The effect of a whole grain diet on reducing cardiovascular risks in obese/overweight adults: a systematic review and meta-analysis

Abstract

Background: Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Overweight, hypertension, and dyslipidemia are clinically recognized as the most significant cardiovascular risk conditions. Studies have shown that whole grains are beneficial to affect glucose metabolism, obesity, blood pressure, lipids and inflammatory markers.

Methods: We did a research in PubMed, Embase and Cochrane for randomized controlled trials (RCTs) and selected the study according to the eligibility criteria and data extraction. Then we evaluate the effectiveness of whole grain foods on body weight (primary outcome) and other CVD risk factor indicators, including plasma low-density lipoprotein-cholesterol level, insulin resistance index, blood pressure, BMI, waist circumference (secondary outcome) in overweight/obese adults.

Results: Our results showed that there are significant decrease of weight (P<0.0001, mean difference -0.5, 95% CI[-0.74, -0.25], I 2 =35%), LDL-C (P=0.05, mean difference -0.08, 95% CI[-0.16, 0.00], I 2 =27%), CRP (P<0.0001, mean difference -0.36, 95% CI[-0.54, -0.18], I 2 =69%) in whole grain group compared with control group (Fig 2-4). There are no significant difference in waist circumference (P=0.76, mean difference -0.12, 95% CI[-0.92,0.68], I 2 =44%), systolic blood pressure (P=0.88, mean difference -0.11, 95% CI[-1.55, 1.33], I 2 =3%), diastolic blood pressure (P=0.39, mean difference -0.44, 95% CI[-1.44, 0.57], I 2 =15%), fasting glucose (P=0.11, mean difference -0.05, 95% CI[-0.12, 0.01], I 2 =31%) between two groups.

Conclusion: This study suggests whole grain food has only a moderate effect on reducing body weight, LDL-C and CRP in obese population, which is obviously showed in patients combined with other chronic metabolic disorders.

INTRODUCTION

CVD remains the leading cause of morbidity and mortality worldwide, including in China, accounting for about one third of all deaths [1]. Overweight, hypertension, and dyslipidemia are clinically recognized as the most effective cardiovascular risk factors. In observational studies, intake of more whole grain foods was associated with a lower frequency of metabolic syndrome [2] and lower mortality from cardiovascular disease (CVD) (including body weight, abdominal obesity, and insulin resistance) [3–6]. Whole grain foods are recommended for the prevention of CVD because they contain many heart protection compounds, including dietary fiber, trace minerals, phytoestrogens and antioxidants [7]. Studies have shown that whole grains are beneficial to affect glucose metabolism, obesity, blood pressure, lipids and inflammatory markers [8–11].

Overweight and obesity are global health problems, their scope and severity are expanding [12], and the demand for global health care system is increasing. Diet and overweight and obesity management are core features of all clinical practice guidelines for reducing the risk of CVD. Nutritional pathways to achieve optimal body weight are important for preventing obesity-related diseases. Whole grain products include endosperm, germ, bran and rich in dietary fiber [13]. Whole grains are thought to have a beneficial impact on body weight because they are generally lower in energy density and satiety than refined grain foods [4, 14–19].

Some observational studies strongly suggest that high intake of whole grains is associated with lower body mass index (BMI) [20–21] and lower long-term weight gain [22–23]. A meta-analysis demonstrated that whole grain intake does not reduce body weight, but may have a slight beneficial effect on body fat mass [9]. A recent systematic review pointed out that the evidence that makes whole grains independent of caloric restriction leading to weight loss was inconsistent in intervention studies [24]. The conclusions of current studies on whether the whole grain foods can reduce body weight are inconsistent. Thus, the objective of this study is to evaluate the impact of whole grain foods on body weight in patients with overweight or obesity through analyzing the results of related randomized controlled trials.

METHODS

Data sources

The Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) were referenced in the reporting of this meta-analysis. We did a research in PubMed, Embase and Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) without time and race restriction. Our search strategy in PubMed was Search ((((((((obesity) [Abstract] OR obese) [Abstract] OR overweight) [Abstract] OR fat)) [Abstract] OR metabolic syndrome [Abstract])) AND (((randomized controlled trial) [Abstract] OR placebo) [Abstract] OR randomized [Abstract])) AND ((((Grain, Whole) [Abstract] OR Grains, Whole) [Abstract] OR Whole Grain) [Abstract] OR Grain Cereal, Whole [Abstract]).

Eligibility criteria and data extraction

Studies would be included when satisfying the following criteria: (1) intervention time lasting more than 2 weeks; (2) randomized controlled trial; (3) assessing the cardiovascular outcomes; (4) trial that includes any of the following outcomes: weight, blood pressure, body mass index (BMI), waist circumference, cholesterol. Records would be excluded if they met any following conditions: not RCT, reviews or meta-analysis, case report, study time lasting less than 2 weeks, trial with inadequate information.

Data were extracted by two independent researchers from the records as following: studies’ characteristics (author, publication year, duration of intervention time, sample size), patients’ baseline information.

Assessment of bias

Assessment of bias of the included articles was analyzed by the Cochrane Collaboration’s tool. The following factors were assessed: random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), other bias. Two independent investigators evaluated the bias of included articles.

Statistical analysis

Odds ratios (OR) and 95% confidence intervals (CI) were applied to dichotomous outcomes, mean difference (MD) and 95% CI were applied to continuous outcomes. The outcome was considered statistically significant when P value was less than 0.05. Data were analyzed by Review Manager (Revman) with the expression of forest plots. I² testing was used to access the heterogeneity. Results were considered high heterogeneity when I² was more than 50%.

Results

Study characteristics

There were 995 studies identified by different investigators including articles from Pubmed (518), Embase (145) and Cochrane (332). We selected 45 relevant studies retrieved for detailed evaluation and 22 randomized clinical trials were finally included. Details of the screening process for eligible studies are shown in Figure 1. The study and population characteristics and a list of all studies included in the meta-analysis are presented in Table 1.

Our results showed that there were significant decrease of weight (P<0.0001, MD = –0.5, 95% CI –0.74 to –0.25, I² = 35%), LDL-C (P = 0.05, MD = –0.08, 95% CI –0.16 to 0.00, I² = 27%), CRP (P<0.0001, MD = –0.36, 95% CI–0.54 to –0.18, I² = 69%) in whole grain group compared with control group (Figure 2–4).. There were no significant difference in waist circumference (P = 0.76, MD = –0.12, 95% CI–0.92 to 0.68, I² = 44%), systolic blood pressure (P = 0.88, MD = –0.11, 95% CI–1.55 to 1.33, I² = 3%), diastolic blood pressure (P = 0.39, MD = –0.44, 95% CI–1.44 to 0.57, I² = 15%), fasting glucose (P = 0.11, MD = –0.05, 95% CI–0.12 to 0.01, I² = 31%) between two groups (Figure 5–8)..

Bias risk of included studies was performed by Revman (Figure 9).. As the randomized controlled trials involved dietary intervention, some researches failed to implement blind intervention on subjects which leading to high performance bias.

DISCUSSION

CVD remains the leading cause of mortality worldwide and obesity is a convinced risk factor for the pandemic of CVD. Slavin J. has reported the mechanism of the protective effect of whole grains in preventing CVD in 2003[25], including changing gut environment by dietary fiber, carbohydrate and short-chain fatty acid, being rich in antioxidants and regulating glucose metabolism and insulin response. With the uncovering of this mechanism, whole grains are recommended in 2003 edition of Australia dietary guidelines[26]. In 2013 edition, guideline emphasized that at least 4 to 6 serves of grain food, mostly whole grains, per day is recommended for adult, especially for people with high risk of CVD and obesity[27]. In our systematic review, we hypothesised that obese patients accepted whole grain diet intervention would have a greater improvement of CVD risk factors, including body weight, LDL-C concentration, systolic BP, waist circumference, CRP, insulin resistance index and BMI. However, compared to control group, we only observed a slightly greater reduction in body weight and LDL-C concentration. Whole grain diet group participants also had a greater reduction in CRP, although the heterogenity among studies is relatively large.

In order to investigate the source of heterogenity, subgroup analysis was conducted in three outcomes with positive results. For weight and LDL-C data, the subgroup whose participants suffer another chronic disease besides obesity, such as type 2 diabetes, abnormal plasma cholesterol, explain more significant results. Specially, these comorbidities are in accord with the diagnosis criteria of metabolic syndrome (MetS). As defined by the US National Heart, Lung and Blood Institute and American Heart Association Consensus Statement, MetS can be diagnosed when patients have at least 3 among 4 risk factors, which include abdominal obesity [waist circumference > 102 cm (men) or > 88 cm (women)], high triglycerides ( ≥ 150 mg/dL), low- and high-density lipoprotein cholesterol [fasting serum HDL cholesterol > 40 mg/dL (men) or > 50 mg/dL (women)], high blood pressure [BP ≥130/≥85 mmHg], and elevated fasting blood glucose (≥ 100 mg/dL)[28]. Metabolic syndrome was reported as an important contributor for CVD incidence and mortality, as well as all-cause mortality. Previous studies demonstrated that whole grain diet can greatly reverse the process of MetS, lowers postprandial plasma insulin and several cholesterol levels[29–32]. To a certain extent, our results are in line with these suggestions and also show that whole grain diet has more significant effects on patients combined with one or two chronic metabolic disorder.

Another factor appeared through subgroup analysis is well-organized study design. Studies included in this review with positive results are in common with high quality of intervention monitoring. One effective method was giving educational lessons or standard 7-day cyclical menu before intervention period or during the visits, which is named as “centralized intervention”[33,34]. Some studies also supervised participants’ diet, suggesting them to provide a 4-d diet record for each visit in a specific nutrition clinic. Professional dieticians were recruited to assess these diet records and to decide whether participants’ diet should be adjusted according to study design [35,36]. Precise baseline information collection is also emphasized in these studies, which introduce a run-in period before the intervention period. In run-in period, participants in both groups were asked to replace their habitual grain products with refined grain only to eliminate the influences from their habitual diet[35,36]. Structured run-in period is confirmed as an important element in clinical trial design, especially for medicine development. Run-in strategy is usually used to vanish prior treatment and has no magnify effect on realistic intervention effect[37,38]. The duration of run-in period is still controversial and in our review this period was designed as 4 to 6 weeks, unequally.

Discrepancies among studies may also be caused by variety of whole grain diet intervention. In our review, the interventions covered barley, oat, wheat, rye and quinoa, and few studies only gave ambiguous definition. Previous studies have showed differences when considering the types of whole grain diet. In a 6-week randomized trial, Suhr J et al reported that compared with refined wheat, whole grain rye, but not wholegrain wheat, lowers body weight and fat mass significantly[39]. In a meta-analysis, Liangkui Li group investigated the effect of buckwheat on improving CVD risk factors in both human and animals. In human, compared with control group, the glucose metabolism, total cholesterol and triglycerides were significantly improved following buckwheat intervention [differences in blood glucose: 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)]. In animals, only triglycerides and total cholesterol show slight differences with high heterogenity[40]. However, in another trial regarding quinoa conducted by Liangkui Li group, they suggested that quinoa consumption can regulate glucose response, while only has minimal effects on other CVD risk biomarkers[41]. As a result, the discrepancies among studies in this review is reasonable, and further subgroup analysis focused the same type of whole grain diet should be conducted.

Interestingly, we found few studies introduced a biomarker, Plasma alkylresorcinols, to quantify the intake of whole grain diet, which can be used to adjusting the indeed effectiveness of whole grain, especially for wheat, rye and barley[42–44]. Alkylresorcinols are a short-half-life phenolic lipid compound abundant in out layer of whole wheat, rye and barley as homologues with odd-numbered hydrocarbon side chains[42,45]. Although its half-life is estimated as about 5 hours, single plasma alkylresorcinols is proved to be reliable biomarker for long-term whole grain food consumption[46]. Concentration of alkylresorcinol is also reported to be a sensitive indicator, whose concentrations were correlated with WG intake and could be used to distinguish between low- and high-WG consumers. And it is also suggested that there was no difference whether alkylresorcinol concentration is expressed as “nmol/mmol total lipids” or “nmol/L”, which means the concentration of alkylresorcinol is not influenced by lipid distribution[47]. In summary, concentration of alkylresorcinol might be a reliable biomarker in evaluating the effect of whole grain diet in later studies.

CONCLUSIONS

In conclusion, our study demonstrated that compared with non-whole grain diet, whole grain food has moderate effects on reducing body weight, LDL-C and CRP in obese population, but has not significant effect in other CVD risk factors. This effect is more obviously showed in patients combined with other chronic metabolic disorders. The discrepancies among studies can be explained by different design in monitoring and types of diet intervention. To adjusting the effectiveness among diverse types of whole grain diet, plasma alkylresorcinol concentration can be used as a biomarker to reflect the consumption of whole grains. Further studies should be conducted in more specific subgroups.

DECLARATIONS

Ethics approval and consent to participate

Ethical approval was not applicable for this systematic review and meta-analysis.

Consent for publication

Not applicable.

Availability of data and materials

All data and materials used in this research are freely available. References have been provided.

Competing interests

All authors declare no competing interests.

Funding

Sponsorship for this study and the article processing charges were funded by the National Natural Science Foundation of China(Grant No.81670763 and 81471050).

Authors’ contributions

WHW and JNL planned the study and searched the literature and selected the trials to be included. XXC entered the data to the RevMan program and carried out the statistical analysis. MY checked that the entered data were consistent with original reports. QP wrote the draft manuscript and LXG participated in the critical revision of the manuscript. Both authors read and approved the final manuscript.

Acknowledgements

Not applicable.

REFERENCES

TABLES

Table 1  Main characteristics of included studies. RCT, randomized controlled trial; BMI, body mass index; SBP, systolic blood pressure; LDL, low density lipoprotein; NA, not available.