ABSTRACT
Refined grain intake is widely assumed to be associated with adverse health outcomes, including increased risk for cardiovascular disease (CVD), type 2 diabetes (T2D), and obesity. The 2015 Dietary Guidelines Advisory Committee recommended that to improve dietary quality, the US population should replace most refined grains with whole grains. This recommendation was based largely on results from studies that examined dietary patterns, not separate food groups. A Western dietary pattern typically includes red and processed meat, sugar-sweetened foods and beverages, French fries, and high-fat dairy products, as well as refined grains, and has been linked to increased risk of many chronic diseases. However, when evaluated as a distinct food category, 11 meta-analyses of prospective cohort studies, which included a total of 32 publications with data from 24 distinct cohorts, demonstrated that refined grain intake was not associated with all-cause mortality, T2D, CVD, coronary heart disease (CHD), stroke, hypertension, or cancer. By contrast, consumption of red and processed meat was consistently associated with increased risk of these same health outcomes. Refined grain consumption up to 6–7 servings/d (1 serving = 30 g) was not associated with higher risk of CHD, T2D, hypertension, or all-cause mortality. Moreover, total grain intake was not associated with risk of CVD, CHD, stroke, or cancer, but was associated with lower risk of all-cause mortality. Consequently, the recommendation to reduce refined grain intake based on results from studies linking a Western dietary pattern to numerous adverse health outcomes is contrary to a substantial body of published scientific evidence. Future research needs to better define refined grain intake to distinguish between staple grain foods and indulgent grain foods, and to better design randomized controlled trials to resolve discrepancies between results from observational studies and such trials with regard to determining the benefits of whole grains compared with refined grains.
Keywords: whole grains, white rice, Western dietary pattern, red and processed meat, cardiovascular disease, stroke, diabetes, all-cause mortality, obesity, hypertension
Introduction
Current US dietary guidelines consider grains as part of a healthy eating pattern and recommend that at least one-half of grain consumption come from whole grains (1). The health benefits of whole grains are well established from the results of many prospective cohort studies (2–9). Unfortunately, only 2–7% of Americans meet the recommendation to consume at least one-half of total grains from whole grains (10, 11), and <1% of the population consumes ≥3 servings/d (1 serving = 1 oz-equivalent) of whole grains (11). Among US children and adults whole-grain intake averages <1 serving/d and refined grain intake averages 5–6 servings/d (12). Because epidemiologic research suggests that substantial reductions in the risk of type 2 diabetes (T2D), cardiovascular disease (CVD), and all-cause mortality can be obtained by increasing intake of whole grains to just 2–3 servings/d (2–4, 6, 13) (1 serving = 30 g in these studies), the case for increasing whole-grain consumption is clear cut. To achieve the recommended balance of whole and refined grains would require increasing whole-grain intake and simultaneously decreasing the intake of refined grains. In fact, the 2015 Dietary Guidelines Advisory Committee (DGAC) recommended that “to improve dietary quality, the US population should replace most refined grains with whole grains” (12). This recommendation was reiterated in the dietary advice of the American Heart Association (14).
The rationale for recommending a reduced intake of refined grains was based on the DGAC's conclusion that there was “strong” evidence that a dietary pattern lower in refined grains was associated with lower risk of CVD, and “moderate” evidence that a reduced intake of refined grains was associated with lower risk of T2D and obesity (12). It is important to note that the DGAC relied almost exclusively on results from studies that examined dietary patterns, and not separate food groups. For example, in addition to emphasizing that vegetables, fruits, whole grains, low-fat or nonfat dairy, seafood, legumes, and nuts were key components of a healthy dietary pattern, the DGAC also asserted that a healthy dietary pattern is “lower in red and processed meat, and low in sugar-sweetened foods and drinks and refined grains.”
The inclusion of refined grains in an unhealthy dietary pattern is quite common in the nutrition literature. This unhealthy, or Western, dietary pattern typically includes red and processed meat, sugar-sweetened foods and beverages, French fries, high-fat dairy products, and refined grains, and has been linked to an increased risk of a number of chronic diseases (12, 15–19). An important question is whether each of the food groups in this dietary pattern is culpable for the increased disease risk. For example, is refined grain consumption associated with higher risk for CVD, T2D, and obesity, as asserted by the DGAC? Or is it possible that the higher risk is not due to consumption of refined grain foods categorically, but is instead a consequence of “guilt by association” with foods that are the real culprits?
The objective of this Perspective is to briefly summarize the published research on refined grain intake and associations with CVD, coronary heart disease (CHD), stroke, T2D, cancer, BMI, and all-cause mortality. The discussion relies primarily on meta-analyses of relevant literature in which refined grain intake was analyzed separately, and not as part of a Western dietary pattern. The Institute for Scientific Information's Web of Science was utilized to identify relevant meta-analyses of prospective cohort studies and randomized controlled trials (RCTs). Additionally, articles were identified through the use of the key words “refined grain intake” and each disease outcome. Finally, reference lists and citation records of all identified articles were searched for additional studies not cited in meta-analyses.
CVD/CHD
Five meta-analyses were identified that evaluated the association between refined grain intake and either CVD (2, 5) or CHD (2, 4, 20) (Table 1). Collectively, these meta-analyses included a total of 12 publications (21–32). In both meta-analyses for CVD (2, 5) and in 2 of the 3 meta-analyses for CHD (2, 4), no association was observed between refined grain intake and either outcome measure in comparisons of highest with the lowest intake groups and in dose-response analyses. Aune et al. (2) also reported no association between intake of white bread or refined grain breakfast cereals and CHD risk.
TABLE 1.
Highest vs lowest intakes | Dose response2 | ||||
---|---|---|---|---|---|
Meta-analysis reference | Number of cohorts included | Relative risk (95% CI) | Number of cohorts included | Relative risk (95% CI) | Outcome |
Aune et al. (2) | 4 | 1.16 (0.84, 1.59) | 5 | 1.13 (0.90, 1.42) | CHD |
Aune et al. (2) | 2 | 1.02 (0.91, 1.14) | 3 | 0.98 (0.90, 1.06) | CVD |
Bechthold et al. (4) | 5 | 1.11 (0.99, 1.25) | 4 | 1.01 (0.99, 1.04) | CHD |
Mellen et al. (5) | 3 | 1.07 (0.94, 1.22) | — | — | CVD |
Chen et al. (20)3 | 8 | 1.09 (1.01, 1.19) | — | — | CVD/CHD/MI |
Aune et al. (2) | 4 | 0.95 (0.78, 1.14) | 5 | 0.91 (0.81, 1.02) | Stroke |
Bechthold et al. (4) | 6 | 1.02 (0.94, 1.11) | 4 | 1.00 (0.98, 1.01) | Stroke |
Chen et al. (33) | 5 | 0.99 (0.84, 1.16) | 5 | 0.95 (0.86, 1.03) | Stroke |
Wu et al. (34) | 10 | 1.02 (0.93, 1.10) | 10 | 0.98 (0.93, 1.03) | Stroke |
Schwingshackl et al. (35) | 3 | 0.95 (0.88, 1.03) | 3 | 0.99 (0.96, 1.02) | Hypertension |
Bechthold et al. (4) | 1 | 0.83 (0.58, 1.19) | 1 | 0.86 (0.68, 1.09) | Heart failure |
Aune et al. (3) | 6 | 0.94 (0.82, 1.09) | 6 | 0.95 (0.88, 1.04) | T2D |
Schwingshackl et al. (13) | 15 | 1.01 (0.92, 1.10) | 14 | 1.01 (0.99, 1.03) | T2D |
Aune et al. (2) | 1 | 0.98 (0.82, 1.16) | 2 | 0.94 (0.90, 0.99) | Total cancer |
Schwingshackl et al. (36) | 2 | 1.27 (1.02, 1.57) | — | — | Colon cancer |
Schwingshackl et al. (36) | 1 | 0.82 (0.48, 1.40) | — | — | Rectal cancer |
Schwingshackl et al. (36) | 2 | 1.46 (0.80, 2.67) | — | — | Colorectal cancer |
Aune et al. (2) | 2 | 1.02 (0.93, 1.12) | 4 | 0.95 (0.91, 0.99) | All-cause mortality |
Schwingshackl et al. (6) | 4 | 0.99 (0.94, 1.05) | 4 | 0.99 (0.97, 1.01) | All-cause mortality |
CHD, coronary heart disease; CVD, cardiovascular disease; MI, myocardial infarction; T2D, type 2 diabetes.
In dose-response analyses, relative risks are per 90 g/d in Aune et al. (2, 3) and Chen et al. (20); and per 30 g/d in Bechthold et al. (4) and Schwingshackl et al. (6, 13, 35).
In this meta-analysis an incorrect outcome variable (metabolic syndrome rather than CHD) was used for one of the studies (27) included in the meta-analysis. See text for discussion.
In the meta-analysis of Chen et al. (20), refined grain intake was associated with a 9.4% higher risk of CHD (which included studies of CHD, CVD, myocardial infarction, and ischemic heart disease). However, this meta-analysis is flawed because the wrong outcome variable (metabolic syndrome rather than CHD) was used for 1 of the studies included in the meta-analysis (27). In this study (27), no association was observed between refined grain intake and CVD mortality. In fact, of the 12 studies included in the 5 meta-analyses, 11 reported no association between refined grain intake and risk of either CVD or CHD (21–31). The only study that reported an increased CHD risk associated with refined grain intake included Chinese adults who had very high total carbohydrate intake, primarily from white rice (32). This is not a consistent finding because white rice intake was not associated with CVD or coronary artery disease (CAD) in an analysis of 3 large US cohorts (37).
In addition to these meta-analyses, refined grain was not associated with progression of CAD over a 3.2-y follow-up in postmenopausal women (38). Also, the only study to date on refined grain intake and heart failure found no association between refined grain breakfast cereal intake and incident heart failure (39).
By comparison, with few exceptions meta-analyses have demonstrated that consumption of red meat and processed meat is associated with greater risk of CHD (4, 40), CVD (41, 42), and heart failure (4). The relationship for processed meat intake is the most consistent, with all meta-analyses reporting significantly higher risk (15–42%) both when comparing the highest with the lowest intakes (4, 41, 42) and in dose-response analyses (4, 40, 42).
Stroke
Four meta-analyses have been published on the association between refined grain intake and stroke risk, and all reported no association both when comparing the highest with the lowest intake groups and in dose-response analyses (2, 4, 33, 34) (Table 1). It is important to note that of the 12 studies included in these 4 meta-analyses, 11 found no association between refined grain intake and stroke risk (21, 22, 24, 25, 28, 29, 37, 43–46), and 1 actually demonstrated a 10% lower risk of stroke associated with nonwhole-grain intake (30).
The lack of association between refined grain intake and stroke is consistent with the lack of association between refined grain intake and hypertension. A meta-analysis that included 3 studies found no association between refined grain intake and incident hypertension both when comparing the highest with the lowest intake groups and in dose-response analyses (35) (Table 1). In 1 of the studies, refined grain intake of ≥6 servings/d was not associated with increased risk of hypertension (47). In another, refined grain breakfast cereal intakes of 2–6 servings/wk and ≥7 servings/wk were associated with a 14% reduced risk of hypertension (48).
By contrast, meta-analyses have reported increased risk of stroke associated with consumption of red and processed meat both when comparing the highest with the lowest intake groups (4, 49) and in dose-response analyses (4). One meta-analysis reported no significantly greater stroke risk associated with either red or processed meat intake, but intake of total meat was associated with higher stroke risk in a dose-response analysis (40). Furthermore, the risk of hypertension was also shown to be higher in a meta-analysis comparing the highest and lowest intake groups for both red and processed meat consumption (50).
T2D
Two meta-analyses have been published on the association between refined grain intake and risk of T2D, and both demonstrated no association both when comparing the highest with the lowest intake groups and in dose-response analyses (3, 13) (Table 1). Of the 12 publications included in these 2 meta-analyses, 5 reported no association between refined grain intake and T2D (51–55) and 3 reported a reduced risk of T2D associated with refined grain intake (56–58). In the Women's Health Initiative Observational Study, the reduced risk of T2D associated with refined grain intake in fully adjusted models was comparable to that for whole-grain intake (57).
Four of the studies included in the meta-analyses reported mixed findings, all pertaining to white rice intake (59–62). One reported that in comparing the highest with the lowest intakes, white rice consumption was not associated with T2D risk in the Health Professionals Follow-up Study and Nurses’ Health Study I, but was associated with increased risk in the Nurses’ Health Study II and in pooled analysis of all 3 cohorts (62). Another showed that white rice intake was associated with T2D risk in only 1 of 2 Iranian cohorts studied (59). White rice intake was associated with T2D risk in Japanese women but not in Japanese men, whereas intakes of bread and noodles were not associated with T2D risk in either sex (61). In the Melbourne Collaborative Cohort study of middle-aged men and women, white rice and pasta intake were not associated with risk of T2D, but white bread intake was (60).
Two meta-analyses have been published on the association between white rice intake and risk of T2D (3, 63) (Table 2). Aune et al. (3) reported no association in comparison of highest with lowest intake groups, but a 23% higher risk of T2D in the dose-response analysis. The meta-analysis of Hu et al. (63) indicated that white rice intake was associated with increased T2D risk in 3 Asian cohorts but not in 4 Western cohorts. It should also be noted that in a Spanish cohort white rice consumption was associated with a reduced risk of T2D (58).
TABLE 2.
Highest vs lowest intakes | Dose response2 | ||||
---|---|---|---|---|---|
Meta-analysis reference | Number of cohorts included | Relative risk (95% CI) | Number of cohorts included | Relative risk (95% CI) | Outcome |
Aune et al. (3) | 7 | 1.17 (0.93, 1.47) | 6 | 1.23 (1.15, 1.31) | T2D |
Hu et al. (63) | 4 (Western) | 1.12 (0.94, 1.33) | — | — | T2D |
Hu et al. (63) | 3 (Asian) | 1.27 (1.04, 1.54) | — | — | T2D |
Aune et al. (2) | 3 | 0.87 (0.76, 1.01) | 3 | 0.98 (0.95, 1.05) | Total cancer |
The results from most of the studies included in these meta-analyses (3, 13), i.e., that refined grain intake is not associated with increased T2D risk, are consistent with the finding that refined grain intake was shown to be unrelated to insulin resistance, as assessed by the HOMA-IR, and weakly inversely associated with glycated hemoglobin concentrations in the Framingham Offspring Study (64, 65). Additionally, refined grain intake was not associated with development of the metabolic syndrome (66).
By contrast, 2 meta-analyses reported that intake of processed meat was associated with 19–37% higher risk of T2D in dose-response analyses (13, 40) and in highest with lowest intake group comparisons (13). Intake of red (13) and total (40) meat were also associated with higher T2D risk. Sugar-sweetened beverages, also included in the Western dietary pattern, have been reported to be associated with higher risk of T2D in most (13, 67–69), but not all (70), meta-analyses. This illustrates that the increased risk of T2D associated with a Western dietary pattern (15) is more likely attributable to consumption of red and processed meat, and possibly sugar-sweetened beverages, than to consumption of refined grains.
Cancer
Two meta-analyses on the association between refined grain intake and cancer risk have been published (2, 36) (Table 1). Both meta-analyses are limited by inclusion of few studies. In 1 of these analyses, a weak inverse association between refined grain intake and total cancer mortality in dose-response analysis was reported, but no association was found when comparing the highest and lowest intake groups (2). In the other, refined grain intake was not associated with risk of rectal or colorectal cancer risk, but refined grain intake was associated with a 27% higher risk of colon cancer (36). White rice intake was not associated with total cancer incidence in the meta-analysis of Aune et al. (2), both when comparing the highest and lowest intake groups and in dose-response analysis (Table 2). In addition to the studies used in these meta-analyses, several other analyses from cohort studies have demonstrated no increased cancer risk associated with refined grain intake (30, 71–75).
By contrast, meta-analyses have shown higher total cancer mortality when comparing highest and lowest intake groups for consumption of processed meat (41, 42), red meat (42), and total meat (41), and higher total cancer mortality in dose-response analyses for both processed and red meat consumption (42). A 2018 meta-analysis reported that consumption of red meat and processed meat was associated with significantly greater colon and colorectal cancer risk both when comparing the highest and lowest intake groups and in dose-response analyses, and greater rectal cancer risk in dose-response analyses (36).
All-Cause Mortality
Six studies have been published on the relationship between refined grain intake and all-cause mortality, 5 of which reported no association between refined grain intake and all-cause mortality (22, 25, 27, 29, 30), and 1 that reported a slight, but statistically significant, inverse association between refined grain intake and mortality (31). Two meta-analyses have been published that included 5 of these studies in their analyses (2, 6) (Table 1). Not surprisingly, both reported no association when comparing the highest and lowest intakes. In the dose-response analysis, 1 reported no association (6), whereas Aune et al. (2) reported a 5% lower all-cause mortality risk for each 90-g/d intake of refined grains.
By contrast, the meta-analysis of Schwingshackl et al. (6) demonstrated that all-cause mortality was significantly related to consumption of red meat and processed meat both when comparing the highest and lowest intake groups and in dose-response analyses. Collectively, these studies show that mortality risk associated with the Western dietary pattern (76) is more likely attributable to consumption of red and processed meat, and not to intake of refined grains.
Obesity
No meta-analyses on the association between refined grain intake and measures of body weight or body fat have been performed. Three systematic reviews reported no consistent relationship between refined grain intake and BMI or measures of adiposity (77–79). Most cohort studies show no association between refined grain intake and BMI (23, 25, 27, 29, 52, 57, 65, 71, 80–85). Although some studies indicate a positive association between refined grain intake and BMI (47, 73, 83, 86–89) or body fat (87), the magnitude of the difference between extremes of refined grain intake is typically very small. For example, in the Nurses’ Health Study (86), over a 12-y period the difference in weight gain between the lowest and highest quintiles of changes in refined grain intake (–0.91 compared with +0.86 servings per 1000 kcal/d) was only 0.43 kg, or ∼0.036 kg/y (i.e., <0.02 lb/y). Although statistically significant, the clinical relevance of this is not obvious.
Definitions of Refined Grain Intake May Confound Interpretation of Findings
As reviewed above, meta-analyses consistently show that refined grain intake is not associated with increased risk of major chronic diseases and all-cause mortality. It is necessary to interpret these results from the perspective of how refined grains have been defined in most of the studies included in these meta-analyses. In addition to staple grain foods such as bread, cereals and pasta, most of the studies that have examined refined grain intake separate from a Western dietary pattern have defined refined grains to include such foods as cookies (29, 38, 55, 65, 83), cakes (25, 29, 31, 38, 44, 47, 52, 53, 55, 65, 86), donuts (29, 83), brownies (29, 83), muffins (25, 31, 38, 44, 47, 53, 64, 71, 84, 86), sweet rolls or buns (25, 31, 44, 52, 53, 55, 83, 86), sweets or desserts made with grains (23, 24, 54, 73), and pizza (23–25, 31, 38, 44, 47, 52–54, 73, 83, 84, 86, 87). These foods frequently contain high amounts of fat or sugar (or both), consumption of which may offset any beneficial effects of staple grain foods. Thus the generally neutral findings in most of the cohort studies of refined grain intake on health outcomes may be biased against yielding positive results.
Total Grain Intake and Chronic Disease
Meta-analyses have shown that total grain consumption is associated with reduced risk of T2D (3), total cancer (2), and all-cause mortality (2) (Table 3). Although meta-analyses indicate that total grain intake is not associated with risk of CHD (2), CVD (2), or stroke (2, 33), all relative risks for CVD and stroke (0.83–0.97) are actually suggestive of a benefit (Table 3). It should be noted that in both meta-analyses of grain intake and stroke risk (2, 33), the association between whole-grain intake and stroke risk was also not statistically significant.
TABLE 3.
Highest vs lowest intakes | Dose response2 | ||||
---|---|---|---|---|---|
Meta-analysis reference | Number of cohorts included | Relative risk (95% CI) | Number of cohorts included | Relative risk (95% CI) | Outcome |
Aune et al. (2) | 3 | 1.07 (0.91, 1.25) | 2 | 1.07 (0.88, 1.30) | CHD |
Aune et al. (2) | 3 | 0.94 (0.84, 1.06) | 1 | 0.83 (0.70, 1.00) | CVD |
Aune et al. (2) | 4 | 0.89 (0.79, 1.00) | 5 | 0.93 (0.85, 1.02) | Stroke |
Chen et al. (33) | 8 | 0.97 (0.83, 1.14) | 6 | 0.97 (0.90, 1.03) | Stroke |
Aune et al. (3) | 4 | 0.74 (0.58, 0.93) | 4 | 0.83 (0.75, 0.91) | T2D |
Aune et al. (2) | 1 | 0.92 (0.80, 1.06) | 2 | 0.97 (0.96, 0.99) | Total cancer |
Aune et al. (2) | 13 | 0.91 (0.87, 0.95) | 7 | 0.96 (0.90, 1.02) | All-cause mortality |
CHD, coronary heart disease; CVD, cardiovascular disease; T2D, type 2 diabetes.
In dose-response analyses, relative risks are per 90 g/d for all studies.
Only 1 meta-analysis has reported on the association between total grain intake and all-cause mortality (2). In this analysis total grain intake was associated with a 9% lower risk of all-cause mortality when comparing the highest and lowest intake groups, which included 13 cohorts. The dose-response analysis, which included only 7 cohorts, produced a nonsignificant relative risk of 0.96 (Table 3).
These results for total grain intake are not surprising in view of the consistently beneficial associations between whole-grain intake and chronic disease risk (2–9) and the largely neutral findings for refined-grain intake (Table 1).
Whole Compared with Refined Grains: The Conundrum of Randomized Controlled Trial Results
Despite the consistent superiority of whole grains reported in observational studies, RCTs have not consistently produced expected findings. Four meta-analyses of RCTs comparing whole and refined grains have been published, with mixed results (7, 90–92) (Table 4). These meta-analyses have included studies that determined the effects of diets higher in whole-grain foods compared with diets higher in refined-grain foods, or usual diet. Studies included in these meta-analyses were relatively short duration (2–16 wk).
TABLE 4.
Outcome | Meta-analysis reference | Number of trials included | Mean difference (95% CI) |
---|---|---|---|
Intervention studies | |||
Fasting glucose, mmol/L | Ye et al. (7) | 13 | –0.93 (–1.65, –0.21) |
Marventano et al. (91) | 15 | –0.04 (–2.26, 0.04) | |
Fasting insulin, pmol/L−1 | Ye et al. (7) | 12 | –0.29 (–0.59, 0.01) |
Marventano et al. (91) | 14 | –2.26 (–6.58, 2.06) | |
HOMA-IR | Marventano et al. (91) | 7 | –0.18 (–0.48, 0.13) |
Fasting cholesterol, mmol/L | Ye et al. (7) | 20 | –0.83 (–1.23, –0.42) |
Kelly et al. (90) | 7 | 0.07 (–0.07, 0.21) | |
Fasting LDL cholesterol, mmol/L | Ye et al. (7) | 19 | –0.82 (–1.31, –0.33) |
Kelly et al. (90) | 8 | 0.06 (–0.05, 0.16) | |
Fasting HDL cholesterol, mmol/L | Kelly et al. (90) | 8 | –0.02 (–0.05, 0.01) |
Fasting triglycerides, mmol/L | Kelly et al. (90) | 8 | 0.03 (–0.08, 0.13) |
Body weight, kg | Ye et al. (7) | 12 | –0.18 (–0.54, 0.18) |
Pol et al. (92) | 31 | 0.06 (–0.09, 0.20) | |
Kelly et al. (90) | 5 | –0.41 (–1.04, 0.23) | |
Body mass index, kg/m2 | Kelly et al. (90) | 5 | –0.12 (–0.24, 0.01) |
Body fat, % | Pol et al. (92) | 9 | –0.48 (–0.95, –0.01) |
Waist circumference, cm | Pol et al. (92) | 11 | –0.15 (–0.51, 0.22) |
Systolic blood pressure, mm Hg | Ye et al. (7) | 7 | –0.06 (–0.21, 0.10) |
Kelly et al. (90) | 8 | 0.04 (–1.67, 1.75) | |
Diastolic blood pressure, mm Hg | Ye et al. (7) | 7 | –0.05 (–0.21, 0.11) |
Kelly et al. (90) | 7 | 0.16 (–0.89, 1.21) | |
Acute feeding studies | |||
iAUC glucose 120, mmol · min · L−1 | Marventano et al. (91) | 23 | –29.71 (–43.57, –15.85) |
iAUC glucose 180, mmol · min · L−1 | 8 | –15.40 (–31.52, 0.73) | |
iAUC insulin 120, mmol · min · L−1 | 7 | –2.01 (–2.88, –1.14) | |
iAUC insulin 180, mmol · min · L−1 | 13 | –3.64 (–5.00, –2.28) | |
Maximum postprandial glucose, mmol/L | 11 | –0.25 (–0.43, –0.06) | |
Maximum postprandial insulin, pmol/L | 8 | –73.78 (–108.56, –38.99) |
iAUC, incremental area under the curve.
In 1 meta-analysis (92), increased consumption of whole-grain foods had no effect on body weight or waist circumference compared with nonwhole-grain foods, but percentage body fat was reduced by 0.48% more after eating more whole-grain foods. The significance of a decrease in body fat of such small magnitude is questionable. In a Cochrane review and meta-analysis (90), diets higher in whole-grain foods had no significant effect on body weight, BMI, total cholesterol, LDL cholesterol, HDL-C, triglycerides, or blood pressure. Similarly, a meta-analysis of RCTs found no effect of whole-grain foods on fasting glucose and insulin, or HOMA-IR (91). The only meta-analysis of RCTs showing a superiority of whole-grain foods reported lower fasting glucose, total cholesterol, and LDL-C, and a trend for a reduction in fasting insulin, but no significant effect on blood pressure or body weight (7) (Table 4). The difference in findings for glucose and insulin (7, 91) and total cholesterol and LDL cholesterol (7, 90) could be due in large part to the different studies included in each of the meta-analyses.
The short duration of the studies (none lasted >16 wk, and most were between 4 and 6 wk) may have contributed to the lack of differences between the diets. If the differences apparent in observational studies are truly due to whole-grain intake, it may reflect habitual intake over years. In addition, the reduced risk of chronic diseases associated with whole-grain intake may be attributable to novel biomarkers of cardiometabolic health not measured in the RCTs. Alternatively, the superior health benefits of whole-grain foods may be due in large part to their postprandial effects. A meta-analysis of RCTs demonstrated clear superiority of whole grains for producing lower maximal postprandial responses and incremental area under the curve for glucose and insulin (91) (Table 4). Elevated nonfasting blood glucose concentration is a risk factor for CVD (93), and postprandial hyperglycemia has been reported to better predict CVD than fasting blood glucose (94).
Replace Refined Grains with Whole Grains, or Just Eat More Whole Grains?
Despite persistent efforts to encourage Americans to eat more whole-grain foods (1), consumption of whole grains remains well below recommended amounts (10–12). Because the health properties of food have a lower priority than taste, convenience, or price (95), it is not surprising that the US population mean whole-grain consumption remains <1 serving/d (12). It is important to note that even though the 2015 DGAC recommended that dietary quality would improve if Americans replaced most refined grains with whole grains, the committee's report also acknowledged that, based on food modeling, consumption of all grains as whole grains, without including any enriched grain products, would result in nutrient shortfalls (12). Consumption of refined grain foods that have been enriched or fortified can help alleviate shortfalls of nutrients, including folic acid, iron, thiamin, niacin, and riboflavin (96, 97). Folic acid is essential for women of childbearing age to help prevent neural tube birth defects, and enriched grains are the largest contributor of folic acid in the American diet (98). The rate of neural tube defects in the United States has decreased by 35% since the fortification of enriched grains began in 1998 (99).
Grain foods contribute 54.5% of all fiber in the American diet (100). Of this, ∼72% of the grain contribution to total fiber intake comes from refined grains (100). Thus ∼39% of dietary fiber intake among Americans comes from refined grains. The contributions of both whole and refined grains to total fiber intake are important because >90% of adults and children fall short of dietary fiber recommendations (101). Cereal fiber intake has been associated with reduced risk of chronic disease (102), and meta-analyses demonstrate that cereal fiber intake has a stronger association with reduced T2D than fiber from fruits and vegetables (103). In these studies the sources of cereal fiber were not separated into whole- or refined-grain foods. Given the fact that most cereal fiber in the US diet comes from refined grains, it would be unreasonable to conclude that the benefits of cereal fiber are exclusively due to whole grains. For example, in the NIH-AARP study, fiber from grains (without distinction between whole and refined), but not other sources, was associated with significant reduction in all-cause, CVD, and cancer mortality (104). Thus refined grain intake may provide an important source of cereal fiber in the US diet. Consequently, reducing intake of refined grains may have unintended consequences.
Conclusion
Eleven systematic reviews and meta-analyses of prospective cohort studies have assessed the association between refined-grain intake and all-cause mortality, T2D, CVD, CHD, stroke, hypertension, and cancer (Table 1). Collectively, they included a total of 32 publications with data from 24 distinct cohorts. These meta-analyses essentially show that refined grain intake is not associated with the chronic diseases widely assumed to be moderately or strongly linked to refined grain consumption (12, 14). The results are remarkably consistent, with virtually all of the 32 publications indicating no higher risk associated with refined grain intake. There is some evidence that white rice consumption is associated with increased risk of T2D, but this appears to be limited primarily to Asian populations, in which white rice consumption is much higher than in Western populations (63).
By contrast, 9 published meta-analyses consistently show increased risk of these same chronic diseases and all-cause mortality associated with intake of red and processed meat (4, 6, 13, 40–42, 49, 50, 36), key components of the Western dietary pattern. Thus it is inaccurate to attribute the adverse health outcomes associated with the Western dietary pattern to refined-grain intake (12, 14). It is possible that the higher risk associated with red and processed meat intake could be related in part to the fact that diets high in either red or processed meat may be lower in overall diet quality, including lower intakes of fruits and vegetables (105, 106). However, not all studies have reported lower intakes of fruits and vegetables among high consumers of red and processed meat (107–109). Moreover, data from the European Prospective Investigation into Cancer and Nutrition study indicated that the higher all-cause mortality risk associated with processed meat consumption was evident in participants who fell both below and above median consumption of fruits and vegetables (106), and results from 2 large Swedish cohorts demonstrated that the higher hazard ratios for all-cause and CVD mortality associated with total red meat consumption were significant, and of similar magnitude, across all categories (low, medium, high) of fruit-and-vegetable intake (107).
Although recommendations to increase whole-grain consumption are scientifically supported, because total grain consumption is unrelated to risk of CHD, CVD, and cancer, and is associated with reduced risk of T2D and all-cause mortality (Table 3), the recommendation to reduce consumption of refined grains (1, 12, 14) is contrary to a substantial body of published scientific evidence.
Refined grain consumption up to 6–7 servings/d is not associated with higher risk of chronic disease or all-cause mortality (3, 4, 47, 48, 56). Also, enriched/refined grains contribute meaningfully to reduce gaps in certain shortfall nutrients (96, 97), including dietary fiber (100). Consequently, the most scientifically sound recommendation may be to encourage increased consumption of whole grains without specific recommendations for reducing refined grain intake. Benefits of whole-grain consumption are most apparent with consumption of 2–3 servings/d (60–90 g, or ∼2–3 oz, per day) (2–4, 6, 13). Current average US intake for whole grains is <1 serving/d. Thus a recommendation to increase whole-grain consumption, by as little as 1–2 servings/d, may be the most uncomplicated, as well as scientifically justified, approach.
It could be argued that increasing whole-grain consumption without recommending a reduction in refined-grain consumption could contribute to greater positive energy balance, thus adversely affecting weight control efforts. However, the lack of any consistent association between refined-grain intake and BMI (23, 25, 27, 29, 52, 57, 65, 71, 77–85) suggests that this should not be a serious concern. Furthermore, prospective cohort studies consistently show an inverse relationship between carbohydrate intake and BMI (77). It must also be noted that in studies showing a positive association between refined-grain intake and either BMI or weight gain, the definition of refined grains in these studies included foods such as cookies, brownies, donuts, sweet rolls, scones, croissants, hush puppies, ice cream bread, muffins, coffee cakes, and pizza (47, 73, 83, 86–89). Thus it is impossible to determine from these studies the separate contributions to body weight and body fat of staple grain foods (i.e., bread, cereals, pasta) compared with indulgent grain foods. Indulgent grain foods have a higher fat and sugar content, and lower fiber content and nutrient density (96, 97).
Therefore, it would be prudent, both in terms of public health recommendations and in future research, to make clear distinctions between health impacts of staple grain foods and indulgent grain foods. As described herein, most published reports have failed to make such distinctions. Benefits of whole grains are based on studies of grain foods that are primarily staple grains, whereas studies on refined grains, mainly prospective cohort studies, include both staple and indulgent grain foods in the definition of refined grains. Another important research gap is to resolve the discrepant findings of observational studies and RCTs with respect to health effects of whole-grain and refined-grain foods. Results from RCTs do not indicate a consistent benefit of whole-grain foods compared with refined-grain foods. This is a dilemma that needs resolution.
Finally, this literature analysis illustrates a pitfall of attributing health risks to specific food groups based primarily on analysis of dietary patterns (12, 15–19). With regard to refined grains, a large and consistent body of evidence from meta-analyses of prospective cohort studies (2–6, 13, 20, 33, 34, 35, 36) suggests that the assumed health risks are largely a consequence of guilt by association with other foods within the Western dietary pattern, and not to refined grains per se.
ACKNOWLEDGEMENTS
The author is solely responsible for all content and approved the final manuscript.
Notes
Preparation of this manuscript was supported in part by a grant from the Wheat Foods Council and Grain Foods Foundation.
Author disclosure: GAG is a member of the scientific advisory boards of the Grain Foods Foundation, the Wheat Foods Council, and Ardent Mills.
Abbreviations used: CAD, coronary artery disease; CHD, coronary heart disease; CVD, cardiovascular disease; DGAC, Dietary Guidelines Advisory Committee; iAUC, incremental area under the curve; NIH-AARP, National Institutes of Health-AARP; RCT, randomized controlled trial; T2D, type 2 diabetes.
References
- 1. US Department of Health and Human Services and US Department of Agriculture. 2015–2020 Dietary Guidelines for Americans. 8th edition [Internet]. 2015. [18 August, 2018]. Available from: http://health.gov/dietaryguidelines/2015/guidelines/. [Google Scholar]
- 2. Aune D, Keum N, Giovannucci E, Fadnes LT, Boffetta P, Greenwood DC, Tonstad S, Vatten LJ, Riboli E, Norat T. Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies. BMJ. 2016;353:i2716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Aune D, Norat T, Romundstad P, Vatten LJ. Whole grain and refined grain consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of cohort studies. Eur J Epidemiol. 2013;28(11):845–58. [DOI] [PubMed] [Google Scholar]
- 4. Bechthold A, Boeing H, Schwedhelm C, Hoffmann G, Knuppel S, Iqbal K, De Henauw S, Michels N, Devleesschauwer B, Schlesinger S et al.. Food groups and risk of coronary heart disease, stroke and heart failure: a systematic review and dose-response meta-analysis of prospective studies. Crit Rev Food Sci Nutr. 2017:1–20. doi:10.1080/10408398.2017.1392288. [DOI] [PubMed] [Google Scholar]
- 5. Mellen PB, Walsh TF, Herrington DM. Whole grain intake and cardiovascular disease: a meta-analysis. Nutr Metab Cardiovasc Dis. 2008;18(4):283–90. [DOI] [PubMed] [Google Scholar]
- 6. Schwingshackl L, Schwedhelm C, Hoffmann G, Lampousi AM, Knuppel S, Iqbal K, Bechthold A, Schlesinger S, Boeing H. Food groups and risk of all-cause mortality: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr. 2017;105(6):1462–73. [DOI] [PubMed] [Google Scholar]
- 7. Ye EQ, Chacko SA, Chou EL, Kugizaki M, Liu S. Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain. J Nutr. 2012;142(7):1304–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Zong G, Gao A, Hu FB, Sun Q. Whole grain intake and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis of prospective cohort studies. Circulation. 2016;133(24):2370–80. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Benisi-Kohansal S, Saneei P, Salehi-Marzijarani M, Larijani B, Esmaillzadeh A. Whole-grain intake and mortality from all causes, cardiovascular disease, and cancer: a systematic review and dose-response meta-analysis of prospective cohort studies. Adv Nutr. 2016;7(6):1052–65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Krebs-Smith SM, Guenther PM, Subar AF, Kirkpatrick SI, Dodd KW. Americans do not meet federal dietary recommendations. J Nutr. 2010;140(10):1832–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. O'Neil CE, Nicklas TA, Zanovec M, Cho S. Whole-grain consumption is associated with diet quality and nutrient intake in adults: the National Health and Nutrition Examination Survey, 1999–2004. J Am Diet Assoc. 2010;110(10):1461–8. [DOI] [PubMed] [Google Scholar]
- 12. Office of Disease Prevention and Health Promotion. Report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines of Americans 2015 to the Secretary of Agriculture and the Secretary of Health and Human Services[Internet].2015. [Accessed 12 July, 2018]. Available from: https://health.gov/dietaryguidelines/2015-scientific-report/, Department of Agriculture, Washington, DC, U.S. [Google Scholar]
- 13. Schwingshackl L, Hoffmann G, Lampousi AM, Knuppel S, Iqbal K, Schwedhelm C, Bechthold A, Schlesinger S, Boeing H. Food groups and risk of type 2 diabetes mellitus: a systematic review and meta-analysis of prospective studies. Eur J Epidemiol. 2017;32(5):363–75. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Van Horn L, Carson JA, Appel LJ, Burke LE, Economos C, Karmally W, Lancaster K, Lichtenstein AH, Johnson RK, Thomas RJ et al.. Recommended dietary pattern to achieve adherence to the American Heart Association/American College of Cardiology (AHA/ACC) guidelines: a scientific statement from the American Heart Association. Circulation. 2016;134(22):e505–e29. [DOI] [PubMed] [Google Scholar]
- 15. Alhazmi A, Stojanovski E, McEvoy M, Garg ML. The association between dietary patterns and type 2 diabetes: a systematic review and meta-analysis of cohort studies. J Hum Nutr Diet. 2014;27(3):251–60. [DOI] [PubMed] [Google Scholar]
- 16. Jannasch F, Kroger J, Schulze MB. Dietary patterns and type 2 diabetes: a systematic literature review and meta-analysis of prospective studies. J Nutr. 2017;147(6):1174–82. [DOI] [PubMed] [Google Scholar]
- 17. Sherzai A, Heim LT, Boothby C, Sherzai AD. Stroke, food groups, and dietary patterns: a systematic review. Nutr Rev. 2012;70(8):423–35. [DOI] [PubMed] [Google Scholar]
- 18. Lopez-Romero L, Silva-Sieger F, Gamboa-Delgado E. [Dietary factors associated with stroke: a literature review]. Rev Neurol. 2016;63(5):211–8. [PubMed] [Google Scholar]
- 19. Medina-Remon A, Kirwan R, Lamuela-Raventos RM, Estruch R. Dietary patterns and the risk of obesity, type 2 diabetes mellitus, cardiovascular diseases, asthma, and neurodegenerative diseases. Crit Rev Food Sci Nutr. 2018;58(2):262–96. [DOI] [PubMed] [Google Scholar]
- 20. Chen M, Li J, Li W, Sun X, Shu H. Dietary refined grain intake could increase the coronary heart disease risk: evidence from a meta-analysis. Int J Clin Med. 2017;10(8):12749–55. [Google Scholar]
- 21. Eshak ES, Iso H, Yamagishi K, Kokubo Y, Saito I, Yatsuya H, Sawada N, Inoue M, Tsugane S. Rice consumption is not associated with risk of cardiovascular disease morbidity or mortality in Japanese men and women: a large population-based, prospective cohort study. Am J Clin Nutr. 2014;100(1):199–207. [DOI] [PubMed] [Google Scholar]
- 22. Jacobs DR Jr, Andersen LF, Blomhoff R. Whole-grain consumption is associated with a reduced risk of noncardiovascular, noncancer death attributed to inflammatory diseases in the Iowa Women's Health Study. Am J Clin Nutr. 2007;85(6):1606–14. [DOI] [PubMed] [Google Scholar]
- 23. Jacobs DR Jr, Meyer KA, Kushi LH, Folsom AR. Whole-grain intake may reduce the risk of ischemic heart disease death in postmenopausal women: the Iowa Women's Health Study. Am J Clin Nutr. 1998;68(2):248–57. [DOI] [PubMed] [Google Scholar]
- 24. Jacobs DR Jr, Meyer KA, Kushi LH, Folsom AR. Is whole grain intake associated with reduced total and cause-specific death rates in older women? The Iowa Women's Health Study. Am J Public Health. 1999;89(3):322–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Liu S, Sesso HD, Manson JE, Willett WC, Buring JE. Is intake of breakfast cereals related to total and cause-specific mortality in men?. Am J Clin Nutr. 2003;77(3):594–9. [DOI] [PubMed] [Google Scholar]
- 26. Lockheart MS, Steffen LM, Rebnord HM, Fimreite RL, Ringstad J, Thelle DS, Pedersen JI, Jacobs DR Jr.. Dietary patterns, food groups and myocardial infarction: a case-control study. Br J Nutr. 2007;98(2):380–7. [DOI] [PubMed] [Google Scholar]
- 27. Sahyoun NR, Jacques PF, Zhang XL, Juan W, McKeown NM. Whole-grain intake is inversely associated with the metabolic syndrome and mortality in older adults. Am J Clin Nutr. 2006;83(1):124–31. [DOI] [PubMed] [Google Scholar]
- 28. Sonestedt E, Hellstrand S, Schulz CA, Wallstrom P, Drake I, Ericson U, Gullberg B, Hedblad B, Orho-Melander M. The association between carbohydrate-rich foods and risk of cardiovascular disease is not modified by genetic susceptibility to dyslipidemia as determined by 80 validated variants. PLoS One. 2015;10(4):e0126104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Steffen LM, Jacobs DR Jr, Stevens J, Shahar E, Carithers T, Folsom AR. Associations of whole-grain, refined-grain, and fruit and vegetable consumption with risks of all-cause mortality and incident coronary artery disease and ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr. 2003;78(3):383–90. [DOI] [PubMed] [Google Scholar]
- 30. Wang JB, Fan JH, Dawsey SM, Sinha R, Freedman ND, Taylor PR, Qiao YI, Abnet CC. Dietary components and risk of total, cancer and cardiovascular disease mortality in the Linxian Nutrition Intervention Trials cohort in China. Sci Rep. 2016;6:22619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Wu H, Flint AJ, Qi Q, van Dam RM, Sampson LA, Rimm EB, Holmes MD, Willett WC, Hu FB, Sun Q. Association between dietary whole grain intake and risk of mortality: two large prospective studies in US men and women. JAMA Intern Med. 2015;175(3):373–84. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Yu D, Shu XO, Li H, Xiang YB, Yang G, Gao YT, Zheng W, Zhang X. Dietary carbohydrates, refined grains, glycemic load, and risk of coronary heart disease in Chinese adults. Am J Epidemiol. 2013;178(10):1542–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Chen J, Huang Q, Shi W, Yang L, Chen J, Lan Q. Meta-analysis of the association between whole and refined grain consumption and stroke risk based on prospective cohort studies. Asia Pac J Public Health. 2016;28(7):563–75. [DOI] [PubMed] [Google Scholar]
- 34. Wu D, Guan Y, Lv S, Wang H, Li J. No evidence of increased risk of stroke with consumption of refined grains: a meta-analysis of prospective cohort studies. J Stroke Cerebrovasc Dis. 2015;24(12):2738–46. [DOI] [PubMed] [Google Scholar]
- 35. Schwingshackl L, Schwedhelm C, Hoffmann G, Knuppel S, Iqbal K, Andriolo V, Bechthold A, Schlesinger S, Boeing H. Food groups and risk of hypertension: a systematic review and dose-response meta-analysis of prospective studies. Adv Nutr. 2017;8(6):793–803. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Schwingshackl L, Schwedhelm C, Hoffmann G, Knuppel S, Laure Preterre A, Iqbal K, Bechthold A, De Henauw S, Michels N, Devleesschauwer B et al.. Food groups and risk of colorectal cancer. Int J Cancer. 2018;142(9):1748–58. [DOI] [PubMed] [Google Scholar]
- 37. Muraki I, Wu H, Imamura F, Laden F, Rimm EB, Hu FB, Willett EC, Sun Q. Rice consumption and risk of cardiovascular disease: results from a pooled analysis of 3 U.S. cohorts. Am J Clin Nutr. 2015;101(1):164–72. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Erkkila AT, Herrington DM, Mozaffarian D, Lichtenstein AH. Cereal fiber and whole-grain intake are associated with reduced progression of coronary-artery atherosclerosis in postmenopausal women with coronary artery disease. Am Heart J. 2005;150(1):94–101. [DOI] [PubMed] [Google Scholar]
- 39. Djousse L, Gaziano JM. Breakfast cereals and risk of heart failure in the Physicians' Health Study I. Arch Intern Med. 2007;167(19):2080–5. [DOI] [PubMed] [Google Scholar]
- 40. Micha R, Wallace SK, Mozaffarian D. Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: a systematic review and meta-analysis. Circulation. 2010;121(21):2271–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41. O'Sullivan TA, Hafekost K, Mitrou F, Lawrence D. Food sources of saturated fat and the association with mortality: a meta-analysis. Am J Public Health. 2013;103(9):e31–42. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42. Wang X, Lin X, Ouyang YY, Liu J, Zhao G, Pan A, Hu FB. Red and processed meat consumption and mortality: dose-response meta-analysis of prospective cohort studies. Public Health Nutr. 2016;19(5):893–905. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43. Eshak ES, Iso H, Date C, Yamagishi K, Kikuchi S, Watanabe Y, Wada Y, Tamakoshi A; JACC Study Group. Rice intake is associated with reduced risk of mortality from cardiovascular disease in Japanese men but not women. J Nutr. 2011;141(4):595–602. [DOI] [PubMed] [Google Scholar]
- 44. Liu S, Manson JE, Stampfer MJ, Rexrode KM, Hu FB, Rimm EB, Willett WC. Whole grain consumption and risk of ischemic stroke in women: a prospective study. JAMA. 2000;284(12):1534–40. [DOI] [PubMed] [Google Scholar]
- 45. Mizrahi A, Knekt P, Montonen J, Laaksonen MA, Heliovaara M, Jarvinen R. Plant foods and the risk of cerebrovascular diseases: a potential protection of fruit consumption. Br J Nutr. 2009;102(7):1075–83. [DOI] [PubMed] [Google Scholar]
- 46. Oba S, Nagata C, Nakamura K, Fujii K, Kawachi T, Takatsuka N, Shimizu H. Dietary glycemic index, glycemic load, and intake of carbohydrate and rice in relation to risk of mortality from stroke and its subtypes in Japanese men and women. Metabolism. 2010;59(11):1574–82. [DOI] [PubMed] [Google Scholar]
- 47. Wang L, Gaziano JM, Liu S, Manson JE, Buring JE, Sesso HD. Whole- and refined-grain intakes and the risk of hypertension in women. Am J Clin Nutr. 2007;86(2):472–9. [DOI] [PubMed] [Google Scholar]
- 48. Kochar J, Gaziano JM, Djousse L. Breakfast cereals and risk of hypertension in the Physicians' Health Study I. Clin Nutr. 2012;31(1):89–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49. Kim K, Hyeon J, Lee SA, Kwon SO, Lee H, Keum N, Lee JK, Park SM. Role of total, red, processed, and white meat consumption in stroke incidence and mortality: a systematic review and meta-analysis of prospective cohort studies. J Am Heart Assoc. 2017;6(9):e005983 doi:10.1161/JAHA.117.005983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50. Zhang Y, Zhang DZ. Red meat, poultry, and egg consumption with the risk of hypertension: a meta-analysis of prospective cohort studies. J Hum Hypertens. 2018;32(7):507–17. [DOI] [PubMed] [Google Scholar]
- 51. Ericson U, Sonestedt E, Gullberg B, Hellstrand S, Hindy G, Wirfalt E, Orho-Melander M. High intakes of protein and processed meat associate with increased incidence of type 2 diabetes. Br J Nutr. 2013;109(6):1143–53. [DOI] [PubMed] [Google Scholar]
- 52. Fung TT, Hu FB, Pereira MA, Liu S, Stampfer MJ, Colditz GA, Willett WC. Whole-grain intake and the risk of type 2 diabetes: a prospective study in men. Am J Clin Nutr. 2002;76(3):535–40. [DOI] [PubMed] [Google Scholar]
- 53. Liu S, Manson JE, Stampfer MJ, Hu FB, Giovannucci E, Colditz GA, Hennekens CH, Willett WC. A prospective study of whole-grain intake and risk of type 2 diabetes mellitus in US women. Am J Public Health. 2000;90(9):1409–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54. Meyer KA, Kushi LH, Jacobs DR Jr, Slavin J, Sellers TA, Folsom AR. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr. 2000;71(4):921–30. [DOI] [PubMed] [Google Scholar]
- 55. Montonen J, Knekt P, Jarvinen R, Aromaa A, Reunanen A. Whole-grain and fiber intake and the incidence of type 2 diabetes. Am J Clin Nutr. 2003;77(3):622–9. [DOI] [PubMed] [Google Scholar]
- 56. Kochar J, Djousse L, Gaziano JM. Breakfast cereals and risk of type 2 diabetes in the Physicians' Health Study I. Obesity (Silver Spring). 2007;15(12):3039–44. [DOI] [PubMed] [Google Scholar]
- 57. Parker ED, Liu S, Van Horn L, Tinker LF, Shikany JM, Eaton CB, Margolis KL. The association of whole grain consumption with incident type 2 diabetes: the Women's Health Initiative Observational Study. Ann Epidemiol. 2013;23(6):321–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 58. Soriguer F, Colomo N, Olveira G, García-Fuentes E, Esteva I, Ruiz de Adana MS, Morcillo S, Porras N, Valdés S, Rojo-Martínez G. White rice consumption and risk of type 2 diabetes. Clin Nutr. 2013;32(3):481–4. [DOI] [PubMed] [Google Scholar]
- 59. Golozar A, Khalili D, Etemadi A, Poustchi H, Fazeltabar A, Hosseini F, Kamangar F, Khoshnia M, Islami F, Hadaegh F et al.. White rice intake and incidence of type 2 diabetes: analysis of two prospective cohort studies from Iran. BMC Public Health. 2017;17(1):133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60. Hodge AM, English DR, O'Dea K, Giles GG. Glycemic index and dietary fiber and the risk of type 2 diabetes. Diabetes Care. 2004;27(11):2701–6. [DOI] [PubMed] [Google Scholar]
- 61. Nanri A, Mizoue T, Noda M, Takahashi Y, Kato M, Inoue M, Tsugane S; Japan Public Health Center-based Prospective Study Group. Rice intake and type 2 diabetes in Japanese men and women: the Japan Public Health Center-based Prospective Study. Am J Clin Nutr. 2010;92(6):1468–77. [DOI] [PubMed] [Google Scholar]
- 62. Sun Q, Spiegelman D, van Dam RM, Holmes MD, Malik VS, Willett WC, Hu FB. White rice, brown rice, and risk of type 2 diabetes in US men and women. Arch Intern Med. 2010;170(11):961–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 63. Hu EA, Pan A, Malik V, Sun Q. White rice consumption and risk of type 2 diabetes: meta-analysis and systematic review. BMJ. 2012;344:e1454. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 64. McKeown NM, Meigs JB, Liu S, Saltzman E, Wilson PW, Jacques PF. Carbohydrate nutrition, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham Offspring Cohort. Diabetes Care. 2004;27(2):538–46. [DOI] [PubMed] [Google Scholar]
- 65. McKeown NM, Meigs JB, Liu S, Wilson PW, Jacques PF. Whole-grain intake is favorably associated with metabolic risk factors for type 2 diabetes and cardiovascular disease in the Framingham Offspring Study. Am J Clin Nutr. 2002;76(2):390–8. [DOI] [PubMed] [Google Scholar]
- 66. Lutsey PL, Steffen LM, Stevens J. Dietary intake and the development of the metabolic syndrome: the Atherosclerosis Risk in Communities study. Circulation. 2008;117(6):754–61. [DOI] [PubMed] [Google Scholar]
- 67. Xi B, Li S, Liu Z, Tian H, Yin X, Huai P, Tang W, Zhou D, Steffen LM. Intake of fruit juice and incidence of type 2 diabetes: a systematic review and meta-analysis. PLoS One. 2014;9(3):e93471. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 68. Greenwood DC, Threapleton DE, Evans CE, Cleghorn CL, Nykjaer C, Woodhead C, Burley VJ. Association between sugar-sweetened and artificially sweetened soft drinks and type 2 diabetes: systematic review and dose-response meta-analysis of prospective studies. Br J Nutr. 2014;112(5):725–34. [DOI] [PubMed] [Google Scholar]
- 69. Imamura F, O'Connor L, Ye Z, Mursu J, Hayashino Y, Bhupathiraju SN, Forouhi NG. Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. BMJ. 2015;351:h3576. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 70. Tsilas CS, de Souza RJ, Mejia SB, Mirrahimi A, Cozma AI, Jayalath VH, Ha V, Tawfik R, Di Buono M, Jenkins AL et al.. Relation of total sugars, fructose and sucrose with incident type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies. CMAJ. 2017;189(20):E711–E20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 71. Farvid MS, Cho E, Eliassen AH, Chen WY, Willett WC. Lifetime grain consumption and breast cancer risk. Breast Cancer Res Treat. 2016;159(2):335–45. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 72. Jain MG, Hislop GT, Howe GR, Ghadirian P. Plant foods, antioxidants, and prostate cancer risk: findings from case-control studies in Canada. Nutr Cancer. 1999;34(2):173–84. [DOI] [PubMed] [Google Scholar]
- 73. Kasum CM, Nicodemus K, Harnack LJ, Jacobs DR Jr, Folsom AR; Iowa Women's Health Study. Whole grain intake and incident endometrial cancer: the Iowa Women's Health Study. Nutr Cancer. 2001;39(2):180–6. [DOI] [PubMed] [Google Scholar]
- 74. Makarem N, Bandera EV, Lin Y, McKeown NM, Hayes RB, Parekh N. Associations of whole and refined grain intakes with adiposity-related cancer risk in the Framingham Offspring Cohort (1991–2013). Nutr Cancer. 2018;70(5):776–86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 75. Nicodemus KK, Jacobs DR Jr, Folsom AR. Whole and refined grain intake and risk of incident postmenopausal breast cancer (United States). Cancer Causes Control. 2001;12(10):917–25. [DOI] [PubMed] [Google Scholar]
- 76. Li F, Hou LN, Chen W, Chen PL, Lei CY, Wei Q, Tan WL, Zheng SB. Associations of dietary patterns with the risk of all-cause, CVD and stroke mortality: a meta-analysis of prospective cohort studies. Br J Nutr. 2015;113(1):16–24. [DOI] [PubMed] [Google Scholar]
- 77. Gaesser GA. Carbohydrate quantity and quality in relation to body mass index. J Am Diet Assoc. 2007;107(10):1768–80. [DOI] [PubMed] [Google Scholar]
- 78. Williams PG. Evaluation of the evidence between consumption of refined grains and health outcomes. Nutr Rev. 2012;70(2):80–99. [DOI] [PubMed] [Google Scholar]
- 79. Williams PG, Grafenauer SJ, O'Shea JE. Cereal grains, legumes, and weight management: a comprehensive review of the scientific evidence. Nutr Rev. 2008;66(4):171–82. [DOI] [PubMed] [Google Scholar]
- 80. Bautista-Castaño I, Sánchez-Villegas A, Estruch R, Martínez-González MA, Corella D, Salas-Salvad J, Covas MI, Schroder H, Alvarez-Pérez J, Quilez J et al.. Changes in bread consumption and 4-year changes in adiposity in Spanish subjects at high cardiovascular risk. Br J Nutr. 2013;110(2):337–46. [DOI] [PubMed] [Google Scholar]
- 81. Bazzano LA, Song Y, Bubes V, Good CK, Manson JE, Liu S. Dietary intake of whole and refined grain breakfast cereals and weight gain in men. Obes Res. 2005;13(11):1952–60. [DOI] [PubMed] [Google Scholar]
- 82. Bradlee ML, Singer MR, Qureshi MM, Moore LL. Food group intake and central obesity among children and adolescents in the Third National Health and Nutrition Examination Survey (NHANES III). Public Health Nutr. 2010;13(6):797–805. [DOI] [PubMed] [Google Scholar]
- 83. Koh-Banerjee P, Franz M, Sampson L, Liu S, Jacobs DR Jr, Spiegelman D, Willett WC, Rimm E. Changes in whole-grain, bran, and cereal fiber consumption in relation to 8-y weight gain among men. Am J Clin Nutr. 2004;80(5):1237–45. [DOI] [PubMed] [Google Scholar]
- 84. McKeown NM, Yoshida M, Shea MK, Jacques PF, Lichtenstein AH, Rogers G, Booth SL, Saltzman E. Whole-grain intake and cereal fiber are associated with lower abdominal adiposity in older adults. J Nutr. 2009;139(10):1950–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 85. Newby PK, Maras J, Bakun P, Muller D, Ferrucci L, Tucker KL. Intake of whole grains, refined grains, and cereal fiber measured with 7-d diet records and associations with risk factors for chronic disease. Am J Clin Nutr. 2007;86(6):1745–53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 86. Liu S, Willett WC, Manson JE, Hu FB, Rosner B, Colditz G. Relation between changes in intakes of dietary fiber and grain products and changes in weight and development of obesity among middle-aged women. Am J Clin Nutr. 2003;78(5):920–7. [DOI] [PubMed] [Google Scholar]
- 87. McKeown NM, Troy LM, Jacques PF, Hoffmann U, O'Donnell CJ, Fox CS. Whole- and refined-grain intakes are differentially associated with abdominal visceral and subcutaneous adiposity in healthy adults: the Framingham Heart Study. Am J Clin Nutr. 2010;92(5):1165–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 88. Esmaillzadeh A, Mirmiran P, Azizi F. Whole-grain intake and the prevalence of hypertriglyceridemic waist phenotype in Tehranian adults. Am J Clin Nutr. 2005;81(1):55–63. [DOI] [PubMed] [Google Scholar]
- 89. Masters RC, Liese AD, Haffner SM, Wagenknecht LE, Hanley AJ. Whole and refined grain intakes are related to inflammatory protein concentrations in human plasma. J Nutr. 2010;140(3):587–94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 90. Kelly SA, Hartley L, Loveman E, Colquitt JL, Jones HM, Al-Khudairy L, Clar C, Germano R, Lunn HR, Frost G et al.. Whole grain cereals for the primary or secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2017;8:CD005051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 91. Marventano S, Vetrani C, Vitale M, Godos J, Riccardi G, Grosso G. Whole grain intake and glycaemic control in healthy subjects: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2017;9(7):769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 92. Pol K, Christensen R, Bartels EM, Raben A, Tetens I, Kristensen M. Whole grain and body weight changes in apparently healthy adults: a systematic review and meta-analysis of randomized controlled studies. Am J Clin Nutr. 2013;98(4):872–84. [DOI] [PubMed] [Google Scholar]
- 93. Levitan EB, Song Y, Ford ES, Liu S. Is nondiabetic hyperglycemia a risk factor for cardiovascular disease? A meta-analysis of prospective studies. Arch Intern Med. 2004;164(19):2147–55. [DOI] [PubMed] [Google Scholar]
- 94. Decode Study Group, the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001;161(3):397–405. [DOI] [PubMed] [Google Scholar]
- 95. Rowe S, Alexander N, Almeida N, Black R, Burns R, Bush L, Crawford P, Keim N, Kris-Etherton P, Weaver C. Food science challenge: translating the Dietary Guidelines for Americans to bring about real behavior change. J Food Sci. 2011;76(1):R29–37. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 96. Papanikolaou Y, Fulgoni VL. Grain foods are contributors of nutrient density for American adults and help close nutrient recommendation gaps: data from the National Health and Nutrition Examination Survey, 2009–2012. Nutrients. 2017;9(8):873 doi:10.3390/nu9080873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 97. Papanikolaou Y, Fulgoni VL. Grains contribute shortfall nutrients and nutrient density to older US adults: data from the National Health and Nutrition Examination Survey, 2011–2014. Nutrients. 2018;10(5):534 doi:10.3390/nu10050534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 98. Dietrich M, Brown CJ, Block G. The effect of folate fortification of cereal-grain products on blood folate status, dietary folate intake, and dietary folate sources among adult non-supplement users in the United States. J Am Coll Nutr. 2005;24(4):266–74. [DOI] [PubMed] [Google Scholar]
- 99. Williams J, Mai CT, Mulinare J, Isenburg J, Flood TJ, Ethen M, Frohnert B, Kirby RS; Centers for Disease Control and Prevention. Updated estimates of neural tube defects prevented by mandatory folic acid fortification—United States, 1995–2011. MMWR Morb Mortal Wkly Rep. 2015;64(1):1–5. [PMC free article] [PubMed] [Google Scholar]
- 100. Kranz S, Dodd KW, Juan WY, Johnson LK, Jahns L. Whole grains contribute only a small proportion of dietary fiber to the U.S. diet. Nutrients. 2017;9(2):153 doi:10.3390/nu9020153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 101. Clemens R, Kranz S, Mobley AR, Nicklas TA, Raimondi MP, Rodriguez JC, Slavin JL, Warshaw H. Filling America's fiber intake gap: summary of a roundtable to probe realistic solutions with a focus on grain-based foods. J Nutr. 2012;142(7):1390S–1401S. [DOI] [PubMed] [Google Scholar]
- 102. Hajishafiee M, Saneei P, Benisi-Kohansal S, Esmaillzadeh A. Cereal fibre intake and risk of mortality from all causes, CVD, cancer and inflammatory diseases: a systematic review and meta-analysis of prospective cohort studies. Br J Nutr. 2016;116(2):343–52. [DOI] [PubMed] [Google Scholar]
- 103. McRae MP. Dietary fiber intake and type 2 diabetes mellitus: an umbrella review of meta-analyses. J Chiropr Med. 2018;17(1):44–53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 104. Park Y, Subar AF, Hollenbeck A, Schatzkin A. Dietary fiber intake and mortality in the NIH-AARP diet and health study. Arch Intern Med. 2011;171(12):1061–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 105. Fogelholm M, Kanerva N, Mannisto S. Association between red and processed meat consumption and chronic diseases: the confounding role of other dietary factors. Eur J Clin Nutr. 2015;69(9):1060–5. [DOI] [PubMed] [Google Scholar]
- 106. Rohrmann S, Overvad K, Bueno-de-Mesquita HB, Jakobsen MU, Egeberg R, Tjonneland A, Nailler L, Boutron-Ruault MC, Clavel-Chapelon F, Krogh V et al.. Meat consumption and mortality—results from the European Prospective Investigation into Cancer and Nutrition. BMC Med. 2013;11:63. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 107. Bellavia A, Stilling F, Wolk A. High red meat intake and all-cause cardiovascular and cancer mortality: is the risk modified by fruit and vegetable intake?. Am J Clin Nutr. 2016;104(4):1137–43. [DOI] [PubMed] [Google Scholar]
- 108. Grosso G, Micek A, Godos J, Pajak A, Sciacca S, Galvano F, Boffetta P. Health risk factors associated with meat, fruit and vegetable consumption in cohort studies: a comprehensive meta-analysis. PLoS One. 2017;12(8):e0183787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 109. Kappeler R, Eichholzer M, Rohrmann S. Meat consumption and diet quality and mortality in NHANES III. Eur J Clin Nutr. 2013;67(6):598–606. [DOI] [PubMed] [Google Scholar]