Resistant starch is a type of dietary fiber that resists digestion in the small intestine and reaches the large intestine intact, where it serves as food for beneficial gut bacteria. It has been associated with a variety of health benefits, including improved insulin sensitivity, lower blood sugar levels, reduced inflammation, and improved gut health. These metabolic responses to resistant starch have potential implications for addressing nutrition-related health problems such as diabetes, obesity, and colon cancer.
Resistant Starch (RS) and Metabolic Responses Starch and Nutrition-Related Health Problems
Glucose produced from the digestion of starch is absorbed into the small intestine mainly by active Na+-dependent transport in apical membranes and enters the bloodstream via glucose transporters in the basolateral membrane. An increase in blood glucose levels will trigger insulin secretion from the pancreatic beta cells, which will stimulate glucose uptake by cells in the body. The amount of glucose entering de novo lipogenesis (DNL) is important in the health effects of glucose. DNL activity is dependent on nutrient composition and will especially increase with an increasing proportion of carbohydrates in the diet, particularly when combined with a total energy intake exceeding the energy requirements.
- Introduction to Resistant Starch
- Structure and Thermal Properties of Starch Granules
- 5 types of Resistant Starch (RS)
- Factors that affect the digestibility of starch
- Resistant Starch (RS) Preparation
- Resistant Starch (RS) Detection
- The Use of Resistant Starch (RS) in Foods
Obesity is a major nutrition-related health problem caused by an excess intake of energy for basal metabolism and physical activity. Starch is the most important source of energy intake and is therefore a major cause of obesity. If the intake of starch matches the energy requirement of the body, the control of glucose metabolism will quickly normalize the blood glucose levels by complete oxidation of glucose. If glucose from food exceeds this oxidative need, an alternative is to store the glucose as glycogen. The maximum storage capacity for glucose is approximately 700 g, with a majority of this capacity in muscle, and only a maximum of approximately 150 g in the liver of a normal 70 kg person. If the glucose intake exceeds both the oxidative and glycogen storage capacities, the conversion of glucose to fat is the only remaining alternative. This de novo lipogenesis occurs mainly in the liver. In the human body, the capacity for storing glucose as glycogen is limited, but the capacity to convert digestible carbohydrate to fat is much larger. Furthermore, the insulin-induced priority of the cells to use glucose as an energy source will result in body- and/or food-derived fat being saved from oxidation and used instead to increase body fat stores.
Type 2 diabetes is caused by a lack of sensitivity of cells to insulin and a reduced capacity of the pancreatic beta cells to produce sufficient amounts of insulin. The result is abnormally high blood glucose levels after ingestion of starch and other digestible carbohydrates. Starch therefore can contribute to both the increasing prevalence of type 2 diabetes and the associated health problems of this disease. However, the risk of type 2 diabetes is not only linked to the intake of glucose but also to how fast the starch is digested and how fast the blood glucose enters the circulation, which can be measured using the glycemic index.
Excessive intakes of starch and/or other digestible carbohydrates result in fat formation through DNL in the liver. Increased DNL can increase the level of very low-density lipoproteins (VLDL) in the blood, which may lead to a lipid profile in blood that is associated with an increased risk of cardiovascular disease. The cholesterol-rich necrotic tissue consists of low-density lipoproteins (LDL) originating from lipoproteins such as VLDL that transport triglycerides in the blood. The main product of DNL is the saturated fatty acid, palmitic acid, which is one of the fatty acids specifically shown to increase the risk of cardiovascular disease.
Resistant Starch (RS) and Metabolic Health
As previously mentioned, as the most important source of energy in the diet, starch may be a major contributor to obesity, type 2 diabetes, and cardiovascular disease. Resistant Starch (RS) possesses a very low digestion rate in the small intestine and consequently leads to a sustained and lower level of glucose release, which can result in improved glycemic and insulinemic responses. However, RS reduces the glycemic response simply as a result of a lack of digestible starch, rather than as a result of other physiological effects.
A series of studies on the effects of RS on metabolic health have been reported. The majority of these studies focused on the commercial ingredient, HAMS-RS2, while other studies focused on the RS from bananas, brown beans, barley, wheat breads, porridges or rice, or novel RS4 or RS3 ingredients. Most studies involved healthy individuals without insulin resistance/type 2 diabetes. Overall, supplementation with RS improved glycemic control. In addition, there was a reduced fasting blood glucose concentration, reduced postprandial response, and enhanced skeletal muscle uptake of glucose. Improvements in insulin secretion and sensitivity were also reported.
Metabolic health is influenced not only by glucose metabolism but also by circulating lipids, hormones, and immune mediators. Previous studies reported a significant reduction in total cholesterol and non-HDL cholesterol after the consumption of a diet rich in RS during a period of 12 months. Other studies reported that RS had the potential to modify lipid oxidation. One study found that RS significantly increased postprandial lipid oxidation, which was consistent with the role of RS in the reduction of fat accumulation. HAM-RS2 has been reported to reduce body fat levels and increase lean body mass. Marked changes in body fat distribution occurred with reduced epididymal and retroperitoneal fat with a diet rich in RS. SCFAs like butyric acid, acetic acid, and propionic acid have been reported to inhibit adipose tissue lipolysis, and in the liver, acetate was thought to inhibit glycogenolysis, which decreased carbohydrate levels and increased fat oxidation.
Resistant Starch (RS) and Colonic Health
As a type of fiber, Resistant Starch (RS) would be expected to confer benefits to gut health, particularly in the large intestine where RS is fermented and results in the release of gases (methane, hydrogen, and carbon dioxide), SCFAs (formate, acetate, propionate, butyrate, and valerate), smaller amounts of organic acids (lactate and succinate), and alcohols (methanol and ethanol). This process involves several key bacterial groups, such as amylolytic gut bacteria (including Firmicutes, Bacteroidetes, and Actinobacteria) which mediate amylose breakdown and butyrogenic archaea (including Eubacterium rectale), which is involved in butyrate production, and methanogenic archaea which are necessary for the production of methane. In general, the influence of RS on gut health has focused on endpoints such as gas production, SCFAs, and bacterial composition.
SCFA Production
SCFAs are the preferred fuel for colonocytes, increasing colonic blood flow, lowering luminal pH, and helping prevent the development of abnormal colonic cell populations. Increases in the amounts of SCFAs, particularly butyrate in the colon, are thought to be beneficial to gut health, with SCFA levels commonly used as a marker of fermentation and colonic health.
A number of human studies reported that Resistant Starch (RS) increased fecal excretion of SCFAs, specifically butyrate. Esterified or acylated forms of RS such as acetylated, butyrated, or propionylated RS4 confer specificity in the delivery of SCFAs, because specific SCFAs are esterified to a carrier starch and released only in the large intestine, leaving the residual starch available for fermentation. Some studies took measurements in the morning following an evening meal of barley kernel bread, which is naturally rich in RS, or a white wheat flour bread control. This study design allowed adequate time for fermentation and a study of the “second meal effects.” Significant increases in fasting breath hydrogen (140–160%), increased total serum SCFAs and acetate (both by 18%), and increased total plasma acetate and butyrate SCFAs (10–30%) were reported.
Other studies involving a novel high-amylose barley variety (Himalaya 292) rich in RS were performed in middle-aged, overweight volunteers who consumed 103 g of foods rich in the Himalaya 292 grain, a whole grain wheat cereal, or refined cereal for 4 weeks. The studies reported a 91% higher fecal excretion of butyrate and a 57% higher total fecal SCFA excretion compared with the refined cereal controls. In a further study using Himalaya 292, the influence of RS from a combination of sources on fecal butyrate concentrations and excretion was examined. Forty-six healthy adults for 4 weeks consumed either 25 g of non-starch polysaccharide (NSP) or 25 g of NSP plus 22 g of RS from a mix of sources (Himalaya 292, canned legumes, and HAMS). Overall, acetate, butyrate, and total SCFA concentrations were significantly higher in the RS group compared with baseline levels and the controls (NSP only group).
The Influence of Resistant Starch (RS) on Gut Bacteria and the Microbiome
The influence of gut bacteria and microbiota on human health is well-known. Gut bacteria may influence the immune function, nutritional acquisition, appetite control mechanisms, disease states such as mental health disorders, and obesity and its associated metabolic imbalances. Because Resistant Starch (RS) almost entirely passes through the small intestine, it has the potential to act as a fermentable substrate for the growth of probiotic microorganisms. The effect of RS on gut microbiota was inferred through its effects on colonic pH, SCFA composition, reductions in harmful metabolites such as bile acids, phenols and ammonia, as well as enzymatic activities associated with bacterial degradative pathways.
Human intervention trials reported reduced fecal ammonia, phenols, and secondary bile acid concentrations in fecal water after intake of RS. Advances in sequencing platforms and culture-independent molecular methods, based on the analysis of 16S ribosomal RNA, have facilitated more detailed studies into how bacterial communities interact with different forms of starch. In a double-blind crossover trial, ten healthy young adults consumed crackers containing approximately 30 g of RS2, RS4, or control (4 g of fiber) for 3 weeks with a 2-week wash-out period. During this short intervention, both forms of RS increased populations of the Actinobacteria and Bacteroidetes phyla and decreased populations of Firmicutes. Although RS2 increased the abundance of Ruminococcus bromii (Firmicutes) and E. rectale (Firmicutes), RS4 was associated with increased Bifidobacterium adolescentis (Actinobacteria) and Parabacteroides distasonis (Bacteroidetes), with the differential activities thought to reflect differences in substrate binding. Ruminococcus bromii has also been found to be abundant in humans and significantly involved in the fermentation of complex carbohydrates, including RS2, while P. distasonis has been reported to facilitate the release of esterified butyrate from butyrated HAMS. In a follow-up in vitro study, R. bromii was identified as a key species for RS breakdown in the colon, facilitating RS fermentation by other species, even bacteria that were weak RS2 and RS3 fermenters when isolated.
A recent study comparing gut microbiota metabolites and the host metabolome in urban vegans and omnivores in the USA suggested that diet as a substrate affected bacterial metabolome rather than regulating gut bacteria community membership. Future studies investigating the influence of RS on gut bacteria should consider the inclusion of tools such as metabolomics, to characterize the complexities of how this fermentable starch may influence the bacterial metabolome and biomarkers of bacterial activity, as well as focusing on bacterial community populations.
The Prevention of Colonic Cancer
Resistant Starch (RS) escapes digestion in the small intestine and enters the bowel where it is fermented by probiotic bacteria to produce SCFAs. Among the SCFAs, butyrate is specifically used to reduce the risk of colon cancer, and butyrate treatment of cultured colon cancer cells can inhibit the proliferation of cancer cells and stimulate apoptosis. The proposed mechanisms explaining the function of butyrate include G-protein activity (GPR 43) and genetic and epigenetic modulation of the Wnt signaling pathway such as inhibition of histone deacetylation, reduced DNA methylation, and altered expression of miRNA.
A randomized, placebo-controlled 4-week crossover trial of 20 healthy volunteers showed no change in cell proliferation or DNA methylation following consumption of 25 g of HAMS. However, reduced cell proliferation in the upper colonic crypt and differential expression of key cell cycle regulatory genes in 65 adult patients with colorectal cancer have been reported following consumption of a 30 g/ day blend of RS2 and RS3 for 4 weeks. Such differences in response may relate to the health status of the tissue where butyrate may increase proliferation in healthy colonic cells but suppress proliferation in cancer cells.
Diets rich in red meat have been linked to an increased risk of colon cancer, particularly in the distal region. It is thought that in the absence of fermentable carbohydrates, red meat may undergo fermentation in the colon. Thus a high protein and reduced carbohydrate diet may alter the colonic microbiota, to favor a more proinflammatory microbiota profile and decreased SCFA production. It has been reported that RS may offset this risk, by allowing greater fiber fermentation in the distal colon and attenuating red meat-induced colorectal DNA lesions. RS in the high meat diet facilitated a switch from the fermentation of protein substrates to carbohydrate substrates (SCFAs), leading to a decrease in the production of promutagenic adducts that arise during protein fermentation. A second proposed mechanism involved increased telomere length, which could protect against DNA damage.