or rebaudioside A, at two levels (500 or 2500 mg/kg body weight (b.w.)) for 5 weeks. Three additional groups: diabetic untreated, diabetic treated with metformin, and healthy, served as respective controls. Blood and dissected internal organs were collected for hematological, biochemical, and histopathological tests. It was found that dietary supplementation with steviol glycosides did not affect blood glucose, insulin, and insulin resistance indices, antioxidant biomarkers, but normalized hyperlipidemia and affected the appetite, as well as attenuated blood liver and kidney function indices, and reduced tissular damage in diabetic rats. Steviol glycosides normalize lipid metabolism and attenuate internal organs damage in diabetes.

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Stevia rebaudiana Bertoni and its glycosides are believed to exhibit several health-promoting properties. Recently, the mechanisms of the anti-diabetic effects of steviol glycosides (SG) have been the subject of intense research. The following study aims to evaluate the results of SG (stevioside (ST) and rebaudioside A (RA)) combined with L-arginine (L-Arg) and chromium(III) (CrIII) supplementation in streptozotocin- (STZ) induced mild type 2 diabetic rats fed a high-fat diet (HFD), with particular emphasis on carbohydrate and lipid metabolisms. The experiment was carried out on 110 male Wistar rats, 100 of which were fed an HFD to induce insulin resistance, followed by an intraperitoneal injection of streptozotocin to induce mild type 2 diabetes. After confirmation of hyperglycemia, the rats were divided into groups. Three groups served as controls: diabetic untreated, diabetic treated with metformin (300 mg/kg BW), and healthy group. Eight groups were fed an HFD enriched with stevioside or rebaudioside A (2500 mg/kg BW) combined with L-arginine (2000 or 4000 mg/kg BW) and Cr(III) (1 or 5 mg/kg BW) for six weeks. The results showed that supplementation with SG (ST and RA) combined with L-arg and Cr(III) could improve blood glucose levels in rats with mild type 2 diabetes. Furthermore, ST was more effective in improving blood glucose levels, insulin resistance indices, and very low-density lipoprotein cholesterol (VLDL-C) concentrations than RA. Although L-arg and Cr(III) supplementation did not independently affect most blood carbohydrate and lipid indices, it further improved some biomarkers when combined, particularly with ST. Notably, the beneficial impact of ST on the homeostatic model assessment–insulin resistance (HOMA-IR) and on the quantitative insulin-sensitivity check index (QUICKI) was strengthened when mixed with a high dose of L-arg, while its impact on antioxidant status was improved when combined with a high dose of Cr(III) in rats with mild type 2 diabetes. In conclusion, these results suggest that supplementary stevioside combined with L-arginine and Cr(III) has therapeutic potential for mild type 2 diabetes. However, further studies are warranted to confirm these effects in other experimental models and humans.