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Whole-grain foods and chronic disease: evidence from epidemiological and intervention studies

Published online by Cambridge University Press:  11 June 2015

Chris J. Seal*
Human Nutrition Research Centre, School of Agriculture Food and Rural Development, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
Iain A. Brownlee
Human Nutrition Research Centre, School of Agriculture Food and Rural Development, Newcastle University, Singapore
*Corresponding author: Chris J. Seal, email
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Cereal-based foods are key components of the diet and they dominate most food-based dietary recommendations in order to achieve targets for intake of carbohydrate, protein and dietary fibre. Processing (milling) of grains to produce refined grain products removes key nutrients and phytochemicals from the flour and although in some countries nutrients may be replaced with mandatory fortification, overall this refinement reduces their potential nutritional quality. There is increasing evidence from both observational and intervention studies that increased intake of less-refined, whole-grain (WG) foods has positive health benefits. The highest WG consumers are consistently shown to have lower risk of developing CVD, type 2 diabetes and some cancers. WG consumers may also have better digestive health and are likely to have lower BMI and gain less weight over time. The bulk of the evidence for the benefits of WG comes from observational studies, but evidence of benefit in intervention studies and potential mechanisms of action is increasing. Overall this evidence supports the promotion of WG foods over refined grain foods in the diet, but this would require adoption of standard definitions of ‘whole grain’ and ‘whole-grain foods’ which will enable innovation by food manufacturers, provide clarity for the consumer and encourage the implementation of food-based dietary recommendations and public health strategies.

Conference on ‘Carbohydrates in health: friends or foes’
Copyright © The Authors 2015 

The concept that whole-grain (WG) foods are associated with health is not new. Both Carl Linnaeus and Thomas Allinson previously extolled the virtue of wholemeal bread as part of a healthy lifestyle in the 18th and 19th century, respectively( Reference Räsänen 1 , Reference Thomas 2 ). An early observational study also noted that Hunzukut males from a remote region of Northern Pakistan habitually consumed WG, other plant-based foods, goat's milk and cheese, grape wine and rice, with high levels of physical activity. These males were described as being particularly vigorous and suggested to frequently live well beyond the age of 100, although this has not been independently verified( 3 ).

Recently, more quantitative population-based studies have highlighted the positive association between higher intake of WG foods and improved outcomes in relation to morbidity and mortality for major diseases such as CVD, type 2 diabetes and some cancers. Of key importance in this area are definitions of ‘whole grain’ and ‘whole-grain foods’ which can be applied to published data and, eventually, to allow for clear public health messages with recommendations for WG intake.

The present focus in WG food-related research and health has shifted towards the evaluation of the quality of the present evidence base in relation to health claims and dietary recommendations. A recent position statement was released by the Scientific Advisory Committee for Nutrition for further consultation in the UK( 4 ). The statement emphasises the importance of WG in the diet and, if implemented, will require a major change in emphasis by Public Health England and other agencies in promoting WG consumption in the UK.

Whole grain definitions

While the definition of a ‘whole grain’ or WG food appears to be simple, controversies as to exact definitions have been apparent since the first formal definition was proposed by the American Association for Cereal Chemists in 1999( 5 ). While the foundation of this definition, which acknowledges that a degree of processing of grains is acceptable as long as bran, germ and endosperm components remain in their natural ratios, has remained constant, further difficulties in defining what a grain is (for example should soya be included in this category) and the type and extent of processing which are acceptable in relation to changes in composition have arisen( Reference Slavin, Tucker and Harriman 6 ).

Most recently, WG have been defined by the European HEALTHGRAIN consortium as those from an inclusive list of commonly available grains, pseudograins and wild rice( Reference van der Kamp, Poutanen and Seal 7 ). The definition of WG proposes that the grains may be processed in a variety of ways which ensures that the natural proportions of bran, germ and endosperm are retained. Crucially, and in contrast to the updated AACCI definition( Reference Ferruzzi, Jonnalagadda and Liu 8 ), this definition also allows for a minimal loss of these three components during the processing of these WG foods( Reference Mellen, Walsh and Herrington 9 ).

Similar issues in the standardisation of a definition for WG foods have also become apparent. A number of definitions agree that WG foods should contain over half their weight from WG sources. The disagreements come in relation to whether this should be expressed as the dry content of the product, or whether it should be based on ingredient declarations( Reference Ferruzzi, Jonnalagadda and Liu 8 ). Such definitions may exclude products with a naturally high water content (e.g. breads) but would also be likely to exclude dried products (e.g. breakfast cereals and staples like brown rice and whole-wheat pasta) as served, due to the high moisture content caused by the addition of milk or water during preparation. While attaching a percentage-content value to a food product may appear a simple solution, it may also discount a range of other products that are frequently consumed in higher quantity in the diet but still provide the consumer with appreciable amounts of WG. A more recent and practicable definition was proposed based on the amount by weight that a portion of WG food might provide. The definition was proposed by an international cross-disciplinary group which suggested that the lowest amount a WG food product must contain was 8 g WG per 30 g product( Reference Ferruzzi, Jonnalagadda and Liu 8 ) in order to be labelled as a ‘whole-grain food’. By making the recommendation in this way the panel aimed to provide WG food manufacturers with a target amount of WG within their products which was nutritionally meaningful. Further follow-up within the next few years will allow assessment of whether such practices have been adopted by manufacturers.

Health benefits of consuming whole grains: what is new?

A series of meta-analyses have previously reported that observational evidence consistently highlights an association between increasing intake of WG foods and reduced risk of CVD( Reference Mellen, Walsh and Herrington 9 , Reference Ye, Chacko and Chou 10 ), type II diabetes( Reference Ye, Chacko and Chou 10 , Reference Aune, Norat and Romundstad 11 ), metabolic syndrome( Reference Ye, Chacko and Chou 10 ) and multiple-site cancers( Reference Aune, Chan and Lau 12 , Reference Jacobs, Marquart and Slavin 13 ). To the authors’ knowledge, there are no previous published intervention studies linking WG consumption to cancer outcomes. The recent UK Scientific Advisory Committee on Nutrition draft report on Carbohydrates and Health( 14 ) showed that consumption of carbohydrates from WG sources led to a significantly reduced relative risk for cardiovascular events. In contrast, the percentage dietary energy from carbohydrates, carbohydrates from legumes, refined grain consumption and intake of low glycaemic index carbohydrates were all not associated with subsequent CVD events. In the case of any CVD event reported in five previous meta-analyses, the pooled estimate of relative risk was 0·95 (95 % CI 0·92, 0·97) for each WG consumption event every 2 d( 14 ). While this effect is small, it must be noted that the frequency of consumption is low, perhaps as a result of low habitual intake of WG at the time of data collection in the original studies. Higher intake of WG by some populations would therefore be expected to have a more marked effect on reduction of the relative risk of all cardiovascular events. Although WG intake is presently low in many countries( Reference Bellisle, Hébel and Colin 15 Reference Mann, Pearce and McKevith 17 ), it does appear to be increasing over time and this might be expected to lead to subsequent reductions in incidence of and mortality from cardiovascular events.

Intervention studies have been carried out in relation to the impact of WG consumption on markers of cardiovascular and metabolic health. The findings from these studies have been less consistent in reporting a positive impact of WG on health outcomes than those in population-based studies. Ferruzzi et al. ( Reference Ferruzzi, Jonnalagadda and Liu 8 ) noted that part of the inconsistency may be a result of different study design and incorporation of different types of WG foods within the intervention diet regimen. In addition, methods for reporting and calculating WG intake vary considerably between studies making interpretation of results and comparison between studies even more difficult( Reference Ross, Kristensen and Seal 18 ).

Whole grains and cardiovascular/metabolic health

Previous meta-analyses of intervention evidence show that existing evidence does not consistently support improved outcome measures as result of WG food-based intervention on body weight, indices of body fatness or blood pressure, although some improvements to the blood lipid profiles were evident( Reference Ye, Chacko and Chou 10 , Reference Pol, Christensen and Bartels 19 ).

Many of the previous population-based studies have suggested that a daily intake of WG, equivalent to about three slices of wholemeal bread, is associated with a reduced risk or prevalence of cardiovascular outcomes. As a result of these findings, specific target on daily WG intakes have been recommended in the USA and in Denmark. Many other countries have less specific recommendations such as ‘eating more whole grain’ or ‘choose WG whenever possible( Reference Ferruzzi, Jonnalagadda and Liu 8 ). It must be noted that WG vary greatly based on the chemical composition of different grain species( Reference Seal, Jones and Whitney 20 ). Therefore, consideration of whether or not individual food items are independently associated with disease outcome is important, particularly as one source of grain may be the predominant staple within some populations (e.g. rye in Northern European countries). To date, only a few studies have focused on single WG staples. For example, Kazemzadeh et al.( Reference Kazemzadeh, Safavi and Nematollahi 21 ) and Sun et al. ( Reference Sun, Spiegelman and van Dam 22 ) demonstrated that brown rice was an independent marker of disease risk. Similarly Rebello et al.( Reference Rebello, Koh and Chen 23 ) recently suggested that wholemeal bread intake was negatively correlated with IHD risk in a Chinese cohort.

Whole grains and control of blood glucose

A recent meta-analysis of cohort studies suggested that increased intake of WG foods resulted in a reduced risk of type II diabetes( Reference Aune, Norat and Romundstad 11 ). Evidence from the Women's Health Initiative Observational Study also found an inverse dose–response relationship between WG food intake and decreased incidence of type II diabetes( Reference Parker, Liu and Van Horn 24 ). In both of these studies, there also appears to be an increased risk or incidence of type II diabetes with consumption of refined grain products. A previous study that focused on analysis of rice consumption patterns in the US population similarly noted that increasing regular brown rice consumption was associated with decreased risk of type II diabetes whereas habitual white rice consumption was associated with increased risk. Multivariate modelling within this pooled analysis also suggested that substitution of white rice for brown rice or other WG foods could reduce the risk of type II diabetes by 16 % per 50 g rice replaced with brown rice, but a greater reduction was predicted if the 50 g rice was with other WG foods( Reference Sun, Spiegelman and van Dam 22 ).

Fewer intervention-based studies have suggested improvements in control of blood glucose as a result of WG intake. A series of recent studies has provided further information on how WG may affect glucose tolerance. Consideration of the types of foods used within the intervention, comparator diet and target group of choice may be key determinants on the outcomes noted. Previously published glycaemic index tables show that WG foods do not necessarily have a lower glycaemic index than comparable refined grain products( Reference Atkinson, Foster-Powell and Brand-Miller 25 , Reference Brand-Miller, McMillan-Price and Steinbeck 26 ), as milling and other processing parameters are likely to affect digestibility of such products. A two-group parallel design study compared the impact of inclusion of a range of WG products in comparison with well-matched refined grain control products in sixty-one men and women with metabolic syndrome over a 12-week period( Reference Giacco, Costabile and Della Pepa 27 ). The WG intervention was found to improve postprandial insulinaemic response to a test meal (a reduction of 29 % compared with the control group) but did not improve glycaemic responses. Improvements in insulinaemic responses (but not glycaemic responses) were also noted in studies carried out with whole rye-included in the SYSDIMET Nordic dietary intervention lasting 24 weeks( Reference Magnusdottir, Landberg and Gunnarsdottir 28 ). Similarly, after 6 months adherence to a New Nordic Diet (high in fruit, vegetables, WG and fish) Poulsen et al.( Reference Poulsen, Due and Jordy 29 ) showed a significant reduction in fasting serum insulin and homeostatic model of insulin resistance compared with the Average Danish Diet with no difference between the groups in fasting plasma glucose concentrations. An effect on glucose concentrations was seen in a 12-week intervention study comparing dietary carbohydrate sources (white rice v. WG, barley and legumes) in Korean type II diabetics and individuals with impaired glycaemic control( Reference Kang, Kim and Chae 30 ). In this study, both fasting blood glucose and insulin concentrations were improved in the group receiving non-refined carbohydrates.

The afore-mentioned evidence appears to provide further support for the idea that WG-rich diets can reduce the risk of type II diabetes. It is interesting to note that the majority of these studies have highlighted an impact on the insulin response rather than affecting fasting or postprandial blood glucose concentrations, suggesting an increased sensitivity to insulin rather than a blunting of postprandial glycaemia. It is important to note that of all the studies listed earlier, however, only that of Giacco et al. ( Reference Giacco, Costabile and Della Pepa 27 ) represents a well-controlled intervention of WG v. refined grains alone, whereas the other studies tend to compare refined grain diets with a healthier dietary template that includes increased WG intake.

Whole grains and body weight or body fatness

The recent meta-analysis of Pol et al.( Reference Pol, Christensen and Bartels 19 ) noted a lack of effect of WG on the reduction of body weight. At the same time, a number of studies have highlighted changes to some (but not all) measures of body fatness as a result of WG-based interventions. For example, in the study of Katcher et al. ( Reference Katcher, Legro and Kunselman 31 ) the reduction in percentage of visceral body fat was higher in the group receiving a reduced energy diet containing WG foods compared with the reduced energy diet alone. Small reductions in percentage of body fat were also noted in the study of Kristensen et al. ( Reference Kristensen, Toubro and Jensen 32 ). In both these studies, a range of other body fatness parameters were also assessed, with no significant difference in these outcomes noted as a result of WG intervention( Reference Katcher, Legro and Kunselman 31 , Reference Kristensen, Toubro and Jensen 32 ). The findings of these studies suggest small but measurable improvements in body fat distribution within an energy-restricted dietary pattern containing WG but these are not seen in the absence of energy restriction.

Whole grains and cancer risk or incidence

Due to a lack of well-defined biomarkers for assessment of risk of cancer, there is no evidence from intervention studies in relation to the impact of WG on cancer risk or outcome. While evidence from a variety of population-based studies from around the world have consistently highlighted a lower incidence rate of cancer with higher consumption of WG, it is surprising that these effects have not been the focus of previous WG health messages. The original WG health claim authorised in the USA( 33 ) cited reduced cancer risk but this was subsequently removed from the health claim when it was revised( 34 ).

A recent study noted that a dietary pattern rich in WG, fruit and vegetables was associated with a reduced incidence of breast cancer in a Greek case-controlled study( Reference Mourouti, Papavagelis and Plytzanopoulou 35 ). A ‘whole food’ dietary pattern (i.e. one with higher consumption of fruit and vegetables, fish, poultry and WG) was also linked to reduced concentrations of pro-inflammatory cytokines in head and neck cancer patients( Reference Arthur, Peterson and Shen 36 ) and also appears to reduce recurrence and mortality rates within this population group( Reference Arthur, Peterson and Rozek 37 ).

A number of previous studies have suggested that increased WG intake is associated with a reduced incidence of colorectal cancer( Reference Aune, Chan and Lau 12 ), including some suggestion that WG intake is associated with a modest reduction in risk of colorectal cancer, whereas total dietary fibre intake does not reduce risk( Reference Schatzkin, Mouw and Park 38 ). The recent study of Knudsen et al. ( Reference Knudsen, Kyrø and Olsen 39 ) noted that inconsistencies in previous findings could be due to the use of FFQ as a (non-specific and self-reported) basis for dietary estimation. They found significant reduction in cancer risks when measured against plasma alkylresorcinol concentrations as a validated biomarker of whole wheat and whole rye intake( Reference Ross 40 , Reference Ross, Bourgeois and Macharia 41 ) either alone or in combination with estimated WG intake by FFQ. While previous evidence would suggest a statistically significant correlation between alkylresorcinols and intake of WG, it must also be noted that the linearity of this association does not appear to be strong enough to effectively predict absolute amounts of intake of whole wheat and whole rye products but may be a useful adjunct to assess habitual/recent high and low dietary intakes of such foods.

Many previous studies on WG intake and colorectal cancer risk have utilised datasets collected in North America and parts of Europe where WG consumption is habitually low and the highest percentile of WG intake may also be modest( Reference Cleveland, Moshfegh and Albertson 42 , Reference Zanovec, O'Neil and Cho 43 ). The recent study of Egeberg et al.( Reference Egeberg, Olsen and Loft 44 ) focused on assessment of cancer risk in a Danish population where the median daily amount of WG foods consumed was high (130 g/d, which would approximate to about 65 g WG/d). The lowest intake noted within the study participants was still in excess of one serving of WG daily (which may represent the upper amount of intake in some previous observational studies). This study noted a modest reduction in colon cancer risk in males but not females( Reference Egeberg, Olsen and Loft 44 ).

Mechanistic studies on whole grains

Previously, a number of studies have compared the in vitro antioxidant content of WG foods to refined grain alternatives( Reference Fardet, Rock and Rémésy 45 ), although previous evidence would suggest that inclusion of high amounts of WG (60 %) in the diet of rats does not improve antioxidant status in comparison with refined grains( Reference Fardet, Canlet and Gottardi 46 ). However, there are surprisingly few studies assessing the impact of WG v. refined carbohydrate consumption on markers of health or disease occurrence in animal models. Some of the most recent data are discussed later.

While the rodent gastrointestinal anatomy and physiology differs significantly from that of human subjects( Reference Kararli 47 ) and rodent chow is not comparable with human diets in terms of form and composition( Reference La Fleur, Luijendijk and Van Der Zwaal 48 ), rat and mice models can at least provide further clues into the understanding of how WG might impact on acute physiology or longer-term disease progression.

Replacement of a high sucrose diet with traditional whole maize products resulted in improved metabolic profiles in rats( Reference Muñoz Cano, Aguilar and Hernández 49 ). While this study used foods prepared in the same way as they would be consumed by human subjects, a direct comparison is not possible between whole and refined grains (but rather WG and refined sugar). A series of recent studies assessed the effect of switching maize starch with 1–2 % by weight powdered millet extracts( Reference Lee, Chung and Cha 50 Reference Park, Jang and Lee 52 ). In these studies, these relatively small changes to the overall diet improved the metabolic profile and body weight of the millet-fed mice v. comparator groups with metabolic syndrome induced by either dietary or genetic manipulation. Substitution of white rice with WG (Job's Tears, buckwheat and glutinous/waxy barley) in rats fed an obesogenic diet resulted in lowered plasma triacylglycerols, total cholesterol and LDL-cholesterol concentrations and a significant reduction in aortic wall thickness suggesting that these grains had a cardioprotective effect( Reference Kim, Shin and Lee 53 , Reference Son, Kim and Lee 54 ). Differential effects between grain types have been observed in mice fed WG wheat or WG rye( Reference Andersson, Rosén and Östman 55 ). In this experiment, WG rye reduced body weight and fatness, improved insulin sensitivity and lowered total cholesterol compared with the mice fed WG wheat. However, the experiment was not designed to compare WG with refined grain-containing diets limiting its value in this regard.

Studies in laboratory animals investigating possible effects of WG on cancer development are sparse. A recent study using a chemically-induced model of colorectal dysplasia involved feeding four parallel groups of rats diets containing refined and unrefined wheat from two different classes (soft white wheat and hard red wheat). The unrefined (WG) diets did not affect the number of aberrant crypt foci (an early mucosal change associated with the early stages of cancer development) occurring within the distal colon but the class of wheat did (with the red, hard wheat having reduced the incidence of aberrant crypt foci)( Reference Buescher and Gallaher 56 ). These results are consistent with those of Maziya-Dixon et al.( Reference Maziya-Dixon, Klopfenstein and Leipold 57 ) also in an experiment with chemically-induced colon cancer in which the end point was tumour incidence, which was significantly lower in mice whole and refined red wheat diets compared with whole or refined white wheat diets. The reasons why the red wheat variety proved beneficial compared with the white wheat is unclear, but presumably is due to differences in phytochemical content between the two cereals.

The porcine digestive tract is anatomically similar to that of human subjects( Reference Kararli 47 ). Nielsen et al. ( Reference Nielsen, Hartvigsen and Hedemann 58 ) compared that the metabolomic responses to test meals containing different types of bread were similar in pigs and human subjects and concluded that pigs were a suitable model for human metabolic studies in food research. However, only a few studies have used pigs to assess the impact of WG consumption on cardiovascular health so more work in this area is needed before firm conclusions about their value. For example, feeding 2–3 kg bread buns daily for up to 10 weeks containing either whole rye and rye bran improved lipid profiles and insulinaemic responses in hypercholesteraemic pigs compared with a control bread made with refined wheat flour and cellulose to match the total fibre content( Reference Lærke, Pedersen and Mortensen 59 ).

While animal models may not always be representative of the human system, their use may allow better insight into how grain-based foods could affect health outcomes. Parallel assessment of changes in bodily organs, such as the liver and brain, are unlikely to be possible in human subjects. Such studies also allow strict control of laboratory animal diets and manipulation of dietary intake or management of multiple comparative dietary treatments is much simpler compared with studies in free-living human subjects. As a result, such studies can provide clearer evidence of cause-and-effect in relation to an original hypothesis than human-based interventions can often provide.

The way forward

A number of countries across Europe, North America, Asia and Australia now include WG-based messages within their public health recommendations( 60 63 ).The available evidence suggests that recommendations for increasing WG foods at a population level are justified in relation to attempting to reduce incidence of CVD. Evidence from intervention studies suggests that WG may have statistically and biologically significant impacts on some markers of cardiovascular health but they also show that not all WG and foods made from them are equal in their impact on cardiovascular health outcomes.

While many of the earlier studies on WG and health have been carried out mainly in North American and European population, recent studies have also provided evidence that WG foods could be part of a healthy dietary template in other parts of the world. Recent dietary pattern analysis observations have suggested that WG foods are part of a healthy dietary template in other regions of the world, including South America( Reference Selem, Castro and César 64 ), Africa( Reference Amankwaa and Annan 65 ) and Asia( Reference Dugee, Khor and Lye 66 , Reference Song, Paik and Song 67 ).

In relation to the findings of these recent dietary pattern studies, it is important to consider the generalisability of WG-based public health messages in the target population. Health messages should be based on what the target population consume, what health challenges they face or are expected to face and what the quality of evidence is in relation to the association of WG food intake with health outcomes in this population group.

While not all intervention studies have shown positive outcomes in relation to health, very few (if any) of these studies have shown negative impacts on the health outcomes tested, as evidenced by recent meta-analyses. As such, messages targeted at increasing WG at a population level are still relevant and attempts by individuals to include more WG in their diets (assuming they have no allergy or intolerance to grain-based foods) are also justified.

One overarching concern that is likely to impact researchers, public health bodies and other government agencies, consumers and WG food manufacturers alike is the lack of the adoption of transparent and standardised definitions for the terms ‘whole grains’ and ‘whole-grain foods’. These terms must be clearly delineated and policy provided in terms of a uniform definition. With the increasing internationalisation of the food market and differences in labelling and other requirements in different regions of the world, this may be more challenging at a global level although it may be feasible in regions with more harmonised food regulation such as the EU, North America and the ASEAN countries.

The recent Scientific Advisory Committee for Nutrition draft report on dietary carbohydrates has stated that ‘The evidence … .. endorses a dietary pattern concerning carbohydrates that is based on whole grains, pulses (e.g. kidney beans, haricot beans, lentils), potatoes, vegetables and fruits’ and also makes note that intake of free sugars from all sources should be limited( 14 ). While this reinforces the idea that WG are an important part of a healthy dietary pattern, the latter recommendation on free sugars may also be important to consider in relation to choice of WG foods and the development of new WG food products. A single serving of certain ready-to-eat breakfast cereals may contain higher amounts of free sugars than the 5 % of daily energy intake suggested by Scientific Advisory Committee on Nutrition( 14 ). A single serving of WG snacks, such as flapjacks and cereal bars is likely to exceed this amount. The recommendation suggested by Ferruzzi et al. ( Reference Ferruzzi, Jonnalagadda and Liu 8 ) would encourage development of products that provided biologically relevant amounts of WG to the consumer and should be used for development of products based on replacement or substitution of refined grain for WG in product formulations. This reformulation should also consider the overall nutrient profile of the product so that the consumer can be confident that ‘whole-grain’ foods are clearly a healthier food option.

Financial Support

The authors have received funding from the UK Food Standards Agency and Cereal Partners Worldwide for whole grain-related research. Unrestricted funding, direct and in kind, has been received from Cereal Partners UK, Nestlé, Kellogg's, Weetabix and Allied Bakeries.

Conflicts of Interest

The authors declare no conflicts of interest and the views expressed within this paper are entirely their own.


I. A. B. and C. J. S. contributed equally to the collation of evidence, and design of content and writing of the paper.


1. Räsänen, L (2007) Of all foods bread is the most noble: Carl von Linné (Carl Linneaus) on bread. Scand J Food Nutr 51, 9199.CrossRefGoogle Scholar
2. Thomas, RA (1894) Medical Essays. London, UK: F. Pitman.Google Scholar
3. Anonymous Editorial (1961) Longevity in hunza land. J AM Med Assoc 175, 706706.CrossRefGoogle Scholar
4. Public Health England (2014) Consultation on draft SACN Carbohydrates and Health report. (accessed January 2015).Google Scholar
5. American Association of Cereal Chemists (1999) Whole grain definition. Cereal Foods World 45, 79.Google Scholar
6. Slavin, J, Tucker, M, Harriman, C et al. (2013) Whole grains: definition, dietary recommendations and health benefits. Cereal Foods World 58, 191198.CrossRefGoogle Scholar
7. van der Kamp, JW, Poutanen, K, Seal, CJ et al. (2014) The HEALTHGRAIN definition of ‘whole grain’. Food Nutr Res 58, 22100. CrossRefGoogle ScholarPubMed
8. Ferruzzi, MG, Jonnalagadda, SS, Liu, S et al. (2014) Developing a standard definition of whole-grain foods for dietary recommendations: summary report of a multidisciplinary expert roundtable discussion. Adv Nutr 5, 164176.CrossRefGoogle ScholarPubMed
9. Mellen, PB, Walsh, TF & Herrington, DM (2008) Whole grain intake and cardiovascular disease: a meta-analysis. Nutr Metab Cardiovasc Dis 18, 283290.CrossRefGoogle ScholarPubMed
10. Ye, EQ, Chacko, SA, Chou, EL et al. (2012) Greater whole-grain intake is associated with lower risk of Type 2 diabetes, cardiovascular disease, and weight gain. J Nutr 142, 13041313.CrossRefGoogle ScholarPubMed
11. Aune, D, Norat, T, Romundstad, P et al. (2013) 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 28, 845858.CrossRefGoogle ScholarPubMed
12. Aune, D, Chan, DSM, Lau, R et al. (2011) Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies. Br Med J 343.CrossRefGoogle ScholarPubMed
13. Jacobs, D, Marquart, L, Slavin, J et al. (1998) Whole grain intake and cancer: an expanded review and meta-analysis. Nutr Cancer 30, 8596.CrossRefGoogle ScholarPubMed
14. Scientific Advisory Committee on Nutrition (2014) Draft SACN Carbohydrates and Health Report. (accessed April 2015).Google Scholar
15. Bellisle, F, Hébel, P, Colin, J et al. (2014) Consumption of whole grains in French children, adolescents and adults. Br J Nutr 112, 16741684.CrossRefGoogle ScholarPubMed
16. Devlin, NFC, McNulty, BA, Gibney, MJ et al. (2013) Whole grain intakes in the diets of Irish children and teenagers. Br J Nutr 110, 354362.CrossRefGoogle ScholarPubMed
17. Mann, KD, Pearce, MS, McKevith, B et al. (2015) Low whole grain intake in the UK: results from the National Diet and Nutrition Survey rolling programme 2008–2011. Br J Nutr 113, 16431651.CrossRefGoogle Scholar
18. Ross, AB, Kristensen, M, Seal, CJ et al. (2015) Recommendations for reporting whole-grain intake in observational and intervention studies. Am J Clin Nutr 101, 903907.CrossRefGoogle ScholarPubMed
19. Pol, K, Christensen, R, Bartels, EM et al. (2013) Whole grain and body weight changes in apparently healthy adults: a systematic review and meta-analysis of randomized controlled studies. Am J Clin Nutr 98, 872884.CrossRefGoogle ScholarPubMed
20. Seal, CJ, Jones, AR & Whitney, AD (2006) Whole grains uncovered. Nutr Bull 31, 129137.CrossRefGoogle Scholar
21. Kazemzadeh, M, Safavi, SM, Nematollahi, S et al. (2014) Effect of brown rice consumption on inflammatory marker and cardiovascular risk factors among overweight and obese non-menopausal female adults. Int J Prev Med 5, 478488.Google Scholar
22. Sun, Q, Spiegelman, D, van Dam, RM et al. (2010) White rice, brown rice, and risk of type 2 diabetes in US men and women. Arch Int Med 170, 961969.CrossRefGoogle Scholar
23. Rebello, SA, Koh, H, Chen, C et al. (2014) Amount, type, and sources of carbohydrates in relation to ischemic heart disease mortality in a Chinese population: a prospective cohort study. Am J Clin Nutr 100, 5364.CrossRefGoogle Scholar
24. Parker, ED, Liu, S, Van Horn, L et al. (2013) The association of whole grain consumption with incident type 2 diabetes: the Women's Health Initiative Observational Study. Ann Epidemiol 23, 321327.CrossRefGoogle ScholarPubMed
25. Atkinson, FS, Foster-Powell, K & Brand-Miller, JC (2008) International tables of glycemic index and glycemic load values: 2008. Diab. Care 31, 22812283.CrossRefGoogle ScholarPubMed
26. Brand-Miller, J, McMillan-Price, J, Steinbeck, K et al. (2008) Carbohydrates-the good, the bad and the whole grain. Asia Pac J Clin Nutr 17, 1619.Google ScholarPubMed
27. Giacco, R, Costabile, G, Della Pepa, G et al. (2014) A whole-grain cereal-based diet lowers postprandial plasma insulin and triglyceride levels in individuals with metabolic syndrome. Nutr Metab Cardiovasc Dis 24, 837844.CrossRefGoogle ScholarPubMed
28. Magnusdottir, OK, Landberg, R, Gunnarsdottir, I et al. (2014) Whole grain rye intake, reflected by a biomarker, is associated with favorable blood lipid outcomes in subjects with the metabolic syndrome – A randomized study. PLoS ONE 9, e110827.CrossRefGoogle ScholarPubMed
29. Poulsen, SK, Due, A, Jordy, AB et al. (2014) Health effect of the New Nordic Diet in adults with increased waist circumference: a 6-mo randomized controlled trial. Am J Clin Nutr 99, 3545.CrossRefGoogle ScholarPubMed
30. Kang, R, Kim, M, Chae, JS et al. (2014) Consumption of whole grains and legumes modulates the genetic effect of the APOA5 -1131C variant on changes in triglyceride and apolipoprotein A-V concentrations in patients with impaired fasting glucose or newly diagnosed type 2 diabetes. Trials 15, 100.CrossRefGoogle ScholarPubMed
31. Katcher, HI, Legro, RS, Kunselman, AR et al. (2008) The effects of a whole grain enriched hypocaloric diet on cardiovascular disease risk factors in men and women with metabolic syndrome. Am J Clin Nutr 87, 7990.CrossRefGoogle ScholarPubMed
32. Kristensen, M, Toubro, S, Jensen, MG et al. (2012) Whole grain compared with refined wheat decreases the percentage of body fat following a 12-week, energy-restricted dietary intervention in postmenopausal women. J Nutr 142, 710716.CrossRefGoogle ScholarPubMed
33. Food and Drug Administration (1999) Health claim notification for whole grain foods. 39.htm (accessed April 2015).Google Scholar
34. Food and Drug Administration (2003) Health claim notification for whole grain foods with moderate fat content. (accessed April 2015).Google Scholar
35. Mourouti, N, Papavagelis, C, Plytzanopoulou, P et al. (2015) Dietary patterns and breast cancer: a case-control study in women. Eur J Nutr 54, 609617.CrossRefGoogle ScholarPubMed
36. Arthur, AE, Peterson, KE, Shen, J et al. (2014) Diet and proinflammatory cytokine levels in head and neck squamous cell carcinoma. Cancer 120, 27042712.CrossRefGoogle ScholarPubMed
37. Arthur, AE, Peterson, KE, Rozek, LS et al. (2013) Pretreatment dietary patterns, weight status, and head and neck squamous cell carcinoma prognosis. Am J Clin Nutr 97, 360368.CrossRefGoogle ScholarPubMed
38. Schatzkin, A, Mouw, T, Park, Y et al. (2007) Dietary fiber and whole-grain consumption in relation to colorectal cancer in the NIH-AARP Diet and Health Study. Am J Clin Nutr 85, 13531360.CrossRefGoogle ScholarPubMed
39. Knudsen, MD, Kyrø, C, Olsen, A et al. (2014) Self-reported whole-grain intake and plasma alkylresorcinol concentrations in combination in relation to the incidence of colorectal cancer. Am J Epidemiol 179, 11881196.CrossRefGoogle Scholar
40. Ross, AB (2012) Present status and perspectives on the use of alkylresorcinols as biomarkers of wholegrain wheat and rye intake. J Nutr Metab, Article ID 462967.CrossRefGoogle ScholarPubMed
41. Ross, AB, Bourgeois, A, Macharia, HNu et al. (2012) Plasma alkylresorcinols as a biomarker of whole-grain food consumption in a large population: results from the WHOLEheart Intervention Study. Am J Clin Nutr 95, 204211.CrossRefGoogle Scholar
42. Cleveland, LE, Moshfegh, AJ, Albertson, AM et al. (2000) Dietary intake of whole grains. J Am Coll Nutr 19, 331S338S.CrossRefGoogle ScholarPubMed
43. Zanovec, M, O'Neil, CE, Cho, SS et al. (2010) Relationship between whole grain and fiber consumption and body weight measures among 6- to 18-year-olds. J Pediatr 157, 578583.CrossRefGoogle ScholarPubMed
44. Egeberg, R, Olsen, A, Loft, S et al. (2010) Intake of wholegrain products and risk of colorectal cancers in the Diet, Cancer and Health cohort study. Br J Cancer 103, 730734.CrossRefGoogle ScholarPubMed
45. Fardet, A, Rock, E & Rémésy, C (2008) Is the in vitro antioxidant potential of whole-grain cereals and cereal products well reflected in vivo? J Cereal Sci 48, 258276.CrossRefGoogle Scholar
46. Fardet, A, Canlet, C, Gottardi, G et al. (2007) Whole-grain and refined wheat flours show distinct metabolic profiles in rats as assessed by a 1H NMR-based metabonomic approach. J Nutr 137, 923929.CrossRefGoogle ScholarPubMed
47. Kararli, TT (1995) Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharm Drug Dispos 16, 351380.CrossRefGoogle ScholarPubMed
48. La Fleur, SE, Luijendijk, MCM, Van Der Zwaal, EM et al. (2014) The snacking rat as model of human obesity: effects of a free-choice high-fat high-sugar diet on meal patterns. Int J Obes 38, 643649.CrossRefGoogle ScholarPubMed
49. Muñoz Cano, JM, Aguilar, AC & Hernández, JC (2013) Lipid-lowering effect of maize-based traditional Mexican food on a metabolic syndrome model in rats. Lipids Health Dis 12, 9.CrossRefGoogle ScholarPubMed
50. Lee, SH, Chung, I-M, Cha, Y-S et al. (2010) Millet consumption decreased serum concentration of triglyceride and C-reactive protein but not oxidative status in hyperlipidemic rats. Nutr Res 30, 290296.CrossRefGoogle Scholar
51. Park, MY, Jang, HH, Kim, JB et al. (2011) Hog millet (Panicum miliaceum L.)-supplemented diet ameliorates hyperlipidemia and hepatic lipid accumulation in C57BL/6J-ob/ob mice. Nutr Res Pract 5, 511519.CrossRefGoogle ScholarPubMed
52. Park, MY, Jang, HH, Lee, JY et al. (2012) Effect of hog millet supplementation on hepatic steatosis and insulin resistance in mice fed a high-fat diet. J Korean Soc Food Sci Nutr 41, 501509.CrossRefGoogle Scholar
53. Kim, JY, Shin, JH & Lee, SS (2012) Cardioprotective effects of diet with different grains on lipid profiles and antioxidative system in obesity-induced rats. Int J Vitam Nutr Res 82, 8593.CrossRefGoogle ScholarPubMed
54. Son, BK, Kim, JY & Lee, SS (2008) Effect of adlay, buckwheat and barley on lipid metabolism and aorta histopathology in rats fed an obesogenic diet. Ann Nutr Metab 52, 181187.CrossRefGoogle ScholarPubMed
55. Andersson, U, Rosén, L, Östman, E et al. (2010) Metabolic effects of whole grain wheat and whole grain rye in the C57BL/6J mouse. Nutrition 26, 230239.CrossRefGoogle ScholarPubMed
56. Buescher, MI & Gallaher, DD (2014) Wheat color (Class), not refining, influences colon cancer risk in rats. Nutr Cancer 66, 849856.CrossRefGoogle Scholar
57. Maziya-Dixon, B, Klopfenstein, C & Leipold, H (1994) Protective effects of hard red versus hard white winter wheats in chemically induced colon cancer in CF1 mice. Cereal Chem 71, 359363.Google Scholar
58. Nielsen, KL, Hartvigsen, ML, Hedemann, MS et al. (2014) Similar metabolic responses in pigs and humans to breads with different contents and compositions of dietary fibers: a metabolomics study. Am J Clin Nutr 99, 941949.CrossRefGoogle ScholarPubMed
59. Lærke, HN, Pedersen, C, Mortensen, MA et al. (2008) Rye bread reduces plasma cholesterol levels in hypercholesterolemia pigs when compared to wheat at similar dietary fibre level. J Sci Food Agr 88, 13851393.CrossRefGoogle Scholar
60. Denmark Ministry of Food (2015) Fuldkorn (Whole Grain). (accessed April 2015).Google Scholar
61. Malaysia Ministry of Health (2015) Dietary guidelines key message 4. uan/diet/KM4.pdf (accessed April 2015).Google Scholar
62. National Health Service (2015) NHS choices, starchy foods and carbohydrates. (accessed April 2015).Google Scholar
63. US Department of Health and Human Sciences (2010) Dietary guidelines for Americans 2010. (accessed March 2015).Google Scholar
64. Selem, SSDC, Castro, MAD, César, CLG et al. (2014) Associations between dietary patterns and self-reported hypertension among Brazilian adults: a cross-sectional population-based study. J Acad Nutr Diet 114, 12161222.CrossRefGoogle ScholarPubMed
65. Amankwaa, A & Annan, R (2014) Dietary patterns and metabolic risk factors for cardiovascular disease among University Students in Ghana. Asian J Clin Nutr 6, 1828.CrossRefGoogle Scholar
66. Dugee, O, Khor, GL, Lye, MS et al. (2009) Association of major dietary patterns with obesity risk among Mongolian men and women. Asia Pac J Clin Nutr 18, 433440.Google ScholarPubMed
67. Song, S, Paik, H-Y & Song, Y (2012) High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population. Diab Res Clin Pract 98, e28e31.CrossRefGoogle ScholarPubMed