UCL researchers have discovered that urolithin B, a substance derived from pomegranate peel, slows the loss of muscle mass. The discovery could lead to a new treatment.
Muscle is the most abundant tissue in the human body, making up 45% of a healthy young male and 35 to 40% of a female. ‘These are muscles that allow us to move around, maintain a standing or sitting posture, even breathe’, says Prof. Marc Francaux, head of the UCL Exercise Physiology and Biochemistry Laboratory (1). ‘Muscles are the body’s biggest consumers of sugars and fats, especially during physical exercise. So they play an important role in metabolism, including glycaemia.’ Significant loss of muscle mass can alter these processes.
When muscles regenerate – or don’t!
Muscles are in a state of constant renewal. ‘A molecular system in muscle continuously synthesises and degrades proteins’, Prof. Francaux explains. ‘This system is like a construction company, with a demolition team (degradation) and a brick-making team (protein synthesis). As long as the system is balanced, all is well and muscle mass remains stable. But if an imbalance between synthesis and degradation occurs, muscles begin to “dissolve”.’
What alters muscular synthesis?
Certain events – cancer, prolonged immobilisation, etc. – increase the speed or volume of muscle degradation. Other factors, such as a low-protein diet or age, affect synthesis. ‘As the body ages it doesn’t respond as well to stimuli that activate muscle synthesis’ (2) Prof. Francaux says. ‘That’s why muscle loss is more frequent, worrying and harder to recover in older people. A senior with less muscle is less mobile and, in the end, less autonomous. Which is why it’s important to exercise throughout your life.’
Strategies for fighting muscle loss
Three strategies can stop, limit or even prevent muscle loss:
- Certain drugs, such as steroids, can stimulate muscle synthesis or prevent degradation. The frequent problem is that the severity of the side effects outweighs the benefits.
- Physical exercise activates muscle synthesis. But it has limits, particularly for hospitalised patients.
- Certain amino acids can boost muscle protein synthesis, such as leucine (whey, egg white) and some polyphenols (pecans, green tea).
It was while studying one of these polyphenols that UCL searchers made their unexpected discovery.
Urolithin B: a pleasant surprise
Ellagic acid is a polyphenol known for its anti-inflammatory and antioxydant qualities. It is found in several fruits and vegetables, and especially in pomegranate peel. ‘But our body doesn’t absorb ellagic acid as is’, Prof. Francaux says. ‘When it arrives in our intestine, certain bacteria of our microbiota transform ellagic acid into urolithin A, B, C or D, which our blood then absorbs.’
While studying the anti-inflammatory and antioxidant properties of urolithins A and B, UCL researchers happened to discover that the latter had a protective effect on muscles. ‘Muscle cells in culture that were in contact with urolithin B became larger than those that were not. We wanted to know why.’
In vitro and in vivo
First, they studied the substance in vitro and found urolithin B has a dual effect: it activates muscle protein synthesis and slows degradation.
Second, the researchers studied the effect of urolithin B in vivo, on mice. ‘It increased their muscle development’, Prof. Francaux says. ‘We also administered it to mice with a severed sciatic nerve resulting in leg paralysis, and the subsequent muscle loss occurred 20 to 30% less quickly and to a lesser extent.’
Any new treatments on the horizon?
The study was only just published (3) but it is promising. If urolithin B’s effects are confirmed by human trials – which are yet to take place – it could open the way to a new treatment for muscle loss, such as a highly concentrated pomegranate peel dietary supplement. That said, several aspects still have to be worked out. ‘First we have to make sure urolithin B is safe and determine any side effects, such as a stimulant effect. Then we have to address metabolism: does everyone have the necessary intestinal bacteria for metabolising ellagic acid into urolithin B? Finally, we have to determine the dose of ellagic acid that will produce genuine benefits for muscles.’
In short, as promising as it is, there’s still work to be done on urolithin B.
(1) The laboratory takes part in the Louvain4Nutrition platform.
(2) Stimuli that activate and increase muscle synthesis include nutrients, hormones and physical exercise.
(3) M. Francaux et al., ‘Urolithin B, a newly identified regulator of skeletal muscle mass’, Journal of Cachexia, Sarcopenia and Muscle, 2017.
A glance at Marc Francaux's bio
1984 Bachelor’s Degree in Physical Education, UCL
1988-93 Head of the Scientific Department of the Belgian Olympic and Interfederal Committee (COIB)
1990 PhD in Exercise Physiology, UCL
1993 UCL faculty member, currently Professor
2002-2005 Chair, Department of Physical Education, Physiotherapy and Rehabilitation
Since 2000 Member (currently Head), International Research Group for Exercise Biochemistry
Since 2000 Founding Member (currently Vice-President), Centre d’aide à la performance sportive (‘Athletic Performance Support Centre’) (CAPS)
Since 2006 Head, Exercise Physiology and Biochemistry Laboratory, UCL
Since 2014 Pro-Rector for Regional Affairs, UCL
Prof. Francaux’s initial research on urolithin B was funded mainly by the Walloon Region and the company Procell.