This study’s aim was to evaluate the effect of Taurine on endothelial dysfunction markers, oxidative stress, inflammation, and glycemic control in type 2 diabetic subjects (T2DM). The results of our study for the first time showed that Taurine improved endothelial function indicators including reduction in the ICAM, VCAM, and MMP-9 levels. Furthermore, Taurine had noteworthy effects on some CV risk factors including BP, glycemic control, and inflammation, and oxidative stress markers. Moreover, participants who lost at least of 2.5 kg in weight post-intervention had considerably enhanced cardiometabolic risk assessment compared to those with unremarkable weight loss (data not shown). When results were stratified by weight changes 25% of the participants experienced weight losses more than 2.5 kg by the end of the study (including 17 subjects of the Taurine group and 13 subjects of the placebo group), but regardless of the given supplement, patients losing > 2.5 kg had a greater decrease in CV risk factors in comparison to those who lost < 2.5 kg (data not shown).

Our results demonstrated that an eight-week period of Taurine supplementation enhanced the serum insulin, and HOMA-IR in the Taurine group; although, the levels of FBG and HbA1c did not significantly differ between the groups in study. A similar conclusion was reached by previous surveys in diabetic experimental animal models [30, 31]. A similar pattern of results was obtained in a pilot clinical trial in which the effect of 3 g/day Taurine supplementation was studied [17]. Contrary to our findings, Shari et al. [32] did not find the effect of 1000 mg Taurine for 12 weeks’ on glycemic control in patients with T2DM. It has been assumed that the conflicting findings reported in the literature can be largely attributed to differences in the dose of supplementation, range of glycemic levels, and duration of intervention. The main mechanisms by which Taurine supplementation might improve insulin and HOMA-IR are not well understood. However, Taurine may directly by activate AMP-activated protein kinas) AMPK( in skeletal muscles, or pancreatic islets cells [19, 20]. Another possible mechanism is preventing of the hepatic glucose synthesis in different ways including phosphorylation of the insulin receptor Β-subunit)IRβ(, the reduced glucagon activity in the liver and the increased levels of the uncoupling protein 1 (UCP1) in adipose tissue [19]. In addition to the anti-diabetic effect by regulating activity of the pancreatic cells, the glucose lowering and anti-inflammatory effects of Taurine are further effects of this amino acids on glycemic control [17, 21, 30]. However, in this study, there was not a significant fall in FBG or HbA1c levels in the intervention group, likely due to the inadequate period of treatment (8 weeks). Since erythrocytes have a long-life span, (120 days), a longer duration of treatment is required to observe the possible changes in HbA1c.

Our findings showed that inflammatory and oxidative stress markers (hs-CRP, TNF, TAC, and MDA) were reduced by Taurine. These findings support the idea that Taurine play a significant anti-inflammatory part. Also, our finding is consistent with previous studies showing the protective functions of Taurine against oxidative stress and inflammation [33, 34]; Silva et al. [35] revealed that Taurine improve oxidative stress in skeletal muscles. A similar conclusion was drawn by Ahmadian et al. [33] which reported that Taurine has anti-inflammatory and cytoprotective effects in patients with heart failure. However, some reports showed that supplementation with 3 g/d of Taurine for 16 weeks did not reduce oxidative stress among patients with T2DM [36]; this can largely be ascribed to the higher inflammatory markers as a result of poor glycemic control among patients with T2DM.

It has been assumed that the anti-inflammatory properties of Taurine arise from its antioxidant capacity to offset hypochlorous acid by the formation of Taurine chloramine [6, 10, 11]. Accordingly, the production of Taurine chloramine at the site of inflammation can regulate the synthesis and secretion of proinflammatory cytokines including TNF, IL-6, and IL-8. Furthermore, Taurine halts generation of superoxides in mitochondria [37].

Patients with T2DM are susceptible to experience numerous challenges including abnormalities in lipid profiles. Another result of the present trial is that Taurine supplementation in patients with T2DM for 8 weeks did not significantly affect lipid profiles. In other studies Taurine through increasing the cholesterol conversion into bile acids, up-regulation of LDL receptors, as well as decreasing the hepatic cholesterol ester pool was shown to improved lipid panel by [38, 39].

Endothelial dysfunction is an early event in development of atherosclerosis and subsequent CVD events that is frequently seen in patients with T2DM [2, 7, 9]. As the main finding, this study showed that in patients with T2DM Taurine exposure for 8 weeks significantly decreased the biomarkers related to endothelial dysfunction including VCAM, ICAM-1, and MMP-9. Although A few studies have considered the effects of Taurine on endothelial markers, to the best of our knowledge, this study was the first clinical trial reporting the effects of Taurine on the biomarkers related to endothelial dysfunction in T2DM. This finding was aligned with those reported by Fennessy, et al. showing that Taurine supplementation improved endothelial function [40]. Similar results were demonstrated by an experimental animal model whereby Taurine was found to reduce acute hyperglycemia-induced endothelial markers in male Sprague Dawley rats [22]. Similarly, Taurine restored endothelial function in type I diabetic rats [41]. There are some mechanisms underlaying the endothelial-protective roles of Taurine including lowering vascular NADPH, restoration of phosphorylation of endothelial NOS (eNOS), and enhancing expression of extracellular superoxide dismutase (EcSOD) [42]. Also, a previous survey confirmed that Taurine by scavenging ROS and attenuating lipid peroxidation has a remarkable antioxidant activity [42].

Interruption of the ROS activity, scavenging ROS, and regeneration of thiol groups are probably the most likely mechanisms underlying the beneficial effect of Taurine in diabetic patients [10, 33]. Furthermore, a pile of studies showed a reverse correlation between plasma concentrations of taurine and FBS as well as diabetes complications [14]. As a functional nutrient, taurine plays a significant part in detoxification, osmoregulation, calcium homeostasis, neuromodulator, and cytoprotection. Also, taurine can alter insulin signaling pathway and regulate the β-cell insulin secretion ability, leading to the more efficient control of glucose metabolism [12, 25, 40]. In conclusion, based on the European Food Safety Authority (EFSA) report in 2012, the daily application of taurine up to 3000 mg seems to be safe, as we showed the same finding in the present study. Although, there were not significant adverse effects in our study, some studies reported a few adverse effects including nausea, vomiting, headache, stomach pain and rarely inhibition of cytochrome P450 enzyme [43, 44]. It’s unclear whether these effects are directly related to the taurine or they may arise from other impurities. Thus, it seems crucial to assess both the concentrations of taurine in the blood and the adverse effects of taurine at the relevant doses in the future studies.

The current study has some limitations, including not assessing the brachial artery flow‑mediated dilation (FMD), as well as the short duration of the supplementations. Long-standing supplementation would be required to show whether Taurine supplementation positively regulates glycemic control. Aside from that, this supplementation could be beneficial for larger confirmatory studies.