Use of dicarboxylic acids in type 2 diabetes

Abstract

Even‐number, medium‐chain dicarboxylic acids (DAs), naturally occurring in higher plants, are a promising alternative energy substrate. Unlike the homologous fatty acids, DAs are soluble in water as salts. They are β‐oxidized, providing acetyl‐CoA and succinyl‐CoA, the latter being an intermediate of the tricarboxylic acid cycle. Sebacic acid and dodecanedioic acid, DAs with 10 and 12 carbon atoms respectively, provide 6.6 and 7.2 kcal g−1 each; therefore, their energy density is intermediate between glucose and fatty acids. Dicarboxylic acids have been proved to be safe in both experimental animals and humans, and their use has recently been proposed in diabetes. Studies in animals and humans with type 2 diabetes showed that oral administration of sebacic acid improved glycaemic control, probably by enhancing insulin sensitivity, and reduced hepatic gluconeogenesis and glucose output. Moreover, dodecanedioic acid intake reduced muscle fatigue during exercise in subjects with type 2 diabetes, suggesting an improvement of energy utilization and ‘metabolic flexibility’. In this article, we review the natural sources of DAs, their fate in animals and humans and their effect in improving glucose metabolism in type 2 diabetes.

Plasma metabolomic biomarkers of mixed nuts exposure inversely correlate with severity of metabolic syndrome

“…In any case, the biological relevance of its increased exposure following nut intake, particularly in subjects with metabolic impairment, may rely on its recognized role as an alternative energy substrate. Once available, in fact, dodecanedioic acid is promptly oxidized and, due to the intermediate biochemical and metabolic characteristics between free fatty acids and glucose, may supply succinyl‐CoA at the end of its β‐oxidation , providing an alternative entry into the tricarboxylic acid cycle and a mean of metabolic improvement . The positive effects of dodecanedioic acid infusion have already been described, particularly in those clinical conditions characterized by altered glycemic control, and range from improved mitochondrial function efficiency to reduction of gluconeogenesis, improvement in glycogen synthesis, and significant increase in lipid oxidation, in turn leading to reduced body fat mass .…”

“…Once available, in fact, dodecanedioic acid is promptly oxidized and, due to the intermediate biochemical and metabolic characteristics between free fatty acids and glucose, may supply succinyl‐CoA at the end of its β‐oxidation , providing an alternative entry into the tricarboxylic acid cycle and a mean of metabolic improvement . The positive effects of dodecanedioic acid infusion have already been described, particularly in those clinical conditions characterized by altered glycemic control, and range from improved mitochondrial function efficiency to reduction of gluconeogenesis, improvement in glycogen synthesis, and significant increase in lipid oxidation, in turn leading to reduced body fat mass . The decrease of sebacic acid, in contrast, was not reported previously and may result from an increased downstream or upstream metabolism, suggesting a possible alteration in the metabolism of ω‐oxidation of fatty acids in the cytosol of the cells .…”

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

“…Nevertheless, the positive C3DC-diabetes association in our study highlighted the role of malonyl-CoA in diabetes pathogenesis. Unlike odd-chain dicarboxylic acids, even-chain dicarboxylic acids are derived from v-oxidation of fatty acids and thereafter undergo b-oxidation (43). Intervention studies indicated that sebacic acid (C10DC fatty acid) and dodecanedioic acid (C12DC fatty acid) had favorable impacts on glycemic control and energy utilization in patients with type 2 diabetes (43).…”

“…Unlike odd-chain dicarboxylic acids, even-chain dicarboxylic acids are derived from v-oxidation of fatty acids and thereafter undergo b-oxidation (43). Intervention studies indicated that sebacic acid (C10DC fatty acid) and dodecanedioic acid (C12DC fatty acid) had favorable impacts on glycemic control and energy utilization in patients with type 2 diabetes (43). In accordance with these findings, the observed inverse associations of C10DC and C12DC acylcarnitines with incident diabetes in our cohort supported potential benefits of sebacic acid and dodecanedioic acid in type 2 diabetes.…”

Nutraceuticals: is there good science behind the hype?

“…Typically the products revolve around the levels of micronutrients (vitamins, minerals) and macronutrients (proteins, lipids, carbohydrates) that need to be consumed in order to alleviate or prevent deficiencies or overconsumption, as well as improving the quality of particularly macronutrients to exert certain health benefits. Examples of this approach are supplementation or fortification products with vitamins and minerals,'light'products with less sugar or fat, alternative energy sources [6], claims related to the health impact of lipids from different omega families [7] and rapidly vs. slowly available carbohydrates. Increasingly, research activities are focussing on the identification and substantiation of novel actions and health benefits of mainstream nutritional components, such as polyphenols [8,9] or dietary nitrate [10].…”