There are several areas of benefits that do not yet have sufficient evidence to be established or verified. It is not a coincidence that these areas are strongly correlated with type 2 diabetes and other aspects of metabolic syndrome. Existing evidence suggests that benefits exist in the following areas:
Numerous studies have demonstrated that resistant starch did not reduce the risk of colorectal cancer. However, a 10-year follow-up of the CAPP2 clinical trial found that the Lynch Syndrome participants who had consumed 10-15 grams of resistant starch/day for a median duration of 29 months 10+ years earlier had 60% less upper gastrointestinal cancers (Mathers et al., 2023). These particular types of cancers kill more people, because they are very difficult to detect and often identified at later stages. Animal studies had previously suggested multiple mechanisms related to cancer prevention – increased differentiation of cancer cells (Malcomson et al., 2015), increased cellular apoptosis (Le Leu et al., 2009), reduced cellular proliferation (Hu et al., 2016), as well as reduced incidence of intestinal cancers (Le Leu et al., 2007). The planned 10-year follow-up of the CAPP2 trial was the first recorded publication that resistant starch prevented cancer in people.
Multiple clinical studies have shown improvements in biomarkers related to inflammation, oxidative stress in individuals with chronic kidney disease. This may occur because the nitrogen-containing compounds are captured by the bacterial mass and excreted through the intestines instead of being disposed through the kidneys. This may not present problems in healthy individuals, but is definitely problematic in individuals with kidney disease.
The first human study (Sirich CJ ASN 2014) suggested that resistant starch assists in reducing the blood levels of p-cresol sulfate and indoxyl sulfate, compounds believed to be toxic in individuals with impaired kidney function. The second human study (Tayebi Khosroshahi HI 2018) found that resistant starch significantly reduced inflammatory and oxidative biomarkers TNF-alpha, interleukin-6 (IL-6), malondialdehyde as well as serum urea and creatinine in hemodialysis patients. The third clinical showed reduced IL-6, thiobarbituric acid reactive substances plasma and indoxyl sulfate in individuals with chronic kidney disease. (Esgalhado FF 2018) The fourth study found that high resistant starch/low-protein flour improved blood glucose and blood lipid levels, decreased serum uric acid and urine beta2-microglobulin, and enhanced the ability to prevent antioxidative stress in patients with early diabetic nephropathy.(Meng JRN 2019) Finally, a Brazilian clinical study recently found that resistant starch reduced inflammatory markers (Regulated upon Activation, Normal T-Cell expressed and Secreted, platelet-derived growth factor and interferon-inducible protein -10, IL-10) in adults with chronic kidney disease. (Paiva IUN 2020). A 2021 meta-analysis concluded that blood urea nitrogen, serum creatinine and interleukin-6 in blood was significantly reduced in hemodialysis patients with end-stage renal disease following consumption of RS2 resistant starch. (Jia IJMS 2021)
Two studies have shown that high levels of resistant starch protected kidney function and improved Vitamin D metabolism in the kidneys in animal models of type 1 and type 2 diabetes. As a result, circulating levels of serum 25-hydroxycholecalciferol (25-hydroxy Vitamin D) were significantly increased. Koh JN 2014, (Smazal JN 2013)
A meta-analysis published in 2020 evaluated 13 clinical studies of the effect of resistant starch (including resistant dextrin) consumption on serum levels of inflammatory biomarkers.They found that these ingredients caused a significant reduction in interleukin 6 and tumor necrosis factor alpha levels. No significant changes were found in C-reactive protein concentrations. The authors concluded that resistant starch (including resistant dextrin) can improve inflammatory biomarkers in humans. This was further confirmed in a 2020 Brazilian clinical trial which recently found that resistant starch reduced inflammatory markers (Regulated upon Activation, Normal T-Cell expressed and Secreted, platelet-derived growth factor and interferon-inducible protein -10, IL-10) in adults with chronic kidney disease. (Paiva IUN 2020)
Two additional clinical trials have been published which found reduced inflammation following high levels of resistant starch consumption.
- Dr. Stephen O’Keefe’s study included an entire diet swap, so the results cannot be isolated to one dietary component. While resistant starch was a major focus of the study, dietary fat and protein was also reduced in the two week diet swap. O’Keefe NC 2015 found reduced mucosal inflammation in the cells of the colon wall after African-Americans living in Pittsburgh ate a South African diet very high in resistant starch (38 grams/day). Reciprocally, South Africans eating the American diet had increased colonic inflammation after two weeks.
- Dr. Denise Robertson’s study fed British adults with well-controlled type 2 diabetes high quantities of unmodified RS2 resistant corn starch (40 grams/day) and found a reduction in obesity-associated inflammation independent from any changes in body fat volume. Bodinham EC 2014.
Animal studies are also confirming resistant starch’s potential in reducing or preventing inflammation through restoration of the gut barrier and other effects of resistant starch’s fermentation. For example, Zhang et al. 2020 found improved systemic inflammation and intestinal permeability in aged mice on a high-fat diet following RS2 resistant corn starch consumption, and Almeida-Junior et al. 2017 found modulation of oxidative stress in the TNBS model of intestinal inflammation following RS2 green banana resistant starch consumption.
Heart Health – Blood Pressure
Three clinical studies have reported improvements in blood pressure. Dr. Maria Cristina de Oliveira Izar and her colleagues at the Universidade Federal de Sao Paulo in Brazil demonstrated that green bananas containing resistant banana starch significantly reduced diastolic blood pressure after six months in individuals with prediabetes and diabetes. Izar A 2018. They also reported reduced weight and Body Mass Index. In addition, Dr. Sandra Tavares da Silva and her colleagues at Universidade Federal de Vicosa in Vicosa, Brazil demonstrated that green banana flour reduced systolic blood pressure and reduced fasting blood glucose after 45 days in overweight women with metabolic syndrome. Tavares NH 2014. This study did not find weight loss or changes in body composition in these women. However, they did report decreased hip circumference. Dr. Francine Marques and her colleagues at Monash University in Australia fed adults with untreated hypertension were fed a specialized RS4 resistant starch in which high amylose corn was competed with additional acetate and butyrate. When the resistant starch is broken down and fermented within the large intestine, additional acetate and butyrate is released. They demonstrated a clinically significant reduction in 24-hour systolic blood pressure independent of age, sex and body mass index. Jama et al., 2023
A recent animal study suggested that the intestinal microbiome and short-chain fatty acids reduced blood pressure as well as reducing gut dysbiosis. Dr. Francine Marques and her colleagues at Monash University in Australia demonstrated that resistant starch’s fermentation increased acetate-producing bacteria. Both resistant starch and acetate supplementation significantly reduced systolic and diastolic blood pressures, cardiac fibrosis and left ventricular hypertrophy in an animal hypertension model, Marques C 2017. This study also reported significant changes in the expression of biomarkers of heart disease. For instance, pro-inflammatory IL-1 signalling was downregulated and GPCR ligand binding and intestinal immune signaling for immunoglobulin A production was upregulated. This research group recently summarized the importance of the gut microbiota for blood pressure in Nature Reviews Cardiology.
In addition, new animal research from Baylor College of Medicine has shown that resistant starch prevented inflammation-induced hypertension. Their research focused on restoring the gut barrier and preventing bacterial translocation that has been implicated in the progression of this type of hypertension. Resistant starch also prevented loss of goblet cells in the intestinal crypts and TNF-alpha expression in the cecum and increased T-reg cells in the brain by 10-fold. The authors concluded that manipulation of the gut microbiota through prebiotics may serve as a novel therapy in the prevention of hypertension. Durgan FJ 2017, Durgan H 2018.
Multiple animal studies from Allen Taylor and his colleagues at Tufts University compared the effects of resistant starch versus highly digestible starch on eye health in rodent models. They found significantly reduced age-related glycation end-products (AGEs) in the eyes. AGEs are a major biomarker for age-related macular degeneration. The early papers attribute the benefits to reduced glycemic index without seeming to consider the well-established fermentation metabolic effects but the later papers confirmed the importance of intestinal fermentation. Uchiki AC 2012, Weikel IOVS 2012, Rowan IOVS 2014, Rowan PNAS 2017, Rowan GM 2018 (review), Rowan FRBM 2020, Aragonès AC, Rowan OPVS 2021.
One animal study demonstrated that resistant starch changes the expression of more than 200 genes in the large intestine – some genes were up-regulated while others were down-regulated. Keenan JNN 2015 While the function of some of these genes is not known, resistant starch changed the expression of genes involved in digestive health and disease (cell growth, proliferation and differentiation of the gut tissues, and apoptosis), immunity (cytokines and lysosome) as well as overall metabolism (insulin sensitivity, hunger and satiety hormones) in animal as well as human studies. Keenan JNN 2015, Zhou IJBM 2015, Sun FM 2015, Malcomson AJCN 2017, Zybaylov B 2018. Further work has also demonstrated changes in genes expression in the hypothalmus region of the brain (Shen O 2009), fat tissue (Robertson JCEM 2012), and liver (Kieffer JN 2016).
There is a tremendous amount of research underway in this area. This demonstrates the potential of nutrigenomics and is very promising.Share...