The main findings of this study were that supplementary antioxidants with B-group vitamins enhanced individual antioxidant capacity and mitigated inflammation in obese diabetic patients. We found no significant effects of antioxidants and B-group vitamins together on markers of oxidative damage possibly due to the lower dose of the vitamins used or small sample size or a combination of both.
Possible mechanisms that relate obesity and diabetes to increased CVD risk include inflammation, oxidative damage, and related insulin resistance. In obese patients subclinical inflammation has been found to correlate with markers of oxidative stress in adipose tissue and this may be the mechanism for obesity-related metabolic syndrome, insulin resistance and diabetes mellitus. Furthermore both oxidative stress and low-grade inflammation may be causatively linked to the development, progression and complications of diabetes in obese patients [2–5]. Oxidative stress is defined as imbalance between the generation of free oxygen radicals and the antioxidant defense system and results from increased production of reactive oxygen species known to trigger cytotoxic reactions that are damaging to membrane lipids, proteins, nucleic acids and carbohydrates. A number of studies revealed the link between oxidative stress, obesity, diabetes and other related complications. Recent research does indeed support a close link between oxidative stress and diabetes evolution, revealing that oxidative stress occurs before the appearance of clinical manifestations of late diabetic complications, suggesting a key role in the pathogenesis of the disease . Results from our study clearly show increased oxidative stress in diabetic subjects with time, as evidenced by a significant increase in MDA and protein carbonyls and reduction of vitamin C and GSH in both the placebo group and the intervention group. In addition a number of studies have reported an association between oxidative stress and insulin resistance and that some antioxidants may improve insulin resistance [4, 5]. A recent systematic review and meta-analysis has reported that increasing daily intake of green leafy vegetables could significantly reduce the risk of type 2 diabetes and this should investigated further . Another recent data also suggest that dietary antioxidants intake may be a predictor of the risk to develop metabolic syndrome features such as adiposity or impairments in systolic blood pressure, serum glucose and free fatty acids, and some inflammatory biomarkers in healthy subjects . A comprehensive obesity prevention report recommended that each country should promote food intake high in fruits and vegetables which are the main sources of antioxidants . Currently a number of ongoing clinical studies are testing the effects of a number of substances including antioxidants on inflammation and metabolic and cardiovascular outcomes in obese patients .
We used a combination of antioxidant vitamins in our study because particular benefits from supplementing with vitamin C and E simultaneously derive from the interaction of these vitamins in vivo. Alpha-tocopherol is found mainly in the lipid compartment of cells and extracellular fluid, whereas ascorbic acid is located in the aqueous compartments. However, in vitro and, recently, in vivo studies point to an interaction such that there may be a mutual “sparing” effect . Ascorbic acid appears to be able to regenerate the reduced, antioxidant form of α-tocopherol through redox cycling . Although B-group vitamins reduced total plasma homocysteine concentrations in this study; they had no additive effects with antioxidants on markers of oxidative damage. This lack of difference may have been due to the lower dose of vitamins used, length of treatment, tissue inflammation, or differences in rate of absorption between subjects or due the small sample size of the study population. Homocysteine may promote oxidative stress through its detrimental effect on the vascular endothelium [6, 18]. Therefore, homocysteine lowering with B-group vitamins may have an indirect antioxidant effect as a result of the decrease in vascular endothelial dysfunction.
Our study sample comes from a population known to have increased visceral obesity which is known to be associated with increased oxidative stress and inflammation . This is because visceral fat secretes a number of factors involved in a range of metabolic and physiological processes, some of these factors having been implicated in the pathologies associated with obesity including diabetes, hypertension and CVD [3, 4].
Limitations and strength of the study
Our sample was small and almost one quarter of subjects refused to give a blood sample at 3 months follow up. Because the daily supplements dose we originally planned to use could only be contained in 3 separate capsules we ended up using a 1/3 of the daily dose (a capsule day) to help aid compliance. It is very likely that a larger dose of the supplement might have produced larger effects on oxidative damage and inflammation. The study has much strength including the random generation of the allocation sequence and allocation of supplements and also the placebo controlled design and the double-blind nature of intervention treatment and assessment.