A Novel Mixture of δ-Tocotrienol, Vitamin D3, Resveratrol (NS-3) Significantly Decreases Diabetes Biomarkers Including Inflammatory in People with Type 2 Diabetes

Aims: Diabetes mellitus is a metabolic disorder identified by hyperglycemia due to insulin resistance. Impaired serum/plasma fasting glucose, HbA1c, hs-CRP are biomarkers, normally used to determine onset of diabetes. d-Tocotrienol, vitamin D3, and resveratrol (nutritional supplement-NS-3) are potent anticholesterolemic, anti-oxidative and anti-inflammatory agents. We hypothesized that a mixture of d-tocotrienol, vitamin D3, resveratrol (NS-3) will be more effective treatment for reducing diabetes biomarkers as compared to its individual components, in people with type 2 diabetes mellitus (T2DM). Methods: To test our hypothesis, evaluation of NS-3 mixture and its individual components was carried out on diabetes inflammatory biomarkers using peripheral blood mononuclear cells (PBMC) obtained from healthy, normal and people with T2DM. A randomized placebo controlled double-blinded prospective trial of individual components (n = 30/component), and NS-3 trial of people with T2DM (n = 52/group), were given two capsules/d of cellulose/olive oil as placebo, individual components, or NS-3 mixture for 24-weeks. Results: Significant down-regulation (15 - 74; P < 0.002) of gene expression was observed with individual components and NS-3 on diabetes biomarkers (IRS-1, SOD-2, GCKR, ICAM-1, VCAM-1, IL-6, IL-8) in PBMCs of T2DM, and in serum values of fasting glucose (11%), HbA1c (10%), hs-CRP (23%), fasting insulin (9%), HOMA-IR (20%), MDA (20%) of NS-3 treated people with T2DM after 24-weeks. Treatment with individual components showed significant decrease but were less effective than the mixture. RT-PCR analysis of blood RNAs obtained from NS-3 treated people with T2DM for 24-weeks resulted in significant (P < 0.01) down-regulation of gene expression in diabetes biomarkers (IRS-1, SOD-2, GCKR, IGFPB-2) compared to pre-dose values. Conclusions: Present results of in vitro and in vivo studies support our hypothesis that NS-3 mixture is more effective in lowering serum levels of several diabetes biomarkers including inflammatory gene expression markers compared to its individual components in people with T2DM.