Study on Beta Glucan Health Aid

In 1942, a non-starch glucose similar to Icelandic lichenin was isolated and extracted from oats. Its structure is different from that of barley β-glucan. In 1986, it was named β-glucan, i.e. oat β-glucan, and research on oat β-glucan began. Beta-glucans are divided into water-soluble beta-glucans and non-water-soluble beta-glucans. The water solubility is mainly affected by the beta-(1→3) glycosidic bond and the degree of polymerization. Oat beta-glucan is a viscous non-starch polysaccharide in the cell walls of oat aleurone and subaleurone [2]. is a linear macromolecule formed by β-D-glucopyranose units linked by 70% β-(1→4) glycosidic bonds and 30% β-(1→3) glycosidic bonds. The continuous β-(1→4) glycosidic bonds are separated and linked by a single β-(1→3) glycosidic bond [5]. Oat β-glucan is mainly found in the bran, and under conditions of uniform concentration, the β-glucan molecule weight (MW) and viscosity in oat bran are greater than those in the endosperm. Therefore, oat bran is mostly used as the raw material for extracting oat β-glucan.

1. 1 Physical and chemical properties

The physiological effects of oat β-glucan are mainly achieved by increasing the viscosity of digestive juices in the intestine, which is affected by various factors such as the chemical structure of oats, MW, dissolution rate and degree, solution rheology, growth, storage conditions, processing, and extraction [1]. The natural chain length of oat β-glucan is about 20,000 glucose units, and the MW is as high as 3 million g/mol. A fairly wide range of average or peak MWs of oat β-glucan has been reported in the literature [5].

The average MW ranges from 1 × 106 to 2 × 106 g/mol, However, because the pyranose chain is easily broken by enzymatic or chemical hydrolysis, mechanical shearing or heat treatment, the MW in commercial foods is between 0.4 × 106 and 2 × 106 g/mol. The US Food and Drug Administration (FDA) recommends that consuming 3 g of oat β-glucan per day can help lower blood lipids, but viscosity, solubility, MW and dosage are equally important and are the basis of its cholesterol-lowering activity [6 - 7]. Viscosity is the main reason for the physiological effect of oat β-glucan, and viscosity is closely related to dosage, MW, and the food matrix (solubility) [5, 7]. Since there has been controversy about the dosage, MW, administration method, and effects of oat β-glucan on different ethnic groups, different scholars have reached different conclusions. An in vitro experiment [7] confirmed the repeatability and reproducibility of the solubility, viscosity and MW of β-glucan in different oat foods.

1.1.1 MW affects lipid-lowering effects

The viscosity and cholesterol-lowering effect of oat β-glucan are positively correlated with its MW. The MW of oat β-glucan must be at least 1,200 kDa in order to produce a cholesterol-lowering effect [2]. A multicenter clinical trial by Wo lever et al. [1] showed that subjects receiving oat beta-glucan with medium to high MW had a significant reduction in LDL-C of 4.8% to 6.5%, with no racial differences, while subjects given low MW had no significant effect. The higher the MW, the higher the viscosity, and the more significant the lipid-lowering effect.

1.1.2 Solubility affects lipid-lowering effect

When oat β-glucan is administered in the form of milk, fruit juice or drinks, each gram of β-glucan can significantly lower serum LDL-C by 0.063, 0.052 and 0.050 mmol/L. The addition of oat beta-glucan to a liquid vehicle may increase its LDL-lowering effect. In contrast, the addition of oat beta-glucan to solid foods, including bread and biscuits, has produced conflicting results [2].

1.2 Safety

1.2.1 Non-toxic to normal cells

A 2018 study by Romanška et al. [8] showed that oat beta-glucan has no cytotoxic effect on normal cells, but has a cytotoxic effect on cancer cells, and the cytotoxicity increases with the concentration of beta-glucan. Long-term use of lipid-lowering drugs can have a long-term effect on people with blood lipid metabolism disorders, especially when used in combination with statins and fibrates [2]. Therefore, its safety is better than that of statins.

1.2.2 Dietary fiber within the recommended intake range does not affect the absorption of other nutrients

Different intake ranges of β-glucan produce different effects. In 2002, the American Dietetic Association (ADA) [9] stated that excessive dietary fiber intake has potential negative effects, including reduced absorption of vitamins, minerals, proteins and energy. However, dietary fibre consumed within the recommended intake range is unlikely to cause nutrient absorption problems in healthy adults. In 2005, the Institute of Medicine [10] proposed that as part of a balanced diet, within the recommended dietary fibre intake range, no significant effect of cereal fibre on mineral absorption (such as iron, zinc, calcium and magnesium) has been found. Therefore, it is recommended to consume dietary fibre within the recommended intake range.

1.2.3 Allergenicity

In 2007, Rashid et al. [11] suggested that oats and oat products may cause allergic reactions in a small number of allergic people, and that oats should not be allowed in a gluten-free diet. However, a study by Hoffmanov á et al. [12] showed that oats can be tolerated by people with celiac disease in remission as part of a gluten-free diet. Oat proteins are more easily digested by proteases than proteins from other cereals such as wheat. These properties significantly reduce their immunogenicity and toxicity for people with celiac disease. People with celiac disease can safely eat pure oats that are not contaminated with other cereals such as wheat. However, individual sensitivity to oat β-glucan cannot be ruled out. The potential allergenicity of β-glucan itself has been studied, but no evidence has been found. To test the potential sensitivity of celiac patients to an oat diet, suitable methods need to be developed to assess the risk of individual oat varieties in celiac patients. In addition, β-glucan is not included in the 2010 FDA list of the 8 major food allergens.

This shows that oat beta-glucan is safe for human application. In clinical studies, subjects did not experience significant gastrointestinal symptoms, except for mild and transient gastrointestinal effects such as flatulence and abdominal discomfort [13]. It is feasible to apply it in patients with elevated blood lipid abnormalities, and it has a wide range of applications and high safety compared to lipid-lowering drugs. Samples containing soluble β-glucan mainly produce a feeling of smoothness, fineness and a viscous residue, and this palatability makes patients more compliant with a gluten-free diet [14-15].

1.3 Application of oat β-glucan

In addition to lowering hyperlipidemia, oat β-glucan can also be used in many other ways, such as lowering blood sugar, antioxidant effects, immunomodulatory and antitumor effects, improving the intestinal environment and increasing satiety.

1.3.1 Blood sugar lowering

A study by Tosh [16] showed that the peak blood glucose response (PB GR) is often more sensitive than the area under the curve (AUC) or the glycemic index (GI). After treatment with 4 g of β-glucan, the PBGR and insulin AUC were significantly reduced. Insulin did not increase significantly in either the experimental group or the control group, indicating that the postprandial insulin response was not disproportionately increased, and oat β-glucan reduced postprandial blood glucose in a dose-dependent manner. Oat β-glucan forms a highly viscous environment in the intestine, which quickly traps high-glycemic-index foods, forming a protective layer that slows glucose absorption, reduces postprandial insulin concentrations and improves insulin sensitivity. However, ingestion of β-glucan has no significant effect on fasting blood glucose or insulin concentrations in hypercholesterolemic patients [17].

1.3.2 Antioxidant

After oat beta-glucan was fed to rats with hyperlipidemia, it could reduce serum malondialdehyde (MDA), the content of cerebral lipofuscin, and also reduce the activity of serum superoxide dismutase (SOD), improve the activity of SOD in the body, and increase the activity of serum total antioxidant capacity (total antioxidant capacity, T-AOC) activity. By reducing the production of oxygen free radicals, scavenging peroxides, protecting biological membranes, and inhibiting lipid peroxidation, it can prevent atherosclerotic lesions induced by hyperlipidemia [18]. Both low- and high-molecular-weight oat beta-glucans showed antioxidant activity in both liver and stomach tissue, resulting in a reduction in the production of reactive oxygen species. High-molecular-weight beta-glucans appear to be more antioxidant in vivo, especially in the presence of inflammation in the gastrointestinal tract. Therefore, foods rich in oat beta-glucans are considered to be effective drugs for treating inflammatory diseases of the gastrointestinal tract [19].

1.3.3 Immune regulation and anti-tumor effects

Beta-glucan is a biological response modifier with potential anti-tumor properties that modulates both innate and adaptive immune responses [20]. Pan et al. [21] showed that oat beta-glucan can induce monocytes to increase the expression and production of tumor necrosis factor (TNF-α) and interleukin 6 (IL-6) mRNA through metabolic reprogramming after stimulation with lipopolysaccharide or Pam 3C SK4.

In addition, consumption of oat beta-glucan powder can lead to transactivation of the nuclear factor NF-κB in intestinal leukocytes (such as dendritic cells (DCs)) and specific intestinal cells (such as M cells), which protects them from stronger attacks during pathogen infection, thereby affecting the intestinal immune response and preventing inflammation [22]. Oat β-glucan induces innate immunity and activates intestinal immune cells through metabolic reprogramming, providing important evidence that dietary fiber can maintain the long-term reactivity of the innate immune system and improve immunity, which may be beneficial for the prevention of infectious diseases or cancer. β-glucan can also exert an anti-tumor effect by activating dendritic cells through contact with Dectin-1 receptors [20]. However, the mechanism by which beta-glucan destroys cancer cells is very complex and not yet fully understood. A study [8] showed that the immunomodulatory and anticancer effects of glucan are related to its structure, MW and conformation.

1.3.4 Improves the intestinal environment

Oat beta-glucan changes the microflora, promotes the formation of short-chain fatty acids (acetic acid, propionic acid, butyric acid, etc.) in the intestine, which lowers the intestinal pH. The acidic environment formed inhibits the growth and reproduction of pathogenic bacteria and saprophytes, reducing the number of pathogenic bacteria and saprophytes in the intestine. This reduces the growth of carcinogens in the intestine at the source, increases the number of probiotics, alters the potential for bile acid metabolism, and can be used as a prebiotic for the human body [23]. Oat β-glucan may be the first choice for dietary interventions to maintain cardiovascular and metabolic health in the long term, and the microbiome reinforces this [24].

1.3.5 Increased satiety

Oat β-glucan can affect satiety by increasing viscosity. When viscosity increases, mRNA expression of neuropeptide Y in the arcuate nucleus of the hypothalamus decreases, anorexic gastrointestinal hormones increase, and satiety increases. However, due to the lack of a standardized method for measuring viscosity and the inherent substances that affect appetite, it is difficult to locate the effect of oat β-glucan on satiety. Overall, it has a positive effect on increasing satiety [5]. Whether oat β-glucan increases satiety and reduces appetite, affecting food intake at the next meal, has prompted further research.

Previous evidence has shown that oats can promote weight control by reducing subjective appetite and food intake at the subsequent meal. However, not all studies are consistent. Zaremba et al. [25] showed that 4 g of high MW oat beta-glucan delayed gastric emptying and reduced appetite, but did not affect the amount of food consumed by the subjects. Wolever et al. [26] demonstrated in 2020 that oat beta-glucan can delay gastric emptying. This is consistent with previous research findings, and no significant effect of oat β-glucan on appetite, food intake, or gastrointestinal hormones that affect appetite was found compared to the control group. This indicates that under the current experimental conditions, neither the dose nor the MW of oat β-glucan affected appetite or food intake compared to the control group. Therefore, further studies are needed to demonstrate the effect of different viscosities on appetite and food intake through standardized methods for measuring viscosity.

2 Oat beta-glucan improves dyslipidemia

2. 1 Oat beta-glucan improves different blood lipid markers

In 2016, the University of Toronto in Canada and the European Journal of Clinical Nutrition conducted a meta-analysis of 58 clinical trials involving 3,974 participants to evaluate the effect of oat β-glucan on cardiovascular disease risk factors (LDL-C, non-HDL-C, apoB). It was pointed out that an average of 3.5 g/d oat β-glucan for 6 weeks had an overall improvement effect on blood lipids, with LDL-C reduced by 4.2%, non-HDL-C reduced by 4.8%, and apo B reduced by 2. 3 % [27]. A randomized double-blind crossover trial in 2020 on patients with moderate hypercholesterolemia showed that oat beta-glucan intake significantly reduced the levels of TC, LDL-C or non-HDL-C, and after a few weeks of the washout period, due to the lack of continuous supplementation with oat beta-glucan, the TC and LDL-C concentrations tended to return to baseline values, which highlights the importance of regular and sustained oat beta-glucan supplementation [14]. The above studies show that oat beta-glucan can improve blood lipid indicators to varying degrees, and that oat beta-glucan should be supplemented regularly and continuously.

2.2 The dose-response relationship between oat beta-glucan and blood lipids

A dose-response relationship between fibre intake and a reduction in serum TC was first given in a meta-analysis, i.e. an average of 0.045 mmol/L and 0.057 mmol/L for TC and LDL-C, respectively, per gram of dietary fibre [28]. There is no clear dose-response relationship between soluble fibre and changes in HDL-C or triglyceride (TG) concentrations. In 60% to 70% of the trials, a high intake of soluble fibre was associated with a significant reduction in TC and LDL [14]. However, the higher the dose, the more pronounced the reduction in blood lipids is not necessarily. The dose-response model shows that TC decreases with increasing doses of beta-glucan, but there is significant nonlinearity at high doses, which may be due to a decrease in adhesion or a biological maximum at higher doses. There is no increase in effect when the daily intake of β-glucan exceeds 3 g [29]. This also supports the proposal by the US FDA since 1997 to consume foods containing oat β-glucan in amounts of more than 3 g per day for the purpose of reducing the risk of cardiovascular disease [2].

2.3 Effect of initial blood lipid concentration on lipid-lowering effect

A subgroup analysis of initial cholesterol concentrations [28] showed that the TC of people with moderate or severe hypercholesterolemia (concentration >6.20 mmol/L or >240 mg/dL) decreased by only slightly more than that of people with lower cholesterol concentrations. There is controversy as to whether lowering cholesterol concentrations in people with normal blood lipids is beneficial. Chen et al. [30] showed in a randomized controlled trial in 2006 that increasing oat bran dietary fiber intake did not significantly lower serum cholesterol levels in individuals without hypercholesterolemia. Therefore, for people at high risk of hyperlipidemia, increasing dietary fiber intake while reducing saturated fat and cholesterol intake can be used to prevent hyperlipidemia.

3 Mechanism by which oat beta-glucan improves dyslipidemia

3.1 Individual differences in the lipid-lowering effect of beta-glucan

Wang et al. [31] showed that the cholesterol-lowering effect of beta-glucan may also depend on individual genetic characteristics. Data show that individuals carrying the allele for the single nucleotide polymorphism (SNP) rs3808607 in the promoter region of the cytochrome P450 family 7 subfamily member 1 gene CYP7A1 are more sensitive to the cholesterol-lowering effect of high MW β-glucan than TT carriers. CYP7A1 encodes cholesterol 7α-hydroxylase (CYP7A1), which is the rate-limiting enzyme in the classical bile acid synthesis pathway.

3.2 Inhibiting cholesterol synthesis

Microorganisms in the intestine ferment fibres to produce short-chain fatty acids (such as acetic acid, butyric acid and propionic acid), which are absorbed into the portal vein. This limits the activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and increases the catabolism of LDL-C to inhibit the synthesis of cholesterol in the liver [23].

3.3 Inhibits cholesterol absorption

Oat beta-glucan forms a water film around food particles in the digestive tract, creating a high-viscosity environment. This not only physically hinders the reabsorption of fats, cholesterol and bile acids in the digestive tract, thereby increasing insulin sensitivity and the feeling of fullness [2], but also alters the circulating levels of bile acids. Fermentation of sterols in the colon increases the production of therapeutic ursodeoxycholic acid, inhibits the absorption of the toxic bile acid chenodeoxycholic acid and reduces the likelihood of cholesterol absorption by converting chenodeoxycholic acid to a nonabsorbable neutral sterol [32].

3.4 Increasing cholesterol excretion

Oat β-glucan binds to bile acids in the intestine, reducing their reabsorption and increasing excretion, thereby lowering bile acid levels. To compensate for this loss, the body synthesizes bile acids de novo, activating CYP7A1. Cholesterol increases bile acid synthesis and the fecal excretion of neutral sterols and cholesterol under the action of this rate-limiting enzyme, thereby reducing cholesterol concentrations [2,6].

3.5 Lowering LDL-C and raising HDL-C

Oat β-glucan can promote de novo synthesis of bile acids in the body, upregulate LDL-C receptors, provide substrates for bile acid synthesis, increase LDL-C removal, and lower LDL-C concentrations. In addition, other studies [14] have shown that oat β-glucan can also regulate the microbiome to achieve a lowering of LDL-C in addition to intervening in the bile acid synthesis pathway. The mechanism by which oat beta-glucan increases HDL cholesterol levels is not yet clear, but some studies [33] have shown that the amount of beta-glucan in the diet is a factor in rising HDL cholesterol levels.

It can be seen that oat beta-glucan can reduce cholesterol synthesis and absorption, increase cholesterol excretion, and also lower LDL-C levels, thereby reducing the occurrence of cardiovascular events.

4 Conclusion

In recent years, oat beta-glucan has been analyzed from multiple angles, at multiple levels, and on multiple levels, including animal experiments and clinical trials, which have yielded a large amount of scientific data confirming its significant lipid-lowering effect. In Europe and the United States, oat beta-glucan has been developed into a food additive and is widely used in lipid-lowering interventions.

In 2014, the Chinese health authorities agreed to designate oat beta-glucan as a new resource food. Current research faces the following problems: 1) Oat beta-glucan is safe and reliable, and has an important role in disease prevention and control, lowering blood lipids and blood sugar, and improving the intestinal environment. It has important application prospects and research value. Early studies have shown that the effect of fiber may be greater than that shown in the meta-analysis. However, methodological problems such as small sample sizes, incomplete dietary measures, and insufficient control of important confounding factors make it difficult to isolate the effect independently of other dietary components. 2) Existing clinical trials have investigated the short-term lipid-lowering effect of oat beta-glucan administered to relatively small samples of the population, and few have involved pregnant patients. During pregnancy, elevated blood lipids can lead to an increased risk of pregnancy complications, affecting the mother and child. In the future, interventions can be carried out in patients with pathological abnormalities of blood lipids during pregnancy, providing a new treatment approach for patients with pathological increases in blood lipids during pregnancy.

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