Emerging science on benefits of whole grain oat and barley and their soluble dietary fibers for heart health, glycemic response, and gut microbiota

Abstract

The aim of this work is to review the major mechanisms by which consumption of whole grain oats and barley, and β-glucans, reduces the risk of coronary heart disease, type 2 diabetes, and other noncommunicable chronic conditions. These effects have been predominantly explained by the role of soluble dietary fibers and smaller bioactive compounds, such as phenolic compounds, in oats and barley. These help to reduce the level of serum low-density lipoprotein cholesterol, decreasing postprandial blood glucose and modulating gut microbiota. In the present review, the role of viscosity development of the intestinal content by β-glucans in these mechanisms is discussed, as well as the impact of processing conditions altering the composition or the physicochemical characteristics of β-glucans.

barley, β-glucans, cholesterol, glycemic response, oats, phenolic compounds, soluble dietary fibers, whole grain

INTRODUCTION

In numerous epidemiological studies, regular consumption of whole grain cereal has been associated with reduced risks of chronic cardiovascular diseases and type 2 diabetes.¹ Whole grain oats and barley have received particular attention owing to their association with these health benefits.²

According to the American Association of Cereal Chemists (2000), “whole grains shall consist of the intact, ground, cracked or flaked caryopsis [kernel], whose principal anatomical components—the starchy endosperm, germ and bran—are present in the same relative proportions as they exist in the intact caryopsis.”³ The HEALTHGRAIN consortium developed this definition further: “Whole grains shall consist of the intact, ground, cracked, or flaked kernel after the removal of inedible parts such as the hull and husk. The principal anatomical components, the starchy endosperm, germ and bran, are present in the same relative proportions as they exist in the intact kernel. Small losses of components – i.e., less than 2% of the grain/10% of the bran – that occur through processing methods consistent with safety and quality are allowed.”⁴

This latter definition highlights the importance of 2 important classes of bioactive compounds found in the germ and bran portions of the grain: dietary fibers and phytonutrients. These compounds play a critical role in the mechanisms by which consumption of whole grain oat and barley, in particular, prevents cardiovascular diseases and type 2 diabetes by reducing risk factors for these diseases, including reduction of serum low-density lipoprotein (LDL)-cholesterol, regulation of postprandial blood glucose levels, and modulation of gut microbiota.

HEALTH BENEFITS OF WHOLE GRAIN OATS AND BARLEY

Serum cholesterol reduction

Serum cholesterol reduction is an established biomarker of reduction of risk of cardiovascular diseases. Therefore, foods that have been demonstrated to reduce serum cholesterol as part of a balanced diet may qualify for a health claim.

The US Food and Drug administration has recognized a significant relationship “between diets that are low in saturated fat and cholesterol and that include soluble fiber from certain foods, and the risk of coronary heart disease.”⁵ Whole rolled oats, oat bran, rolled oats, whole oat flour, oatrim, whole grain barley, dry milled barley, and barley betafiber are eligible for this claim as sources of soluble fiber β-glucans. Furthermore, eligible foods must contain at least 0.75 g of soluble fibers per serving for oat and barley products. This claim therefore excludes whole grain cereals other than oats and barley. This is consistent with a Cochrane review on the effect of whole grain cereals on coronary heart disease, which found no supporting evidence for reduction of the risk of coronary heart disease for whole grain cereals other than oats.⁶

Canada, the European Union, Australia and New Zealand, and other jurisdictions have allowed similar health claims for oat and barley foods, though the minimum β-glucan per serving varies between 0.75 and 1.0 g per serving.^7–10

These health claims have been supported by numerous clinical studies showing the lipid- and cholesterol-lowering capacity of oat and barley β-glucans. Significant examples are 4 meta-analyses performed on human clinical trials involving whole grain oats or barley, or β-glucan supplementation. At a large scale, a meta-analysis of epidemiological studies concluded that the daily consumption of 3 g of oat or barley β-glucan led to significant decreases in blood cholesterol.¹¹ A meta-analysis conducted on 28 randomized controlled clinical trials confirmed a significant reduction in total and LDL-cholesterol with dietary doses of ≥3 g/d of oat β-glucans, whereas high-density lipoprotein (HDL)-cholesterol and serum triglyceride levels were unchanged.¹² Two other meta-analyses of human clinical trials confirmed that increased consumption of barley products led to significant decreases in total and LDL cholesterol.^13,14

To explain these results, it has been proposed that the viscous soluble dietary fibers of oats and barley, β-glucans, are solubilized throughout digestion, increase the viscosity of the meal bolus and entrap bile acids and cholesterol, and limit their reabsorption. As a result, bile acids necessary for the digestion of subsequent meals need to be replaced through synthesis of bile acids from circulating cholesterol, which has the effect of lowering serum cholesterol levels. The key physico-chemical property of the soluble fibers in whole oats and barley is their viscosity [η], linked to their effective solubility and the molecular weight (MW), following the Mark-Houwink law: $\left[\eta \right]\propto c{M}^{\alpha }$⁠, where c is the polymer concentration in solution, M is the average MW of the polymer in solution, and α is a factor representative of the spatial conformation of the polymer in solution.¹⁵

Key experiments to demonstrate this mechanism have involved controlled feeding trials with intact vs partially depolymerized β-glucan from oat and barley.

In a randomized parallel clinical trial, 367 participants in 5 research centers in Canada, Australia, and the UK were given 3 or 4 g/d of oat β-glucans in extruded cereals, for 28 days. The MW of oat β-glucans incorporated in the cereals was controlled and ranged from 2 210 × 10³ to 210 × 10³ g·mol⁻¹ in order to achieve a meal bolus viscosity ranging from high to low during digestion of the cereals. In parallel, the meal bolus viscosity was estimated using an in vitro digestion protocol. The magnitude of serum LDL-cholesterol reduction was strongly correlated with estimated intestinal viscosity development, as shown in Figure 1, and provided strong evidence that this viscosity development may be the mechanism of action for reduction of serum cholesterol levels.¹⁶

Figure 1

Relations between log (viscosity) and serum LDL-cholesterol, and log (MW × C) and log (viscosity). Values are means ± SEMs for the 5 treatments: 1 = wheat-bran cereal (n = 87); 2 = 4 g low-MW β-glucan (n = 63); 3 = 3 g medium-MW β-glucan (n = 64); 4 = 4 g medium-MW β-glucan (n = 67); 5 = 3 g high-MW β-glucan (n = 86). Solid line shows regression analysis. The P values for the correlation was obtained using analysis of covariance. Adapted from Wolever et al (2010).¹⁶Abbreviations: C, concentration; LDL, low-density lipoprotein; MW, molecular weight; SEMs, standard error of the means.

In a second randomized clinical trial with a crossover design, 30 mildly hypercholesterolemic adults consumed food containing either 3 g/d of intact barley β-glucans (MW = 1349 × 10³ g·mol⁻¹), 3 g/d of partially hydrolyzed barley β-glucans (MW = 288 × 10³ g·mol⁻¹), 5 g/d of partially hydrolyzed barley β-glucans (MW = 292 × 10³ g·mol⁻¹), or a control diet without soluble dietary fibers.¹⁷ Whereas LDL-cholesterol, HDL-cholesterol, and triglycerides were not significantly affected by the treatments where the barley β-glucans had been partially hydrolyzed, the diet with intact barley β-glucan significantly lowered total cholesterol compared to the control diet, showing the critical role of β-glucan solubility and MW in meal bolus viscosity development and the cholesterol-lowering effect of β-glucans.

This mechanism has been further corroborated by studying the cholesterol response to consumption of whole grain barley by patients according to their genetic variations of the CYP7A1 (cytochrome P450 family 7 subfamily A member 1) gene.¹⁸ Indeed, the CYP7A1 gene encodes the enzyme cholesterol 7 α-hydrolase, which participates in the conversion of cholesterol to bile acids. A CYP7A1 mutation can reduce the rate of this conversion and is associated with high plasma LDL levels and high hepatic cholesterol content. Following a barley-based diet aimed at reducing serum cholesterol levels, participants identified with such CYP7A1 mutations had higher serum LDL levels than the control group (Figure 2). This demonstrated that the decrease of LDL-cholesterol observed with consumption of barley products is strongly associated with entrapment, excretion and replacement of bile acids.

Figure 2

Relation between changes in serum cholesterol concentrations and log (viscosity) of β-glucan in mildly hypercholesterolemic adults who consumed 3 g LMW β-glucan/d, 5 g LMW β-glucan/d, 3 g HMW β-glucan/d, and WR control diet, each for 5 weeks. A, TC changes in G allele carriers (GG homozygotes and GT heterozygotes) against log (viscosity) of β-glucan. B, LDL cholesterol changes in G allele carriers against log (viscosity) of β-glucan. C, TC changes in homozygous T allele carriers against log (viscosity) of β-glucan. D, LDL cholesterol changes in homozygous T allele carriers against log (viscosity) of β-glucan. P values were obtained from a linear regression test. Adapted from Wang et al (2015).¹⁸Abbreviations: HMW, high molecular weight; LDL, low-density lipoprotein; LMW, low molecular weight; TC, total cholesterol; WR, wheat and rice.

Nevertheless, more remains to be explored on the cholesterol-reducing capacity of oat and barley β-glucans. Indeed, the leading hypothesis that β-glucans may limit reabsorption of bile acids throughout the gastrointestinal tract may be reflected by greater excretion of these bile acids in feces. However, in a study in pig models fed with a diet enriched in β-glucans,¹⁹ bile acid excretion did not increase. Instead, bile acids appear to be fermented and transformed into neutral sterols. The role of these neutral sterols on cholesterol levels shall be explored further.

Finally, most cholesterol-reduction claims associated with whole grain oat and barley, and their β-glucans, are based on the premise that blood lipid and cholesterol levels are reliable biomarkers of cardiovascular health. This premise was confirmed by a study that investigated the effect of oat bran supplementation on cardiovascular risk markers beyond cholesterol.²⁰ This study showed that oat bran supplementation also improved hemostatic factors such as plasminogen activator inhibitor-1 and factor VII, supporting the role of whole grain oat and barley in improving cardiovascular health.

Reduction in postprandial blood glucose

Diabetes Canada suggests that replacing high glycemic index (GI) carbohydrates with low-GI carbohydrates in mixed meals may have clinically significant benefit for glycemic control in people with type 1 or type 2 diabetes. This is crucial as the prevalence of diabetes has nearly doubled since 1980, rising from 4.7% to 8.5% in adults, with an estimated 425 million adults living with diabetes in 2017.²¹ Through modulation of glycemic response, whole grain oats and barley may play a critical role in the management of diabetes.

At first sight, whole grain oats, barley, and β-glucans don’t appear to have an effect on blood glucose levels, according to 2 meta-analyses of human clinical trials or epidemiological studies focusing on oat and barley products.^11,13 However, focusing on postprandial glycemic response to whole grain oats, barley, and β-glucan–containing products provides better insights into their capacity to help achieve glycemic control.¹⁴

As early as 1994, Braaten et al²² showed that the glycemic response to oat bran porridge was lower than that to cream of wheat porridge. Additionally, cream of wheat porridge enriched with purified β-glucans lowered glycemic and insulin responses down to levels equivalent to those of oat bran porridge. Since then, multiple studies have shown that there is a dose-response effect of β-glucans on the attenuation of postprandial glycemic response. For example, a study on semolina spaghetti enriched with barley β-glucans showed a dose dependence of GI on β-glucan content with a reduction of up to 54% of GI with the incorporation of 10% barley β-glucans into the spaghetti product, making this product a markedly low-GI food (GI = 29 and 64, for semolina spaghetti and control spaghetti, respectively).²³

These observations were confirmed in the meta-analysis conducted by Tosh (2013).²⁴ For over 119 foods tested in 34 research articles, oat β-glucans had a significant effect on the 2-h blood glucose area under the curve (AUC). Each gram of oat β-glucan consumed led to an average reduction of 5.1 ± 0.8 mmol·min·L⁻¹ of blood glucose AUC, from an AUC of 184 mmol·min·L⁻¹ for the glucose controls.

Once again, the capacity of β-glucan to increase intestinal viscosity appears to explain its effects on glycemic response to food. In a 1994 study, intact oat β-glucans significantly reduced the glycemic response to a 50-g oral glucose load, whereas hydrolyzed (and hence less viscous) β-glucans eliminated this capacity.²⁵ Similarly, the postprandial blood glucose response to various oat products seemed to be highly correlated to viscosity measured through an in vitro digestion protocol, as shown in Figure 3.²⁶ A proposed mechanism for these observations is that high viscosity of the intestinal content may slow down digestion of starch (by decelerating the diffusion of α-amylase towards its starch substrate) and the absorption of glucose (by decelerating the diffusion – towards the intestinal epithelium – of sugars and α-dextrins resulting from starch digestion).

Figure 3

Relationship between glycemic responses of human subjects (AUC of the postprandial blood glucose curve) and the apparent viscosity (at 30 mPa·s) of the β-glucan extracted by simulated digestion. AUC = −25 log(η) + 134 (r² = 0.85). Adapted from Tosh (2013)²⁶Abbreviations: AUC, area under the curve.

Therefore, the effect of whole grain oats and barley, and β-glucans, on glycemic response is expected to depend on the physicochemical properties of β-glucans and on their processing conditions. A meta-analysis has been conducted to evaluate the role of barley food products in blood glucose control, and a systematic review investigated the influence of processing on human glycemic response to oat products.^27,28 Overall, the results showed that food containing barley, barley β-glucans, oats, or oat β-glucans tended to have lower GI than controls (Figures 4 and 5). However, the magnitude of GI reduction or the qualification of the food on the scale from low to high GI seems to depend largely on the physical form of the food and therefore on its processing and transformation conditions, which in turn affect the physical properties of β-glucans.

Figure 4

Forest plot of the effect of barley or β-glucan from barley on incremental area under the curve for the glucose response. The effects in individual trials are depicted as squares with 95%CIs. Pooled estimate with 95%CIs is depicted as a diamond. Reproduced from AbuMweis et al²⁷ with permission. Abbreviations: CI, confidence interval; GI, glycemic index.

Figure 5

Glycemic responses to different types of whole grain oat products. Individual measurements are indicated with the median value. For columns labeled a, b, and c, those with the same letter above them are not significantly different. *Rolled oats refer to treatments where the type of oat was not specified. ◊ Outlier removed from the statistical analysis (Tosh and Chu 2015).²⁸

It must be noted that secondary mechanisms may play a role in the ability of β-glucans to reduce glycemic response to foods. In particular, β-glucans have been shown to downregulate the expression of sodium-glucose cotransporter type 1 and glucose transporter type 2 in intestinal epithelial cells from rats,²⁹ beyond a simple physical mechanism based on viscosity development and reduction of glucose and α-amylase diffusion.

Finally, it has been assumed that whole grain oats and barley, and β-glucans, may improve glucose control through better control of postprandial glycemia. This assumption has been verified by a glucose challenge in diabetic fatty rats after a 6-week period of chronic consumption of whole grain barley flour. The rats fed with whole grain barley flour had a significantly lower glycemic response and improved insulin resistance during the glucose tolerance test compared to the control group.³⁰ These observations further support the role of whole grain oat and barley in improving glucose control and insulin resistance.

WHOLE GRAIN OATS AND BARLEY TO SUPPORT HEALTHY GUT MICROBIOTA

The role of microbiota in maintaining good health is now clearly established and whole grain oats and barley can support the growth and maintenance of gut microorganisms. Indeed, the bran fraction of these cereals is rich in dietary fibers, the major source of energy for gut microbiota, and phytochemicals, which can themselves modulate the microbiota.

Prebiotic effects

Gibson and Roberfroid³¹ were the first to formally define prebiotic compounds as “non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improve host health.” However, further research showed that the characteristic of prebiotic compounds associated with selective and specific growth of colonic bacterial species was not a necessary condition for host health benefits.³² Therefore, Bird et al³³ broadened the definition of prebiotics to “undigested dietary carbohydrates” that are fermented by colonic bacteria, yielding short-chain fatty acids (SCFAs) as end products. Nevertheless, more specific characteristics of dietary fibers as prebiotics are often associated with health benefits, such as promoting an abundant and stable microbial flora with high species diversity, favoring Bacteroidetes over Firmicutes spp., especially Bifidobacterium, Lactobacillus, and Prevotella spp.

In vitro models were used to evaluate the prebiotic effect of oat β-glucans. Even though oat β-glucans did not appear to promote the growth of particular bacterial species compared to other common prebiotic fibers (inulin or xylooligosaccharides), they were highly fermentable and produced significant amounts of propionate.³⁴ Interestingly, MW seemed to play a significant role in the fermentation patterns of β-glucans in mice models, influencing the type of SCFAs produced, in particular the ratio of (proprionate + butyrate)/acetate.³⁵ In porcine models, whole grain oats, barley, and β-glucans have generally shown prebiotic properties via an overall increase in colonic microbial population and activity, particularly favoring Lactobacillus and Bacteroidetes spp., and an increase in SCFAs.^36,37

In humans, β-glucans also elicited significant shifts in intestinal microbial population following a dietary intervention. In a 2016 intervention,¹⁷ 30 mildly hypercholesterolemic adults consumed food containing either 3 g/d of intact barley β-glucans (MW = 1349 × 10³ g·mol⁻¹), 3 g/d of partially hydrolyzed barley β-glucans (MW = 288 × 10³ g·mol⁻¹), 5 g/d of partially hydrolyzed barley β-glucans (MW = 292 × 10³ g·mol⁻¹), or a control diet with low levels of soluble dietary fibers. The shifts in intestinal microbial population are summarized in Table 1 and show, in particular, an increase in Bacteroidetes over Firmicutes spp., which may be correlated to a reduced risk of coronary heart disease. This shift was enhanced as the dose of barley increased or as the molecular weights increased.

Table 1

Relative abundances of bacterial phyla in feces after β-glucan intervention. Adapted from Wang et al (2016)¹⁷

Phylum	Diet				P value
	Control (wheat and rice)	Partially hydrolyzed (3 g/d)	Partially hydrolyzed (5 g/d)	Intact β-glucan (3 g/d)
Bacteroidetes	4.99a	7.59a	9.95ab	14.22b	<0.0014
Firmicutes	89.69a	87.50a	82.36ab	77.91b	<0.0014
Actinobacteria	0.64	0.71	1.07	0.55	0.335
Proteobacteria	0.18	0.10	0.14	0.32	0.665
Tenericutes	0.086	0.066	0.093	0.19	0.475
Verrucomicrobia	0.14	0.39	0.19	0.39	0.285

^a&bIndicates significant difference within the same row (P < 0.05).

The particular role of β-glucans in the growth of Bacteroidetes spp. has been investigated in a study by Tamura et al (2017),³⁸ showing that a vast majority of humans possess Bacteroidetes spp. capable of utilizing β-glucans, therefore, confirming the prebiotic character of β-glucans.

Two incidental studies further supported the beneficial role of β-glucans towards the gut microbiota. A study on polypectomized patients revealed an increased SCFA production upon supplementation with β-glucans, as observed elsewhere, and also a significant decrease in bloating and abdominal pain scores over the course of a month-long treatment.³⁹ Another study coupled β-glucans with Lactobacillus probiotic strains used as probiotics; the β-glucans were found to promote the growth of the probiotic and positively influence probiotic-enterocyte interaction, thus enhancing the effect of the probiotic alone.⁴⁰

Role of phytochemicals

Whole grains are an abundant source of phytonutrients, particularly phenolic acids, at levels up to 1500 mg/100 g.⁴¹ They are predominantly covalently bound to the fibers, although up to 10 mg/100 g are in free form.⁴² They have recognized antioxidant and anti-inflammatory properties, and their low absorption in the small intestine makes them available for uptake by the colonic microbiota. Up to 90% of the phenolic compounds ingested are metabolized by the intestinal microbiota,⁴³ which is able to release covalently bound phenolics from fibers and metabolize them into more bioavailable bioactive compounds.^44–48 These phenolic metabolites can then be absorbed into the general circulation and can exert antioxidant and anti-inflammatory activities, as well as interfere with cell-signaling and gene regulation, in the gut and in other tissues. Interestingly, the biotransformation of phenolic compounds may favor specific bacterial species and in turn impact the degradation pathway of dietary fibers.⁴⁹ This 3-way relationship between colonic microbiota, dietary fibers, and phenolic compounds from whole grain cereals is complex and not completely understood. Nevertheless, there is now solid evidence that bioactive phenolic compounds play an important role in the health benefits of whole grain cereals.⁴¹

Phytonutrients less widespread than phenolic compounds, such as methionine, betaine, choline, inositol, and folates are believed to also have biological activity and participate in the biological activity of whole grain oats and barley.⁵⁰ In particular, oat avenanthramides (Figure 6) have been shown to be potent antioxidant, anti-inflammatory, and antigenotoxic compounds.^51–53 However, there has been a long debate about the overall consumption and bioavailability of these compounds and, therefore, their effective impact on health. It has been recently determined that avenanthramides are particularly stable through processing and storage of oats⁵⁴ and that the mean avenanthramide intake among oat consumers ranges from 0.3 to 2.1 mg/d,⁵⁵ whereas their bioavailability ranges from 0.16% to 2.71%.⁵⁴ Despite this low intake and bioavailability, avenanthramides were shown to exert antioxidant and anti-inflammatory capacity in vivo.^56–58

Figure 6

Structure of avenanthramides. Reproduced from Bratt et al⁵¹ with permission.

CONCLUSION

Health benefits from whole grain oats and barley are now evident from epidemiological and controlled intervention studies. However, demonstrating the mechanisms responsible for these health benefits has been, and continues to be, challenging given the complexity of whole grains, their structure and chemical composition, and the impact of processing them into food. Nevertheless, viscous soluble β-glucans have been shown to play a major role in reducing cholesterol and postprandial blood glucose. Additionally, dietary fibers and phytonutrients from whole oats and barley also play a role in maintaining a healthy gut microbiota. However, the interplay between dietary fibers, microbiota, and phytochemicals (also known for their beneficial bioactivity) is still to be thoroughly investigated and understood. Finally, whereas numerous studies have shown and elucidated the health benefits of whole grain oats and barley, other cereals such as whole grain rye, sorghum, millet, teff, or wild rice have not yet received sufficient research attention.

Acknowledgments

This article stems from a presentation given at the symposium on whole grains, dietary fiber, and public health held in Beijing, China on May 11, 2018. The symposium was cohosted by ILSI Focal Point in China, the Chinese Institute of Food Science and Technology, the Institute of Nutrition and Health at the Chinese Center for Disease Control and Prevention, and the China Food Information Center.

Funding for the symposium and publication of the proceedings was provided by PepsiCo, Nestlé, Wilmar, Amway, McDonald’s, and Starbucks. All non-industry speakers were offered reimbursement for their travel expenses to facilitate their participation in the symposium; no funding was provided to symposium presenters to prepare the articles in this supplement.

The opinions expressed herein are those of the authors and do not necessarily reflect the views, positions, or policies of the symposium hosts or its funders.

Author contributions. S.M.T. and N.B. contributed equally to the conception, design, and preparation of the manuscript.

Funding. No external funds supported this work.

Declaration of interest. S.M.T. and N.B. have no relevant interests to declare.