Porous silica particles made from purified sand could one day play a role in weight loss efforts.
Previous clinical trials have already shown promising results, but the actual weight-reduction mechanism behind the potential treatment has been poorly understood.
To find out the key variables, the researchers have now tested a variety of sizes and shapes of silica in a simulation of the human gut after a large meal.
The results support the idea that porous silica can “impede the digestive processes” that are usually triggered by enzymes that break down fat, cholesterol, starches and sugars in the stomach and intestines.
Furthermore, the size of the administered nanoparticles appears to determine how much digestive activity is inhibited.
The authors acknowledge that their model is too simple to perfectly mimic the complexity of the human gut during digestion, but given the ethics surrounding human clinical trials, gut simulations and animal models are closer than the researchers could obtain otherwise.
Unlike other human gut models, this new one takes into account both fat and carbohydrate digestion. The authors also analyzed the degree to which organic matter could be absorbed within the gastrointestinal tract.
It’s possible that porous silica also leads to reduced weight gain in other ways, but the new findings provide additional research with a more solid place to start.
In 2014, researchers found that mice on high-fat diets weighed significantly less when fed porous silica nanoparticles (MSP). Their total body fat percentage also decreased. However, this effect appeared to be based on the relative size of the silica particles used. Larger particles were ultimately more effective.
Follow-up studies in mice supported these results. The right size and shape of the porous silica particles appeared to determine the power of mouse digestion in the small intestine.
In 2020, the first clinical data from 10 healthy obese humans showed that MSPs can reduce blood glucose levels and blood cholesterol levels, both known risk factors for metabolic and cardiovascular complications.
Even better, the treatment did not cause abdominal discomfort or changes in bowel habits, which cannot be said for current weight gain drugs like Orlistat.
The current research elaborates on these promising findings by comparing a series of 13 porous silica samples of different widths, sorption potentials, shapes, sizes, and surface chemistries.
These samples were each introduced into a human gastrointestinal model simulating a fed state after a high-carbohydrate, high-fat meal. The model allowed for half an hour of gastric digestion and one hour of intestinal digestion and absorption.
Fat digestion was monitored by assessing the fatty acids of what was absorbed, while starch digestion was monitored by measuring the concentration of absorbed sugars.
The authors say the ideal silica samples were silica microparticles with pore widths between 6 and 10 nanometers. These sizes seemed to inhibit the best examined enzymes.
The pores don’t just seem to trap enzymes, either. It’s more complicated than that, researchers think.
Some pores that were optimally sized to inhibit starch digestion, for example, were too large to optimally trap enzymes associated with fat digestion.
Porous sand particles also appeared to absorb digested and undigested nutrients from the gastrointestinal tract before they could pass into the systemic bloodstream.
This could be another way in which the particles counteract the calorie input.
Those particles with larger surface areas but smaller pores that cannot affect digestive enzymes absorbed the most organic matter in the models.
Further research in animal models will be needed to replicate these results. Perhaps after that, the proposed mechanism can be validated in human clinical trials.
The study was published in Pharmaceutics.