SATIETY

Yes, it’s that time of year when our minds (and expanded tummies) inevitably think about that dreaded 4-letter word diet. But do we still need to restrict food? Isn’t there an easier way? I know our readers have heard about the new weight loss drugs such as Ozempic and Wegovy that seemingly work like magic to help us curb our appetite (1). Without a great deal of will power, exercise or conscious effort, people find themselves losing significant weight gradually. Have you ever wondered how they do that?

It all started with a lizard called a Gila monster whose venom contains a hormone that stimulates insulin production and is similar in structure to the human hormone GLP-1, which remains active in the body for hours rather than minutes. An early drug form was called liraglutide and marketed to treat type 2 diabetes. Soon after, a second version called semaglutide that lasted longer was developed. It is marketed by the pharmaceutical company NovoNordisk under the name Wegovy for weight loss and Ozempic for diabetes (2). Thousands of people are now taking these drugs worldwide.

GLP-1 or glucagon-like peptide-1 is produced naturally by the body, specifically in the lower part of the small intestine in cells called L-cells. It’s released into the blood where it circulates to receptors in the pancreas (where it stimulates insulin secretion), and GLP-1 receptors in the brain’s appetite centre. Once locked into place, we have a pleasant feeling of being satisfied with what we have eaten. That feeling is called satiety. Depending on our biology, we might feel it for a few minutes or for hours. Not only that, it also makes us more sensitive to the effects of insulin which means we don’t need a lot of insulin to drive glucose from the blood into places where it belongs (e.g. into glycogen in the liver or muscle cells).

When NovoNordisk developed Ozempic (2), it had in mind people with type 2 diabetes who needed to overcome their insulin resistance to bring blood glucose levels down. They were somewhat surprised when trials showed that people lost up to 20% of their body weight within a few months. Indeed, it was close to miraculous. Side-effects were relatively few, perhaps some nausea to start, and sometimes vomiting, diarrhoea, or constipation, although for some individuals there were serious adverse effects such as pancreatitis. It wasn’t for everyone, but it was certainly working for many.

Eventually, the company developed better versions of the molecule that had fewer side effects and lasted longer. It could be injected just once a week. Soon trials showed that the GLP-1 analogues were helpful not just for improving blood glucose management, but for reducing the risks of heart disease, stroke, kidney failure and other complications that often come with diabetes and that are also associated with obesity (3). Surprisingly, it also seemed to reduce addictions to alcohol, illegal drugs, and even gambling (4). The reward centre in the brain appeared to be much more satisfied.

You’ll be pleased to hear that some foods can produce the same feelings of pleasant satiety as these drugs because they stimulate the secretion of naturally occurring GLP-1 from the L-cells in the small intestine. They don’t have the same half-life (in other words, the effect is temporary, rather than all week), but it’s helpful in the long run to curb appetites in the right direction. We wondered if there were differences among individual foods of different composition.

Around 30 years ago, the team at University of Sydney (Susanna Holt and colleagues) developed a satiety index in order to rank foods according to a nominal scale from 0 to 100 (5). We made white bread the reference food (= 100) and gave all foods in 1000 kJ portions (about 250 calories). To measure the rise and fall in satiety, we asked our participants to put a mark on a rating scale before they ate, and then at 15-minute intervals for 2 hours. We calculated the ‘area under the curve’ and compared it with the area for white bread. For each food, we tested at least 10 to 12 healthy participants. The final number was an average that allowed us to rank foods with respect to each other. We showed it was reproducible from day-to-day and in different groups of people.

The first surprise was that white bread wasn’t particularly satiating. There were many foods that had a satiety index more than 100, including porridge, popcorn, rice and even jellybeans. The most satiating was potatoes (SI = 323) and the least satiating was a croissant (SI = 47). In fact, 1000 kJ in the form of croissants was only half a croissant, but it amounted to 3 small-medium potatoes (in terms of kilojoules).

We investigated whether it was possible to predict the satiety index on the basis of the weight of a serving or the amount of protein, fat or carbohydrate in a 1000 kJ portion. Most of the fruits (where energy comes in the form of sugars) were more satiating than bread. The strongest determinant was weight of a serve, followed by water, fibre and fat content. The higher the water content, the more satiating the food (potatoes are high in water) and the higher the fat, the lower the satiety (think croissants and chocolate). Indeed, foods that we find very palatable were among the least satiating (think cakes, cookies, donuts, Mars Bars).

In further studies, we found an inverse correlation between the GI of 5 breakfast cereals and their satiety index. All-Bran with a low GI was much more satiating than Rice Bubbles (high GI) and this was corroborated by the rise in a satiety hormone called CCK. However, this relationship isn’t perfect. Most potatoes have high GI values, yet the earlier study found them very satiating. However, if we had been able to test a low GI potato such as Carisma (not available at the time), chances are it would have been more satiating.

I think we still have a lot to learn about satiety. The new weight loss drugs tell us that it’s the brain that determines how satisfied we feel after eating and how long that feeling lasts. In other words, it’s our biology and probably dictated by genes. People who weigh more have a higher appetite naturally, just like a growing child. If we are feeling stressed, tired, or sleep-deprived, cortisol levels are higher, and we will unconsciously eat more than we otherwise would (5). It doesn’t take many extra calories to gain weight. I often recall Kevin Hall’s paper that modelled the obesity epidemic (6). It takes only 30 kJ per day over and above weight maintenance to gain 0.5-1 kg a year (5-10 kg every decade). That’s only one bite of an apple.

So, the food for thought this month is to give yourself a break when you’ve feeling hungry and want more. You’ve not weak or gluttonous, it’s just your tired old brain. Nonetheless, there are many reasons to choose a healthy diet based on a mixture of low GI carbohydrate foods (think fruit, dairy, pasta, grainy breads, beans), unsaturated fats (olive oil, canola oil) and sustainable sources of protein (fish, eggs, poultry and beans again). And remember, a party is a party, and a celebration is a special occasion. Rules don’t apply! An extra walk or two after will do the trick.

Read more:

1. MAYO CLINIC. Prescription weight-loss drugs: Study the pros and cons of medicines to treat obesity. October, 2022.
2. NovoMedlink. Wegovy. Novo Nordisk, 2024
3. Lincoff and colleagues. SELECT Trial Investigators. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023
4. Wang, and colleagues. Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. Nat Commun, 2024
5. Holt and colleagues. A satiety index of common foods. Eur J Clin Nutr. 1995
6. Hall and colleagues. Quantification of the effect of energy imbalance on bodyweight. Lancet. 2011

Emeritus professor Jennie Brand-Miller held a Personal Chair in Human Nutrition in the Charles Perkins Centre and the School of Life and Environmental Sciences, at the University of Sydney until she retired in December 2022. She is recognised around the world for her work on carbohydrates and the glycemic index (or GI) of foods, with over 300 scientific publications. Her books about the glycemic index have been bestsellers and made the GI a household word.