Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
You recently gave a talk as part of the 21st Century Medicine Lecture Series entitled ‘Why Diets (usually) fail’. How frequently do diets fail and what do you think are the main reasons for this?
The statistic that you often hear is that 95% of diets fail, but in actual fact, emerging research is now showing that it’s around 70% of diets that fail. That means that around 30% of people who are losing weight are actually keeping it off. So we’re doing better now than we were doing in the past, but there’s still work to be done.
The problem is not losing weight, people can always lose weight. But the challenge comes in keeping the weight off after the diet. There are many reasons for that.
One of the reasons is physiology, the way our bodies work. We know that when people lose weight, their body mounts what I call a famine reaction which increases appetite, which can make people feel lethargic, and which also reduces metabolic weight. Those factors together contribute to people tending to gain the weight back quickly.
This, combined with this obesity environment where there’s food everywhere, is an explosive combination.
Please can you outline the ‘famine reaction’ and what is thought to cause this?
The famine reaction occurs because our body defends our weight. When you start losing too much weight or too quickly, the body brings on this defence mechanism to protect you from wasting away. These are the mechanisms of increased appetite, lethargy, and also reduced metabolic rate.
The trouble is that the famine reaction seems to occur even though people may be carrying 20, 30, or 50 kilos in excess of a healthy weight. That’s something that we don’t yet understand. Why is it that people are triggering a famine reaction even though they may be overweight or obese?
We know for a fact that larger people, who are overweight or obese, do mount a famine reaction, but we don’t know why their body would be trying to defend a higher body weight. It’s as if the body has come to say, “We’ve been this weight for a long time, this must be the new set point.” Then the body tries to defend that higher set point.
How much research has been carried out on the ‘famine reaction’?
There’s absolutely no debating that there is a famine reaction. There’s been a lot of research describing the famine reaction. In the literature you’ll read all the different aspects of this famine reaction. It’s been studied in monkeys, mice, rats and also humans – both lean and obese.
There was a paper recently that showed how the parts of the brain that assess the desirability of foods get differentially activated when people are losing weight. When you’re in energy deficiency, the attractiveness of food is increased.
There’s also a whole range of research showing that metabolic rate drops when you’re too far below the set point. It’s irrefutable. It’s well known that with dieting there’s an increase in hunger. There’s also evidence on physical activity dropping with energy restriction. It’s seen in some studies but not in all studies.
On the other hand there’s also research looking at, for example, the hormones that control hunger, hormones like ghrelin or peptide YY from the gastrointestinal tract. These are known to be altered with energy restrictions in a way that would tend to promote hunger.
Basically from this large body of research, it gives a very solid story of the body just not wanting to lose excess fat, which is a real problem because that’s what a large majority of adults in the world today need to do.
Is the ‘famine reaction’ thought to be universal or does it occur more intensely in some individuals?
It does happen in some and not in others. For example, there are a lot of people who are overweight, and some people who are obese, who will join a weight loss program or go and see their doctor or a dietitian and then bang, bang, bang, they’ll lose half a kilo, a kilo, maybe 2 kilos a week until they reach their ideal weight and then everything’s fine (as long as they maintain healthy new habits for life).
With these people it would seem that their set point was always down there at a lean level and their body was just re-establishing equilibrium and getting back to the set point, which is at a lean level for those people. It would seem that this would be the case for a lot of people who are overweight or mildly obese. It’s much easier to lose weight if you’re in that situation. Your set point hasn’t been pushed up and you can lose weight without too much resistance from your body.
The famine reaction will kick in eventually for everyone and it may kick in it at some stage along the journey, but for people who are overweight or mildly obese, the famine reaction doesn’t seem to be as much of a problem as it is for people who are very obese.
On the other hand, for some people in the very obese BMI range, the famine reaction can seem to kick in even after losing just 5 or 10 kilos, even when they’re still very, very heavy and very much over their ideal weight.
There are likely to be genetic differences that are causing that, and there’s likely also to be epigenetic influences that are contributing to that. Not just the genes that we’re born with, but a combination of our genes as well as the diet that we’re exposed to throughout the duration of our life. Those genetic and epigenetic factors together, combined with the environment that they live in, seem to work together to mean that some people have this very tenacious famine reaction that seems to kick in sometimes even if they just think about losing weight! I have personally been in that situation before. When I was younger and starting my scientific research career I was 28 kilos heavier than my healthiest weight. Even though I weighed 93 kilos and felt enormous, and even though I followed healthy, sensible, nutritionally balanced weight loss plans, I would still feel the famine reaction and that nagging hunger kicking in after losing just a few kilos. I got to a stage where I knew diets would eventually leave me feeling ravenously hungry, so I’d binge on very large quantities of food before starting every new diet. It was a vicious and depressing cycle.
Is it thought possible to reduce the intensity of the ‘famine reaction’?
We’re doing research into exactly that at the moment; the whole aim of my research has been to reduce that famine reaction. One way of doing that is with pharmacotherapy.
We’ve been looking at various genes, for example if we knock out various genes that we think are involved in the famine reaction, can we get a better weight loss result?
Obviously this is very early research. There’s a lot of research in the world going on looking into pharmacotherapy for reducing the famine reaction but it’s a very complex area of research because the famine reaction is controlled by the brain, largely by the hypothalamus of the brain. The hypothalamus also controls a lot of other essential components of life such as blood pressure, heart rate, sexual function, temperature regulation. This means that any pharmaceutical agent that affects the famine reaction is highly likely to have unwanted side effects on other functions that are also controlled by the hypothalamus. It is getting harder and harder to get new weight loss drugs approved by regulatory bodies such as the FDA.
Pharmacotherapy to reduce the famine reaction – I do believe will get there but it might not be for another 20 years or so before we get really effective solutions. And of course, pharmacotherapy for obesity will only be effective when combined with lifestyle modifications of improved diet and regular physical activity.
The slowness of pharmacotherapy research for the famine reaction is what prompted me to look more at food as a means of reducing the famine reaction. We’re investigating at the moment ketogenic, very fast, very low-calorie, diets. It seems paradoxical that a fast weight loss diet might reduce that famine reaction, but it’s been shown in some research internationally, and also some great research from the University of Melbourne, that when people are on these very low calorie diets, liquid diets, with severe energy restriction, they produce ketone bodies, in a salvation response, that gives the brain something to eat when there is not enough carbohydrate in the diet.
When there’s not enough carbohydrate in the body, it produces ketones and it seems that those ketones are getting into the brain and reducing appetite.
Increased appetite is one of the major hallmarks of the famine reaction. People can be on very low calorie diets, losing 1.5-2 kilos a week for weeks on end and they don’t actually feel hungry, which is phenomenal because usually with a reducing diet after some weeks, people will start to feel very hungry on their diet.
We are investigating these ketogenic very low calorie diets further because we think, if they’re cutting hunger while people are on this weight loss diet, maybe those ketogenic diets are also reducing other aspects of the famine reaction, such as that drop in metabolic rate, or that propensity to move less. That’s what we’ll be looking at in the clinical trial that we’re running at the moment at the University of Sydney.
Do you have any concerns over the safety of these severe very low calorie liquid diets? Could the build-up of ketone bodies be toxic?
The important thing to note with these very low calorie diets is that they do need to be done under medical supervision. I always shudder when I see people going to the pharmacy to buy some kind of liquid diet or some detox diet, they just buy something off the shelf and they do it themselves. This is a really, really dangerous thing to do because unless you’ve got perfect kidney and liver function, you can get into a lot of trouble with very low-calorie diets.
Also people who have a propensity for eating disorders, such as binging, or eating disorders that involve binge eating, that can be exacerbated by these kinds of severe diets.
On the other hand, if a very low calorie diet is done using a product that’s nutritionally balanced, and there aren’t that many products that are nutritionally balanced, but if it’s done using a product that’s nutritionally balanced and which meets national nutrition guidelines, and if it’s done under medical supervision when there are no contraindications, then there’s no reason why they aren’t safe.
With the ketone levels, people often think of ketones as being dangerous, they think of diabetic ketoacidosis, but with diabetic ketoacidosis circulating ketone levels are going up to around 20 mM, but with very low calorie diets, ketone levels are only going up to about 0.8 mM or 1 mM. So it’s a very low level of ketone production and that’s been shown in the research so far to be safe.
What do you think the future holds for diets and weight loss strategies?
I think the future of dieting and weight loss strategies is definitely intermittent because we know that with this famine reaction, the longer you persist with energy restriction, the longer that famine reaction persists.
People and the weight loss industry just think that if you stick with a diet for long enough then the famine reaction will just go away. You can see that this is how the weight loss industry thinks because the advice that they give reflects that thinking.
For example, when people are hungry when they’re on a diet, they’re given this list of free foods that they can select from and they can eat anything from that list of free foods, as much as they want. The list of free foods includes things such as diet jelly and zero calorie soda and non-starchy vegetables and all the stuff that you wouldn’t really want to eat when you’re feeling really hungry and having a famine reaction.
They encourage you to drink more water and if your weight loss slow down or plateaus, which is a sign of the famine reaction at work, they encourage you to just keep going and to exercise more to try and rev up your metabolic weight.
It’s really funny because all of these strategies have been shown in research to not make the famine reaction go away. If anything they actually make the famine reaction worse because you’re persisting with energy restriction at a time when your body is fighting against the energy restriction, so your body just fights back even harder and usually the body wins because the famine reaction has been evolving for hundreds of thousands of years and it’s pretty clever – much more clever than the diet industry!
I think in the future, successful weight loss strategies will involve an intermittent approach and that’s where you’re not on the diet all the time and you’re not trying to lose weight all the time. There is emerging research, it’s a very new field, that is starting to show that if you take a break from dieting, then your metabolic weight can come back up to normal again. This has been shown in some but not all studies.
In the studies that show this phenomenon of recovery of metabolic rate, most studies show the complete recovery of metabolic rate after taking a break from energy restriction. There are other studies that show at least partial recovery of metabolic weight when you take a break from dieting. That’s another strategy that we’re incorporating into our research to see if we can get a better weight loss result, by encouraging people to take a break from dieting. I think intermittent dieting is the way of the future.
5:2 diets seem to be very popular at the moment. What are your thoughts on those?
I think they’re a very good start, but I think they could be better by adjusting the severity of the energy restriction and the timing of energy restriction and breaks.
Some studies have shown that aspects of the famine reaction are reversible. It was shown that the effect of the famine reaction on metabolic rate was reversed after 10-14 days.
I think 5 days may not be enough to deactivate the famine reaction. Probably a higher protein intake during energy restriction and longer metabolic rest periods could be advantageous, and that’s something we’re investigating in the research that we’re doing at the moment.
Where can readers find more information?
About Associate Professor Amanda Salis
With a BSc (Hons) from the University of Western Australia and a PhD from the University of Geneva, Switzerland, Associate Professor Amanda Salis (nee Sainsbury) leads a research team at the University of Sydney’s Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders that aims to help people to attain and maintain an optimum body weight and composition. Adept in translating novel research findings into human benefits, Amanda's research into hypothalamic control of energy homeostasis spans studies with conditional transgenic mice to randomized controlled clinical trials in humans. Many of Amanda's first or senior-author publications are in highly esteemed journals such as Proceedings of the National Academy of Sciences of the USA, The Journal of Clinical Investigation, Genes & Development, Diabetes, or Cell Metabolism, and she has written popular books on weight management for the general public. Amanda’s research is funded by highly competitive project grants from the National Health and Medical Research Council (NHMRC) of Australia, and her full-time research position is funded by an NHMRC Senior Research Fellowship. Photo credit: mlai.org.