October 2024 Issue

CPE Monthly: Recent Research on the Use of Beta-Glucans in CVD and Immune Health
By Danielle VenHuizen, MS, RDN
Today’s Dietitian
Vol. 26 No. 8 P. 38

Take this course and earn 2 CEUs on our Continuing Education Learning Library

Beta-glucans, a type of soluble fiber (SF) derived from several plant sources, have been postulated as having many therapeutic health benefits. Used in traditional Chinese medicine for thousands of years, only in recent decades has more interest gone into understanding the science behind these purported benefits.1 This course will look at the various sources of dietary and supplemental beta-glucans, the effects they may have on various disease states and physiological functions, and ways to incorporate beta-glucans into the diet. The role of the RD in diet assessment and education around the use and recommended intakes of beta-glucans will also be discussed.

Definition and Types of Beta-Glucans
SF is a type of dietary fiber that is characterized by its ability to dissolve in water. Unlike insoluble fiber, which is formed by dense hydrogen bonds that resist hydrolysis, SF has a high affinity for water. Types of SF include psyllium, pectin, gums, fructooligosaccharides, methylcellulose, and most forms of beta-glucans, among others. The solubility of each varies by chemical structure and types of glycosidic bonds, which are bonds between monosaccharides. These factors also determine its physiological effects on human health. Some SFs are more viscous, for example, and may show promise in reducing cholesterol and blood sugar, while others are fermentable and may support a healthy microbiome. Some SFs play a role in both.2 Other SFs, because of their unique structure, may even modulate the immune system.3

Beta-glucans are SFs (although some have insoluble properties as well) formed by D-glucose molecules linked by beta-glycosidic bonds.4 The most concentrated sources are found in foods including oats, barley, mushrooms, seaweed, and baker’s yeast (Saccharomyces cerevisiae). While similar in structure, the position and branching of their glycosidic bonds differentiates their potential health benefits.

Beta-glucans in oats and barley, for example, contain 1,3 and 1,4 glycosidic linkages. They appear to have potent effects on cardiovascular health and modulate the microbiome.3 They may have some effects on enhancing immune function as well, although the evidence is less clear.1 Beta-glucans from fungi, seaweed, and yeast, on the other hand, contain 1,3 and 1,6 linkages. Research shows that these 1,6 linkages allow these beta-glucans to have potent benefits on immune stimulation by binding with immune receptors. They appear less likely to significantly impact CVD risk factors, however.3 Given these important distinctions, recent research in each of these key health areas will be examined with particular attention to types of beta-glucans and their potential benefits.

Beta-Glucans and Cardiovascular Health
CVD is one of the leading causes of mortality worldwide. While much research has gone into pharmaceutical interventions, studies have also shown that diet and lifestyle are key pieces to prevention.5 For this reason, more research has been focused on dietary approaches to manage key risk factors, including high cholesterol, elevated blood glucose (BG), hypertension, and weight management.

The use of beta-glucans has garnered interest in recent decades as evidence has shown they may help in many of these conditions pertaining to heart health. In fact, many countries have approved beta-glucan health claims. There has been enough conclusive research on the role of beta-glucans in cardiovascular health to date that the European Food Safety Authority issued a recommendation that 4 g of beta-glucan from either oats or barley should be consumed daily per every 30 g of total carbohydrate in the diet.6 Similarly, the FDA created a statement recommending at least 3 g of oat or barley beta-glucans daily for cardiovascular health.7 The focus on oats and barley appears to be due to their higher molecular weight and unique structure, over other sources such as fungi and yeast, which give these sources more potent effects on cardiovascular risk factors.8

Cholesterol
There is strong evidence that beta-glucans help manage cholesterol. A 2017 review paper on beta-glucans and cholesterol reported that studies over the past 20 years have suggested a cholesterol-lowering effect from diets supplemented with beta-glucans. The exact mechanisms by which this happens are still not entirely clear, but it appears that dietary beta-glucans help increase the viscosity of contents in the digestive tract, thereby preventing the reabsorption of bile acids.3 Beta-glucans also increase the production of short-chain fatty acids (SCFAs), which is linked to reductions in cholesterol by upregulating genes that increase the uptake of serum cholesterol by the liver and, additionally, may even decrease the activity of the enzyme HMG-CoA reductase, in the mevalonate pathway, responsible for cholesterol synthesis.9

A recent 2022 meta-analysis looking at studies on dietary oat beta-glucans found that across 13 trials with over 927 participants, there was a significant decrease in total cholesterol and LDLs. The daily consumption ranged between 1.6 and 6 g of oat beta-glucans per day and the interventions ran from three to eight weeks.10 The BELT study, a 2020 placebo-controlled trial by Cicero et al, looked at 83 Italian participants with mild hypercholesterolemia over eight weeks. They found that 3 g per day of oat beta-glucans reduced total cholesterol by 8.9% after eight weeks and non-HDLs were reduced by 12.1%.11 A 2023 randomized crossover trial of 32 mildly hypercholesterolemic participants looked at the effect of both oat and barley intake on cholesterol levels. They supplemented participants’ diets with either 80 g of oat flakes (providing 3 g beta-glucan per 100 g flakes), 80 g of barley flakes (providing 4 g beta-glucan per 100 g flakes), or traditional white bread. Overall, they also found significant reductions in total cholesterol and LDL among both the oat and barley supplemented groups.12 These recent studies reinforce previous research on the ability of beta-glucans to reduce cholesterol, lending more support to the European Food Safety Authority and FDA recommendations.

Blood-Glucose Management
Beta-glucans may help manage BG levels, and there are a couple of ways this is theorized to occur. Fiber itself in sufficient quantity may delay gastric emptying, reducing the rate at which glucose is absorbed and thereby lowering postprandial BG.12 Beta-glucans also appear to enhance the activation of an enzyme called P13K/AKT. This enzyme is known to have a key role in normal glucose metabolism and is often decreased in people with type 2 diabetes (DMII).13,14 In addition, recent research elucidated another mechanism by which beta-glucans may control BG. It appears that beta-glucans may interact directly with brush-border enzymes that regulate the absorption of glucose across the intestinal barrier. The reduced activity of these transporters, namely Glut-2 and SLGT1, decrease postprandial BG.15

A recent review in 2020 by Zurbau et al analyzed 35 studies looking at BG and beta-glucan supplementation. Most of the 538 participants were healthy, although 11% presented with DMII. All of the interventions involved oat beta-glucans added to various food products so that the total daily consumption of beta-glucans was approximately 4.2 g per 50 g of carbohydrate consumed. Across the interventions, they found statistically significant reductions in postprandial BG and insulin levels.6 Another review in 2021 looked at five studies on oat beta-glucan intake and DMII. They found a lower risk for DMII overall, although it was not statistically significant. However, two of the articles that used data from the Danish Diet, Cancer, and Health study noted that intake of over 21 g per day of fiber from whole grain cereal flakes, including oatmeal and muesli, showed a significantly reduced risk for developing DMII.16,17 A study in 2020 looking specifically at barley beta-glucans found that adding this fiber in the diets of people with DMII, at the level of 7.2 g per 100 g of carbohydrate consumed, significantly lowered postprandial BG levels.18 Another study on mice showed similar results when supplemented with barley flour that comprised 5% of the total fiber intake.19 All of these outcomes demonstrate the potent effects beta-glucan intake may have on BG management. While the exact mechanisms by which this occurs may not be entirely yet known, it is clear that oat and barley beta-glucans likely positively impact those with DMII.

Hypertension
Beta-glucans may improve BP in people with hypertension. Many earlier papers have noted improvements in hypertensive patients with the supplementation of beta-glucans from various sources, but more recent studies are few and the mechanisms remain unclear.20,21 It has been postulated that beta-glucan as an SF modulates the microbiome to improve gut microbial balance and the production of SCFAs, which may reduce BP.22 In addition, their role as an antioxidant may also confer antihypertensive benefits. Beta-glucans appear to reduce oxidative stress, a state that is known to worsen endothelial function, and this may be ameliorated by beta-glucan rich foods.23,24

Despite the low abundance of current research, a small handful of recent trials provide some new evidence for the use of beta-glucans in patients with hypertension. Not only oat but also mushroom-derived beta-glucans may help reduce BP and decrease the use of BP-lowering medications. Researchers Raj et al supplemented hypertensive mice with either beta-glucans, avenanthramide (a compound found in oats), or a combination of both. Their results were noteworthy; it was only the beta-glucan group that saw significant reductions in BP. The groups receiving avenanthramide only or the combination treatment did not see similar results, causing the researchers to postulate that oat beta-glucans played the main role in producing BP improvements.25 A 2021 randomized control trial (RCT) evaluated the use of oat bran supplements in hypertensive patients. While not singling out the beta-glucans directly, they did find that the use of oat fiber resulted in statistically significant reductions in BP when compared with controls, and there was reduced usage of blood pressure medications and favorable changes in the microbiome amongst the supplemented group.26 A systematic review paper in 2020 attempted to single out mushroom beta-glucans and evaluate their impact on a variety of cardiometabolic risk factors, including hypertension. Unfortunately, they could only find a small handful of quality, randomized control studies specifically related to hypertension. Most did find improvements in both diastolic and systolic BP in the short-term, but long-term results were mixed.27 It appears likely that beta-glucans from both grains and mushrooms may confer benefits for people with hypertension, but more studies are needed, especially to determine what role differing types of beta-glucans specifically play and what quantities may provide therapeutic benefit.

Weight Management
Beta-glucans may have a positive impact on obesity and weight management. Dietary fiber in general is well documented to have positive effects on satiety, calorie intake, and body weight.4 Whole grain intake has repeatedly shown to have an inverse relationship with body weight and risk for obesity, and SFs in particular have shown benefits for increasing satiety.4,28 Beta-glucans may have benefits independently.

Several papers have reported that both barley and oat flour have effects on increasing satiety from both whole grain and supplemental forms. It has been postulated that the high viscosity of these fibers delays gastric emptying, thereby slowing digestion and quickening the release of satiety signals.4 Additionally, lowering postprandial BG leads to improved satiety by balancing insulin output. A third mechanism for how beta-glucans may induce satiety is via the microbiome. By enhancing the production of SCFAs, beta-glucans may directly stimulate the release of several gut hormones that also help influence satiety.4 They may also increase beneficial bacteria, specifically species of Bifidobacterium, which are known to exist in lower quantities in obese participants.28

Recent studies looking at beta-glucans specifically in relation to obesity and weight management are few. Alptekin et al looked at the intake of beta-glucan on weight management outcomes including satiety, calorie intake, and body weight. They supplemented 24 women with 6 g of oat beta-glucan per day for five weeks. Results included improved satiety, reductions in energy intake, and statistically significant weight loss.29 Raimondi de Souza et al randomized 132 Brazilian participants to either 40 g of oat bran per day or placebo. Both groups had similar diets and calorie intake and received nutrition counseling. After 12 weeks, both groups reported reductions in weight loss, BMI, and waist circumference; no significant differences between the groups were noted.30 Additionally, a double-blind study conducted in Japan supplemented 100 overweight participants with 4.4 g of barley beta-glucans daily for 12 weeks. They also noted weight loss and BMI reductions in both groups, with the only significant difference being a decrease in visceral fat amongst the supplemented group.31 A meta-analysis in 2019 reviewed 20 studies on beta-glucans and weight management. They found a significant association with lowered body weight and BMI but no effect on waist circumference and total energy intake.32 Another review looked at six high-quality studies on cereal beta-glucans and adiposity. They reported trends showing reductions in body weight, BMI, and body fat with beta-glucan-supplemented diets.28 These studies appear to show a positive role for beta-glucans in weight management; however, more research is needed to elucidate the role of beta-glucan specifically apart from other fibers and dietary influences on weight management, as well as further understand if specific types of beta-glucans are more effective than others and appropriate amounts.28

Overall, the evidence appears to lend credence to the claim that beta-glucans from a variety of sources may positively impact CVD risk factors, particularly in the areas of cholesterol, hypertension, BG, and weight management. So far those from oats and barley seem to have the most research and evidence, although it’s possible fungal sources may play a role as well. A systematic review in 2021 looked solely at mushrooms and CVD; unfortunately, they could not find any significant decrease in risk with consumption of five or more servings of mushrooms per week over those consuming less, so more research is needed in this area to better understand the differences between these beta-glucan sources.33

Beta-Glucans and Immune Function
Another manner in which beta-glucans may exert positive effects on health is via immune modulation. Many types of mushrooms and yeast, which have been used medicinally for thousands of years, are good sources of beta-glucans. They have been known to have immunostimulatory effects, and only in recent decades has more research uncovered that beta-glucans are a key player in this process.3 It is the unique chemical structure of these types of beta-glucans that give them this ability. The 1,6 glycosidic bonds, which are absent in grains such as oats and barley, appear to allow fungal and even yeast beta-glucans to bind with immune receptors.34

Both fungal and yeast beta-glucans, upon ingestion, interact with the mucosal immune system in the digestive tract. They are absorbed by the intestinal epithelium and presented to immune cells. Beta-glucans then bind to the receptors, primarily dectin-1, which is found on the surface of macrophages, natural killer cells, neutrophils, and dendritic cells. This process initiates a cascade of reactions that increase the activation of B cells, cytokines, nitric oxide, and other proinflammatory mediators.3,34 Due to this documented ability to stimulate an immune response, the use of beta-glucans as a pharmaceutical product has been approved for use not only in the United States but also in Canada, Sweden, Japan, and China, among others.35

Beta-Glucans and Infections
Fungal and yeast beta-glucans may enhance the immune response to ward off potential viral and microbial infections. A recent study by Stothers et al sought to examine this effect by injecting mice with beta-glucan and then introducing an infectious microbial agent. The mice received intraperitoneal injections of beta-glucans on days one and two of the trial, and then were infected with a microbe one, three, seven, or 14 days later. The researchers found increases in immune mediators within hours after the injections, and this conferred protection against infection for up to 14 days. While not directly applicable to humans, they were able to demonstrate a temporary immune stimulation in mice that resulted in protection against microbial infection.36 Another recent animal study found similar immune-stimulating benefits, but in this case against a viral agent. Researchers infected both mice and chicks with a high dose of influenza virus. The following day fungal beta-glucans were administered orally for seven days postinfection. They found significant increases in immune mediators compared with controls, as well as a significant decrease in infiltration to the lungs and an overall increase in survival rates.37

Interest in human studies has been ongoing as well, particularly in children and older adults. A 2021 systematic review compiled high-quality RCTs involving upper respiratory tract infections in human participants. Thirty-four RCTs from 2005 to 2020 were included. The trials included yeast beta-glucans, typically from Saccharomyces cerevisiae, or products utilizing mushroom beta-glucans from oyster and shiitake. Dosages ranged from 2.5 mg to 1 g, and the study durations ranged from four to 26 weeks. Participant ages ranged from young children all the way to 65 and older. Overall, they concluded that beta-glucans appear to strengthen the immune response, particularly against upper respiratory tract infections, and help ward off infections. They even found a positive benefit for seasonal allergy sufferers.38

Due to this preponderance of evidence in immune health, several papers have postulated that beta-glucans may also have a role in preventing or reducing the severity of COVID-19 infections.39,40 In fact, it has been postulated that lentinan, the beta-glucan found in shiitake mushrooms, may even be effective in reducing the cytokine storms that often exacerbate severe COVID-19 cases.41 A recent pilot study in 2022 showed that indeed that may be the case.42 Unfortunately, studies on COVID-19 patients are lacking; however, many papers have outlined the immune-stimulating effects of beta-glucans previously mentioned and have provided thorough explanations on how this might benefit COVID-19 patients, from bolstering the immune system prior to infection to actually helping the vaccines produce a stronger response.43,44

Cancer
Due to the strong evidence of beta-glucans as immune modulators, the use of beta-glucans for cancer risk reduction has garnered significant interest. Many have theorized that beta-glucans may be one of the most natural tools available to enhance immune function and target cancer specifically.45 In fact, enough evidence has been compiled on one particular beta-glucan, lentinan from shiitake mushrooms, that it has been approved for use in the treatment of gastric cancer in Japan.46 Many studies have demonstrated that beta-glucans appear to exhibit potent antitumor properties.

A recent study by Zhang et al sought to examine the effects of lentinan on the growth of colon cancer cells. They found that both in mice and in vitro there was a significant reduction in tumor growth. A review paper in China that looked at how lentinan may impact lung cancer treatment found that across 38 RCTs and over 3,000 participants, lentinan was helpful for enhancing chemotherapy treatment and additionally in improving quality of life.47 Another paper examined lentinan with regard to breast cancer and suggested that the use of fungal beta-glucans may provide a new strategy for treating estrogen receptor-positive breast cancers by suppressing tumor growth and promoting apoptosis of cancerous cells.48

A 2020 study conducted on mice sought to look at the effects of beta-glucans from a variety of sources, including yeast, algae, bacteria, oats, and mushrooms, and their effects on tumor progression in mice. They found that all of the beta-glucans demonstrated some benefits, especially the nongrain forms. Oat beta-glucan showed the weakest effect on immune stimulation and tumor weight.45 This correlates with other research on beta-glucans in that those with the 1,6 linkages, namely yeast, algae, bacterial, and fungal sources, have a stronger ability to interact with immune receptors.34

Interestingly, one paper singled out oat beta-glucans and attempted to elucidate their potential role in cancer prevention and treatment. Choromanska et al looked at lung cancer cells with oat beta-glucans in vitro and reported that grain-derived beta-glucans induced the death of cancer cells but did not affect healthy ones. The beta-glucans appeared to induce oxidative stress in the cancerous cells yet simultaneously acted as an antioxidant to protect noncancerous cells.49 One theory as to how beta-glucans lacking the 1,6 branched linkages can stimulate the immune system is via the microbiome. Soluble beta-glucans have been shown to increase metabolites in the gut that directly stimulate the immune system and also stimulate apoptosis of cancerous cells.1

Another possible role is the potential ability of fungal beta-glucans to act as adjuvants in cancer treatment. Steimbach et al conducted a systematic review of US-based clinical trials in 2021 on this specific topic. Their review included 16 studies that involved a total of 1,650 patients, with each study ranging from nine to 200 participants. Over nine types of cancers were evaluated, and the sources of beta-glucans were from yeast, mushrooms, or nondefined fungal sources. Results were mixed, with the authors noting that the diversity in types of studies and methods used made obtaining any results of statistical significance difficult. They did note enhanced recovery in patients’ immune function after chemotherapy treatment, but unfortunately could not report on any other significant findings.50

While more studies are needed on the role of beta-glucans in immune support and particularly in the role of cancer prevention and treatment, to date the studies indicate that they do exert positive effects on stimulating the immune system. The potential benefits are far reaching and may include preventing or fighting infections as well as acting as a potential adjuvant to cancer therapies.

Recommended Intake, Supplements and Safety Concerns
As previously outlined, the European Food Safety Authority and the FDA have established beta-glucan dietary intake guidelines for those with CVD risk factors. The guidelines, with ample support from research studies, suggest that 3 to 4 g per day of beta-glucans from foods such as oats and barley may help prevent or improve CVD. For reference, 11/2 cups of cooked oats provide about 3 g of beta-glucans, while 1 cup of cooked barley provides 2.5 g.51

The amount of mushrooms for therapeutic benefit is less clear. Most studies used supplemental forms, and while there are plenty of supplement products on the market, it may be difficult for patients to ensure they are taking the appropriate form and the correct dosage. Studies suggest that somewhere between 100 and 500 mg may provide immune-stimulating benefits, but it’s not certain if dietary mushrooms provide the same benefit, and if so, in what quantity.52 Also, many supplements contain much higher doses, and toxicity concerns in humans are still unclear.

RDNs can play an important role in helping patients understand the different benefits of various beta-glucan sources and decide which foods or supplements might be best to incorporate. Assisting clients to find ways to add oats, barley, and mushrooms to the diet seems warranted and safe. Supplemental forms have no recommended intake guidelines so care must be taken to conduct a thorough health assessment and remind patients that immune stimulation may not be without potential side effects. For patients with family history of cancer or otherwise at higher risk, supplementation might be warranted. For those undergoing cancer treatment, any supplementation should only be done in conjunction with the physician given our limited knowledge of outcomes in this area thus far.

Areas for Future Research
Considering the potentially useful role of beta-glucans in health management for a wide range of conditions as outlined, more research is needed to better understand how beta-glucans exert their effects and what forms and doses are best for optimal health outcomes. While its role as an SF for diseases such as DMII, hypertension, hyperlipidemia, and weight management is more established with published recommendations for intake, a better understanding of all the pathways by which beta-glucans affect serious health conditions that impact cardiovascular and immune health is needed.

Particularly in terms of stimulating immune function, more evidence is strongly needed in order to make safe recommendations for dosages in forms that are tolerated and effective. Interestingly, very little is known regarding the immune-stimulating effects of beta-glucans and autoimmune conditions, and whether this might impact those sufferers negatively in any way. Given the number of supplements that are coming into the market and no established guidelines for intake across the board, more RCTs would be immensely helpful in parsing out how and when to use beta-glucans in ways that are not only safe but also effective.

Putting It Into Practice
Overall, there do appear to be numerous positive effects on human health from beta-glucans. From cardiovascular health to immune stimulation to microbiome modulation, there is a wide body of research suggesting that beta-glucans support a range of physiological functions. While clearly much more research is needed to understand which beta-glucans to use in particular health conditions and best ways to consume, it is clear that beta-glucans have properties that may be very beneficial to human health.

RDs should recommend that patients with cardiovascular risk factors consume the recommended amounts of beta-glucans in their diets. There is clearly ample evidence as to their benefit in managing BG, cholesterol, blood pressure, and even weight management. How and when to use beta-glucans for immune benefit is less clear; for patients interested in their use for stimulating immune function, education should be provided around the potential benefits but also the lack of clear evidence around appropriate dosing, safe, and effective products, and even how long these products should or shouldn’t be used.

As researchers have suggested, beta-glucans may be one of the most potent natural tools we have for supporting overall health due to its impact on CVD, the microbiome, and the immune system, but more evidence is needed. RDs can help their patients use these foods and supplements safely while we strive to learn more about this versatile compound.

— Danielle VenHuizen, MS, RDN, is a Seattle-based dietitian and owner of Food Sense Nutrition.

 

Learning Objectives
After completing this continuing education course, nutrition professionals should be better able to:
1. Define the term beta-glucans and list dietary sources.
2. Educate clients on ways specific beta-glucans may provide therapeutic health benefits.
3. Assist clients with specific strategies to incorporate beta-glucans into their diet.

 

Examination

1. How many grams of dietary beta-glucans are recommended per day by the FDA for mitigating the risk for CVD?
A. 1 g/day
B. 3 g/day
C. 4 g/day
D. 6 g/day

2. Research seems to suggest that the best sources of beta-glucans for reducing cardiovascular risk come from which sources?
A. Saccharomyces cerevisiae
B. Shiitake and oyster mushrooms
C. Barley and oats
D. Algae

3. In the BELT study, researchers found that inclusion of 3 g of beta-glucans per day over eight weeks reduced total cholesterol in participants by what percentage?
A. 6.5%
B. 8.9%
C. 10%
D. 25%

4. In the study by Stothers et al looking at beta-glucan intake on mice, for up to how long did the beta-glucans stimulate the immune system after injection with an infectious agent?
A. Five days
B. Seven days
C. 11 days
D. 14 days

5. Which of these is not a way in which beta-glucans may help with weight management?
A. Improving muscle mass
B. Increasing satiety
C. Slowing gastric emptying
D. Increasing the production of short-chain fatty acids


6. Beta-glucans that appear to play a stronger role in immune stimulation have which particular glycosidic linkages?
A. 1,3
B. 1,4
C. 1,6
D. 1,8

7. Which beta-glucan may help reduce the cytokine storm associated with COVID-19 infections?
A. Lentinan
B. Saccharomyces cerevisiae
C. Oat beta-glucan
D. Barley beta-glucan

8. What supplemental dosages of beta-glucan do studies suggest are effective in stimulating an immune response in humans?
A. 100 to 200 mg
B. 200 to 800 mg
C. 100 to 1,000 mg
D. 100 to 500 mg

9. What is one way in which beta-glucans are theorized to help in cancer treatment?
A. Reducing tumor size
B. Slowing the rate of cancer growth
C. Prolonging survival rates
D. Improving quality of life

10. What is one area of immune health in which we have very little published research regarding the immune-stimulating effects of beta-glucans, warranting further study?
A. Breast cancer
B. Autoimmune disease
C. Gastric cancer
D. Upper respiratory infections

 

References
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2. Guan ZW, Yu EZ, Feng Q. Soluble dietary fiber, one of the most important nutrients for the gut microbiota. Molecules. 2021;26(22):6802.

3. Cerletti C, Esposito S, Iacoviello L. Edible mushrooms and beta-glucans: impact on human health. Nutrients. 2021;13(7):2195.

4. El Khoury D, Cuda C, Luhovyy BL, Anderson GH. Beta glucan: health benefits in obesity and metabolic syndrome. J Nutr Metab. 2012;2012:851362. 

5. Sima P, Vannucci L, Vetvicka V. β-glucans and cholesterol (review). Int J Mol Med. 2018;41(4):1799-1808. 

6. Zurbau A, Noronha JC, Khan TA, Sievenpiper JL, Wolever TMS. The effect of oat β-glucan on postprandial blood glucose and insulin responses: a systematic review and meta-analysis. Eur J Clin Nutr. 2021;75(11):1540-1554. 

7. Code of Federal Regulations. Title 21: 101.81 Health claims: soluble fiber from certain foods and risk of coronary heart disease (CHD). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-101/subpart-E/section-101.81. Updated July 1, 2024. Accessed May 1, 2023.

8. Ciecierska A, Drywień ME, Hamulka J, Sadkowski T. Nutraceutical functions of beta-glucans in human nutrition. Rocz Panstw Zakl Hig. 2019;70(4):315-324.

9. Vourakis M, Mayer G, Rousseau G. The role of gut microbiota on cholesterol metabolism in atherosclerosis. Int J Mol Sci. 2021;22(15):8074. 

10. Yu J, Xia J, Yang C, et al. Effects of beta-glucan intake on lipid profiles in hypercholesterolemic adults: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2022;14(10):2043. 

11. Cicero AFG, Fogacci F, Veronesi M, et al. A randomized placebo-controlled clinical trial to evaluate the medium-term effects of oat fibers on human health: the beta-glucan effects on lipid profile, glycemia and intestinal health (BELT) study. Nutrients. 2020;12(3):686. 

12. Reiners S, Hebestreit S, Wedekind L, et al. Effect of a regular consumption of traditional and roasted oat and barley flakes on blood lipids and glucose metabolism — a randomized crossover trial. Front Nutr. 2023;10:1095245.

13. Chen J, Raymond K. Beta-glucans in the treatment of diabetes and associated cardiovascular risks. Vasc Health Risk Manag. 2008;4(6):1265-1272.

14. Huang X, Liu G, Guo J, Su Z. The P13K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci.2018;14(11);1483-1496.

15. Malunga L, Ames N, Zhouyao H, Blewett H, Thandapilly SJ. Beta-glucan from barley attenuates post-prandial glycemic response by inhibiting the activities of glucose transporters but not intestinal brush border enzymes and amylolysis of starch. Front Nutr. 2021;8:628571.

16. Wehrli F, Taneri PE, Bano A, et al. Oat intake and risk of type 2 diabetes, cardiovascular disease and all-cause mortality: a systematic review and meta-analysis. Nutrients. 2021;13(8):2560. 

17. Kyrø C, Tjønneland A, Overvad K, Olsen A, Landberg R. Higher whole-grain intake is associated with lower risk of type 2 diabetes among middle-aged men and women: the Danish diet, cancer, and health cohort. J Nutr. 2018;148(9):1434-1444.

18. Fuse Y, Higa M, Miyashita N, et al. Effect of high β-glucan barley on postprandial blood glucose and insulin levels in type 2 diabetic patients. Clin Nutr Res. 2020;9(1):43-51.

19. Mio K, Yamanaka C, Matsuoka T, Kobayashi T, Aoe S. Effects of β-glucan rich barley flour on glucose and lipid metabolism in the ileum, liver, and adipose tissues of high-fat diet induced-obesity model male mice analyzed by DNA microarray. Nutrients. 2020;12(11):3546.

20. Maki KC, Galant R, Samuel P, et al. Effects of consuming foods containing oat beta-glucan on blood pressure, carbohydrate metabolism and biomarkers of oxidative stress in men and women with elevated blood pressure. Eur J Clin Nutr. 2007;61(6):786-795.

21. Chen J, Raymond K. Beta-glucans in the treatment of diabetes and associated cardiovascular risks. Vasc Health Risk Manag. 2008;4(6):1265-1272.

22. Kim S, Goel R, Kumar A, et al. Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure. Clin Sci (Lond). 2018;132(6):701-718. 

23. Agita A, Alsagaff MT. Inflammation, immunity, and hypertension. Acta Med Indones.2017;49(2):158-165. 

24. Wouk J, Dekker RFH, Queiroz EAIF, Barbosa-Dekker AM. β-glucans as a panacea for a healthy heart? Their roles in preventing and treating cardiovascular diseases. Int J Biol Macromol. 2021;177:176-203. 

25. Raj P, Ames N, Joseph Thandapilly S, Yu L, Netticadan T. The effects of oat ingredients on blood pressure in spontaneously hypertensive rats. J Food Biochem. 2020:e13402.

26. Xue Y, Cui L, Qi J, et al. The effect of dietary fiber (oat bran) supplement on blood pressure in patients with essential hypertension: a randomized controlled trial. Nutr Metab Cardiovasc Dis. 2021;31(8):2458-2470. 

27. Dicks L, Ellinger S. Effect of the intake of oyster mushrooms (Pleurotus ostreatus) on cardiometabolic parameters — a systematic review of clinical trials. Nutrients. 2020;12(4):1134. 

28. Mathews R, Shete V, Chu Y. The effect of cereal b-glucan on body weight and adiposity: a review of efficacy and mechanism of action. Crit Rev Food Sci Nutr. 2023;63(19):3838-3850.

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