Resistant Starch in Clinical Trials

My ongoing project to analyze resistant starch in common food starches is progressing well. I’ve raised $1250 through my Indiegogo Project, and a bit more through PayPal donations. Please donate if you are so inclined and would like an early look at the results. With the funds now available, I’ll be able to get 12-15 different RS tests…enough to provide excellent data on the real RS contents of the starches we’ve been discussing for several years. In this post, I want to show you the different clinical trials in progress that are using RS as a therapeutic fiber supplement.

potato-diet-study

Clinical Trials

The National Institutes of Health maintain a database of all ongoing and completed clinical trials. ClinicalTrials.gov is used by people with devastating diseases to find new treatments for deadly diseases. Each entry in the database indicates whether the particular clinical trial is “recruiting” for patients, but also gives a brief synopsis of the what’s being studied and the drugs being used.

I’ve been keeping an eye on ClinicalTrials.gov for several years because resistant starch enjoys widespread use in clinical trials to treat diabetes, obesity, and other metabolic diseases. If you type “resistant starch” in the search bar, you’ll get 52 hits. Scrolling through the selection shows 11 of these trials are in the pre-recruiting or recruiting phase. Feel free to do the search and browse on your own, but here’s a breakdown of the studies in early design phase:

1. Effects of Resistant Starch on Bowel Habits, Fecal Short Chain Fatty Acids and Gut Microbiota in Parkinson Disease (RESISTA-PD).

The investigators will investigate the effects of an 8-week resistant starch (RS) supplementation (5 g twice a day) in patients with Parkinson Disease and matched controls on:

  1. symptoms of constipation (assessed by clinical scores);
  2. fecal short chain fatty acid concentrations (measured by chromatography);
  3. gut microbiota composition.

Eligibility

Ages Eligible for Study: 18 Years and older   (Adult, Senior)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: Yes

2. Resistant Starch and Whey Protein on Energy Metabolism

Recent evidence shows that dietary supplementation with resistant starch (RS) increases fat catabolism and resting energy expenditure and decreases plasma insulin and glucose responses as well as the gut-derived hormone, glucose-dependent insulinotropic polypeptide (GIP). Consumption of whey protein has also been shown to increase energy expenditure and favorably affect gut hormones. Thus, investigators tested consumption of both RS and whey protein on energy expenditure and gut hormones in lean and obese women and men.

 

Condition Intervention
Weight Loss Other: waxy maize starch
Other: waxy maize starch and Whey Protein
Other: Resistant Starch
Other: resistant starch and whey protein
Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Detailed Description:

Consumed separately, resistant starch (RS) and whey protein (WP) favorably affect energy metabolism and gut hormones, as well as suppress feelings of hunger. These findings are important because release of certain gut hormones (i.e., GIP) is associated with a lower resting energy expenditure (REE) in healthy humans. Interestingly, a recent study showed that ingestion of RS reduces postprandial GIP and increases postprandial REE and fat utilization in healthy men and therefore may be an effective strategy in weight management. Thus, there is a need to replicate these findings in a healthy cohort of lean and obese women and men.

The purpose of this study was to examine the effects of RS on the number of calories burned after eating a meal, as well as specific hormones that are released from the stomach and intestines following meal ingestion in healthy lean and obese women and men. Investigators used a single ingestion of a meal supplemented with or without the resistant starch and whey protein.

Ages Eligible for Study: 30 Years to 65 Years   (Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: Yes

3. Resistant Starch Supplementation Effects on the Intestinal Tract Profile and Cardiovascular Markers in Renal Patients (Starch)

Primary Outcome Measures:

  • Change in gut microbiota profile measured by denaturing gradient gel electrophoresis after supplementation of resistance starch treatment [ Time Frame: Change from Baseline microbiota gut at 6 weeks ]
    after 6 weeks with resistance starch the chronic kidney disease patients should have the gut microbiota modulated


  • Change in cytokines plasma levels measured by ELISA after supplementation of resistance starch [ Time Frame: Change from Baseline inflammation at 6 weeks ]
    after 6 weeks with resistance starch the chronic kidney disease patients should have the cytokines levels reduced
Estimated Enrollment: 30
Study Start Date: December 2015
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: resistance starch for CKD

– Intervention period (6 weeks): Group A – patients will receive 6 cookies/day containing resistant starch (18g/day); Group B – patients will receive 6 cookies/day containing placebo
Dietary Supplement: ‘resistance starch for CKD

Intervention period (6 weeks): Group A – patients will receive 6 cookies/day containing resistant starch (18g/day); Group B – patients will receive 6 cookies/day containing placebo
Experimental: cross-over period

intervention period (6 weeks): Group B – patients will receive 6 cookies/day containing resistant starch (18g/day); Group A – patients will receive 6 cookies/day containing placebo
Dietary Supplement: Placebo

Intervention period (6 weeks): Group B – patients will receive 6 cookies/day containing resistant starch (18g/day); Group A – patients will receive 6 cookies/day containing placebo

Detailed Description:

Patients with chronic kidney disease (CKD), especially those who are on dialysis have a high prevalence of cardiovascular mortality and, among the risk factors include inflammation and oxidative stress. Recently this scenario, beyond those alterations found in these patients, it has been suggested that the balance of the intestinal flora in these patients might be a new factor of cardiovascular risk. Some treatment strategies have been studied in order to modulate the gut microbiota as the use of pre, pro or synbiotics. Although few studies, supplementation with prebiotics has been recommended. However, the use of resistant starch as a source of prebiotic for modulation of the intestinal flora in these patients has not yet been evaluated, but the study of Prof. Vaziri the University of California Irvine, USA, with nephrectomized rats showed that the resistant starch was able to attenuating the progression of failure of renal function, inflammation and oxidative stress and minimize the abnormalities of intestinal epithelial barrier. The objective of this study is to assess whether supplementation with resistant starch from the rice-flour coffee developed by EMBRAPA, as well as from an already industrialized product (Hi-Maize of Ingredion®) could modulate the intestinal microbiota of patients with CKD ( both patients under conservative treatment, such as dialysis treatment), as well as exerting a beneficial effect with respect to reducing levels of inflammatory markers of oxidative stress, uremic toxins and in addition, markers of cardiovascular disease.
Ages Eligible for Study: 18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: Yes
Criteria

Inclusion Criteria:

  • Hemodialysis patients with arteriovenous fistula as vascular access in the upper limb and on maintenance dialysis for at least 6 months;
  • Patients under conservative treatment in stages 3a and 3b (30 to 60 mL / min) of chronic kidney disease and receiving nutritional treatment for at least 6 months (adequate supply of energy 30-35kcal/kg/day and hypoproteic 0.6 g/kg/day.

Exclusion Criteria:

  • Patients with autoimmune and infectious diseases, diabetes, cancer and AIDS;
  • Patients with catheter for hemodialysis access;
  • Patients using catabolizing drugs, supplements as antioxidant vitamin, probiotics, prebiotics, synbiotics and antibiotics.
  • Patients who exercise are also deleted.

4. Resistant Starch, Epigallocatechin Gallate and Chlorogenic Acid for Body Weight Loss in Menopause

Primary Outcome Measures:

  • Body weight [ Time Frame: 3 months ]
    Difference in change in body weight between patients receiving the experimental product and those not assigned to its use

Secondary Outcome Measures:

  • Body weight [ Time Frame: 6 months ]
    Difference in change in body weight between patients receiving the experimental product for 6 months and those assigned to its use for 3 months


  • Insulin resistance [ Time Frame: 3 months ]
    Difference in change in homeostasis model assessment of insulin resistance between patients receiving the experimental product and those not assigned to its use


  • LDL cholesterol [ Time Frame: 3 months ]
    Difference in change in LDL cholesterol between patients receiving the experimental product and those not assigned to its use


  • Triglycerides [ Time Frame: 3 months ]
    Difference in change in triglycerides between patients receiving the experimental product and those not assigned to its use


  • Insulin resistance [ Time Frame: 6 months ]
    Difference in change in homeostasis model assessment of insulin resistance between patients receiving the experimental product for 6 months and those assigned to its use for 3 months


  • LDL cholesterol [ Time Frame: 6 months ]
    Difference in change in LDL cholesterol between patients receiving the experimental product for 6 months and those assigned to its use for 3 months


  • Triglycerides [ Time Frame: 6 months ]
    Difference in change in triglycerides between patients receiving the experimental product for 6 months and those assigned to its use for 3 months


  • Visceral adiposity [ Time Frame: 3 months ]
    Difference in change in anthropometric parameters describing fat distribution (waist circumference) between patients receiving the experimental product and those not assigned to its use


  • Visceral adiposity [ Time Frame: 6 months ]
    Difference in change in anthropometric parameters describing fat distribution (waist circumference) between patients receiving the experimental product for 6 months and those assigned to its use for 3 months


  • Fat free mass [ Time Frame: 3 months ]
    Difference in change in body composition parameters (measured by bioelectrical impedance analysis) between patients receiving the experimental product and those not assigned to its use


  • Fat free mass [ Time Frame: 6 months ]
    Difference in change in body composition parameters (measured by bioelectrical impedance analysis) between patients receiving the experimental product for 6 months and those assigned to its use for 3 months


  • Menopausal symptoms [ Time Frame: 3 months ]
    Difference in change in the severity of menopausal symptoms (using the Green Climacteric Scale) between patients receiving the experimental product and those not assigned to its use


  • Menopausal symptoms [ Time Frame: 6 months ]
    Difference in change in the severity of menopausal symptoms (using the Green Climacteric Scale) between patients receiving the experimental product for 6 months and those assigned to its use for 3 months


  • Quality of life [ Time Frame: 3 months ]
    Difference in change in quality of life (measured by the SF-36 Health Survey) between patients receiving the experimental product and those not assigned to its use


  • Quality of life [ Time Frame: 6 months ]
    Difference in change in quality of life (measured by the SF-36 Health Survey) between patients receiving the experimental product for 6 months and those assigned to its use for 3 months
Estimated Enrollment: 144
Study Start Date: September 2016
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nutritional counseling

Nutritional counseling consists in: personalized dietary prescription associated with dietetic advise (on a monthly basis and upon patient’s request) by a registered dietician.
Other: Nutritional counseling

Nutritional counseling consists in: personalized dietary prescription associated with dietetic advise (on a monthly basis and upon patient’s request) by a registered dietician.
Experimental: Equikilon-3 months

The patient will receive 2 sachets per day of a dietary supplement containing resistant starch, epigallocatechin gallate and chlorogenic acid (Equikilon) for 3 months and nutritional counseling.

Nutritional counseling consists in: personalized dietary prescription associated with dietetic advise (on a monthly basis and upon patient’s request) by a registered dietician.

Dietary Supplement: Equikilon-3 months

The patient will receive 2 sachets per day of a dietary supplement containing resistant starch, epigallocatechin gallate and chlorogenic acid (Equikilon) for 3 months and nutritional counseling.

Nutritional counseling consists in: personalized dietary prescription associated with dietetic advise (on a monthly basis and upon patient’s request) by a registered dietician.

Experimental: Equikilon-6 months

The patient will receive 2 sachets per day of a dietary supplement containing resistant starch, epigallocatechin gallate and chlorogenic acid (Equikilon) for 6 months and nutritional counseling.

Nutritional counseling consists in: personalized dietary prescription associated with dietetic advise (on a monthly basis and upon patient’s request) by a registered dietician.

Dietary Supplement: Equikilon-6 months

The patient will receive 2 sachets per day of a dietary supplement containing resistant starch, epigallocatechin gallate and chlorogenic acid (Equikilon) for 6 months and nutritional counseling.

Nutritional counseling consists in: personalized dietary prescription associated with dietetic advise (on a monthly basis and upon patient’s request) by a registered dietician.

Ages Eligible for Study: Child, Adult, Senior
Sexes Eligible for Study: Female
Accepts Healthy Volunteers: No


5. Types of Resistant Starch and Their Effect on Appetite (NST)

Primary Outcome Measures:

  • Subjective and behavioral satiety responses after consumption of the resistant starch composites by visual analog scales and subsequent food intake. [ Time Frame: 3 hour postprandial study ]

    Meals will be provided under fasting conditions and thereafter subjects will record satiety reponses at 30 mins, 60, 90, 120, 150 and 180 on a visual analog scale (VAS). The subject will answer a series of questions on the VAS describing their feelings of hunger, fullness and desire to eat at the above mentioned time points.

    Satiety will also be determined on the quantity of the test lunch meal consumed. This test meal will be served three hours after consumption of the starch composites.

Enrollment: 40
Study Start Date: August 2010
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Starch Composite B Dietary Supplement: Starch composite B

fiber mixture
Active Comparator: Starch Composite C Dietary Supplement: Starch composite C

fiber mixture
Active Comparator: Starch Composite D Dietary Supplement: Starch composite D

fiber mixture
Placebo Comparator: Placebo Dietary Supplement: Placebo

placebo

Detailed Description:

This study will require one initial screening visit (approximately 1 hour) and four study visits each lasting approximately 4 hours. All visits should be done in 2 months. We are looking for healthy, non-smoking, premenopausal female volunteers older than 18 with no medical history of diabetics, heart, lung, kidney, stomach, or liver disease.

The initial screening visit will determine subject eligibility through height, weight and waist circumference measurements, blood glucose finger prick and eating, health and mood surveys.

If willing and eligible to participate, subjects will have four study visits. All study visits will be scheduled according to each individual subject’s menstrual cycle. At each visit subject will be asked to eat the cookie bar and then answer questions about their feelings of hunger, fullness and desire to eat. Subject will continue to answer questions about their feelings of hunger, fullness and desire to eat at specific time points up to 3 hours after eating the yogurt. After 3 hours a lunch meal will be served. The lunch meal consists of typical deli items, such as pasta, rolls, salad, etc. Subject will be allowed to eat as much or as little of the lunch as they’d like.

Ages Eligible for Study: 18 Years and older   (Adult, Senior)
Sexes Eligible for Study: Female
Accepts Healthy Volunteers: Yes


6. Randomized Controlled Trial of Resistant Starch to Reduce Colon Cancer Risk in Alaska Native People.

Alaska native people (AN) have the highest recorded incidence and death rate from colon cancer in the world (>90:100,000). We hypothesize that the AN, despite their high consumption of anti-inflammatory and antineoplastic n-3 fish oils, are at increased risk of colon cancer because of colonic butyrate deficiency resulting from their remarkably low consumption of fiber-containing foods. We hypothesize that fiber supplementation of their usual diet will result in a bloom of butyrate producing microbes in the colon, resulting in increased butyrate production, which will suppress their high microbial secondary bile acid production, antagonize the actions of other food (smoked fish) and environmental carcinogens (tobacco, alcohol), and interact with the high circulating levels of n-3 fish oils to suppress colonic inflammation and cancer risk. In order to investigate this, we will conduct a randomized double-blinded 4-week clinical trial in up to 100 randomizable healthy, middle-aged AN undergoing screening colonoscopy, with the objective of obtaining 60 completed interventions. The interventions will consist of either a high-dose soluble fiber supplement given as a drink, together with their usual diet which currently contains about 15g total fiber/d, or to a control digestible starch drink plus their usual diet. The primary endpoint will be a clinically significant reduction in Ki67 proliferative colonic mucosal biomarkers of cancer risk. Microbiome and metabolome mechanisms responsible for the anticipated changes in mucosal biomarkers will also be investigated. Our results in extreme risk AN will be further evaluated by comparison to similar measurements previously made in minimal risk rural Africans and intermediate risk African Americans. Our results will be used to provide the scientific basis for a definitive large-scale high-fiber supplementation study (to achieve >50g total fiber/d) to suppress adenomatous polyp recurrence following colonoscopy.

Primary Outcome Measures:

  • colonic mucosal proliferation [ Time Frame: 4 weeks ]
    biomarker of cancer risk


Secondary Outcome Measures:

  • colonic microbiota [ Time Frame: 4 weeks ]
    fecal and colonic microbiota analysis


  • colonic secondary bile acids [ Time Frame: 4 weeks ]
    fecal and colonic conjugated bile acid analysis
Arms Assigned Interventions
Active Comparator: Resistant Starch

70g high-amylose maize starch which contains 42g of type 2 resistant starch
Dietary Supplement: Resistant starch

70g high-amylose maize starch
Placebo Comparator: Digestible Starch

70g of fully digestible starch comprised of amylopectin corn starch.
Dietary Supplement: 70g of fully digestible starch amylopectin corn starch

Fully digestible amylopectin corn starch

Detailed Description:

Randomization for the double blind, placebo controlled, clinical trial: Recruitment will continue until 60 volunteers have completed the intervention study. Based on previous experience with similar studies, we anticipate 20% of screened patients to be ineligible or drop out, which means, so we plan on consenting and screening approximately 100 potential participants. Baseline data from these participants will be retained. Individuals will be randomized via minimisation (based on age, sex, polypectomy, high fish consumption, and BMI – factors that might influence microbiota composition and function)) to either the resistant starch (RS) group or the control digestible starch (DS) group upon completion of the Stabilization Period.

  1. RS Group: Participants will continue with their usual diet plus fiber supplement given as a daily dose of 70g high-amylose maize starch (HAM-RS, HI-MAIZE®260: Ingredion Incorporated, Bridgewater, NJ), which contains 42g of type 2 resistant starch, for 4 weeks. Data from previous studies[69] suggests that their usual diet will contain approximately 13g dietary fiber/day, chiefly insoluble, indicating that total fiber intake would be approx. 55g/d. Supplements will be pre-weighed out in batches from the same source and kept in airtight containers. The supplement may be taken as a single or divided dose dissolved in 250ml water, low fat milk, or orange juice
  2. DS (Control) Group participants will continue on their usual diet, plus 70g of fully digestible starch (waxy corn starch comprised of amylopectin, AMIOCA® corn starch, Ingredion Incorporated, Bridgewater, NJ ) weighed out, analyzed, and prepared as previously. The RS and control supplements will appear and taste similar, allowing for coding and distribution in a double-blind fashion. The supplements will be equicaloric.

Interventions will include fecal and colonic content sampling for measurement of the microbiome and metabolome, and flexible sigmoidoscopy to obtain mucosal biopsies before and after the dietary supplementation.

Monitoring During the Clinical Trial: This will follow the scheme laid out on Figure 7. On day 0, participants will visit the clinic and will be asked to save their first fecal sample using our standard operating procedure developed and proven to be effective in our last study. They will then be given their first supplement drink made up in their vehicle of choice, and taken with a standard meal provided by the diet kitchen. During the trial, they will be instructed on the use of a simple diary to be completed at home. This will record the major food items consumed each day, the timing and completion of drink supplements, as well as the bowel function questionnaire to assess daily GI tolerance, i.e. abdominal discomfort, distension, gas, bowel frequency, nausea, vomiting. They will be asked to return to the clinic for a follow-up appointment on day 7, 14 and 21 in order to repeat the fecal and breath tests described above. At the same time, body weight will be monitored using one scale. At the end of 4 weeks, participants will be asked to return to the clinic for repeat of the colonic sampling performed at baseline.

 

7. Effects of MSPrebiotic on Gut Health in the Elderly

The purpose of this clinical trial is to study the effects of potato resistant starch on the microbiota (microorganisms or bacteria) and short chain fatty acids levels of the gut. Levels will be measured and compared between elderly adults and in pre-elderly, adults from the general public. A correlation between the use of potato resistant starch and specific clinical and quality of life endpoints between elderly adults and in pre-elderly, adults from the general public will be studied.

Hypothesis 1: The investigator hypothesizes that the microbiome in elderly adults (≥70 years) is less diverse and more prone to imbalance compared to adults (30-50 years) from the general population and that this imbalance of the gut microflora in the elderly adults is partially related to inadequate RS in their diet.

Hypothesis 2: The investigator hypothesizes that ingestion of potato resistant starch of food grade quality (MSPrebiotic) will stabilize the gut microbiome (i.e. high Firmicutes/Bacteroides ratio)in LTC residents (i.e. similar to that of adults from the general population), thereby improving gut health and reducing the risk of diarrhea and/or gut infection.

Primary Outcome Measures:

  • Tolerability [ Time Frame: 2, 6, 10 and 14 weeks ]
    Changes from baseline in the tolerability of ingestion of 30 g once/day of MSPrebiotic with respect to gastrointestinal side effects (excessive flatulence, changes in bowel movements, abdominal pain and bloating) at 2, 6, 10 and 14 weeks.


  • Gut health improvements [ Time Frame: 2, 6, 10 and 14 weeks ]
    Changes from baseline in gut health improvements including: reduced constipation (i.e. improved ease of bowel movements without stool softeners), microbiome composition (i.e. favourable Firmicutes to Bacteroides ratio) at 2, 6, 10 and 14 weeks.


  • Levels of short chain fatty acids in stool and lipid level in blood [ Time Frame: 2, 4, 6, 10 and 14 weeks ]
    Changes from baseline of short chain fatty acid levels in stool including; acetate, propionate, butyrate, isobutyrate, valerate, isovalerate at 2, 4, 6, 10 and 14 weeks.


  • Inflammatory marker [ Time Frame: 2, 6, 10 and 14 weeks ]
    Changes from baseline of Inflammatory marker (IL-10, C-reactive protein, TNFα) levels in blood at 2, 6, 10 and 14 weeks.


Secondary Outcome Measures:

  • Changes from baseline in overall health at 2, 6, 10 and 14 weeks [ Time Frame: 2, 6, 10 and 14 weeks ]
    This will be assessed based on completion of a daily health log that assesses a wide variety of parameters.


Estimated Enrollment: 80
Study Start Date: September 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Elderly adults with MSPrebiotic

30 g of MSPrebiotic (potato resistant starch) per day taken with 1 glass (approximately 250 mL) of non-heated fluid or non-heated semi-solid food. If the participant is taking any medications, they will be advised to either take the product 2 hours before or 2 hours after any medications.
Dietary Supplement: MSPrebiotic

Potato Resistant Starch
Other Name: Potato Resistant Starch
Placebo Comparator: Elderly adults with Placebo

30 g of corn starch per day taken with 1 glass (approximately 250 mL) of non-heated fluid or or non-heated semi-solid food. If the participant is taking any medications, they will be advised to either take the product 2 hours before or 2 hours after any medications.
Experimental: General adult population with MSPrebiotic

30 g of MSPrebiotic (potato resistant starch) per day taken with 1 glass (approximately 250 mL) of non-heated fluid. If the participant is taking any medications, they will be advised to either take the product 2 hours before or 2 hours after any medications.
Dietary Supplement: MSPrebiotic

Potato Resistant Starch
Other Name: Potato Resistant Starch
Placebo Comparator: General adult population with Placebo

30 g of corn starch per day taken with 1 glass (approximately 250 mL) of non-heated fluid. If the participant is taking any medications, they will be advised to either take the product 2 hours before or 2 hours after any medications.

Detailed Description:

To assess the impact on the potato resistant starch on the microbiota, pyrosequencing will be performed on stool samples to determine the original composition and assess any changes over the study period. In addition the impact of the potato resistant starch on inflammatory markers will be assess through blood samples collected over the study period.
Ages Eligible for Study: 30 Years and older   (Adult, Senior)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: Yes


8. Role of Gastrointestinal Microbes on Digestion of Resistant Starch and Tryptophan Availability to Humans

There is currently a critical gap in knowledge of how intestinal bacterial communities alter metabolic substrates available to the host thereby influencing central and enteric nervous system (CNS/ENS) neurotransmitter levels involved in regulating carbohydrate consumption in humans. Understanding these relationships is essential for developing strategies to improve blood glucose control and to reduce the risk of transitioning from prediabetes to type-2 diabetes (T2D). The investigators’ long-term goal is to determine the biological underpinnings of behaviors that impact food intake and blood glucose control that contribute to the development of T2D. The objective of this proposal, which is an essential next step in attaining the investigators’ long-term goals, is to determine how bacterial populations in the digestive system impact circulating tryptophan (TRP) and large neutral amino acid (LNAA) levels that regulate production of monoamine 5-hydroxytryptamine (5-HT, serotonin) in the ENS and in gastrointestinal system and the brain. The central hypothesis is that a reduced ratio of TRP producing (TRPp) to TRP consuming (TRPc) bacteria (decreased TRPp:TRPc ratio) in the gut will decrease TRP availability following a carbohydrate meal lowering the plasma TRP:LNAA ratio and resulting in less TRP for ENS/CNS production of 5HT. Further, dietary interventions that promote TRPp bacterial abundance within the gut will increase TRP availability to the host. The investigators will test the central hypothesis and, thereby, accomplish the overall objective for this project by pursuing the following specific aims: 1) Assess impact of divergent microbiota on plasma TRP:LNAA ratio in response to acute carbohydrate consumption, and 2) Assess the impact of dietary supplementation with resistant starch (RS) on gut microbiota and circulating TRP:LNAA ratio. During Aim 1, stool samples will be collected from healthy participants. Participants will be stratified based on gut TRPp:TRPc ratio and the response to an acute meal will be assessed by determining plasma TRP:LNAA ratios. During Aim 2 the capacity for 4-weeks of pre-biotic RS (Potato Starch) supplementation to increase the TRPp:TRPc bacterial ratio in the gut will be determined from stool samples. Additionally, plasma TRP:LNAA ratio following acute carbohydrate consumption before and after supplementation will be determined. The scientific contribution will be to determine the impact of RS on TRPp and TRPc bacteria abundance in the gut, and how bacterial populations impact circulating TRP:LNAA levels, that can impact ENS and CNS 5HT production in humans. This contribution will be significant because it will have direct translational implications for human diseases with altered 5HT signaling.
Primary Outcome Measures:

  • Plasma Amino Acid Levels [ Time Frame: Baseline ]
  • Plasma Amino Acid Levels [ Time Frame: Following 4 weeks of supplementation ]
Secondary Outcome Measures:

  • Change in Plasma Amino Acid Levels [ Time Frame: Baseline vs. 4-weeks ]
    Difference in plasma amino acid levels between baseline and following 4-weeks of supplementation


Estimated Enrollment: 20
Study Start Date: January 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Potato Starch (Bob’s Red Mill)

Daily dietary supplementation with Potato Starch (48g total/day) suspended in water. 24g will be consumed 2 times per day.
Dietary Supplement: Potato Starch (Bob’s Red Mill)

Subjects will be assigned to Potato Starch (active) following assessment of their gut microbiome.
Placebo Comparator: Resource ThickenUp Pregelatinized Starch

Daily dietary supplementation with Pregelatinized Starch (48g total/day) suspended in water. 24g will be consumed 2 times per day.
Dietary Supplement: Pregelatinized Starch (Resource ThickenUp)

Subjects will be assigned to Pregelatinized Starch (placebo) following assessment of their gut microbiome.
Ages Eligible for Study: 18 Years to 65 Years   (Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: Yes


9. The Alberta FYBER (Feed Your Gut Bacteria morE fibeR) Study

Too much body-fat has been linked to a low-grade inflammation throughout the body. This inflammation is thought to then cause different diseases, like heart disease and diabetes. A lower amount of inflammation is usually seen in people that follow a high fiber diet. A reason for this is the microbes that live in our gut. Fiber is a main food source for these microbes. This allows fiber to actually change the type of microbes that live in our gut. Also, when fiber gets fermented by these microbes, health-promoting waste products get released. We aim to determine how exactly our gut microbes contribute to the health properties of fiber.

We hypothesize that fiber’s health properties depend on how the gut microbes respond to the fiber. To test this, we plan to add three different fibers to the diets of healthy overweight and obese individuals for six weeks. We then will determine how the different fibers affect an individuals’ health by looking at how established markers of health change from adding the fiber. Following this, we will see how an individual’s gut microbes respond to the added fiber. The response will be decided by looking at changes to the microbe community, as well as their ability to ferment the fibers. By connecting health outcomes to the gut microbes’ response, we can test if the gut microbes’ response to the fiber determines the fiber’s ability to effect health. If we can understand how our gut microbes respond to different fibers and the importance of that response. Then we could personalize diets to have a greater impact on improving health.

Primary Outcome Measures:

  • Prediction of the Clinical Improvements of Dietary Fiber [ Time Frame: 6-week period ]
    The primary objective of this study is to determine the ability of the fecal microbiome to predict clinical improvements of dietary fiber treatments relevant to the etiology of obesity-associated pathologies.

Secondary Outcome Measures:

  • Dietary Fiber Associated Changes in Sub-clinical Inflammation [ Time Frame: 6-week period ]
    The markers of sub-clinical inflammation that will be measured are: C-reactive protein, tumor necrosis factor-alpha, interleukin-6, interleukin-8, interleukin-18, interleukin-10, lipopolysaccharide binding protein, and adiponectin.


  • Dietary Fiber Associated Changes in Insulin Resistance and Blood Cholesterol. [ Time Frame: 6-week period ]
    Dietary fiber associated changes in fasting glucose, insulin, and glucagon will be quantified; and the homeostatic model assessment-estimated insulin resistance will used to calculate insulin resistance. Changes in incretins (glucose-dependent insulinotropic peptide and glucagon-like peptide-1) and blood cholesterol (triglycerides, low-density lipoprotein, high-density lipoprotein) will also be quantified.


  • Dietary Fiber Associated Changes in Satiety and Dietary Intake. [ Time Frame: 6-week period ]
    Dietary fiber associated changes in hunger and satiety will be quantified via satiety hormones (ghrelin, leptin, and peptide YY), self-reported satiety, and subsequent dietary intake and anthropometric measurements.


  • Dietary Fiber Associated Changes in Trimethylamine-N-Oxide (TMAO). [ Time Frame: 6-week period ]
    Dietary fiber associated changes in TMAO-a relatively new cardiovascular disease biomarker linked to the gut microbiome-will be quantified in plasma.


  • Dietary Fiber Associated Changes in Bile Acid Derivatives. [ Time Frame: 6-week period ]
    The influence of dietary fiber on the formation of bile acid derivatives, and its association with the observed clinical outcomes, will be determined.


  • Dietary Fiber Associated Changes in Gut Microbial Structure and Metabolic Function. [ Time Frame: 6-week period ]
    Fecal microbial composition will be characterized at baseline (week 0), 6 days (±1 day) post fiber initiation (week 1), and post intervention (week 6) by 16S rRNA sequencing; while fecal microbiota function will be assessed through whole metagenomic sequencing, fecal SCFA concentrations, as well as parallel in vitro fermentations with subsequent SCFA quantification.
Estimated Enrollment: 200
Study Start Date: July 2015
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Microcrystalline Cellulose (Control)

Microcrystalline cellulose will be used as a placebo control, as it is known to be an insoluble, non-viscous fiber that is essentially not fermented by the human gut microbiota. However, it is important to note that cellulose does have fermentation potential within the gastrointestinal tract and may be associated with improved health benefits; indicating a role as an active comparator.
Other: Microcrystalline Cellulose Supplementation

Fifty overweight and mildly obese subjects will supplement their normal dietary intake with a significant yet tolerable amount of MCC (Females: 25 g; Males: 35 g) daily for six consecutive weeks.
Other Name: Microcel MC-12; Blanver Farmoquímica Ltda.
Experimental: Acacia Gum

Acacia gum is composed largely of arabinogalactan, and is considered to be a relatively non-viscous, soluble fiber this is highly fermented by the gut microbiota and well tolerated.
Other: Acacia Gum Supplementation

Seventy five overweight and mildly obese subjects will supplement their normal dietary intake with a significant yet tolerable amount of AG (Females: 25 g; Males: 35 g) daily for six consecutive weeks.
Other Name: Agri-Spray Acacia Fibre; Agrigum International Ltd.
Experimental: Resistant Starch Type 4

Cross-linked phosphorylated resistant starch (type IV) is generally insoluble and with low viscosity; yet it tends to have physiologic properties similar to soluble fibers, such as fermentability.
Other: Resistant Starch Type 4 Supplementation

Seventy five overweight and mildly obese subjects will supplement their normal dietary intake with a significant yet tolerable amount of RS4 (Females: 25 g; Males: 35 g) daily for six consecutive weeks.
Other Name: Fibersym RW; MGP Ingredients, Inc.
Ages Eligible for Study: 19 Years to 50 Years   (Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: Yes


10. Modification of the Intestinal Microbiome by Diet Intervention to Mitigate Acute Graft-Versus-Host Disease

Investigators are evaluating the feasibility, safety and early efficacy of administering a commercially available dietary supplement containing potato-based resistant starch to subjects undergoing allogeneic SCT (stem cell transplant). The intervention will begin immediately prior to the conditioning phase and continue through day 100. Investigators hypothesize that short term administration of a resistant starch is capable of increasing levels of butyrate within the intestine that will reduce rates of acute GVHD (Graft-Versus-Host Disease).

Primary Outcome Measures:

  • Incidence of grade II-IV GVHD [ Time Frame: Day 100 ]

    The incidence of grade II, III and IV GVHD (Graft Versus Host Disease) as documented on day 100

    Grade II: Rash 25-50% of Body Surface Area (BSA), Bilirubin 3.1-6mg/dL, adult stool output 1000-1500mL/day or child 20-30mL/kg/day.

    Grade III: Rash greater than 50% BSA, bilirubin 6.1-15mg/dL, adult stool output greater than 1500mL/day or child stool output greater than 30mL/kg/day

    Grade IV: generalized erythroderma plus bullous formation and desquamation greater than 5% BSA, bilirubin greater than 15mg/dL, severe abdominal pain with or without ileus, or grossly bloody stool.

Estimated Enrollment: 70
Study Start Date: December 2016
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bob’s Red Mill®

Patients will follow the standard BMT (bone marrow transplant) diet and add potato-starch produced by Bob’s Red Mill® beginning on day -7 and continuing through day +100.Patients will consume 24 g of Bob’s Red Mill®, Potato-based dietary starch, orally twice daily.
Dietary Supplement: Bob’s Red Mill® Other: Standard BMT Diet

Standard bone marrow transplant (BMT) diet.
Placebo Comparator: Standard Diet

Patients will follow a standard BMT diet.
Other: Standard BMT Diet

Standard bone marrow transplant (BMT) diet.
Ages Eligible for Study: 10 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No


11. Effect of Potato Fiber on Appetite and Fecal Fat Excretion (POFIBA)

Primary Outcome Measures:

  • Fecal fat excretion [ Time Frame: Based on total feces collection the last 3 days of the 21-day intervention periods ]
  • Subjective appetite sensations [ Time Frame: Assessed on 3-hour meal test on last day of the 21-day intervention periods ]
    Assessed by visual analogue scales (VAS)

Secondary Outcome Measures:

  • Ad libitum energy intake [ Time Frame: Assessed 3 hours after intake of the test meal on last day of the 21-day intervention periods ]
  • Fecal energy excretion [ Time Frame: Measured based on total feces collection the last 3 days of the 21-day intervention periods ]
  • Blood lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) [ Time Frame: Measured before and after the 21-day intervention periods ]
  • Insulin and glucose [ Time Frame: Measured before and after the 21-day intervention periods, and every 30 minutes during the 3-hour meal test on last day of the 21-week intervention periods ]
  • Gut permeability marker [ Time Frame: Measured before and after the 21-day intervention periods ]
  • Gastric emptying rate (w. paracetamol) [ Time Frame: Measured every 30 minutes during the 3-hour meal test on last day of the 21-day intervention periods ]
  • Gastrointestinal symptoms (questionnaire) [ Time Frame: on day 1, 7, 14 and 22 of the 21-day intervention periods ]
  • Body weight [ Time Frame: up to 21-day intervention periods ]
  • Blood pressure [ Time Frame: up to 21-day intervention periods ]
  • Breath hydrogen [ Time Frame: up to 21-day intervention periods ]
  • Gut microbiota [ Time Frame: Measured in a fresh feces sample from day 19-21 of the intervention periods ]
Estimated Enrollment: 18
Study Start Date: September 2016
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FiberBind Dietary Supplement: FiberBind

Potato pulp consisting of 68% fiber (5.5 soluble, 76.7% insoluble and 17.8% resistant starch), 9.7% water, 0.3% fat, 7.2% protein and 14% carbohydrates (starch).
Experimental: RG-I fiber Dietary Supplement: RG-I fiber

Soluble fiber extracted from potato pulp consisting of 95% fiber and 5% water.
Placebo Comparator: Placebo Dietary Supplement: Placebo

Low-fiber control
Ages Eligible for Study: 20 Years to 40 Years   (Adult)
Sexes Eligible for Study: Male
Accepts Healthy Volunteers: Yes
Criteria

Inclusion Criteria:

  • Healthy Men
  • BMI between 18.5 and 27.0 kg/m2
  • Age 20-40 years

Exclusion Criteria:

  • Intake of potatoes with main meals more frequent than 4 times per week
  • Chronic diseases (known diabetes, cardiovascular disease, irritable bowels disease, colitis ulcerosa, crohn disease, or other chronic diseases which could affect the results of the present study)
  • Gluten allergy
  • Use of daily prescription medicine (mild analgesics are allowed)
  • Use of lipid-lowering agents (e.g. Becel, HUSK)
  • Use of food supplements of relevance to the study (such as pre- and probiotics)
  • Irregular intake of vitamin /mineral supplements (two weeks prior to and during the entire study period)
  • Smoking
  • Elite athletes (>10 hours of strenuous physical activity per week)
  • Blood donation (<1 month before study commencement and during study period)
  • Participation in other clinical studies (<1 month before study commencement and during study period)
  • Inability (physically or psychologically) to comply with the procedures required by the protocol judged by the Investigator\

Conclusion

I hope you at least scanned through the list, I included too much, I’m sure, but I thought some of you might be interested in the extent that resistant starch is being studied. If anybody has a condition that’s being looked at, there’s contact information provided at ClinicalTrials.gov, in case you wanted to volunteer to be part of the study.

Over half of the trials are using Bob’s Red Mill potato starch, which I found quite delightful. Most of the others were using Hi-Maize, which was the industry standard until somebody started talking about potato starch, lol. The rest just mentioned using “resistant starch,” almost as if it were an afterthought.

As part of my fund-raising efforts, I emailed each one of the lead researchers in these 11 trials. I heard back from 8. They were all very interested in the outcome of my project, but, alas, none were in a position to donate to my cause. The common theme in these emails was, “We’re broke!” And I can understand that. A few that I had the pleasure of conversing with mentioned that they independently test the RS sources they used, but the vast majority had not even given it a thought, just assuming that all RS is created equal.

After talking with the people behind these clinical trials, it makes me even more excited to test the RS contents in the starches they use, and the starches we have been supplementing with.  We have not heard the end of this crazy little powder called resistant starch by a long-shot!

I’ll do my best to keep you all up-to-date on what’s happening.

Tim Steele

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