The Effect of High-Intensity Interval Training with Vitamin D Intake on Interleukin-10 and Lipid Peroxidation Levels in Overweight Women with Low Vitamin D Status: A Randomized Clinical Trial

Sedentary life and vitamin D deficiency are considered related factors to increased inflammation and oxidative stress in obese conditions. Being overweight and obese is determined by increased adipose tissue due to hypertrophy and hyperplasia of fat cells (1). Previous research has shown that overweight and obesity are associated with vitamin D deficiency (3). Vitamin D deficiency is one of the most important and common health problems associated with several diseases such as kidney disease, diabetes, cardiomyopathy and Alzheimer's disease. Vitamin D plays an important role in regulating several cellular pathways for the synthesis of antioxidants (4).The best biomarker to determine the status of vitamin D is the concentration of 25-hydroxyvitamin D. Serum levels below 20 ng /ml are defined as vitamin D deficiency (3).Large adipocytes with complete local oxygen consumption induce hypoxia, which may lead to cellular inflammation and secretion of inflammatory cytokines by activating oxidative stress pathways (4). Oxidative stress, in turn, plays a causal role in obesity (6). A strong association between oxidative stress and vitamin D deficiency has been reported (8).Vitamin D has anti-inflammatory effects and affects inflammatory processes and immune cells through different pathways, including regulating the production of anti-inflammatory cytokines (12).Interleukin 10(IL-10) is a potent anti-inflammatory cytokine that is synthesized in several organs (13). It has been observed in experimental studies that with obesity, serum IL-10 levels decreased in mice on a high-fat diet, and this reduction played a very important role in obesity-induced inflammation in other organs (15, 16). Exercise is recommended as an important non-pharmacological treatment for the prevention or treatment of obesity and its metabolic and somatic cellular complications (19). Systematic studies and available meta-analyzes have shown that high-intensity interval training (HIIT) has more significant effects on reducing abdominal and visceral fat and improving cardiorespiratory fitness in overweight and obese adults than moderate-intensity continuous exercise (21, 22). Today, lack of time is one of the main reasons for non-participation of people in regular sports activities (23). Due to the association of obesity and overweight with inflammatory factors and oxidative stress, it is necessary to conduct further studies focusing on the effect of low-risk and cheaper interventions such as HIIT and/or vitamin D consumption in the prevention or treatment of oxidative-inflammatory complications. Therefore, the present study investigated the HIIT with vitamin D intake on IL-10 and lipid peroxidation levels in overweight women with IL-10 deficiency.

This single-blind clinical trial was conducted on 52 overweight women with vitamin D deficiency and ages ranging 23-29 years old. After selecting the subjects by the available sampling method, they were randomly divided into control, interval, vitamin D and combination groups. The HIIT was performed with the 12x1-min running bouts at 80-90% maximum heart rate (HRmax) interspersed with 1-min active recovery at 50% HRmax in between bouts for 8 weeks. Vitamin D and combination groups took vitamin D once a week with food for 8 weeks (30).The vitamin D and combination groups received 50,000 IU of vitamin D per week (29). Levels of 25-hydroxyvitamin D less than 20 ng /ml were considered as vitamin D deficiency. Blood samples were collected in the pre- and post-test stages, followed by 12 hours of fasting and serum was frozen at -80 ° C. The serum was then frozen at -80 ° C and used to measure the research variables. Then, serum levels of variables were determined using a special commercial kit and laboratory methods. Malondialdehyde (MDA) levels were measured as an indicator of lipid peroxidation. One-way analysis of variance test with repeated measures and Bonferroni post hoc was also used to compare intergroup differences. In addition, the rate of change of variables was tested through Kruskal-Wallis and U Mann-Whitney tests. The significance level was considered P<0.05 and all statistical analysis was performed using SPSS software version 22.

The results of one-way analysis of variance test with repeated measures showed that there is a significant difference between IL-10 and MDA levels of inactive women during the two stages before and after eight weeks, regardless of the group factor. Also, the effect of group (regardless of time factor) and the interactive effect of time×group on the levels of these variables are significant (P<0.05). The MDA levels in interval, vitamin D and combination groups decreased significantly and IL-10 levels increased significantly after 8 weeks(P<0.001). But the combined intervention had a stronger effect on the change of MDA and IL-10 levels compared to the other two interventions (P<0.001). In addition, the effect of HIIT on decreasing MDA levels was greater than vitamin D intake (P= 0.018), and no significant difference was found between the amount of IL-10 changes in these two groups (P=0.184).

Both vitamin D deficiency (9) and obesity (33) cause overproduction of ROS, increasing oxidative stress. Reactive oxygen species (ROS) interacts with unsaturated lipids within the cell membrane and causes lipid peroxidation, which in turn significantly increases MDA levels, leading to the inactivation of many proteins and cellular receptors, causing cell membrane damage (34). Vitamin D can exert its strong anti-inflammatory activity by inhibiting the expression and activation of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kB), which has optimal effects on oxidative stress (32). Regular exercise can greatly improve the efficiency of enzymatic and non-enzymatic antioxidant defense systems and enhance the body's ability to eliminate peroxidants. Exercise can inhibit NF-κB activation in human T cells by reducing ROS-producing factors, such as tumor necrosis factor-α (40). Exercise can also reduce oxidative stress by increasing the bioavailability of nitric oxide (42). However, the effect of HIIT on reducing MDA and consequent oxidative stress has been more effective than vitamin D supplementation, which may be related to the synergistic effects of these two interventions in the oxidation-antioxidant balance shift towards the superiority of antioxidant defense. It seems that HIIT and vitamin D intake can be exert their protective effects in overweight individuals with vitamin D deficiency by a decrease in the MDA and increasing the anti-inflammatory index of IL-10. Although these effects developed with combined intervention, but HIIT was associated with a greater reduction in MDA than vitamin D intervention.