Food additive that could reduce appetite

NHS. UK: Appetite suppressing propionate additive could be added to food to reduce appetite.
This reports on a study that showed that short-chain fatty acids (SCFAs) are released from gut bacteria as they break down dietary fibre. These SCFAs then stimulate the release of hormones that signal to the brain that we are full.

The problem is that many people don’t eat a high-fibre diet, despite the numerous benefits. Therefore, finding new ways to increase SCFAs in people’s diets would be useful.
This study looked at an SCFA called propionate. Eaten by itself, propionate is said to taste like vinegar, and is broken down by the small bowel.
In this study, researchers managed to bind propionate to a polymer, helping to mask the taste and deliver it to the large bowel intact.
60 healthy overweight adults were given either this chemical or a control daily for 24 weeks. The chemical reduced further weight gain compared to the control, and also reduced the proportion of body fat around the tummy.
This is promising proof-of-concept research. However, more research is needed to see if this supplement is effective and safe enough to become more widely available.

Where did the story come from?

The study was carried out by researchers from Imperial College London, University of Glasgow, and other research institutions in the UK and Australia, and was funded by the UK Biotechnology and Biological Sciences Research Council.
The study was published in the peer-reviewed medical journal Gut on an open-access basis, so can be read for free or downloaded as a PDF.
The UK’s media reported the study accurately, though it is a little too early to suggest that this discovery could combat the obesity crisis.

What kind of research was this?

This was a preliminary laboratory study, followed by a randomised controlled trial (RCT).
The study aimed to investigate whether giving a particular chemical to humans can satisfy appetite and reduce weight gain.
The researchers explained how the normal bacteria in the large bowel help to break down fibre in the food we eat, and in so doing produce SCFAs. These SCFAs stimulate the release of certain gut hormones, called peptide YY (PYY) and glucagon-like peptide-1 (GLP-1). These hormones signal to the appetite centres in the brain that we are full. This is why high-fibre foods – such as wholemeal bread and root vegetables such as carrots – make us feel much fuller than processed foods such as burgers.
Previous studies have found that giving these hormones to humans and animals enhances feelings of fullness and reduces food intake.
Research has shown that SCFAs stimulate the release of these hormones by stimulating a particular bowel receptor called FFAR2. Of all the SCFAs produced by the breakdown of dietary fibre, one called propionate has been shown to have the highest affinity for this receptor.
Therefore, researchers wanted to see whether giving propionate could help to regulate the appetite. Giving SCFAs by mouth is unpalatable. They are said to have an extremely bitter taste, similar to drinking very strong vinegar.
SCFAs are rapidly absorbed by the small bowel before they even get to the large bowel. Therefore, the researchers developed a novel delivery system that would release small quantities of propionate into the first part of the large bowel. The researchers expected this to stimulate the release of the PYY and GLP-1 hormones, which suppress appetite.

What did the research involve?

The researchers first carried out laboratory tests to confirm that propionate did indeed cause a release of PYY and GLP-1 hormones from large bowel cells.
They then produced a “carrier molecule”, which could deliver propionate to the large bowel intact. This involved propionate being chemically bound to a natural dietary fibre called inulin.
Their first human test involved looking at the effect of single doses of inulin-propionate upon energy intake and the release of PYY and GLP-1 hormones in 20 volunteers. They then examined the effect on stomach emptying in another 14 volunteers.
The researchers then went on to conduct an RCT to investigate whether giving inulin-propionate over 24 weeks to overweight adults would decrease weight gain. They included 60 people who were aged between 40 and 65, with a BMI of 25 to 40, and who didn’t have any significant physical or mental health illness, including diabetes. These people were randomly assigned to supplementation with either inulin-propionate or inulin-control.
The trial was double blinded, meaning participants and researchers didn’t know which had been given.
These supplements were supplied in 10g ready-to-use sachets that, once a day, could be mixed into the content of their normal diet. Participants were advised to maintain their normal diet and activity patterns.
At the start of the study and after 24 weeks, participants completed self-reported diet and physical activity records, in addition to having their weight and other body measurements taken. These measures included having blood samples taken to measure PYY and GLP-1 concentration. The main outcome they looked at was change in body weight and food intake.

What were the basic results?

In the trial, 49 of the 60 participants (82%) who completed the 24-week study were analysed. There was no difference between the two groups in compliance or completion, and ratings of nausea were also no different.
Flatulence was the only other adverse effect reported, which was experienced more than half of the time in the control group, compared to a quarter of the time in the propionate group.
Weight gain was significantly less in the intervention group: 1 out of 25 participants in the inulin-propionate group (4%) gained 3% or more of their baseline body weight, compared with 6 out of 24 in the control group (25%). None of the participants in the inulin-propionate group had substantial weight gain (defined as 5% or more gain) compared with 4 out of 24 (17%) of the control group. There was a trend towards greater weight loss in the inulin-propionate group, but this was not significant compared to the control group. The intervention group also had a significantly lower proportion of their body fat tissue distributed in the abdomen compared to the control group.
When looking at food intake, there was no significant difference between the groups in terms of food intake at the end of the trial. There was a trend towards reduced food intake in the inulin-propionate group, but this was not significant. There was no difference in blood glucose control between the two groups. Total blood cholesterol and HDL (“good”) cholesterol were found to reduce in both groups, though LDL (“bad”) cholesterol was only reduced in the intervention group.

How did the researchers interpret the results?

The researchers say that their data “demonstrate for the first time that increasing [large bowel] propionate prevents weight gain in overweight adult humans”.

Conclusion

This interesting study has developed from the understanding that SCFAs are released from gut bacteria as they break down dietary fibre. These SCFAs then stimulate the release of hormones that signal to the appetite centres in the brain that we are full.
Of the SCFAs, propionate demonstrated the greatest affinity for receptors in the bowel, so therefore seemed the best candidate for study. The researchers then managed to develop a novel system that would deliver propionate intact to the large bowel, without the molecule first broken down in the small bowel.
In their first 24-week trial in 60 overweight adults, they found that it reduced further weight gain compared to the control group, which was the main outcome they set out to investigate. The trial benefits from being fairly long in duration and that it was double blind, which should remove the risk of biased reporting of outcomes from either participants or investigators.
However, there are various points to consider:

• The trial was quite small, including only 60 people; just 49 completed it. Participants were middle-aged, overweight adults with no significant health problems. Therefore, the results may not be applicable to other groups.
• We don’t know how this supplement could be taken practically outside of this trial's context – for example, whether this would be taken in the long term or just for short periods. If taken continuously in the longer term, we don’t know whether it would continue to prevent weight gain, or lead to significant weight loss.
• This trial studied effects alongside the continuation of previous diet and activity patterns. We don’t know how the effects may differ if other lifestyle aspects were also altered.
• The way this drug works needs to be studied further. For example, despite the treatment reducing weight gain, there was no difference in reported food intake between the treatment and control groups. Given that the proposed method of action of this treatment was to tell our brains we are full and so suppress appetite, this doesn’t seem to correlate. 
• The trial only briefly reported on gastrointestinal adverse effects, though increased flatulence was frequently reported. If this supplement were to be used more widely, safety needs to be studied further. This includes looking at effects on body biochemistry and other aspects of health. Possible interactions with other medical drugs would also need to be considered. 

Overall, this is promising proof-of-concept research into the use of a novel chemical to try to prevent weight gain. However, further study is needed before this supplement could ever become more widely available.
For the time being, if you want to eat foods that make you feel fuller without adding lots of calories to your diet, a high-fibre diet – such as wholemeal bread, bran, cereals, nuts and seeds, as well as fruit, such as bananas and apples – is recommended.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.