Extreme diets: Science vs the hype

Amanda Salis wants to investigate whether extreme diets work and the longer-term impact that rapid weight loss has on our bodies and health.

By Andrew Stevenson

Image of Amanda Salis

Amanda Salis

There are almost as many claims, contributions and comments on food, diets and obesity as there are opportunities in the modern world to consume large quantities of energy-dense foods. Rare is the person who can seamlessly move from one sphere to the next, carrying with her the calm voice of reason and authority – backed both by scientific rigour and personal experience.

Associate Professor Amanda Salis has been the eye on the end of the microscope, the mind leading large-scale research projects, the advocate for sensible eating practices in mainstream media and the confused girl trying to make sense of competing claims about food and nutrition.

This uncertainty set her on a path to where she is today – a National Health and Medical Research Council Senior Research Fellow at the University of Sydney’s Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders (which will be moving into the newly opened Charles Perkins Centre later this year).

“I was very concerned about my own weight (as a teenager) and I would read things in diet books or the media and get so confused by all the rubbish which is out there.”

Eventually, the young Perth girl’s inquiries led her to a book by Dr Wolfe Segal, a senior lecturer in Biochemistry at the University of Western Australia. “He had published a little book which was a collection of his newspaper articles. He was selling it so my Mum called him up and asked where she could buy a copy, and he invited us to his house to pick one up,” she recalls.

That meeting changed her life. “He was approaching nutrition with facts and research, so he could speak with real authority,” she explains. “Meeting him was the whole inspiration for my career. I wish I had told him [how much it meant]. You should never take those conversations that you have with young people for granted.”

Salis’s career began with a Bachelor of Science, majoring in Physiology and Biochemistry at UWA and extended to include a PhD in Medical Sciences at the University of Geneva. She then returned to Australia to head up a team at the Garvan Institute of Medical Research.

Having struggled with her own weight issues as a young woman, Salis wanted “to find out what it was that was causing that hunger” and started researching what she calls the Famine Reaction, which is triggered by chemical changes in the brain when there isn’t enough food intake to sustain your body weight.

Not only does it trigger hunger, but it winds-down movement and energy levels and, even if you “white-knuckle” it to stick to the diet and keep exercising, weight loss will slow down and stop because the Famine Reaction also drops the metabolic rate.

“It’s an evolutionary response: your body is telling you not to waste energy chopping vegetables and chewing them, just go straight to the chocolate aisle.”

Using rats and mice, Salis spent years looking for the magic bullet to switch it off. “We would identify the genes we thought were involved in mediating the Famine Reaction and knock them out in mice. We used state-of-the-art genetic techniques to do this but the famine reaction is much cleverer and undoubtedly switched on different genes because the resulting mouse lines ended up fatter than if we hadn’t deleted the original gene.”

Image of a waist and tape measure

She decided to change direction, doubting we will be able to overcome the Famine Reaction through genetic or pharmacological interventions in her working life. That brought her to the University of Sydney, where her focus has shifted to translating what she already knows about the Famine Reaction and how to tame it into real-world clinical practice for more effective weight loss.

New research has given Salis ideas for alternative, dietary approaches to reducing the Famine Reaction. One such approach that Salis is investigating involves severely restricted diets called very low calorie diets (VLCDs). She has been awarded an NHMRC grant to set up the TEMPO Diet trial, recruiting obese women living in Sydney (with a Body Mass Index of 30-40 kg/m2) to study the longer-term consequences of VLCDs.

Specifically, she aims to assess whether the rapid weight loss brought about by VLCDs affects metabolic health, body fat content and distribution, muscle mass and strength, and bone density in post-menopausal women (see accompanying story).
Although VLCDs work – people can lose up to around 20-24 kg in three months compared to about 5-10 kg on conventional diets – Salis was, initially, not impressed. “I was a real advocate of eating enough, not going hungry, and not trying constantly to lose weight too fast,” she explains.

“I was disturbed when I saw a lot of health professionals such as endocrinologists and GPs using these very low calorie diets, which consist of liquid meal replacements, thinking ‘that just can’t be good, it must exacerbate the Famine Reaction’.

She set out to prove them wrong, with a research study designed to show how bad these very low calorie diets are. “However, the more research I did, the less I found to give evidence to the idea they were bad and the more I realised they might actually be beneficial in terms of keeping the famine reaction under control,” she admits.

“There is some funny stuff happening. People use VLCDs because they don’t feel hungry on these diets. After the first three or four days their body is breaking down so much fat, converting it into ketones to provide the fuel the brain needs, and those ketones appear to have other, interesting effects.”

"The more research I did, the more I realised the diets might actually be beneficial in terms of keeping the Famine Reaction under control."

Ketones seem to keep appetite under control and, interestingly, research from the University of Melbourne shows that when a dieter switches from a VLCD to a weight maintenance diet and stops producing ketones they feel hungry within a week. One of the aims of Salis’s current research is to determine whether VLCDs also keep other aspects of the Famine Reaction under control, such as the reductions in metabolic rate or physical activity levels that have been shown to thwart the efforts of even the most determined of dieters.

Salis is the first to acknowledge this is an extreme diet that needs medical supervision because it can cause significant health problems in people with kidney or liver issues. But it works – and so quickly and with such freedom from hunger – that it keeps people highly motivated. The challenge now – and another focus of her current research (see separate story) – is to thoroughly review the impact of very low calorie diets on fat mass and distribution, muscle function and bone.

The professor also has serious personal credibility in this area, having lost nearly 30kg herself – and kept it off. “I did have a lot of weight troubles as a teenager. I was a fat kid. In those days fat kids weren’t that fat, but I was a fat kid and when I was going through university, I was very fat. I was 93 kg at my heaviest and that’s when I decided I wanted to work in weight management,” she says, describing her work as “a 100 per cent personal crusade”.

That crusade took her into the laboratory looking to find – and knock out – what she, and many other dieters, had found to be her worst enemy. “I could do a diet but after losing a bit of weight I would hit this invisible wall of resistance, get really hungry and stop losing weight even if I was sticking to the diet and exercise regime,” Salis explains.

“Nobody seemed to understand that invisible wall and that you can feel ravenously hungry even though you are obese. Nobody gave me, as a big person, the permission to feel hungry.”

Having moved from one side of the scales to the other, Salis is also aware of the toll that obesity takes on individuals, and is worried that the outcome may be irreversible. “People often think oh I am too big, too fat, I should do something about it. I’ll do it when I have more time to take care of myself, after I get my promotion, after I move house, after the kids leave home, when I retire, or whatever – as if they have a choice about when they can change their weight. But if you’re carrying excess weight it is actually an urgent situation. You should do something about it right away because you might not be able to do anything about it in the future,” she says.

“I know from my research with rats and mice and knowledge of the scientific literature that if you are exposed to a poor diet for long enough then there are changes in expression of the genes that cause the Famine Reaction, making them even stronger and more tenacious and making it almost impossible to lose weight. Nobody knows yet if that is permanent or if the same thing happens in humans, but we think it might be so.

“My Nanna always said don’t pull an ugly face because if the wind changes you will be stuck like that. I say ‘don’t eat an ugly diet because if your brain changes, you might be stuck with permanent obesity’. So don’t delay; the sooner you do something about any excess weight you may be carrying, the better.”


Our inner labrador

Amanda Salis admits to a degree of frustration that her work is so needed to combat the effects of a society that just encourages us to eat all the time. “We need moderate energy reduction across the whole community but people can’t do it on their own. When I go to conferences and I listen to symposia on health policy I want to scream and tear my hair out.

“Can’t we just get governments to put higher taxes on chips and chocolates and a subsidy on split peas? Oh no, that would be too complicated,” she throws up her hands.

“I think we are all labradors at heart and if there is food there, we will eat it. Unless you are constantly vigilant about what you eat – and constantly making the choice not to eat and not to have extra calories – then it just happens. You grow bigger and bigger.”

Ultimately, her advice is simple: “We should just eat normal, nutritious food, exercise and lobby the government so we don’t have rubbish in our faces 24/7. Eat normal food and listen to your body; eat when you are hungry and do something else when you are not.”


The TEMPO diet trial

The TEMPO Diet trial is recruiting obese women living in Sydney (with a Body Mass Index of 30-40 kg/m2) to study the longer-term consequences of very low calorie diets (VLCDs), to assess whether losing weight quickly affects metabolic health, body fat content and distribution, muscle mass and strength, and bone density in post-menopausal women.

“We will do a head-to-head comparison of fast versus slow weight loss,” says Amanda Salis, using a 12-month weight loss program with a further two years of follow-up.

While the participants focus on losing weight, Salis and her team will be addressing the ‘what happens then’ questions. “We are going to a huge effort to measure body composition, combining a series of techniques including magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DXA) scanning, tests with de-uterated water and a form of air displacement weighing to measure changes in fat, muscle and bone,” she says.

“If there are no bad effects on body composition from the very low calorie diet – and we will also be measuring psychology, eating habits, relationship with food and well-being – I will be fully converted and I will say ‘yes, use it’.”

She is also leading a sub-study of the PREVIEW Study Australia, the main study being led by another University of Sydney researcher, Professor Jennie Brand-Miller. This will explore similar themes but compare whether there are differences in the effects of weight loss on body composition between older and young people.

Do older people who lose weight lose more muscle strength and bone mass than young people – increasing the risk of frailty or osteoporosis – or not?

The study will also look at the effect of weight maintenance diets differing in protein content and glycaemic index to see if the impact of weight loss can be mitigated.

The PREVIEW Study Australia will ask participants (overweight men and women at risk of diabetes and aged 25-45 or 55 to 70 years of age) to follow an eight-week low calorie diet, followed by a weight maintenance diet for a total of 12 months, with ongoing review for a further two years.

To participate or learn more about these clinical weight loss trials, visit the website.