Carbonfiberboy 

While I was looking into the effects of various diets, I happened upon this study:
Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance
https://jama.jamanetwork.com/article....icleid=1199154

A summary of its findings can be found here in Science Daily:
Dieting? Study Challenges Notion That a Calorie Is Just a Calorie
https://www.sciencedaily.com/releases...0626163801.htm

Why is it so hard to lose weight after the first loss, when one plateaus? Basically, after an initial 10% weight loss, they fed subjects 3 eucaloric diets, meaning diets with all the same calorie content. The diets were low carb high fat, low fat high-glycemic carb, and low-glycemic medium carb. They found that their subjects Resting Energy Expenditure (REE) and Total Energy Expenditure (TEE) decreased the most on the low fat, high-glycemic high carb diet, TEE/day by 300 calories! Unfortunately the study does not say whether these subjects gained weight during their low fat diet intervention, but I suspect they did. On the low carb diet, TEE decreased the least.

Though it seems from the weight loss implications of this study that a very low carb diet would be best, the authors do not recommend it due to other factors noticed during the study:
This above, however is just the lead-in to the subject of this post: Leptin. The researchers theorize that the decrease in TEE is due to low leptin levels. Other researchers have found that they can restore "healthy" leptin levels through leptin injections, which reverses the decrease in TEE:
Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight.
https://www.ncbi.nlm.nih.gov/pubmed/16322796
and:
Effects of weight loss and leptin on skeletal muscle in human subjects.
https://www.ncbi.nlm.nih.gov/pubmed/21917907

There are even websites which tell us that eating certain foods and supplementing with leptin will get us back on track with weight loss, by increasing our TEE and REE:
https://www.wellnessresources.com/leptin_diet.php
Maybe that's true.

But what if we've already lost weight and now want to improve our endurance performance? What if we want to be able to go further and faster on the same food? What if we want to bike or run like the Kenyan marathoners? Well then, we should adopt a diet which is proven to improve our muscular efficiency and thus dietary efficiency by decreasing our leptin levels: the low fat, high carb diet studied in my first link, which has similar macros to the Kenyan marathoner diet.

Very good article on this complex subject here:
Decreasing total body fat mass in endurance athletes.
https://arquivo-v1.federacao-triatlo....cao/nt_006.htm

ThermionicScott 

I used to follow low-carb/CKD bodybuilding stuff, and this came up a lot... seems like they concluded pretty early on (like 1996 or so) that if you could just inject more leptin, the last part of the diet would go much quicker, without as much lean-body mass loss. Cost was a prohibitive factor at the time.

Carbonfiberboy 

Yes. The thrust of my thesis is that low leptin is preferable for endurance athletes, as it stimulates Type 1 fibers, even though it makes weight loss more difficult.

hamster

I have a slightly different interpretation of this finding. Human body has a weight setpoint, and weight loss moves it out of the setpoint, triggering leptin reduction which would normally make you hungrier on average and bring you back to zero. It is a long-term homeostasis process and it normally goes both ways (returning you to zero after short-term weight loss as well as after short-term weight gain). One of the areas of interest has been the failure of this process in overweight individuals. It seems that some foods (read: McDonalds) make you resistant, or "desensitized" to leptin: even if its levels are high, you don't stop eating as you should.

By this logic, in principle, yes, leptin supplementation would help with reduced weight maintenance, as long as you stay out of McDonalds. I did not realize that such a thing is possible, except in the lab. It's a pretty novel chemical, it's only been isolated in the 90's. Wikipedia says that a synthetic leptin analog has been approved in Japan last year. I don't think that the wellnessresources site has any leptin supplements.

Also, don't quote me on that but I think that the setpoint ends up adjusted anyway during weight maintenance. So, a person who just lost 30 lbs and a person who lost 30 lbs and kept them off for a year might have same leptin levels, but potentially different RMR, etc.

P.S. Apparently, manufacturers of synthetic leptin (metreleptin) just tried to get FDA approval in the U.S. (there was a hearing last month) - not even for obesity or DMII but for a rare genetic leptin deficiency disorder - and they didn't even get that. There were a few lymphomas in the test group (people with that disorder are pretty sick in general) and it could not be conclusively stated that they weren't caused by the drug. And the review noted that the drug triggered an immune system response, generating leptin antibodies. (They mention that the immune response was due to "supraphysiological concentrations", that is, higher than normally occurring in the body. Not clear why you'd want this.) https://www.fda.gov/downloads/advisor.../ucm377928.pdf

So, lesson 1, it's still hard as heck to get even a wonder drug approved by the FDA, and lesson 2, off-label self-medication with leptin (assuming you get a package shipped to you from Japan) may have some pretty undesirable side effects.

The review mentions obesity trials of the drug, might be interesting to dig up reports on those.

Carbonfiberboy 

Of course you are correct. But, as the researchers found, it seems possible to maintain low leptin levels through diet. I'm wondering how long it might be possible to maintain these lowered levels, which researchers say are due to increased activity of Type 1 fibers over Type II.https://ajpregu.physiology.org/content/301/5/R1259

hamster

Found a study looking at leptin supplementation in dieters. We have leptin, a different little-known hormone (Pramlintide) and both (no placebo group, unfortunately). They see an average 18 lb weight loss in 20 weeks on either Pramlintide or metreleptin and 26 lb weight loss on a combination of both. Seems pretty remarkable for a counseling based diet.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754219/

As in the FDA approval request above, both drugs here are administered intravenously. I'm guessing that, being proteins, they are badly degraded by the stomach acid.

hamster

Low leptin levels are low simply because you don't have much adipose tissue which normally generates leptin. If you lose weight and stick with it, your leptin levels will remain low. These lowered levels, possibly working together with some other consequences of weight loss, drive higher muscular efficiency.

Claimed 20% increase in muscular efficiency was only seen at the power output level of 10 W. Looking at table 2 in https://ajpregu.physiology.org/content/285/1/R183, I see that the effect amounts to about 20-30 calories/hour and comes mostly, if not completely, from having lighter legs.

Carbonfiberboy 

Ah, I see that in your link. I don't get why the effect should be so much larger at low energy expenditures. If the effect is really because of increased oxidation in Type 1 fibers vs. Type II, then I would think that would still be the case at higher workloads. To find this reference, search for "triiodothyronine" in the R183 document. Comment?

I was thinking that perhaps the Kenyan diet being so similar to the diet which produced the low leptin levels was not a coincidence.

Dunbar

I thought the Leptin studies failed to prove any real efficacy in terms of weight loss except in certain cases of people with Leptin deficiencies (which is not everybody who is obese.)

hamster

Are you sure? Off the bat I can find his one, that reports a positive result https://xa.yimg.com/kq/groups/2334294...MA+-+LICOB.pdf

From what I read, leptin may not necessarily make severely overweight people lose weight (because they have high levels to begin with, they just happen to be resistant), but it may be helpful once those levels start dropping as the dieting progresses.

Dunbar

This is what I'm referring to:

"As it turns out, leptin injections only worked on mice (and people) who were genetically leptin deficient — only about 5-10% of obese subjects. The other 90-95% were out of luck."

https://www.precisionnutrition.com/leptin-ghrelin-weight-loss

hamster

OK. I don't see this statement substantiated by any of the references the article gives. There are a few articles saying that only 5-10% of obese subjects have low leptin levels. It does not necessarily follow that only 5-10% can benefit at all.

Carbonfiberboy 

The protocol that resulted in the (possible) low leptin levels was a bit complicated. First the subjects were put on a very calorie restricted diet until they had lost ~10% body weight. Then they were put on a 4 week low fat, high carb diet. Only those who were on that particular diet developed the 300 kcal/day decrease in TEE which is thought to probably be due to low leptin levels. However all of the study subjects rotated through that diet and were similarly affected.

So it wasn't so simple as putting obese people on a diet and watching leptin levels.

I think the authors' takeaway was that dieters are more likely to plateau on a high carb low fat diet, and less likely to do so on either a high fat low carb, or on a moderate carb low glycemic diet. This may be the reason that people have good luck with weight loss from low carb diets.

I read a couple of studies where the lowered TEE was completely reversed by leptin injections, but I don't have the links handy.

Dunbar

My understanding of the studies is that only people with low leptin levels responded to the leptin injections.

ThermionicScott 

Ah, I didn't catch that the first time around, although I should have. It makes sense -- our bodies have so many adaptations to cope with starvation, that I can see a priority given to endurance over strength.

Carbonfiberboy 

Yes, it makes sense. However, I'm interested in seeing evidence of that thesis. As far as I can tell with current research, it's an effect rather than a cause of improved training adaptation.