An innovative combination of readily available natural products has shaped up to be an alternative to drugs like Ozempic to tackle obesity, type 2 diabetes, liver function and gut inflammation – without the invasiveness, cost or negative side effects that are associated with GLP-1 receptor agonists.
University of South Australia researchers have developed a microcapsule that’s smaller than a red blood cell, which promises an alternative to GLP-1 receptor agonist obesity drugs and has the added benefit of bolstering good gut bacteria rather than hampering it – which is a common impact of many medications.
“We know obesity is a state of systemic inflammation, resulting from complex biochemical pathway, rather than simply excess calories,” said PhD researcher Amin Ariaee. “But despite this, current treatments tend to ignore role of the gut microbiome, instead focusing on downstream effects, such as body weight and hyperglycaemia.
“Anti-obesity drugs also tend to upset the gut microbiome, which not only leads to unpleasant side effects such as nausea, stomach pain, and diarrhea, but can also exacerbate long-term inflammation and weight gain.”
The two factors in this novel treatment are medium-chain triglyceride (MCT), a type of bioactive lipid, and inulin, a gut-protecting probiotic found in many fruits and vegetables. They’ve each been studied independently for their health benefits, with MCTs associated with more effective ketonic diet outcomes and inulin for having positive impacts on lowering blood sugar, inflammation and weight management.
“We looked at firstly eating fats to lose fat, but not just any types of fats,” Ariaee told New Atlas. “So we wanted to look at medium chain triglycerides, or MCT oils as they’re commonly known, because this helps reduce systemic inflammation that’s associated with obesity. Then we combined that with inulin, which is a fiber that promotes good gut bacteria, to engineer these InulinMCT microcapsules.”
The team sourced inulin from chicory root and spray-dried it around nanoemulsion spheres of Miglyol 812, a mixture of coconut and palm kernel oil MCTs, essentially providing the microcapsule with a robust outer layer that could withstand premature degradation in the upper gastrointestinal tract. While both inulin and MCT oil supplements are available from health food stores, this hybrid treatment and its innovative design is key to the promising health outcomes here.
Then, the inulinMCT treatment was administered to diet-induced obese rats in a 21-day trial that tracked weight and other, broader health markers. After the three-week trial, there was a reduction in diet-induced weight gain, a 15% drop in blood sugar levels, a 78% reduction in inflammatory markers – a key factor in obesity-related diseases – and up to 47% less liver enzyme activity. Elevated liver enzymes, which are linked to a bad diet and obesity, can cause abdominal pain, fatigue, jaundice and nausea.
What’s more, there was a mean 8.3-fold improvement in microbial diversity, including beneficial bacteria like Bifidobacterium and Akkermansia muciniphila, helping the body to build its own natural defense against inflammation. A. muciniphila is a handy bug to have around for controlling fat absorption and adipose tissue accumulation. Meanwhile, Bifidobacterium can also moderate weight gain and influence how fat is distributed around the body.
“I should be clear, it’s definitely more modest weight loss compared to Ozempic, but we did see other biomarkers being reduced quite significantly as well, like 15% lower blood sugar levels, up to 78% less systemic inflammation, improved liver health, and almost nine times higher gut microbiome abundance,” Ariaee said. “The more gut bacteria we have in general, the healthier we are as individuals.”
InulinMCT also decreased pro-inflammatory markers TNF-α and IL-6 significantly, returning those to levels you’d see in a rat (and human) on a more balanced diet. HDL cholesterol was lowered to a normal range, and there was an uptick in the production of short-chain fatty acids (SCFAs) like acetate and propionate, which play important roles in inflammation regulation and gut health.
“With the inulin MCT, we want to have a more holistic approach of targeting the root causes of obesity – an imbalanced gut microbiome and systemic inflammation,” the researcher explained to New Atlas. “As opposed to drugs like GLP-1 RAs, like Ozempic, which target specific mechanisms. In that case, it’s appetite suppression.
“In doing so, we want to have a holistic approach for long-term weight loss, as opposed to drugs like Ozempic, where there are studies to show that once you stop your prescription, you gain back the weight than you originally lost,” he added.
While not being oversold as a ‘weight loss wonder drug,’ it has other advantages over the GLP-1 RA class that promote adherence (and therefore continued benefits).
“This is made completely from food-grade ingredients, both the inulin and the MCT oil, so it’s natural, and it’s expected to be well tolerated in humans in the longer term,” Ariaee said. “Now, we haven’t tried this in humans yet, but that’s what we expect, given that it’s food grade; it’s generally recognized as being safe by the leading therapeutics authorities as well.”
And because it’s food-grade, not a synthetic compound, inulinMCT could essentially be in supplement form that could be taken as a tablet or as a powder. And, the researcher confirmed, it could be on the market within a couple of years, human trial pending. The timeline for synthetic drugs, from discovery to clinical use, is an average of 12 years, with some compounds taking as long as 30 years to see the light of day.
“It’s definitely an easier regulatory process compared to a synthetic drug, because this will fall under the bracket of maybe a supplement or a nutraceutical, we could probably expect to see in human use in just two to three years,” Ariaee told us. “We want to test the effects of this formulation in humans, as well. So a clinical study would be beneficial, but that will require additional funding.”
Another advantage of inulinMCT is its delivery mode. While the team is yet to optimize this, it would certainly not be administered via injections like many weight-management drugs.
“We mentioned the word capsules in microcapsules, but you won’t be able to see them with the naked eye,” he explained. “So you just see a powder, and this could be tabulated. So you can have a tablet, you can put it in a capsule. [As a powder] you could mix it with your smoothie, perhaps.
“We want to provide something that’s more patient friendly,” he added. “Now we’re not going to see the same weight-loss effects as you see with those [GLP-1 RA] drugs; it’s more modest, but we want to provide an alternative to what’s on the market. It’s less of a magic pill, more of a inclusion as part of other lifestyle changes.”
In the meantime, the team is working on engineering a way to get the hybrid microcapsule to pass through the body untouched until it reaches the colon, where it could do its best work.
“We want to target the colon, and we haven’t shown that we’ve done that, but the inulin is degraded by bacteria – good gut bacteria, any gut bacteria – most of which is in the colon, the large intestine,” Ariaee said. “So we want to have this microcapsule formulation that reaches the gut, the large intestine, and can actually promote those healthy gut bacteria.”
Senior researcher Paul Joyce added, “Cardiovascular disease, type 2 diabetes, stroke, kidney disease, and even mental health conditions are all associated with obesity. But rather than addressing just one symptom, such as excess weight, we’re taking holistic approach to treatment to address all.”
The study was published in the journal Advanced Therapeutics.
Source: University of South Australia
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