Researchers found that one fiber supplement seemed helpful while another appeared harmful — but study participants’ reactions varied.
April 28, 2022
Not all dietary fiber is created equal.
A Stanford Medicine study that dug into two types of common digestive fiber supplements showed stark differences in how we react to them, and it’s not always good.
The study also revealed insights into how one type of fiber reduces cholesterol — a mystery scientists have been chasing for years.
“We all know that high-fiber diets are good for us, but published reports of their effects can be highly contradictory,” said Michael Snyder, PhD, professor and chair of genetics and the senior author of the study, which was published April 28 in Cell Host & Microbe.
Snyder, the Stanford W. Ascherman, MD, FACS, Professor in Genetics, and his colleagues monitored thousands of molecules involved in metabolism and the microbiome, tracking the ebb and flow of the molecules as healthy volunteers ingested different amounts of two common dietary fibers — inulin and arabinoxylan.
The results showed that while arabinoxylan was overall a boon for reducing “bad” cholesterol, high doses of inulin caused a spike in inflammation in some people. There was, however, one volunteer whose body reacted well to high doses of inulin but not arabinoxylan. “Overall, this study revealed the effects of common fibers on human health and suggests strategies for personalized dietary interventions,” Snyder said.
The fiber debate
Dietary fiber generally refers to the indigestible carbohydrates that are naturally present in fruits, vegetables, nuts and grains. Snyder’s team focused on arabinoxylan, a grain fiber and active ingredient in Metamucil and psyllium husk, and inulin, a fiber found in some fruits and vegetables, such as bananas and asparagus. Inulin has recently gained traction as an additive to diet foods. (More fiber roughly equates to feeling more full.)
Past studies showed that arabinoxylan can help manage LDL cholesterol (the “bad” one) and other cardiovascular risk factors, but inulin’s effects are murkier. It’s been linked to some health benefits — and some dangerous side effects such as inflammation and liver damage.
In this study, the researchers analyzed molecular profiles — which detailed factors like the microbiome and other markers of metabolism changes — of volunteers to understand the effect of different types and doses of fiber. They also wanted to see how gut bacteria and other parts of the body react to both fibers.
Eighteen healthy trial participants volunteered for three 3-week sessions. For the first session, participants were randomly assigned to take 10 grams per day of either chicory inulin or arabinoxylan. After the first week, doses were raised to 20 grams per day, and in the third week, to 30 grams per day.
Participants took six to eight weeks off, resuming their regular diet. For the second session, they switched to the other supplement, following the same protocol. Another break ensued. Then, for the third session, all participants took an equal mixture of five fiber supplements, which included inulin and arabinoxylan, for three weeks.
Examining the impact of fiber
Throughout the study, the participants logged what they ate, including other sources of fiber. They also provided blood, urine and stool samples; underwent routine medical exams; and answered questions designed to assess gastrointestinal health. From the samples, the researchers measured the activity levels of thousands of gut bacteria, genes, proteins and lipids — something the team calls a “multiomic” approach. They then compared the data with the results of the medical exams and questionnaires.
“Essentially, we tried to get a complete readout of every possible metabolic and microbiological effect that each fiber may produce,” Lancaster said. “In other words, if our study is thought of as a detective story, then what the multiomic techniques enabled us to do was to simultaneously follow hundreds of leads. Without this technology we would be able to follow only a few at time.”
Of all the measurements taken during the study, those related to gut bacteria varied the most — some bacteria increased as consumption of arabinoxylan increased, while other bacteria decreased; and some groups of bacteria increased regardless of the amount of fiber consumed — followed by changes in blood proteins and lipids. Many of the bacteria that waxed and waned in response to fiber supplements appeared to play a role in either the processing of fibers or of lipids, according to the researchers. All of the supplements tested appeared to shift the composition of a participant’s microbiome.
How fiber may reduce cholesterol
For many participants, higher arabinoxylan was linked to fewer cardiovascular risk factors, particularly a drop in low-density lipoprotein or LDL cholesterol. Researchers also saw a reduction in LDL levels during the mixed supplement cycle, but it was not as pronounced as the drop induced by just arabinoxylan, suggesting that purified supplements may be more effective at reducing cholesterol.
One of the big lessons we learned from this study is that each participant had a unique profile of responses to dietary fibers.
Exactly how fiber tamps down LDL has yet to be determined, but in this study, researchers caught a glimpse of how that may happen. The study showed that high fiber consumption led to a rise in gut-bacteria-derived bile acids, which break down cholesterol and other lipids, and that there was a decrease in certain lipids. The results suggest that the microbiome’s response plays an important role in reducing LDL.
“For years scientists have been trying to figure out how arabinoxylan reduces cholesterol. Our results suggest that, at least for some people, this is driven by the microbiome’s reaction to arabinoxylan,” Lee-McMullen said.
Not all participants experienced this benefit, and some experienced a smaller decrease in LDLs while consuming arabinoxylan. A comparison of strong responders with non-responders revealed several potentially key differences: Strong responders ate higher levels of protein during arabinoxylan supplementation and had higher levels of liver and stomach proteins that play a role in converting cholesterol to bile.
Too much inulin
Like arabinoxylan, inulin supplementation also seemed to affect certain groups of bacteria, depending on the dose. But at the highest dose of inulin, 30 grams, most participants experienced a spike in inflammation throughout the body. And for three participants, the increased inulin seemed to trigger a spike in an enzyme called alanine aminotransferase, a sign of liver damage. These participants were immediately taken off the inulin supplements. Exactly why inulin caused the spike in the liver damage marker is unknown.
For one participant, however, the 30-gram-per-day dose of inulin prompted a surprisingly healthy fiber response, including decreased inflammation.
That, Snyder said, aligned with one of the main takeaways of the study: Every participant had a unique, or outlying, response to supplementation. “One of the big lessons we learned from this study is that each participant had a unique profile of responses to dietary fibers,” he said. “In the future, we plan to explore methods for tailoring diets that suit each individual’s personal needs.”
Other Stanford co-authors of the paper are postdoctoral scholars Aaron Horning, PhD, Sara Ahadi, PhD, Jeniffer Quijada, PhD, Heyjun Park, PhD, and Michael Tang, PhD; former postdoctoral scholars Charles Abbott, PhD, Aaron Robinson, PhD, and Daniel Hornburg, PhD; dietician Dalia Perelman; graduate students Chia-Jui Hung and Dylan Peterson; director of metabolomics and lipidomics Kévin Contrepois, PhD; research coordinator Melanie Ashland; Tracey McLaughlin, MD, professor of endocrinology, gerontology and metabolism; former research assistant Anna Boonyanit; and Justin Sonnenburg, PhD, associate professor of biology and immunology.
This study was supported by the Stanford Center for Genomics and Personalized Medicine Sequencing Center, the National Institutes of Health (grants S10OD025212, P30DK116074 and 5T32AI007290), the Stanford Genetics Bioinformatics Service Center, the Stanford Human Immune Monitoring Center and the Stanford iPOP.
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