Inositol and antioxidant supplementation: Safety and efficacy in pregnancy

Abstract

Pregnancies complicated by diabetes have largely increased in number over the last 50 years. Pregnancy is characterized by a physiologic increase in insulin resistance, which, associated with increased oxidative stress and inflammations, could induce alterations of glucose metabolism and diabetes. If not optimally controlled, these conditions have a negative impact on maternal and foetal outcomes. To date, one can resort only to diet and lifestyle to treat obesity and insulin resistance during pregnancy, and insulin remains the only therapeutic option to manage diabetes during pregnancy. However, in the last years, in a variety of experimental models, inositol and antioxidants supplementation have shown insulin-sensitizing, anti-inflammatory, and antioxidant properties, which could be mediated by some possible complementary mechanism of action. Different isomers and multiple combinations of these compounds are presently available: Aim of the present review article is to examine the existing evidence in order to clarify and/or define the effects of different inositol- and antioxidant-based supplements during pregnancy complicated by insulin resistance and/or by diabetes. This could help the clinician's evaluation and choice of the appropriate supplementation regimen.

Keywords: antioxidants; diabetes; glucose metabolism; inositol; pregnancy; safety.

Figure 1

Role of inositol in insulin signalling pathway (inspired on Larner and Brautigan34). Upon binding with its receptor (IR), insulin induces IRS‐1 recruitment and activation. One of the principal IR/IRS target, PI3K, then generates Phosphatidilinositol to activate PDK1 and subsequently PKB/Akt. These actions are involved in GLUT4 translocation and in glycogen synthesis. According to the theory of Larner and Brautigan,34 IR activation might also be coupled to a heterotrimeric G protein, which in turn activates a phospholipase responsible for Glycosilphosphatidylinositol hydrolysis with the production of soluble inositol phosphoglycans. Upon insulin receptor activation, inositol phosphoglycans are released outside the cell and subsequently reimported by SMIT. Inositol phosphoglycans may act as a putative second insulin messenger. In the cytoplasm, inositol phosphoglycan binds to and allosterically activates PP2Cα and/or IRS, with the consequent direct stimulation of glycogen synthase. In the mitochondria, activated PDHP stimulates PDH and consequently glucose oxidative metabolism. Abbreviations: GLUT‐4 glucose transporter 4; GSK3, glycogen synthase kinase 3; IR, insulin receptor; IRS insulin receptor substrates; PDH, pyruvate dehydrogenase; PDHP, pyruvate dehydrogenase phosphatase; PDK‐1 phosphoinositide‐dependent kinase 1; PI3K, phosphoinositide 3 kinase; PKB/Akt, protein kinase B/Akt; SMIT, sodium/myo‐inositol transporter; PP2Cα, phosphoprotein phosphatase 2C alpha