Anitra C. Carr

Chronic low-grade inflammation is a characteristic of people with metabolic syndrome and is thought to contribute to the condition progressing to the more severe type 2 diabetes and cardiovascular disease (CVD). The aim was to carry out a double-blind randomised placebo-controlled trial in people with metabolic syndrome to determine if supplementation with a micronutrient formula containing 1000 mg/d vitamin C could attenuate inflammation in people with metabolic syndrome. We recruited 72 adults aged a median of 52 years with metabolic syndrome, defined as obesity (based on waist circumference or BMI), and at least two of hyperglycaemia, raised triglycerides, lowered HDL cholesterol, hypertension, or taking medications for these conditions. A further inclusion criteria comprised C-reactive protein (CRP) concentrations ≥ 3 mg/L, i.e., high risk of CVD. The participants were randomised to daily micronutrient formula (n = 37) or matched placebo control (n = 35) for 12 weeks. The primary outcome was change in CRP concentrations and secondary outcomes included changes in vitamin C concentrations, pro-inflammatory cytokines (IL-6, TNFα), oxidative stress marker (F2isoprostanes), glycaemic indices (glucose, insulin, HbA1c), lipid markers (triglycerides, LDL and HDL cholesterol), anthropometric parameters (weight, BMI), insulin resistance and insulin sensitivity, and metabolic severity score. The participants had a low median (Q1, Q3) vitamin C status of 29 (15, 41) µmol/L and a high proportion of hypovitaminosis C (38%) and outright deficiency (19%). Following 12 weeks of micronutrient supplementation, at least 70% of the participants reached adequate vitamin C status (≥50 µmol/L), however, there was no change in CRP concentrations relative to the placebo group (Δ−0.3 [95%CI −2.7, 2.1] mg/L, p = 0.8). Similar trends were observed for IL-6, TNFα and F2isoprostanes (p > 0.05). Instead, there were small improvements in BMI, fasting glucose and HbA1c concentrations, insulin sensitivity and metabolic severity score in the micronutrient group relative to placebo (p < 0.05). Overall, 12-week micronutrient supplementation was unable to mitigate systemic inflammation in people with metabolic syndrome but may improve several metabolic health indices.

Elevated inflammation has been associated with adverse mood states, such as depression and anxiety, and antioxidant nutrients, such as vitamin C, have been associated with decreased inflammation and improved mood. In the current study comprising a cohort of pregnant women with depression and anxiety, we hypothesised that elevated inflammation would be associated with adverse mood states and inversely associated with vitamin C status and that multinutrient supplementation would optimise vitamin concentrations and attenuate inflammation. Sixty-one participants from the NUTRIMUM trial had blood samples collected between 12 and 24 weeks gestation (baseline) and following 12 weeks of daily supplementation with a multinutrient formula containing 600 mg of vitamin C or active placebo. The samples were analysed for inflammatory biomarkers (C-reactive protein (CRP) and cytokines) and vitamin C content and were related to scales of depression and anxiety. Positive correlations were observed between interleukin-6 (IL-6) and all of the mood scales administered (p < 0.05), including the Edinburgh Postnatal Depression Scale, the Clinical Global Impressions—Severity Scale, the Montgomery and Åsberg Depression Rating Scale, the Depression Anxiety Stress Scale 21, and the Generalized Anxiety Disorder-7 (GAD-7). CRP correlated weakly with GAD-7 (p = 0.05). There was an inverse correlation between CRP and the vitamin C status of the cohort (p = 0.045), although there was no association of the latter with the mood scales (p > 0.05). Supplementation with the multinutrient formula resulted in a significant increase in the vitamin C status of the cohort (p = 0.007) but did not affect the inflammatory biomarker concentrations (p > 0.05). In conclusion, greater systemic inflammation was associated with worse mood states; however, 12-week multinutrient supplementation did not alter inflammatory biomarker concentrations. Nevertheless, the vitamin C status of the cohort was improved with supplementation, which may aid pregnancy and infant outcomes.