Wednesday, May 18, 2011

Why is it so Hard to Maintain a Reduced Body Weight?

Yesterday, I had the pleasure of attending a lecture by Rudy Leibel from Columbia University, who is perhaps best known for his considerable contributions to our current understanding of energy metabolism.

The talk was hosted by William Colmers as part of the University of Alberta Merck Translational Lecture Series.

In his presentation, Leibel addressed the issue of why it is so hard to keep weight off – in fact, even in people who undergo bariatric surgery, weight always comes back when surgery is reversed.

One of the key underlying problems is that when people lose weight, their energy expenditure does not simply fall to that of the energy expenditure of a person ‘naturally’ at that lower weight – it drops to levels far greater than expected.

Thus, a formerly-obese person burns 20% less calories than a never-obese person of that lower weight – or in other words a 200 lb person, who loses 40 lbs burns about 20% fewer calories than someone who is 160 lbs, but has never been obese. On top of this, the formerly-obese person experiences hunger, cold intolerance, and other behavioural and metabolic changes that make sustaining this lower body weight difficult.

From an evolutionary sense, this makes a lot of sense, as maintaining or ‘defending’ fat stores in the past has always been vital for human survival and therefore complex biological systems have evolved to readily take up and store excess calories when available and reduce caloric expenditure when times are tough.

In a large series of carefully conducted energy balance studies in humans, Leibel examined the impact of weight loss on energy expenditure, energy intake, neuroendocrine function, autonomic physiology, metabolism and brain imaging.

Whereas a short-term increase in body weight by 10 % results in a transient increase in energy expenditure, this returns to baseline, when the weight is lost. This means that weight-loss per se does not reduce energy expenditure.

On the other hand, a 10% drop in body weight immediately reduces energy expenditure by as much as 20%.

Interestingly, this fall in energy expenditure is not simply due to a fall in metabolic rate, but largely due to a decline in activity expenditure. This means that the body ‘saves’ energy not simply by turning down the furnace, but by becoming substantially more ‘fuel efficient’ during activity. In other words, someone who loses weight, will burn substantially fewer calories for a given amount of exercise than for the same amount of exercise performed before weight loss.

Much of this increase in ‘muscle efficiency’ can be attributed to the remarkable fall in the fat tissue-derived hormone leptin that occurs with weight loss.

Obese individuals apparently need a higher level of leptin to sustain energy balance. When they lose weight, thereby lowering their leptin levels, the system will aim to increase body fat levels to once again produce enough leptin to suppress the orexogenic response. Thus, weight reduction looks like ‘leptin deficiency’ to the brain, which it seeks to correct, by promoting weight gain.

The importance of leptin in this ‘defense’ response is clearly evident from both animal and human studies, in which leptin levels were maintained at or restored to pre-weight loss levels despite weight loss, by injecting leptin at levels just high enough to ‘mimic’ baseline levels.

In all of these experiments, using exogenous leptin to restore leptin levels to baseline, abolished the ‘defense’ mechanisms including the decline in total non-resting energy expenditure, thus making it easier to keep the weight off.

This ‘relative leptin-deficiency’ dependent improvement in muscle efficiency with weight loss can be clearly and consistently demostrated at the functional (exercise), imaging (MRI) and biological (biopsy) level.

Apart from reversing the improvements in muscle efficiency, Leibel also showed how the increased activation of hunger and appetite centres in the brain with weight loss can be reversed by leptin replacement. Thus, administration of leptin to individuals post-weight loss, reverses the decreased/delayed satiation and decreased perception of caloric density that would act to restore body weight to baseline.

Increases in the weight set-point occur with chronic weight gain, neuronal loss of aging, puberty and pregnancy. Unfortunately, lowering this threshold is far less likely, requiring such drastic measures as hypothalamic lesions or cachexia.

Thus, from an energy regulatory perspective, weight loss induces a ‘non-physiological’ state that can be restored to a ‘physiological’ state by leptin administration at levels high enough to mimic baseline levels.

So why is leptin not being sold to maintain weight loss? Because there is currently no regulatory pathway to license drugs that prevent weight regain. Regulators like the FDA and the EMEA simply lack a sound understanding of the complex physiology of weight regulation because after all, in weight management, the problem is never how to lose weight – the problem is always how to keep it off.

Unfortunately, based on the current guidelines for obesity drugs, there is no way for a pharma company to even apply to have a drug licensed that does not help reduce body weight (which leptin does not) but merely helps people keep weight off (which leptin does).

This is a shame, because in the end replacing leptin may well be the safest way to restore the ‘physiological’ state of being obese by correcting the ‘unphysiological’ state of having lost weight, which essentially drives weight regain.

AMS
Edmonton, Alberta

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31 Responses to “Why is it so Hard to Maintain a Reduced Body Weight?”

  1. DebraSY says:

    Questions (asked with some desperation): Do you know of any trials that one might enroll in? Do you know whether a US physician could prescribe off label?

    I am considering printing off this post and taking it with me to a consult with an Endocrinologist.

  2. B. Matthews says:

    “So why is leptin not being sold to maintain weight loss? Because there is currently no regulatory pathway to license drugs that prevent weight regain.”

    This is the saddest thing I have ever heard. Here we have a society bemoaning obesity rates and beating up on overweight people, yet we cannot get ourselves together to make available a substance which would help to alleviate the misery of millions who are struggling to maintain a healthy weight. That this comes down to a regulatory problem is pathetic.

  3. Anonymous says:

    I’d say it would be a good idea to add this information to the steps a doctor should take in treating patients with obesity, or in warning patients who are overweight to avoid obesity.

    I can’t remember all your 10 points for doctors dealing with overweight and obese patients, but I’m sure informing patients about the nature of obesity is in there somewhere, and this information about change in energy metabolism is important for people to know.

    I’m in exactly the category you mention. 6 years ago I lost 63 lbs. Over the last 3 years I have regained 30 lbs, that’s regaining about a pound a month. For the last 2 months I’ve resumed my weight loss program, and I’m down 2 lbs (Not much, but it’s a start.)

    This information helps because it gives an accurate picture of what I need to do, ie reduce calorie intake a lot. Knowing there’s a reason why I have to do this makes it easier.

    I still have to avoid eating poorly for social and psychological reasons, but at least I can plan my diet knowing how my calorie requirements have been affected by obesity.

  4. M says:

    Did Leibel indicate if this decline in energy expenditure persists for a lifetime? I.e. if someone lost weight, managed it to keep it off (through above and beyond diligent efforts), would their metabolic rate graduatelly increase over towards a similar rate as an always-normal weight person? Thanks for sharing this information.

  5. Rhodia says:

    As someone who is trying to maintain a large weight loss, I find this horribly depressing. I sometimes feel my only hope is to be a totally hardcore nutrition and fitness nut for the rest of my life.

  6. L says:

    I was at Dr. Leibal’s talk yesterday, too. It was very interesting and left me feeling both affirmed and discouraged at the same time. Affirmed because although I was never obese, I did lose about 20% of my body weight through calorie restriction and exercise. Gained some of that back and through trying to lose what I’d gained, following the same methods, being frustrated that I was getting the same results. Requiring 20% fewer calories than before and burning 20% fewer calories doing the same exercise can, at times, feel like an exercise in frustration (if I was strictly doing it for calorie burn).

    I left with a few questions: why encourage people to lose weight at all if it so difficult to maintain a weight loss and they are basically living in hypometabolic state? What can people do to help maintain a weightloss (without leptin)?

    Dr. Sharma, can you briefly explain the “why” behind the weight gain according to Dr. Leibel. He was talking about people requiring about 900,000 calories a year, then if one has lost 20% body mass, they require, say, about 400 calories less….then I got lost. So, they are likely to gain 12kg/year because that 400 calories isn’t accounted for in their calories needs and so they consume the extra 400 cal/day/year??

  7. L says:

    edit from above “being frustrated that I was NOT getting the same results” by eating the same and exercising the same as initial weight loss.

  8. Margaret says:

    What a thoughtful post.

    Your readers are voicing my thoughts exactly, that, despite the biggest health crisis to face many generations, there are still so many excuses for keeping status quo.

    What a pity.

    Cheers for the insights,

    MYL

  9. Arya M. Sharma, MD says:

    @DebraSy: sorry, no trials with leptin that I know off – like I said in the post – drug companies don’t know how to apply for licensing such drugs, so they’re not investing in studies.

    @M: unfortunately, the ‘hypometabolic’ state appears to be for life – so ‘no cure’

  10. Anon1 says:

    Not sure if this helps or not, but there is an American certified nutritionist named Byron Richards who has developed what he calls “the Leptin Diet”. Here is a link to his book by the same name: http://www.leptindiet.com/. Might be worth a read.

  11. Maddy says:

    There is a small group that IS capable of keeping off a large amount of weight. How are they doing that? Also has Leptin been given to humans in any study to see if it is safe? Is it approved to be used for any medical purpose? Thanks

  12. A says:

    There have been studies of leptin in rat models for weight loss, but has not been successful for weight loss in humans. That is why there are no clinical trials yet – they have not proven efficacy (or perhaps safety for that matter). That is my understanding.

    I agree with Anonymous above – reading Dr. Leibel’s research was actually help to me – I have struggled with maintaining weight (loss is not a problem for me), and knowing I will always have to eat a little less and know that I cannot completely let loose once I’m at my ideal size is useful. I can live with a 20% calorie reduction to maintain the size I want.

  13. Mark says:

    Dr. Sharma – I’ve seen some research to suggest that a brief period of higher calorie, higher carbohydrate feeding can increase leptin levels.

    Further to this point, I’ve also seen that many bodybuilders and fitness enthusiasts implement a similar “refeed day” every so often to stave off the potential metabolic slowing as a result of weight loss so they can continue to lose fat for competition.

    Do you think that there is any merit to this idea and, if so, do you think there is any possible use for this in managing obese patients?

  14. Kyle says:

    Excellent read. From what I’ve read by Lyle McDonald, it cost ~500 dollars a day for exogenous leptin treatment. I’m not sure if thats for synthetic leptin. There is also the issue of obese people being resistant to the effects of leptin. I wonder if their resistance decreases as fat decreases? If the leptin resistance remained after the weight loss, then maybe finding ways to increase leptin sensitivity may be a better solution that administering leptin.

  15. fredt says:

    Leptin. Yum. Good, for those few who are short. Dr. R Lustig also has a few comments on leptin for the obese. (I am just overweight now.)

    One leptin “resistance diet” is low carb, low omega 6, no fructose, no lactose, no grains.

    Lustig interesting quote is as follows:

    Obesity is characterized by hyperinsulinemia. Although hyperinsulinemia is usually thought to be secondary to obesity, it can instead be primary, due to autonomic dysfunction. Obesity is also a state of leptin resistance, in which defective leptin signal transduction promotes excess energy intake, to maintain normal energy expenditure. Insulin and leptin share a common central signaling pathway, and it seems that insulin functions as an endogenous leptin antagonist.

    Suppressing insulin ameliorates leptin resistance, with ensuing reduction of caloric intake, increased spontaneous activity, and improved quality of life. Hyperinsulinemia also interferes with dopamine clearance in the ventral tegmental area and nucleus accumbens, promoting increased food reward.

    Accordingly, the First Law of Thermodynamics can be reinterpreted, such that the behaviors of increased caloric intake and decreased energy expenditure are secondary to obligate weight gain. This weight gain is driven by the hyperinsulinemic state, through three mechanisms: energy partitioning into adipose tissue; interference with leptin signal transduction; and interference with extinction of the hedonic response to
    food.

  16. Bill Graber says:

    there are studies showing mitocondrea in obese people are not as efficient as in lean people or people who have lost weight, I think Dr. Dent may have done some work on this. So yes lean peoll eand people who loos weight are more energy efficient, I have not seen any studies where IV leptin will stop weight regain in people, were they published? Leptin is not the only hormon that may drop with weight loss. Neuropeptide Y (NPY), triiodothyronine (T3), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estrogen can drop as well.

    thanks

  17. Marion@affectionforfitness says:

    I used to weigh 35 more pounds 4 years ago and had a little dip of weight gain last year, but kept more than 20 pounds off for more than 4 years. I think that when I realized that I would have to watch my weight for the REST OF MY LIFE, I cried for a long time. That was years ago. I’ve gotten over that and have changed my life to be more athletic. I go to the gym and meet my fun gym buddies instead of eating bakery rolls on Saturday mornings. My life is much more fun since I work out–even though I eat less calories now. I thank you for informing us on these facts, but it is also equally important to then throw this depressing information out of our heads and go have fun with a healthy life, regardless of whether or not we can eat as much as another person. :-) Marion

  18. A says:

    Mark: I have a coach who coaches clients with their training and diet/nutrition, and also preps people for physique competitions, and he uses a “refeed” day or meal “at critical points” he says. He says they have to be pretty lean for the re-feed to spike leptin, and that this does not work in everybody due to leptin resistance (nor does it work if cheat days cause one psychological distress). He has clients on what he calls the cycle diet, in which they eat below maintenance calories throughout the week, and then have a cheat day (or for some, just a meal) where they eat whatever they want but essentially spiking their calories (but not bingeing or to the point of sickness). He put me on this cycle diet a few years back, and it seemed to work well in the beginning. In fact I lost a little more weight doing this (although I had become pretty lean at that point). But then for whatever reason, I started to gain after a month or two, so I stopped. He thought it may have been due to leptin resistance, but who knows. I know he has a lot of clients (who don’t compete) on this cycle diet though. Just didn’t work well for me.

  19. Alexie says:

    Hi Dr Sharma,

    Could you keep writing on this topic? I lost 25 kilos (a bit under a third of my body weight) last year due to cancer cachexia and, so far, have managed to keep it off. I do all the recommended things – food journal, daily weighing, portion control, eating regular meals etc etc but I am beginning to wonder if my body has re-set itself somehow. Admitteldy it’s only been eight months, but I seem to be metabolically different than before. Previously, I seemed to be a magnet to attract weight (I had a BMI of 28), but now I’m maintaining a BMI of 19 with relative ease. Do you think it’s possible that the body can re-set itself under some conditions? Though I do feel cold easily!

    A

  20. DeeLeigh says:

    I first noticed this when I left for University and lived in a dorm. I’d been raised by a (short, thin, weight conscious) mom who was constantly trying to eat 1200 calories a day and taught me that I should do the same. As a teenager, I thought I was a real pig for eating more than that, let me tell you. I thought that was how thin people ate, and I couldn’t understand why trying to eat like that left me famished, irritable, and unfocused.

    So, when I left for University, I moved into a dorm that served three meals a day and later lived in apartments with other girls. As an 18-year-old who felt guilty for eating more than 2 pieces of pizza, I watched the skinny girls polish off whole pizzas without gaining any weight. I ate salads. They ate heaping plates full of mexican food. I snacked on raw vegetables. They snacked on candy bars. And, they weren’t skipping meals, nor were they more physically active than I was.

    After a while, it dawned on me: the 2000 calories that’s cited as the right amount for women to eat on the nutrition labels? It’s not wrong. That was actually around the (minimum) amount that the other girls were eating. I also made other discoveries, like the fact that, for food to come out well, you need to use enough oil to cover the bottom of a hot pan when you saute. I’d been taught to wipe the pan with a paper towel dipped in oil or use spray oil. I started to eat higher calorie, higher fat meals (with an awareness that some fats are healthier than others, obv.) and became more physically active – and I actually lost around 10 pounds. Actually, I lost 30 pounds if you take my freshman-20 weight as the baseline, because you’d better believe that I gained weight on the dorm food even though I was eating less than most other people. The ten pounds stayed off for a decade, and I didn’t get back up to my freshman 20 weight until I had an injury that kept me from exercising in my late thirties.

    So, while I applaud the fact that the medical establishment is acknowledging that formerly fat people need to eat a lot less than naturally thin people in order to maintain a weight loss (and that’s true), I don’t think it’s the whole story. I’m not convinced that undereating is a positive thing. I think that it can actually contribute to weight gain by putting our bodies into a starvation-alert state. And let me tell you, some of our bodies can really pack on the pounds when they think they’re being starved – even when all we do is occasional let loose and eat like normal people; even one big meal. Living in a constant state of deprivation is unpleasant and precarious, and I’m not convinced it’s healthy, either.

    For me, the answer was to normalize my eating (i.e. stop trying to starve myself) while continuing to pay attention to good nutrition, get some regular and enjoyable exercise, and let my weight take care of itself. And it has. I’ve lost and gained small amounts of weight as an adult, always attributable to changes in my life. But basically, I’ve stayed the same size. For 25 years, I’ve been within 20 pounds of what I weighed when I graduated from high school.

  21. DeeLeigh says:

    Oh – and I weighed 200 pounds when I graduated from high school.

  22. Arya M. Sharma, MD says:

    @M: unfortunately, this decline persists for a lifetime and seems to get worse over time as people age – so all obesity treatments essentially need to be for life, as weight will always bounce back, even after years of keeping it off successfully.

    @Anonymous: good point – the ‘chronicity’ and life-long nature of obesity is implied in several of the 10 rules including understanding that this is a chronic condition, finding a management plan that patients can continue for life and dealing with relapse.

  23. jennifer says:

    If you have a weight problem it will never go away and only gets more difficult to manage the older that you get. People who suffer with a weight problem have to be told the truth from childhood. This is a chronic physcal condition that is genetic, it is not their fault. I do not suffer from this condition but I have witnessed their lifetime of desperation. I wish that there was somerthing that I could do to help them. Any suggestions?
    Thank you

  24. Sarah from Rugby, UK says:

    This article definitely makes sense. I lost about 65lbs 4 years ago (using a VLCD) and have managed to keep the weight off, however I am only doing this by rigorously tracking my food. I’ve found that I have to set the counter on my calorie tracking tool as though I want to lose 1/2 lb a week just to keep my weight stable.

  25. Long Term Low Carb Dieter says:

    While this article sounds discouraging, it is possible to lose weight and keep it off. I suggest reading Gary Taubes new book Why We Get Fat and What to Do About it.

    I have lost 87 pounds over the past 5.5 years, generally 15-20 pounds per year, on a low-carbohydrate diet, with very little exercise involved. This means most days, most weeks, nothing happens. I believe it is the quick weight loss schemes that cause metabolic chaos and weight regain.

    I strongly believe slow weight loss allows the body to adapt, and that insulin levels must come down, permanently, to maintain weight loss. This means never going back to eating flour, sugar, or other processed foods. Eating real, whole food is the answer, not drugs.

  26. Review Best Diets says:

    Yes its very true that it is not easy to maintain the weight after heavy weight loss but it is not impossible as one need to go for deterministic approach. This is quite essential that one should take proper care of their diet and fitness regime.
    Also one another factor which plays a very important role over here is that sustainable weight loss is only possible through slow weight loss. Its all about taking control over temptations and cravings.

  27. FatBastard says:

    Sharma is full of crap. High or low leptin levels cannot change the laws of physics.

    The truth is.. The most a basal metabolic rate can very in individuals of the same age, weight and gender is 35 calories a day. Sharma is a hack.

  28. CB says:

    Oh… I see… Leptin solves all… I see an infomercial coming on.

    Once again, I don’t understand how someone who weighed 130, let’s say, who gains weight to be, I don’t know, 170, is now somehow naturally 170 lbs and not the 130 they were their entire life. Sure, metabolism changes. Sure, gaining weight has its consequences, but if you weren’t naturally 170 to begin with, why are you now naturally 170, even if you were only 170 briefly? This makes no sense.

  29. Razwell says:

    FatBastars

    Who told you that information? It is completely false. Dr. Sharma is no crank. His information is congruent with what Dr. Douglas L. Coleman and Dr. Jeffrey Friedman have discovered.

    Only laughably misinformed Internet gurus would call Dr. Sharma a crank. He has many years experience treating obesity and attending lectures from the world’s very best obesity scientists.

  30. Nikki says:

    Very interesting post! Just came across it and it has helped me to understand a great deal of what I have been going through in my struggle with weight. I have yo-yo dieted for decades and always struggled with hunger and cravings that lead me to put the weight back on. I would definitely consider myself leptin resistant.

    This time I am trying a different approach that seems to be working. I am eating a whole food diet that is low in carbs from grains although I do have a couple of portions of whole grains a day. I have a lean protein and some healthy fat with every meal. The bulk of my diet comes from fruit and vegetables. My goal is simple: to eat food with as much nutrition and as low calories as possible while never allowing myself to become hungry. Hunger is the enemy for me and I have decided to fight hunger instead of fat. I count calories, but not with a view to restricting them as such, rather with a view to observing which eating patterns naturally result in the lowest calorie intake while not resulting in hunger or cravings. I don’t take any diet pills or appetite suppressants and only supplement with fish oil.

    With this approach I have lost 20% of my body weight very easily, and I have absolutely no desire to return to my former eating habits. I still have a long way to go but I love my food and have no hunger pangs or cravings. I know what it feels like to be comfortably full and have no desire to continue eating for the first time in decades. My hunger patterns have completely changed. I have gone from not being hungry in the morning and ravenous in the afternoon and evening, to being really hungry in the morning and then losing complete interest in food from late afternoon onwards. Supper used to be my biggest meal of the day, followed by mindless snacking until bedtime. I now eat almost half my calories for the day at breakfast, then taper off to the point where I don’t particularly feel like supper and if I have anything at all it is a salad or a piece of fruit. My calorie intake is between 1300 and 1500 a day which seems to be enough of a deficit for me to consistently and slowly lose weight. I also exercise 5-6 days a week.

    I am trying to do this gently, working with my body, focusing on eating whole foods that are satisfying and nutritious as well as pleasurable and watching how my body responds. So far I don’t feel like I am fighting against myself for the first time in my life. It remains to be seen whether I will lose all the weight and maintain this loss, but I feel like I may have found an approach that isn’t an uphill battle. Whatever the outcome I think I am currently experiencing normal hunger signals and a healthy appetite, possibly for the first time in my life. I do believe there is hope for a normal life for obese people who lose weight slowly and adopt a life style change that includes a whole food diet and regular exercise. In addition, a better understanding of the action of different hormones in hour bodies and how we might influence them is a huge help!

  31. V says:

    It has nothing to do with leptin resistance but absolute leptin levels and fat cell numbers and size. When you’re superfat there are not only overfull fat cells but lots more of them. When fat is lost you end up with shrunken cells & low leptin production the only way this could ever be normalized after dieting down to ‘normal’ weight is leptin supplementation which absolutely works (there has been at least one randomized clinical human trial in the past few years in the US) and the effects of which would be bolstered by the kind of ‘cosmetic’ surgery often undertaken to purportedly remove ‘excess skin’ which ofcourse in a dieted former fat person also means excess fat tissue and all that goes with it. I don’t buy the ‘pharmas don’t know how to get a licence’ line because if there’s money in it they will find a way the more likely reason is the upset leptin replacement would cause to the multi-billion dollar diet industry and all it’s allies. For every person who is successful on their first ‘diet’ there are probably 10 who aren’t and leptin-replacement would kill all of the repeat customers that are the diet-industry’s mainstay. On a macro level, there is more invested in keeping people on the diet treadmill than there is in efforts to ‘solve obesity’ no matter how much they pretend otherwise. Whenever there is a question to which the answer is obvious (ie how to maintain fat loss? Supplement with leptin) but its mysteriously not being implemented the answer usually has something to do with $.

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