The aim of this study was to investigate the role of oxidative stress in the incidence of MetS and OSA to understand the associated health risks. We used a sample of male bakery workers, on the basis that this was an active occupation where exposure to an environment conducive to oxidative stress would permit a suitable investigation. Prevalence rates of MetS and OSA among the 163 male bakers were relatively low, which was in keeping with a sample with relatively low obesity and smoking levels. Of relevance, the rate of MetS in this study (12.3%) was in keeping with the 10.88% reported for the same city in a recent cohort study [19]. Similarly, the prevalence of OSA was close to the recent estimate that one in seven adults in the general population have OSA [20].
We found BMI, regular exercise, smoking, daily work hours and oxidative stress (as measured by malondialdehyde levels) had statistically significant roles in the development of these diseases. However, BMI, regular exercise, and smoking are common prognostic tools in both diseases. This study replicated such findings and for the first time looked at MetS and OSA concurrently to examine the contribution of oxidative stress to understanding these diseases. We found obesity was the biggest predictor of both MetS and OSA. The results from our study also suggest that oxidative stress can activate pathways that play an important role in the development of MetS. That is, oxidative stress can be considered an initiator of the MetS process due to the reactions it creates in the body. However, there was no significant association of oxidative stress and OSA.
Our findings that oxidative stress contributes to MetS in obese men is not at odds with the literature. Specifically, adipose tissue can secrete substances that play a major role in triggering MetS inflammation [21]. Macrophage infiltration of adipose tissue, especially visceral fat, is one of the characteristics of mild inflammation in obesity and there is a positive correlation between BMI and the amount of macrophage infiltration within adipose tissue. Macrophages that are activated in adipose tissue can secrete large amounts of pre-inflammatory adipokines [21]. Increased activation of NF-kβv pathways through oxidative stress and adipokine production can contribute to increased adipokine release [22]. Moreover, adiponectin is an important adipokine that plays a major role in the regulation of muscle metabolism as a plasma protein. The beneficial effects of adiponectin include its anti-inflammatory and insulin sensitivity effects [23]. Plasma levels of adiponectin, strongly associated with MetS, are lower in obese people than in non-obese people [24], and people with the lowest adiponectin levels probably have MetS [25]. Leptin is also an important adipokine and is increased in obese people [26]. Leptin can increase oxidative stress and pre-inflammatory factors [22].
The lack of an independent role for oxidative stress in participants with symptoms of OSA was unexpected. There are several potential reasons for this result. First, we have to acknowledge that whilst STOP-Bang is able to appropriately detect OSA [15], it is a screen for OSA. Polysomnography is required to determine severity of OSA. In their cross-sectional study of the role of oxidative stress in OSA, Yamauchi et al. [27] recruited from a sleep disorders clinic and found it was only the group with severe OSA that had high oxidative stress markers. In our sample of artisan bakers, the prevalence of OSA was modest, and we cautiously suggest that the findings may align with those of their mild OSA sample, whilst recognizing the different methodology. Nevertheless, there are other studies that have also shown no association between the incidence of OSA and increased oxidative stress [28, 29]. A potential reason for this evolves from the severity angle, and the thesis of Lavie [3]. Drawing upon a range of studies she suggested that the repetitive cycle of upper airway collapse and recovery results in a frequent hypoxia / reoxygenation process which can induce oxidative stress by an overproduction of free radicals. Moreover, support for this involvement comes from evidence that oxidative stress is reduced in OSA patients following continuous positive airway treatment [3]. In sum, we can understand our results do not deny the relationship of MetS and OSA, if we recognize that oxidative stress is involved in each disease, if in a different way. That is, increased severity of OSA increases oxidative stress, and oxidative stress is involved in the pathogenesis of MetS.
To address the challenge of accurate measurement of oxidate stress [18] we used three measures of oxidative stress. These were malondialdehyde (MDA), nitric oxide (NO), and total antioxidant count (TAC). We found MDA levels were significantly raised in participants who had MetS compared to those who did not have MetS. There was no difference in the same participants according to their OSA status. MDA is a commonly used biomarker, and whilst this measure of lipid oxidation has criticized for being prone to artifacts, it has also been considered to have clinical relevance in inflammatory diseases [9]. We did not, however, find an excess of NO, a free radical and a marker of oxidative stress, according to either MetS or OSA. It remains that the measurement of NO is fraught with difficulty because of its low concentrations in serum, and short half-life [30], nevertheless the ELISA assay kits we used were an established methodology. We also took TAC measures, following the rationale that low levels of TAC suggests oxidative stress, and it routine use. We found no difference in TAC according to MetS or OSA status. Young [18] argues that despite its attraction, TAC is not a good measure of oxidative stress because TAC assays actually measure chain breaking antioxidant activity. In summary from this short discussion, we report that despite the challenges of measuring oxidative stress, we are confident the finding of role for MDA in the prediction of MetS is useful, although there was no difference for the other two different biomarkers we used in our sample. It remains to say, that this finding should be replicated in due course.
As expected, we found that the absence of regular exercise is associated with both MetS and OSA. Regular exercise is known to improve insulin sensitivity and reduce the risk of MetS and obesity-related diseases [31]. There is also evidence that antioxidant enzyme activity is increased in various tissues after aerobic and anaerobic exercise [32]. A regular exercise-induced adaptation can be justified by Hormesis theory [33], and evidence of a decrease in the production of free radicals after 12 weeks of exercise [34]. Smoking was another prognostic tool in both diseases. Some studies have shown that smoking can contribute to increased abdominal obesity [35] which could be the link.
Strengths of this study are a substantial sample of relatively healthy bakers doing very similar work in conditions which allowed us to consider the new variables we were interested in – oxidative stress indicators – in relation to our research questions. We were able to show the role of MDA in the prediction of MetS despite the prevalence of MetS in this sample being relatively low. Similarly, we were able to suggest that oxidative stress does not act as a precursor to OSA, but that OSA is likely to increase oxidative stress. A limitation of our study was the use of a male only population. This was a consequence of the study design. We recognize the need for similar studies to replicate our findings. Such studies could be extended to include females.