This is the first research that dealt with the evaluation of the impacts of magnesium and zinc combined supplementations on the metabolic profiles in the female suffering with T2DM and CHD. This RCT demonstrated that magnesium plus zinc combined supplementation to the female suffering from CHD and T2DM affected usefully the FPG, insulin, HDL-cholesterol, CRP, total nitrite, levels of TAC as well as BDI and BAI scores.
Impacts on the glycemic control and serum lipoproteins
Our findings showed that magnesium and zinc combined supplement in the female suffering from CHD and T2DM during 12 weeks caused a considerable decline in the FPG and insulin levels, and considerable enhancement in the level of HDL-cholesterol, but it had no effect on the HOMA-IR, QUICKI, total cholesterol, triglyceride, VLDL-cholesterol and LDL-cholesterol level. According to previous studies, chronic hyperglycemia and dyslipidemia increase the risk of diabetic and atherogenic complications [25, 26]. A meta-analysis indicated that magnesium intake is associated a significant improvement in FPG, triglycerides, HDL-cholesterol and LDL-cholesterol levels . Our previous study showed that supplementing with magnesium oxide (250 mg/day) in the pregnant female suffering from GDM during 6 weeks caused a remarkable improvement in the FPG, insulin concentration, HOMA-IR, QUICKI, and triglycerides levels, but it caused no change other serum lipoproteins . However, magnesium lactate with a dose of 360 mg per day during 12 weeks did not apply remarkable effects on HbA1c, FPG, levels of insulin, HOMA-IR and lipid profiles in normomagnesemic patients suffering from T2DM . One of the meta-analyses conducted in the field showed that supplementing zinc to the patients suffering diabetes mellitus has been associated with a considerable decline in FPG, HbA1c, total cholesterol, and a remarkable augment in the levels of HDL-cholesterol, but there has been no significant association with triglycerides . Another research performed by Islam et al.  revealed that zinc supplementations (30 mg per day of zinc sulphate) for 6 months improved FPG, insulin resistance, insulin sensitivity and decreased triglycerides levels without causing any considerable changes in the level of the LDL-cholesterol and HDL-cholesterol. A combination of magnesium-zinc-calcium-vitamin D during a 12 week period has been correlated with a remarkable decline in the levels of HOMA-IR, insulin, triglyceride, total cholesterol, and VLDL-cholesterol and a considerable increase in the QUICKI scores, but it has been not accompanied by changes in the level of LDL-cholesterol, FPG, and HDL-cholesterol in the PCOS patients . Hyper-insulinemia and insulin resistance have been related to hyperglycemia which is the main symptom of diabetes mellitus. Hyperglycemia affects the glycation of lipoproteins but has a lot of other unfavorable effects which cause accelerated atherosclerosis [30, 31]. Moreover, researchers demonstrated that magnesium is one of the crucial cofactors in the enzymatic processes that require adenosine triphosphate and kinase, and therefore it plays an important role in glucose metabolic pathways . Zinc is also important in physiological processes such as glucose metabolism. For instance, zinc is involved in the phosphorylation of insulin and the regulation of signaling by tyrosine phosphatase [13, 32].
Effects on oxidative stress and inflammation
In this research, we showed a considerable decline of CRP and a remarkable enhancement in the levels of TAC and total nitrite via the combined magnesium and zinc supplementations to the patients suffering from CHD and T2DM over a 12 weeks period. Oxidative stress and inflammation are important risk factors for diabetes and diabetes‐associated atherosclerosis . Asemi et al.'s  research indicated that magnesium supplement (250 mg/day of magnesium oxide) in pregnant women with GDM for 6 weeks considerably decreased hs-CRP, but changes in TAC and GSH concentrations were not significant. Nevertheless, magnesium supplement (magnesium oxide) with a dose of 250 mg per day during eight weeks to over-weight female did not associate with any changes in inflammatory markers . In another study, zinc supplement (30 mg per day of zinc sulphate) in the women with prediabetes for 6 months did not associate with any considerable change in the levels of CRP . However, combining magnesium-zinc-calcium-vitamin D supplement for 12 weeks in the female suffering from PCOS has been correlated to the considerable decline of CRP level . Combined magnesium-zinc-calcium-vitamin D supplementation in another similar study had association with a remarkable decline decrease in the levels of hs-CRP and MDA, and a considerable enhancement in the level of TAC without any significant change in nitric oxide (NO) and GSH levels . A recent study reported that combined magnesium and zinc supplementation (250 mg/day of magnesium oxide plus 220 mg/day zinc sulfate) to the female suffering from PCOS during 12 weeks affected usefully the levels of hs-CRP and TAC; yet, it no significant effects have been seen on NO, MDA and GSH levels .
Magnesium is assumed to possess anti-inﬂammatory properties caused by the respective antagonist effects to the calcium which contributes significantly to the inﬂammations, transmembrane ion transport, and protein synthesis . Magnesium also increases production of NO and prostacyclins . Zinc seems to have effects on hemostasis by influencing on coagulation and platelet accumulation . Zinc deficiency influences calcium channels and calcium uptake defects and subsequent second-messenger performance most probably stems from an unusual sulfhydryl redox states in the membrane channel protein having an impact on CVD. .
Effects on depression and anxiety
Our findings indicated that combined magnesium and zinc supplementation to patients with CHD and T2DM during 12 weeks improved BDI and BAI scores. The prevalence of depression and anxiety in CHD subjects is high and it is responsible for an increased risk of mortality . A study using food frequency questionnaire and general health questionnaire reported a reverse correlation between dietary magnesium intake and depression and anxiety . Data from a review suggested that zinc deficiencies are prevalent in mood disorders and that zinc supplement can have therapeutic impacts in these subjects . Nonetheless, Fard et al.'s  research showed that supplementing with 27 mg per day zinc sulfate or 320 mg/day magnesium sulfate did not improve postpartum anxiety and depressive symptoms after 8 weeks. In another study by Nikseresht et al., acute administration of combined 30 mg/kg zinc chloride, 30 mg/kg magnesium chloride and 50 mg/kg thiamine-HCl in mice with postpartum depression symptoms improved depression symptoms and anxiety-like behavior. Zinc and magnesium act as cofactors and contribute significantly to synthesis and release of neurotransmitters and thereby can have antidepressant and anxiolytic effects . For example, zinc and magnesium prevent binding of N-methyl-D-aspartate receptors to glutamate and may be associated with an antidepressant and anxiolytic effects .
This study has some limitations. The most important one is relatively small number of patients despite the fact that the power analysis showed that the number of participants is sufficient.