To our knowledge, this meta-analysis is the first to evaluate the impact of whole grain diet on cardiovascular risk factors in obese/overweight adults. Our analysis suggests that whole grain diet is associated with a decrease in body weight, LDL-C and CRP, compared with the control group, with no significant differences between the two groups in waist circumference, SBP, DBP and fasting glucose levels. This meta-analysis supports previous studies recommending whole grain diet for CVD patients.
CVD remain the leading cause of mortality worldwide, and obesity is a main risk factor for the pandemic of CVD. Slavin et al. reported the protective mechanisms of whole grain diet in CVD, including antioxidant effects and alteration of gut environment by dietary fibers, carbohydrates and short-chain fatty acid, but also by regulating glucose metabolism and response to insulin. By revealing these mechanisms, whole grains consumption was recommended in the Australia dietary guidelines in 2003 . In the 2013 edition, the guidelines highlighted that at least 4 to 6 serves per day of grains food, mainly whole grains, is recommended for adults, especially for people with high risk of CVD and obesity. In our systematic review, we assumed that obese patients receiving whole grain diet intervention would have lower CVD risk factors, such as body weight, LDL-C concentration, SBP, waist circumference, CRP, insulin resistance index and BMI. However, we only observed a slight reduction in body weight and LDL-C concentration in subjects on whole grains diet, compared with the control group. In addition, subjects on whole grains diet also had a greater reduction in CRP, although the heterogeneity among the studies was relatively large.
In order to investigate the source of heterogeneity, subgroup analysis was conducted for three outcomes using the positive results. For weight and LDL-C data, the subgroup whose participants had another chronic disease besides obesity, such as type 2 diabetes, abnormal plasma cholesterol, showed more significant results. Specially, these comorbidities are in accordance with the diagnosis criteria of metabolic syndrome (MetS). As defined by the United States National Heart, Lung and Blood Institute and by the American Heart Association Consensus Statement, MetS can be diagnosed when a patient has at least 3 of the 4 risk factors, which include abdominal obesity [waist circumference >102 cm for men, or >88 cm for women], high triglycerides ( ≥150 mg/dL), high LDL-C and high-density lipoprotein cholesterol (HDL-C) [fasting serum HDL-C >40 mg/dL for men, or >50 mg/dL for women], high blood pressure [BP ≥130/≥85 mmHg], and elevated fasting blood glucose (≥ 100 mg/dL). MetS was reported as an important contributor for CVD incidence and mortality, as well as for all-cause mortality. Previous studies have demonstrated that whole grains diet can greatly reverse the process of MetS, lower postprandial plasma insulin and cholesterol levels[29-32]. Our results were in line with these findings, but also showed that whole grains diet can exert more effects on patients with more than one chronic metabolic disorders.
Another factor that was highlighted by the subgroup analysis was well-organized study design. Indeed, studies with positive results in this review showed high quality intervention monitoring. One effective method was “centralized intervention”, which relies on giving educational lessons or standard 7-day cyclical menu before intervention period or during the visits [33,34]. Certain studies also supervised participants’ diet by providing a 4-day diet record at each visit in a specific nutrition clinic, for which professional dieticians were recruited to assess these diet records and decide whether participants’ diet should be adjusted according to the study design [35,36]. Precise baseline information collection was also emphasized in these studies, which introduced a run-in period before the intervention period. In the run-in period, participants in both groups were asked to replace their habitual grain products with refined grains only to eliminate the habitual diet influence [35,36]. In fact, structured run-in period was reported as an important element in clinical trial design, especially in medical studies and clinical trials. Run-in strategy is usually used to diminish the effect of prior treatments, while it has no significant effect on realistic intervention outcomes[37,38]. The duration of run-in period is still controversial, and this period was designed as 4 to 6 weeks, unequally, in our review.
Discrepancies among studies may also be caused by a variety of whole grains diet interventions. In our review, the diets included barley, oat, wheat, rye and quinoa, and few studies only gave ambiguous definitions. Previous studies showed differences when considering the type of whole grains diet. In a 6-week randomized trial, Suhr et al. reported that whole grain rye, but not wholegrain wheat, significantly lowered body weight and fat mass, compared with refined wheat . In a meta-analysis, Li et al. investigated the effect of buckwheat on CVD risk factors in both human and animals. In human, buckwheat intervention significantly reduced glucose metabolism (0.85 mmol/L, 95% CI[1.31, 0.39]), total cholesterol (0.50 mmol/L, 95% CI [0.80, 0.20]) and triglycerides (0.25 mmol/L, 95% CI [0.49, 0.02]), compared with the control group. However, only triglycerides and total cholesterol showed slight differences in animals, with high heterogeneity. On the other hand, another trial on quinoa suggested that quinoa consumption can regulate glucose response, with only minimal effects on other CVD risk biomarkers. As a result, the discrepancies among studies in this review could be related to different diets, and thus, further subgroup analysis should be conducted based on the type of whole grains diet.
Interestingly, we observed that only few studies investigated plasma alkylresorcinols as a biomarker to quantify the intake of whole grain diet, which can lead to more accurate measurement of the effectiveness of whole grains diet, especially for wheat, rye and barley[42-44]. Alkylresorcinols are a short-half-life phenolic lipid compounds that are abundant in the outer layer of whole wheat, rye and barley, and is homologues with odd-numbered hydrocarbon side chains[42,45]. Although its half-life is estimated to be around 5 hours, single plasma alkylresorcinols measurement has been shown to be a reliable biomarker for long-term whole grain food consumption. The concentration of alkylresorcinol has been also reported as a sensitive indicator that is correlated with whole grain intake, and it could be used to distinguish between low- and high- whole grain consumers. Besides, it was suggested that there is no difference if the alkylresorcinol concentration is expressed by “nmol/mmol total lipids” or “nmol/L”, which indicates that the concentration of alkylresorcinol is not influenced by lipid distribution. In summary, the concentration of alkylresorcinol should be used as a reliable biomarker for evaluating the true effect of whole grain diet in future studies.
There are some limitations about in this study that are worth to mention. First, only 22 studies including 1865 subjects met our inclusion criteria. Hence, the issue of bias and heterogeneity might not be fully investigated using such as relatively small sample size. Second, some of the included RCTs lacked baseline information and/or outcome data for the comprehensive meta-analysis. Third, the difference in the composition of whole grains in each article may cause deviations in the results. Therefore, the outcomes and overall conclusions should be interpreted with these limitations in mind.