Successful Use of Prebiotin Prebiotic Fiber in NIH/NIDDK Study to Reduce Inflammation in Kidney Patients

When you consider research coming out of the National Institutes of Health, most likely, you’re expecting the next new drug to fight cancer or lower blood pressure. “Inclusion of Prebiotin is a rare instance of a supplement being part of a significant National Institutes of Health (NIH) research study,” says Prebiotin CEO, Ron Walborn Jr.

Prebiotin® Prebiotic Fiber was the chosen supplement for “Gut Microbiome and p-Inulin in Hemodialysis (TarGut-ESRD) [end stage renal disease],” also called the “ESRD study.” [see end of blog for discussion of ESRD]

“Participating in an NIH-funded study can be seen as a ‘badge of excellence,’ since only about 18 percent of applications are funded,” Walborn explains. “Qualifying for NIH grant funding is clearly difficult; any funded study has gone through a very thorough and arduous review process. We are, therefore, thrilled our product was chosen for such an important study.”

According to Walborn, most supplement manufacturers don’t have the resources to set up traditional multi-phase clinical trials. These types of trials can cost in the millions and take years to complete. “NIH studies are a great alternative, especially for a supplement product. We donate the product used in the research studies through our parent company, Jackson GI Medical. Results are unbiased—we have absolutely no impact on study findings or resulting journal articles.”

“Participating in an NIH-funded study can be seen as a ‘badge of excellence.’”  – Ron Walborn Jr., Prebiotin CEO

The ESRD study

The ESRD study is one of two studies funded by an NIDDK U01 grant awarded to Dominic Raj, MD, director of the division of nephrology and professor of medicine at the George Washington University (GW) School of Medicine and Health Sciences:  “Gut Microbiome and p-Inulin in CKD (TarGut-CKD) Study” [the “CKD study”] and “Gut Microbiome and p-Inulin in Hemodialysis (TarGut-ESR) [the “ESRD study].

These multi-million dollar studies are to examine the effect of p-inulin (Prebiotin® Prebiotic Fiber) on the gut microbiome profile by 16s sequencing, change in metabolite, by untargeted and targeted analyses, and markers of inflammation.

Previous work from Dr. Raj’s laboratory showed that patients with kidney disease may have a higher level of release of endotoxin from the bacteria in the gut, which can move into the bloodstream and promote inflammation.

“This research is focused on finding a safe and effective treatment that reduces inflammation and prolongs survival of these patients.”  Dominic Raj, MD, Director of the Division Of Nephrology and Professor of Medicine at the George Washington University (GW) School of Medicine and Health Sciences

The ESRD study is conducted by the National Institute of Diabetes and Digestive and Kidney Diseases’ (NIDDK) Hemodialysis Novel Therapies (HDNT) Consortium and examines the tolerability and safety of p-inulin (Prebiotin™ Prebiotic Fiber) and the feasibility of biosample collection to inform the design of future studies with this agent.

According to the HDNT Consortium web page (on the Perelman School of Medicine  website), these studies are to “fill some of these gaps in anticipation of ultimately investigating the therapeutic potential of altering the composition and/or function of the gut microbiome in this patient population.”

“Alterations in the intestinal microbiome (dysbiosis) are increasingly recognized as potential causes of inflammation and cardiovascular disease in patients with end-stage renal disease (ESRD). There are important potential benefits of intervening to restore symbiosis to the gut microbiota in these patients.” – HDNT Consortium webpage

Treatment with Prebiotin® Prebiotic Fiber

The ESRD pilot study group participated in three study phases: 8 weeks before treatment with Prebiotin, 12 weeks of treatment with two daily 8-gram doses of Prebiotin Prebiotic Fiber, for a total of 16 grams per day sprinkled into beverages or on food; and, similar to the first phase, 8 final weeks without Prebiotin. Blood and stool samples were taken in each phase of the study.

One participant dropped out to have a kidney transplant. The 12 participants who finished the study all tolerated the Prebiotin treatment well. Differences in concentrations of selected stool and plasma metabolites (nominal p<0.05) were evident between the pre-treatment and p-inulin (Prebiotin®) treatment periods.

Preliminary results indicated that participants not only tolerated Prebiotin® Prebiotic Fiber but successfully performed aliquoting procedures (exactly dividing into smaller sections) on stool samples obtained at home (3382 aliquots among 13 participants). Full results are expected to be released by the end of 2017. Due to the early positive results, a larger 100 to 200 patient phase two study is currently under discussion to further explore the role of a prebiotic fiber (and possibly a probiotic) on the microbiome as it relates to inflammation.

Study researchers

HDNT is comprised of a group of experts on kidney disease including:

Clinical Centers:

• Brigham and Women’s Hospital (Harvard University) – D. Charytan
• George Washington University – D. Raj (HDNT chair)
• University of Washington – J. Himmelfarb
• Vanderbilt University – T.A. Ikizler
• Data Coordinating Center:  University of Pennsylvania – l. Dember, JR Landis
• Steering Committee Chair: A. Kliger, Yale University
• NIDDK:  P. Kimmel, J. Kusek.

The CKD study consortium includes Cleveland Clinic, the University of California San Diego, Northwestern University, Duke University, and the University of Utah. This study will be discussed in a future report.

Inflammation and chronic kidney disease CKD

In a 2015 review article in the Blood Purification Journal, on inflammation and chronic kidney disease, the authors discuss the impact of inflammation:

“Persistent, low-grade inflammation has been recognized as an important component of CKD [chronic kidney disease], playing a unique role in its pathophysiology and being accountable in part for cardiovascular and all-cause mortality, as well as contributing to the development of protein-energy wasting…Chronic inflammation should be regarded as a common comorbid condition in CKD and especially in dialysis patients. A number of interventions have been proven to be safe and effective in well-designed clinical studies. This includes such inexpensive approaches as a modification of physical activity and dietary supplementation.”

“These types of studies support a broadening appreciation that by changing the microbiome, Prebiotin may play an important role in a broad range of chronic inflammatory diseases.”  —  Wilson F. Jackson, MD, Medical Director for Prebiotin

To address inflammation, researchers are now studying the impact of supplements like Prebiotin® Prebiotic Fiber to nurture the “good” bacteria in the microbiome, among other investigations.

Says Greg Cooper, Prebiotin’s Director of Business Development, “As research scientists prove the fundamental importance of the microbiome in health and wellbeing—and include Prebiotin in their research—we hope the public recognizes our product has a legitimate, researched impact on the microbiome and can play an important role in therapeutic responses to dysbiosis, the microbial imbalance in the body leading to inflammation.”

Other research studies with Prebiotin® Prebiotic Fiber

Prebiotin’s full-spectrum prebiotic fiber is comprised of oligofructose-enriched inulin (OEI) derived from chicory root through a proprietary process that does not involve chemicals. While OEI has been in dozens of research studies, Prebiotin’s formula was specifically selected as the prebiotic fiber in two 2017 research studies that indicate prebiotic fiber can be helpful in appetite control and obesity:

• Prebiotic supplementation improves appetite control in children with overweight and obesity: a randomized controlled trial. American Journal of Clinical Nutrition (2017)
• Prebiotic Reduces Body Fat and Alters Intestinal Microbiota in Children With Overweight or Obesity. Gastroenterology (2017)

 Current studies involving only Prebiotin® Prebiotic Fiber

• The NIH has invested $6.5 Million in two human trials currently underway—the “ESRD study” is part of this research effort.
• National Kidney Foundation (called the “PD study”) – funding research to look at the effect of p-inulin on the microbiome of ESRD patients treated with peritoneal dialysis.
• Health Canada – Human clinical trial on IBD [Inflammatory Bowel Disease] – University of Alberta
• University of Calgary School of Medicine – Title: Prebiotic Reduces Body Fat and Alters Intestinal Microbiota in Children With Overweight or Obesity
• University of Maryland School of Medicine:
• Prebiotic Treatment of Cognitive Impairments in Schizophrenia – Human Trial
• The Amish Study – increasing in butyrate-producing bacteria – Human Trial

What is ESRD?

Kidney failure treated with dialysis or kidney transplant is called end-stage renal disease (ESRD).

According to the CDC fact sheet on chronic kidney disease or CKD, CKD is a condition in which the kidneys are damaged or cannot filter blood as well as healthy kidneys. Because of this, excess fluid and waste from the blood remain in the body and may cause other health problems, including inflammation. About 30 million people or 15% of all adults are estimated to have CKD.

Most people don’t have visible symptoms until the kidneys are severely impaired. About 96% of people with kidney damage or mildly reduced kidney function are not aware of having CKD, while 48% of those with severely reduced kidney function but who are not on dialysis are not aware of having CKD.

Some individuals progress to kidney failure, called end-stage renal disease (ESRD). According to CDC statistics, more than one-third of male and female Medicare patients with advanced kidney disease are not seeing a kidney doctor before developing kidney failure, although the percentage seeing a nephrologist has increased from 57% to about 63%, from 2006 to 2015.  

Risk factors for developing CKD include:

• Diabetes
• High blood pressure
• Heart disease
• Obesity
• Family history of CKD

Kidney disease usually gets worse over time, though treatment has been shown to slow progression. When the kidneys stop working, dialysis or kidney transplant is needed for survival.

Not all patients with kidney disease progress to kidney failure and, in some patients, kidney disease progresses to kidney failure even with proper treatment.

Diabetes and ESRD

According to the CDC, end-stage renal disease (ESRD) is a major complication of diabetes and requires dialysis or transplantation for survival. Statistics from the National Kidney Foundation tell us that about 30 percent of patients with Type 1 (juvenile onset) diabetes and 10 to 40 percent of those with Type 2 (adult onset) diabetes will eventually suffer from kidney failure.

“Some 30 million Americans (1 in 7 U.S. adult population) suffer from CKD—a figure experts predict will rise due to high obesity rates (1/3 of all adults)–the link between obesity, diabetes and high blood pressure (all risk factors) and the aging of the Baby Boom generation (since age is another risk factor for CKD).” – Dr. Leslie Spry, MD, FACP,  Ask the Doctor, National Kidney Foundation

With diabetes, the small blood vessels in the body, including those in the kidneys, are damaged.  When the kidneys do not work effectively, blood is not properly filtered, allowing the body to retain more water and salt than is healthy.

Diabetes can also damage the nerves that allow us to completely empty the bladder. Pressure from the full bladder can back up and injure the kidneys. If urine with a high sugar content (as is the case with diabetes) remains in the bladder, bacteria quickly multiplies and results in frequent infections.

All of these factors related to diabetes can eventually lead to severely damaged kidney function.

Symptoms of kidney disease related to diabetes:

• Most people do not have visible symptoms until the kidneys are severely impaired.
• Early sign of kidney disease in patients with diabetes: increased excretion of albumin in the urine
• Weight gain and ankle swelling (advanced kidney disease)
• More need to urinate during the night
• High blood pressure

As kidneys fail: People with advanced kidney failure may develop a group of symptoms referred to as uremia:

• Blood urea nitrogen (BUN) levels will rise as well as the level of creatinine in the blood
• Nausea, vomiting, a loss of appetite, weakness, increasing fatigue, itching, muscle cramps (especially in the legs), and anemia (a low blood count)
• Build-up of fluid around the heart
• Nerve problems
• Changes in mental status, including drowsiness, seizures, or coma
• Needless insulin because diseased kidneys cause less breakdown of insulin

Productivity losses associated with diabetes in the U.S.

According to Phillip Jacobs, PhD, and JA Johnson, PhD, in Diabetes Care, “Diabetes has a considerable impact on economic behavior in the labor force. Controlling for variables such as age, sex, and health status, the presence of diabetes itself reduced employment by 3.5%, and the presence of complications reduced employment by 12% compared with the absence of complications…those who had complicated diabetes worked 3.2 days less every 2 weeks than those whose diabetes were without complications.” The economic cost for the United States is estimated to be $127 billion in 2017 and $161 billion by 2020, according to Statista, the Statistics Portal.

Quality of life declines with ESRD:

An individual with ESRD faces many impairments in his or her quality of life. More than 50% of patients report having dry skin, fatigue, itchiness (pruritus), and/or bone and joint pain. A recent study shows that 42% of prevalent dialysis patients have moderate to severe pruritus that was associated with poor sleep quality, physician-diagnosed depression, and poor quality of life. The international observational study of more than 10,000 patients indicated nearly 20% of the cohort had depression, which leads to shorter survival times; pain is present in about 50% of the dialysis patients.

After taking lithium for decades, Barbara Abram’s kidneys had eroded to end-stage renal disease: “Just mentioning the term ‘end stage’ makes my whole body shiver. My life would never be the same again,” she writes in “The Worst Day of My Life” in the American Association of Kidney Patients publication RENALIFE. “Everything familiar to me would take a back seat for the new adjustments. The most significant hurdle involved my eating habits…the diet material consisted of 3 pages of forbidden foods…could it get any worse? Don’t ask me how. I felt overwhelmed.”

Facts about ESRD:

According to the CDC, in 2014, 118,000 people in the United States started treatment for ESRD, and 662,000 were living on chronic dialysis or with a kidney transplant.

• Men are 64% more likely than women to develop ESRD (although women are estimated to have higher rates of CKD–16% vs. 13%).
• African Americans are 3 times more likely than whites to develop ESRD.
• Hispanics are 35% more likely than non-Hispanics to develop ESRD.
• Native Americans (American Indians and Alaska Natives) have the highest rates of kidney failure because of diabetes (this group has a greater chance of having diabetes than any other US racial group).
• In US adults aged 18 years or older, the main reported causes of new cases of ESRD are diabetes and high blood pressure.
• In US adolescents aged 13 to 17 years, the main reported cause of new cases of ESRD is glomerulonephritis (inflammation of the kidneys).

Health consequences:

Having kidney disease increases the chances of also having heart disease and stroke. Managing blood pressure, blood sugar, and cholesterol levels—all risk factors for heart disease and stroke—is more difficult, but much more important in the presence of CKD.

Premature death from both heart disease and from all causes is higher in adults with CKD compared with adults without CKD.

Financial consequences:

The NIH devotes $574 million of its funding to kidney disease research to improve therapies and discover cures. It represents just 1.7 percent of the annual total cost of care for the condition. – United States Renal Data System

The Medicare program provides reimbursement for greater than 90% of ESRD treatment in the United States. Medicare costs for CKD and End-Stage Renal Disease (ESRD) exceed $70 billion annually according to the United States Renal Data System (USRDS) data.

“The impact of renal insufficiency on workplace productivity is substantial,” says Paul M. Just in an article in Nephrology Dialysis Transplantation on the economic factors that influence dialysis modality choice around the word. “There is a significant reduction in workforce participation among patients with renal dysfunction aged 18–64 years. A conservative estimate of lost productivity from workforce non-participation associated with renal dysfunction in 1994 was ∼$665 million.”

Medicare beneficiaries with CKD account for 16.5% of Medicare costs in the year the disease is diagnosed, and 11.1%  in the next year. According to the United States Renal Data System (USRDS), the savings to Medicare for each patient who does not progress to dialysis is estimated to be $288,000. Therefore, improving the health and well-being of CKD patients could have a substantial economic impact.

“Reducing the state of exploding healthcare costs will be a priority no matter how the health care issue is resolved. Reducing expenditures on traditional medical approaches and increasing the use of far less expensive nutritional solutions which provide better outcomes, should be at the top of the nation’s healthcare agenda.”   –Ron Walborn Jr., Prebiotin CEO

Medicare spending for CKD:

• Medicare spending for patients with CKD ages 65 and older exceeded $50 billion in 2013 and represented 20 percent of all Medicare spending in this age group.
• More than 70 percent of Medicare spending for CKD patients ages 65 and older was incurred by those who also had diabetes, congestive heart failure, or both.
• Spending was more than twice as high for patients with all three chronic conditions of CKD, diabetes, and congestive heart failure ($38,230) than in patients with only CKD ($15,614).
• Medicare fee-for-service spending for ESRD beneficiaries rose by 1.6 percent, from $30.4 billion in 2012 to $30.9 billion in 2013, accounting for 7.1 percent of the overall Medicare paid claims costs.

Slowing the progression of ESRD:

To slow the progression of diabetes-associated renal disease, it is important to control hyperglycemia and hypertension, as well as obesity that can cause adult-onset diabetes.

Prebiotin WM designed to bring obesity-related dysbiosis into balance

Obesity is associated with a wide range of illnesses from diabetes and renal disease, to at least 13 types of cancer. According to the CDC Vital Signs series, Cancer and Obesity, around 55% of cancers diagnosed in women and 24% of cancers diagnosed in men are overweight- and obesity-related cancers. Of these cancers, about 2 in 3 occur in adults 50-74 years old.

It is important to note that Prebiotin’s weight management product, Prebiotin WM, is designed to bring obesity-related dysbiosis into balance. Virtually all overweight people have a bad bacterial mix (dysbiosis) in the colon that supports obesity:

• Undesirable bacteria in the gut produce twice the number of calories that are produced by “good” bacteria.
• An unhealthy balance of bacteria leads to leaky gut, which allows toxins to enter the bloodstream, promoting weight gain.
• Dysbiosis makes control of blood sugar more difficult.
• Undesirable bacteria trigger hunger hormones and reduce the hormones that signal satiety (fullness).

Prebiotin Weight Management acts to favorably reverse these unwelcome changes in the gut and body.

Research confirms the impact of prebiotics to control weight in children and adults:

The following are three of many articles that indicate prebiotic fiber can be helpful in appetite control and obesity:

• Hume MP, Nicolucci AC, Reimer RA. Prebiotic supplementation improves appetite control in children with overweight and obesity: a randomized controlled trial. The American Journal of Clinical Nutrition. 2017 Apr 1;105(4):790-9.
• Nicolucci AC, Hume MP, Martínez I, Mayengbam S, Walter J, Reimer RA.Prebiotic Reduces Body Fat and Alters Intestinal Microbiota in Children With Overweight or Obesity. Gastroenterology. 2017. doi: 10.1053/j.gastro.2017.05.055.
• Verspreet J, Damen B, Broekaert WF, Verbeke K, Delcour JA, Courtin CM. A critical look at prebiotics within the dietary fiber concept. Annual review of food science and technology. 2016 Feb 28;7:167-90.

These individual studies using Prebiotin are of course important to us as a company, and we want our readers to know why.

Mission

Our Mission at Jackson GI Medical is to empower improved gut microbiome health worldwide, eliminating gut imbalance through the development and responsible marketing of natural prebiotic fiber supplements backed by medically credible third-party research.

Vision

A world free of gut imbalance-caused diseases and conditions due to the lack of prebiotic fiber.

Value

Our guiding Value is to treat our customers, affiliates and Prebiotin team members as we would want to be treated: with honesty, respect, compassion, and transparency.