The FastDay Forum

[carorees]

I've just been reading this fascinating review paper that explains in detail how our bodies conspire to encourage weight gain once we have lost weight. Numerous mechanisms are at play including reduced energy expenditure, blunted hormonal responses to eating, increased appetite, increased tastiness of calorie dense foods and an inability to recognise how much food has been eaten. #weightregain

When researchers did a brain scan of people being shown pictures of food and non-food items, they found certain brain areas that were more active in responsive to food vs. non-food pictures following weight loss than in people who had not lost weight (including the reward systems and systems responsible for decision-making functions). Other studies showed that some of these same brain areas had similar patterns of neuronal activation in response to food in individuals who had been successful at sustaining weight loss and individuals who had been subjected to a prolonged fast. The reviewers consider that these results demonstrate that reduced weight is accompanied by changes in the emotional response to food and its rewarding properties, coupled with decreased “restraint”. The reviewers do not comment on the similarity between successful weight maintenance and fasting, sadly.

They go on to discuss activity in a brain area called the hypothalamus. The hypothalamus contains neurons that mediate both hunger and satiety (feeling full). Following weight loss, there is a decrease in hypothalamic activity and it is thought that this essentially takes the brakes off eating resulting in weight gain. Now, interestingly, the studies by Mark Mattson (who featured in Dr Mosley's Horizon programme) have shown that intermittent fasting increases activity in the hypothalamus link.

The reviewers then turn to leptin. Leptin is one of around 50 currently known molecules that are capable of influencing eating and/or energy expenditure. The authors say that the main function of leptin is to tell the brain that energy stores are below a critical level (for that individual). This “threshold” is determined by genetic, developmental and extant metabolic circumstance. A decline in leptin concentrations below this critical level makes the body try to correct the low energy reserve by increasing fat stores. Injecting leptin into people maintaining a 10% weight reduction reversed the reduced metabolic rate and the hunger feelings and improved the ability to judge how much food had been eaten.

So, can we speculate on whether intermittent fasting might be different from other diets with respect to being able to keep the weight off? I'll try, but of course, the story is a lot more complicated than I've laid out above so I could well be wrong! I think that, yes, it is possible that intermittent fasting may be different. First, we have the changes in the hypothalamus seen by Mark Mattson, second, we know that the day after fasting, instead of overeating as the theory above suggests, mostly we don't overeat, and third, we know that while leptin levels decrease during fasting, they rise again on feeding. I think we have some reason to hope, but of course time will tell...

I suspect that there may well be a psychological effects as well as the physiological/hormonal ones.

In most diets you are forbidden to eat whole categories of food and so they become inherently attractive. With IF any particular foodstuff is no big deal - if you really want it then you can have it tomorrow! So there isn't really the same falling off the wagon, or coming to the end and rushing out to eat chocolate cake (substitute your "naughty" food of choice) that can easily happen on a more traditional diet.

All very interesting, and not much in depth study done so far. Am looking forward to see how I (and everyone else ) does. The progress tracker is fascinating...

It's great to have a place like this to keep up to date - thanks!

I've just been reading this fascinating review paper that explains in detail how our bodies conspire to encourage weight gain once we have lost weight. Numerous mechanisms are at play including reduced energy expenditure, blunted hormonal responses to eating, increased appetite, increased tastiness of calorie dense foods and an inability to recognise how much food has been eaten.

Very interesting, thank you. I'm hoping that by switching over to 5:2 now, after 6 months of weight loss through conventional calorie restriction, I can avoid the 'regain' pitfall and keep on losing through to my target weight. The other fasting-related health gains seem to be considerable but I am concerned that after all this time restricting my daily calories (and seeing that get gradually less effective for weight loss) my metabolism will think 'Yippee' on non-fasting days and try to build up fat again. I just can't bear to think of going back to what I've been for so many years. I suspect I'll have to be pretty careful in the first week or two.

[carorees]

I also found this study in which the researchers checked how the hunger and appetite hormones behaved after weight loss. They found that the levels of these appetite hormones that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss.

It's hardly surprising then that the weight creeps back on!

[carorees]

And here is another really interesting review that summarises the #setpoint and #weightregain situation nicely:

The most common diet is the restricted consumption of low-fat foods, which is sometimes, but not always, accompanied by regular exercise. ...these dramatic changes in environmental and behavioral pressures initially work in concert with the biological adaptations to induce weight loss. However, the homeostatic system immediately begins to adapt to prevent the individual from wasting away. At some point, a balance is achieved at a lower, steady state weight, and the individual hits the well-known “wall” or plateau in their weight loss efforts. To lose more weight, the environmental and behavioral strategies must be stepped up a notch. To maintain the reduced weight, these weight loss strategies must be maintained indefinitely, as the homeostatic system does not appear to “reset” at this lower weight, at least in DIO [obesity prone] rodents, even with long-term weight reduction. Unfortunately, most people view their weight loss program as a transient change in their lifestyle and dietary habits or have difficulty in sustaining the changes that they have made to lose the weight. If the strategies are not maintained, the biological adaptations become a driving force for weight regain.

Two critical points emerge from this... Initially, our biology, or this homeostatic system, is actually working for us in an attempt to minimize the impact of obesogenic environmental and behavioral pressures, although with better results in OR [obesity resistant] than in OP [obesity prone] individuals. Second, because of the upward retuning of the homeostatic system, at least for those prone to obesity, metabolic conditions after weight loss may not be the same as they were prior to gaining the weight in the first place. Instead of working in our favor to prevent weight gain, biology becomes one of the driving pressures that underlie weight regain.

The authors then go on to explain in detail how the different systems work to promote weight gain with discussion of leptin, energy expenditure etc.

They also introduce an interesting concept, metabolic inflexibility, that I believe is the cause of the initial discomfort people feel when starting with fasting:

Metabolic inflexibility refers to an organismal impairment in regulation, which manifests as the inability to appropriately shift fuel preference in the face of metabolic challenges, like fasting, exercise, a meal, or overfeeding. The inflexible state of metabolism results from a discordant attempt of numerous peripheral tissues to respond to changing fuel needs and nutrient availability, yielding little or no discernable response.

This supports my theory that the body is reluctant to turn to fat burning when we first start to fast but it does become more flexible and so the early unpleasant effects disappear. It would be interesting to find out whether there was any correlation between starting BMI and how easy the first fast was felt to be!

What is more interesting is that, once metabolic flexibility returns (by weight loss or perhaps just by fasting), when overfeeding occurs, the improved response to ingested energy results in a more efficient refilling of adipose stores. For those on a traditional diet approach, this means that once you stop the diet the fat stores are rapidly increased. However, the authors of this review go on to discuss the role of fatty acids circulating in the bloodstream (called FFAs). When we fast and go into fat burning, FFAs increase as the fat is released from adipose stores to be converted for fuel.

FFAs are sensed, just like glucose, in central and peripheral nutrient sensing systems. Dietary fat can impact hypothalamic FFA levels, and FFAs reduce subsequent food intake when infused into the gut, into the circulation, or directly into the brain. Unlike glucose and TGs, FFAs in postobese subjects decline postprandially and during weight regain. With every meal, every bout of overfeeding, and sustained periods of a positive energy balance, the suppressive effects of FFAs on the energy gap would be minimized. As such, FFAs represent one signal of nutrient status after energy-restricted weight loss that could sustain a message of nutrient deprivation during the dynamic metabolic state of weight regain.

To me, this may explain the appetite reduction we experience after fasting, and perhaps offers some hope that we will find it easier not to regain weight.

Then there is the role of the liver in controlling energy metabolism:

Studies in humans suggest that when hepatic regulation is intact, as it is after weight loss, chronic overfeeding of a low-fat, high-carbohydrate diet leads to the trafficking of glucose to fat depots rather than glycogen pools

The role of skeletal muscle:

Unlike lean subjects, energy-restricted weight loss in obese subjects fails to increase skeletal muscle oxidative capacity unless the energy-restricted diet is accompanied by regular exercise. Mitochondrial respiratory capacity declines, glycolytic capacity declines, and the expression of enzymes associated with β-oxidation and mitochondrial enzyme activities remain low and, if anything, decline. Collectively, these adaptations in muscle underlie the reduced energy requirements, the increased metabolic efficiency, and the enhanced muscle work efficiency observed with energy-restricted weight loss in postobese subjects. These adaptations also limit the body's capacity to dissipate excess fat when overfeeding occurs.

Interestingly, the HIIT protocol for exercise that Dr Mosley investigated in his earlier Horizon programme is believed to increase the oxidative capacity of skeletal muscle by improving mitochondrial respiratory capacity. So, it may be that the HIIT protocol could help protect against this tendency for skeletal muscle to contribute to weight regain.

Finally, the role of fat cells (adipocytes):

Reducing the size of adipocytes with energy-restricted weight loss primes them to take up and store excess energy when overfeeding occurs...The impact on nutrient clearance may be further exacerbated by the formation of new adipocytes. Our studies of weight regain in rats that are prone to obesity revealed the emergence of a population of very small (<20 μm) adipocytes during the early stages of weight regain. Their appearance was accompanied by an increase in total number of adipocytes in the depot. As weight gain proceeded, preferential hypertrophy of these small cells was observed, while the higher cell number persisted. By 10–14 days of relapse, the small cells become indistinguishable from the preexisting adipocytes in the fat pad. As the relapse to obesity continues, hypertrophy occurs more broadly across the entire depot, and the increase in cell number continues to persist. Most animals in this DIO model gain more weight than they originally lose before the rate of gain normalizes. Yet, after surpassing their previous weight, these relapsed animals still have smaller adipocytes on average and more adipocytes per fat pad than an obese rat that had never lost or regained the weight

I would be interested to know whether the process of autophagy induced by fasting affects the turnover of adipocytes.

The authors conclude:

It is the dieting and the deviation from the “steady-state” weight that awakens the body's defense system. The biological response is persistent, saturated with redundancies, and well focused on the objective of restoring the body's depleted energy reserves. Any weight loss strategy that fails to acknowledge and plan for this emerging metabolic influence is likely to have little success in facilitating long-term weight reduction.

Even so, the overarching message about our biology's response to weight loss should not be misconstrued into a conciliatory surrender to the inevitability of weight regain. The biological drive to regain lost weight can be countered with environmental, behavioral, and pharmaceutical interventions. Composition of the weight maintenance diet (high protein, low carbohydrate; type of dietary fat) has a significant impact on several aspects of this homeostatic response, as does the amount of physical activity and regular programmed exercise.

Sorry for this massively long post, but I thought it was very interesting and explains a lot about the biology of weight loss and regain.

That is extremely interesting, thank you. So, it's basically going to be constant vigilance for some time (after extended weight loss) in the hope that *eventually* our systems re-set themselves to some extent. At least it's helpful to know that there are recognised biological processes at work, rather than just oneself failing.

[carorees]

Yes, exactly! I think the constant 'failing' is particularly depressing so to know that there are good reasons behind what is going on, while not exactly a cause for joy, it does make one feel better about oneself.

Caroline, this is fascinating but I remain a bit puzzled. Leaving aside all the complexities of the types of foodstuffs and how our body processes them, surely there is a simple equation at work in all of us:

Calories in - Energy metabolised = Net energy retained => Net weight gained

Considering purely weight loss/gain (and not other health issues) this is achieved by altering our calorie intake and/or our metabolic rate. The rest is just about how to do it, isn't it?

Sorry if I am being thick, I would really like to understand!

[carorees]

Hi Dominic

I think the issue is not with the basic equation, which is of course correct, but that for most people who have lost weight the biological drive to go into positive energy balance is hard to overcome because our appetites are increased while the energy metabolised is lowered. Facing a lifetime of dietary restriction, most people fall off the wagon either intentionally (because the diet is too restrictive) or accidentally (because they did not realize that their energy use is lower than it should be for their height and weight). What happens as a result is that they not only regain the weight lost but a bit more because of the upward drift of the set point.

Looking at the population of dieters it is not the weight loss that is the issue, it is maintaining the healthy weight afterwards for most people.

The fact that the 5:2 lifestyle is sustainable indefinitely and the potential for it to have a different effect metabolically than traditional methods of calorie restriction gives us hope that it really will turn out to be the 'one'!

Hi Caroline, thanks for the clarification. I agree (as I find I always do, once I understand it!) with everything you say...

Caroline, this is fascinating but I remain a bit puzzled. Leaving aside all the complexities of the types of foodstuffs and how our body processes them, surely there is a simple equation at work in all of us:

Calories in - Energy metabolised = Net energy retained => Net weight gained

Considering purely weight loss/gain (and not other health issues) this is achieved by altering our calorie intake and/or our metabolic rate. The rest is just about how to do it, isn't it?

Sorry if I am being thick, I would really like to understand!

One problem is that "calories in" and "energy metabolized" are not entirely independent variables. How much we eat, what we eat, and when we eat, all seem to have an effect on what our bodies do with whatever we do end up eating.

I recall that Varady, in the Horizon program, said that people who indulge in more fat during the feeding days did a bit better, in terms of weight loss. One reason for this might be that, in eating more fat they are resisting the temptation to "diet" seven days a week, undermining the "intermittent shock" effect of IF, but that's just a guess.

This thread is really fascinating, and it's certainly one of the questions I had in mind when I first read about this diet. I had become a bit disillusioned about the effectiveness of dieting long term after reading this article (http://www.nytimes.com/2012/01/01/magaz ... .html?_r=0) in the NYTimes called "The Fat Trap" and of course my own extensive experience with regaining weight after dieting. Thanks for posting all the links, Caroline! I'm impressed by your reliance on the real literature for information.

>>Calories in - Energy metabolised = Net energy retained => Net weight gained

I get tired of this being quoted at me and I've come to believe that it's too simplistic to be universally true.

I eat less than almost everyone I know and am fatter. I've never understood why. I know I've got an underactive thyroid, but I can't eat cakes, biscuits, lots of carbohydrates and all sorts of other 'naughty' foods because of multiple food intolerances. I live on salads and veggies with some low-fat cheese mainly and a little lean red meat (I hate fat).

I'm losing slowly on 5:2, but am wondering if it's time to stop for a few months and try to maintain this new weight.

The only time in the past 40 years that I've kept off weight permanently is when I've lost a few kilos (between 3 and 5 usually) and then stabilised for a few months - though I always put 1kg back on first.

I'm now over 20kg less than I was, but it's been incremental and taken about 12 years. All the times I lost a lot of weight, I put it on very quickly, as per this discussion topic.

How do I know what to do about the 5:2 diet?

It's great to have research quoted - thank you! - but is there any research on incremental slow dieting?

I'm not an expert on this by any means, but I have two comments. On the "calories in" part of the equation: the hormonal changes associated with weight loss mentioned in the references means that one is hungrier and eats more. Unless you're keeping track of that and make sure it doesn't happen, that's a problem. The other thing is the second part of the equation "energy metabolized". I think this is something that is hugely variable between people, even if you take into account the amount they exercise. I think it is also something that can change when you lose weight. So, I think there are some complications built into a seemingly simple equation.

I've been incredibly frustrated by the weight I've gained in the last five years. I don't eat so much and I exercise a lot. Then I remembered: I sit at a desk all day now rather than running around the lab as I used to. I've recently switched to a standing desk as well as going on this diet. I hope it works! I'm surrounded by tiny Japanese ladies who seem to eat all the time and never exercise. It really drives me mad!

Yes I think our RMRs (resting metabolic rates) do vary a lot and that they can change. Dieting can often reduce RMR I think, and one reason why 5:2 works better than some other diets is that the metabolism goes back to a higher level on the feed days, whereas continuous calorie restriction might leave RMR permanently depressed. Again this depends on the person though.

Curiously, I have had a pretty bad week diet-wise, it was Easter and then because of some business travel I have eaten and drunk too much. Before my one and only fast day this week (yesterday) my OH commented that I was so hot in bed all night - and I don't think she meant it in that good way. So I wonder if my metabolism went into overdrive when it got a load of calories? Not enough to cancel them out it seems, because I put on 0.7kg.

saj, putting back on 1kg when you stop dieting is to be expected because of water gain. But the logic of losing slowly is good I think. Losing too quickly is not only unsustainable and prone to relapse it can also be really bad in itself (gallstones - another current topic).