I have previously written that if slimming were a drug, it wouldn’t be allowed for sale given that after 5 years of treatment, less than 5% would be successful in their weight loss. This is worse than the cure rate for the worst cancer. To many in public health nutrition, this relapse tendency is utterly ignored as some arcane piece of physiology, which quite simply is inconvenient to their strategy and, anyway, not as important as is made out to be. Indeed “Look at all the people who have lost weight” they cry, while all the time ignoring the far greater numbers who weren’t so lucky. A new paper from the NIH National Institute for Diabetes and Digestive and Kidney diseases, led by Prof Kevin Hall who is doing stalwart work in this field, throws strong light on this issue of relapse and is well worth reflecting on.
When we organise experimental weight loss programmes, we use dietary advice on weight loss and comparable expert advice on physical activity. There can be no placebo. We can have a control group who receive little structured and certainly not personalised or customised advice, but until now, the experimental advantages of a placebo controlled diet is almost impossible to achieve, Until now that is. A drug, with the silly name Canagliflozin, which, as the lawyers say, hereinafter is known as the “drug treatment” has been used in this study. It is presently available for the management of type 2 diabetes and leads to a sizeable excretion of glucose each day. That means that the subjects pee out a lot of untapped calories and therefore this drug leads to some weight loss. The key question the researchers set out to address was that in a placebo controlled blind trial using this drug, how did subjects respond in terms of compensating energy intake to the weight loss anticipated from the drug.
As is seen from the attached figure, the drug did lead to weight loss but it reached a plateau. The daily drug-induced loss of untapped calories from urinary glucose remained for the 54 weeks but the initial weight loss was checked by a compensatory rise in energy intake. Normally energy intake is measured using dietary assessment methods but in this case the change in energy intake was related back to changes in bodyweight using a complex equation that had been previously shown to be valid against very robust biomarkers (doubly labeled stable isotope water along with multiple dual-energy X-ray absorptiometry scans). The authors estimated that the energy intake compensation was 100 kcal per day per kg of weight loss. Adaptations in terms of changes in energy expenditure were minimal.
In this study, half the subjects (153 Type 2 diabetics) received the drug and half the placebo and there was no advice on weight loss. So there was no psychological effect of the intervention on weight loss or on appetite. As weight was shed, appetite responded to a strong and lasting effect, which minimised the process of weight loss. As the authors point out, those who successfully diet and who achieve significant and prolonged weight loss, battle by ‘heroic and vigilant efforts’ against the powerful effect of this compensatory rise in appetite. Maybe there is a threshold of weight change below which the body choses to ignore in which case we can win limited success in mass weight loss programmes. But if as this study shows, weight loss is not minimal (>3kg average), then we will need to have a much better understanding of how to motivate people for that long term battle against compensatory weight loss. May I end this blog by once again citing the Sir David King FRS formerly Chief Scientific Adviser to HM Government, and Head of the Government Office for Science who in the UK Foresight Report on Obesity wrote: “What quickly becomes apparent to anyone who examines the body of evidence from several different disciplinary sources is that the answers are neither straightforward nor, as is popularly supposed, necessarily known. Although a great deal of research has been done into the problem, much of the evidence is not integrated”. What is the threshold of weight loss for energy intake compensation? What aspects of appetite adaptation are most affected by the most and least successful dieters? What are likely to be the most helpful strategies to those who want to lose weight and must battle this enhanced appetite phenomenon? There are no simple answers.