7

votes

watershed moment on leptin?

Answered on September 12, 2014
Created April 25, 2011 at 6:47 PM

stephan announced on his blog that he will release his idea on "a method that goes beyond symptomatic treatment and allows the body to naturally return to a lower fat mass". being that he has written extensively about leptin in the past, i'm sure that leptin sensitivity and set point theory will factor in it to some degree. i also just finished reading the amazing back and forth between dr rosedale and dr k on a recent paleohacks post. there seems to be momentum towards the idea of leptin sensitivity and set point theory making it's way into mainstream consciousness much the way the ideas of insulin resistance and metabolic syndrome has in the last ten years. i'm not a science-oriented guy so i'm left wondering where does it fit in with what we've been learning and applying based on our theories on insulin resistance for the last ten years? does leptin regulation trump insulin regulation or is it a totally different pathway(if that's the right terminology)?

06d21b99c58283ce575e36c4ecd4a458

(9948)

on September 07, 2013
at 01:28 AM

The only true criteria for acupuncture is...does the patient feel better?

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 07:00 PM

"Leptin also controls all of the hormonal signals that also control how we partition calories. Its the one hormone that dictate to every other one. That is what makes it biologically powerful"...very true..

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 06:57 PM

Reading only Byron Richards take on leptin I am afraid will not get people to appreciate the true science behind leptin, as much of the basic important points are missed or misinterpreted..Therefore trying to base diet on his information will lead one in the wrong direction.

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 06:48 PM

I have measured leptin and treated perhaps a thousand people with leptin resistance. The most important factor in reducing leptin and therefore leptin resistance is to reduce non-fiber carbs that otherwise cause spikes in leptin and keep it high. You do treat leptin resistance as you would treat insulin resistance which makes sense since they both work synergistically to accomplish biologically the same thing. Please see my answer below. One should also see the PowerPoint http://www.meandmydiabetes.com/2010/05/07/ron-rosedale-insulin-leptin-and-the-control-of-aging/ and/or read my book...

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 03:44 AM

"Obesity due to leptin resistance is not one disease. It appears to be multifactorial in etiology".. I believe that leptin resistance itself can and should be called a disease, and then it causes multiple metabolic derangements that can lead to obesity and many other symptoms that are then generally called diseases.

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 03:33 AM

Dr. K; I may have misunderstood what you were trying to say about leptin at the hypothalamus, and if so, I apologize. Please clarify.

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 03:27 AM

The detrimental effects of fructose metabolism, fructose being an isomer of glucose and therefore metabolized differently, has been known for well over a decade and far preceded Lustig. The primary detriment of fructose is that it readily is converted into and stored as fat in the liver contributing to fatty liver and therefore hepatic insulin resistance. Hyperleptinemia is perhaps even more important in this regard.

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 03:16 AM

"Excess palmitic acid from excess carbohydrate intake" is not the major signaling factor for leptin at the hypothalamus. It is leptin itself, leptin being a major signaling hormone, perhaps the major signaling molecule in the hypothalamus, regulating most everything it does. Palmitic acid is not. It's major function is for storage in triglycerides as what I call second generation carbohydrates.

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 27, 2011
at 02:27 AM

Amgen's trials on their synthetic leptin drugs have completely changed the way research scientists are now looking at leptin function and signaling. As Dr Rosedale speaks of it appears after someone has lost a ton of weight normally or via bypass surgery their response to infusion of leptin is paradoxical and we believe now it has to due with the context of receptors and the IGF 1 pathways and the interaction at PPAR gamma with hormonal influence and biochemical signaling of the mitochondria and the state of backround inflammation in the cytosol and leakiness of the first cytochrome.

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 27, 2011
at 02:22 AM

Excess palmitic acid from excess carbohydrate intake is the major signaling factor at the hypothalamus for leptin. De novo lipogenesis plays a roll in this. Lustig and others believe that is precisely how fructose has shifted the NHANES curves for kids. Lustig also has interesting ideas on "other" forms of obesity as well. Obesity due to leptin resistance is not one disease. It appears to be multifactorial in etiology. Once leptin resistance sets in it effects the delicate relationship of PPAR gamma, mitochondrial signaling, and hormonal regulation of metabolism.

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 02:06 AM

To restore and maintain leptin sensitivity, I feel it is best to keep leptin levels low by maintaining a low, non-fiber carbohydrate, moderate protein diet as much as possible. I have not likely read the “set point” theory that you are referring to, but the “set point” that has been talked about for decades pertaining to body weight and fat storage is set and regulated by hypothalamic signals that in turn are controlled more by leptin sensitivity I feel than any other factor.

Be1dbd31e4a3fccd4394494aa5db256d

(17969)

on April 27, 2011
at 01:52 AM

Arg, my copy of Mastering Leptin hasn't arrived yet. Soon, though. My guess is a big chunk of it has to do with eicosanoid activity in the hypothalamus. It is regulated by eicosanoids and they have been known to go awry on the SAD. Gut flora can make you fat and gut flora powerfully influence inflammation although I don't know if that inflammation ties in to inflammation in the hypothalamus. As we know, various SOCS molecules also cause leptin resistance. Solution: go paleo? I'll have to wait to hear what Stephan Tha Lawd and Savior (praise him!) is onto.

66e6b190e62fb3bcf42d4c60801c7bf6

(12407)

on April 27, 2011
at 01:38 AM

Thank you for your comments, dr. So, if a person is trying to lose bodyfat, do they still keep carbohydrates low or does cycling carbohydrates a la a cyclical ketogenic approach more conducive to making one more leptin sensitive? also, what do you think about the "set point" theory?

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 01:37 AM

This, by the way, comes from one who, through numerous talks around the world from over 15 years ago, was largely responsible for popularizing the importance of insulin and insulin resistance. Please see, "Insulin and its Metabolic Effects" that is all over the Internet.. I still believe that insulin is tremendously important and works in concert with leptin to regulate sugar and fat metabolism, and therefore much of chronic disease..

77877f762c40637911396daa19b53094

(78467)

on April 26, 2011
at 01:45 PM

BTW, anybody wanting to read and see free podcasts by Byron Richards can look here: http://www.wellnessresources.com/

77877f762c40637911396daa19b53094

(78467)

on April 26, 2011
at 01:45 PM

I just got through reading Richards' "The Leptin Diet" this past weekend. It almost seems too simple. Just don't snack, eat three meals spaced fairly far apart and eat well ahead of bedtime. He doesn't seem to be particularly low-carb, except to say that you shouldn't stuff yourself on any particular food. My understanding is that "Mastering Leptin" is more detailed, so maybe I will get that.

2f54dbe892ec89b12d1db686568e885a

(919)

on April 26, 2011
at 08:41 AM

it works on racehorses - no placebo effect at work here

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 26, 2011
at 03:04 AM

read Mastering leptin by Byron Richards. Its like learning about leptin as an overview. ITs a good place to start. The devil however is in the details. The hypothalamic signaling of leptin and how it ties to PPAR gamma are white hot.

66e6b190e62fb3bcf42d4c60801c7bf6

(12407)

on April 26, 2011
at 01:09 AM

so did i actually ignorantly reset my leptin setpoint after losing a great deal of weight by "teaching" my body how to use starchy carbs again by refeeding after strenght training instead of just randomly throwing carbs back into the diet? i can pretty much go up to 150g of carbs(don't do it often because it actually hard to do for me on the type of paleo protocol i'm on) pretty often with no weight gain...

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 26, 2011
at 12:33 AM

Leptin also controls all of the hormonal signals that also control how we partition calories. Its the one hormone that dictate to every other one. That is what makes it biologically powerful.

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 26, 2011
at 12:31 AM

no you dont. Insulin treatment is simple. void foods that cause its release. Hard for some to do. But doable. Leptin is concerns carbs too but timing is much more critical than you can imagine.

77877f762c40637911396daa19b53094

(78467)

on April 26, 2011
at 12:10 AM

So, in that case, do you treat leptin resistance just as you would treat insulin resistance? Is reducing carbs sufficient to cure leptin resistance, in your experience, Dr. K?

77877f762c40637911396daa19b53094

(78467)

on April 26, 2011
at 12:08 AM

Dr K. How do you test for leptin resistance? Or does one just make such a conclusion based upon a set of symptoms?

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 25, 2011
at 10:27 PM

Lots of stuff I have done did not work.....and its called medicine. This is a problem patients have......medicine is an art meshed within a science. Not all we do works and not all we dont do does not either.

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 25, 2011
at 10:26 PM

i refer patients out for accupuncture and I dont think its pseudoscience. If it helps it helps.

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 25, 2011
at 09:46 PM

leptin trumps insulin. You must be leptin resistant to be insulin resistant unless you had to have your pancreas removed due to blunt trauma. Its how our biochemstry is constructed. This fact is lost on 99% of practicing docs.

66e6b190e62fb3bcf42d4c60801c7bf6

(12407)

on April 25, 2011
at 09:01 PM

http://wholehealthsource.blogspot.com/2011/04/obesity-and-fluid-in-fluid-out-therapy.html

77877f762c40637911396daa19b53094

(78467)

on April 25, 2011
at 08:29 PM

Where on Stephan's blog does he announce this?

4781cf8ae1bfcb558dfb056af17bea94

(4359)

on April 25, 2011
at 08:05 PM

I don't know how you could prove that results are not due to a placebo since patients obviously know when they are being stuck and when not. Or is the theory that it matters precisely where you get poked not only if you get poked? If so, are there randomized placebo trials where some people get poked in the wrong spot. are there trials in unconscience people? If not, it's kind of hard to falsify... Doesn't make it pseudoscience per se but makes it hard to believe.

66e6b190e62fb3bcf42d4c60801c7bf6

(12407)

on April 25, 2011
at 07:57 PM

http://paleohacks.com/questions/33775/what-kind-of-fat-do-you-eat-on-dr-rosedales-high-fat-diet#axzz1KXVEi2Sf

1f24d4895246892ef4ee4d79b7f9eeeb

(373)

on April 25, 2011
at 07:46 PM

Where would I find the "amazing back and forth between dr rosedale and dr k on a recent paleohacks post?" Thanks.

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4 Answers

10
5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 01:23 AM

The merit worthy "grand theory" of obesity and health will unlikely be new, but will likely be connected with insulin, leptin and leptin resistance. The point missed by most everybody concerning leptin resistance is that leptin levels and leptin resistance is not primarily determined by how much fat you have, but how much fat you have is determined by leptin and leptin resistance. Leptin levels and therefore leptin resistance is determined more by acute nutrient related spikes in serum leptin levels similar to what happens with insulin. I have maintained for decades that the primary (though not only) cause of insulin resistance is due to insulin spikes secondary to glucose spikes, primarily from high non-fiber carbohydrate meals. This constant high exposure of cells to insulin causes varying degrees of insulin resistance depending on the cell type, similar to being in a room with a powerful odor where one's ability to smell that odor diminishes over time. I believe the same happens with leptin, whereby repeatedly high spikes in leptin in response to particular nutrients including sugars (including those from non-fiber carbohydrates) and certain amino acids, result in leptin resistance. The leptin resistance then diminishes the body's attempt to tell the brain how much fat is stored i.e. how fat it is, thereby impairing leptin's ability to properly regulate fat storage, not just how much, but also where it is stored, being then overly stored in visceral tissues. I talked about this many years ago, a good example being the following; http://articles.mercola.com/sites/articles/archive/2004/12/01/leptin1.aspx

As far as the relationship between insulin and leptin, I will quote myself from that article of seven years ago; ???Metabolism can roughly be defined as the chemistry that turns food into life, and therefore insulin and leptin are critical to health and disease. Insulin works mostly at the individual cell level, telling the vast majority of cells whether to burn or store fat or sugar and whether to utilize that energy for maintenance and repair or reproduction.

Leptin, on the other hand, controls the energy storage and utilization of the entire republic of cells allowing the body to communicate with the brain about how much energy (fat) the republic has stored, and whether it needs more, or should burn some off, and whether it is an advantageous time nutritionally-speaking for the republic to reproduce or not."

Insulin is evolutionarily older and harks from a time when glucose was a primary fuel in single-celled organisms prior to oxygen inhabiting much of the atmosphere. That took plant life to inhabit the earth. Fatty acid oxidation requires oxygen and thus it had to wait for oxygen to be available. However in humans, fat is meant to be our primary fuel, with glucose available as an emergency anaerobic backup, i.e. for severe and emergency situations, such as running from a sabertooth tiger (that we have carried into the future as stress-related work situations where the elevated sugar is not burned causing continued adverse effects on glycation, insulin resistance, leptin resistance etc.)

Now, however, oxygen is readily available and now fat ought to be the primary fuel burned. The fact that it is not, and glucose is in most people, is, in my opinion, the primary cause of the chronic diseases of aging and accelerated aging itself. The control of fat metabolism is paramount, and the primary hormone that controls this is leptin.

Even in those physiologic situations in humans where insulin is thought to be most important, such as glucose "regulation", leptin may even supersede insulin. New studies are showing that even small amounts of leptin infused centrally, through centrally mediated processes, can greatly alleviate, if not eliminate hyperglycemia in non-insulin producing animals. It apparently controls, to a great extent, gluconeogenesis in the liver perhaps centrally through the vagus nerve, and also by powerfully affecting the SNS. Rather than infusing leptin into the brain, however, we can increase leptin's sensitivity in the brain, to accomplish many of the same benefits on glucose and fat metabolism and therefore obesity, aging, and its chronic symptoms. The way to do this, I firmly believe, is rather than keep leptin high that many others are espousing, it is paradoxically much better to keep leptin low, just as low serum insulin in a non-type 1 diabetic indicates better insulin sensitivity and health, and high insulin indicates insulin resistance and frequently T2 diabetes. Lower leptin is also a nearly universal finding in caloric restricted animals, with many believing that this is partly responsible for the reduced aging phenotype and its benefits.

To keep leptin levels low, and to prevent the chronic spikes in leptin that I believe are responsible primarily for leptin resistance, one must avoid those foods that cause these spikes. These foods are sugars, including those from starches, and the metabolism of particular amino acids from excess protein. Oddly enough, the macronutrient that least affects spikes in leptin are fats. I have written much over the years on this subject and a simple Google search under my name should find some of these.

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 03:44 AM

"Obesity due to leptin resistance is not one disease. It appears to be multifactorial in etiology".. I believe that leptin resistance itself can and should be called a disease, and then it causes multiple metabolic derangements that can lead to obesity and many other symptoms that are then generally called diseases.

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 03:33 AM

Dr. K; I may have misunderstood what you were trying to say about leptin at the hypothalamus, and if so, I apologize. Please clarify.

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 01:37 AM

This, by the way, comes from one who, through numerous talks around the world from over 15 years ago, was largely responsible for popularizing the importance of insulin and insulin resistance. Please see, "Insulin and its Metabolic Effects" that is all over the Internet.. I still believe that insulin is tremendously important and works in concert with leptin to regulate sugar and fat metabolism, and therefore much of chronic disease..

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 02:06 AM

To restore and maintain leptin sensitivity, I feel it is best to keep leptin levels low by maintaining a low, non-fiber carbohydrate, moderate protein diet as much as possible. I have not likely read the “set point” theory that you are referring to, but the “set point” that has been talked about for decades pertaining to body weight and fat storage is set and regulated by hypothalamic signals that in turn are controlled more by leptin sensitivity I feel than any other factor.

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 03:16 AM

"Excess palmitic acid from excess carbohydrate intake" is not the major signaling factor for leptin at the hypothalamus. It is leptin itself, leptin being a major signaling hormone, perhaps the major signaling molecule in the hypothalamus, regulating most everything it does. Palmitic acid is not. It's major function is for storage in triglycerides as what I call second generation carbohydrates.

5dffdd2f807170dcc66d6d687f4e2ba4

on April 27, 2011
at 03:27 AM

The detrimental effects of fructose metabolism, fructose being an isomer of glucose and therefore metabolized differently, has been known for well over a decade and far preceded Lustig. The primary detriment of fructose is that it readily is converted into and stored as fat in the liver contributing to fatty liver and therefore hepatic insulin resistance. Hyperleptinemia is perhaps even more important in this regard.

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 27, 2011
at 02:22 AM

Excess palmitic acid from excess carbohydrate intake is the major signaling factor at the hypothalamus for leptin. De novo lipogenesis plays a roll in this. Lustig and others believe that is precisely how fructose has shifted the NHANES curves for kids. Lustig also has interesting ideas on "other" forms of obesity as well. Obesity due to leptin resistance is not one disease. It appears to be multifactorial in etiology. Once leptin resistance sets in it effects the delicate relationship of PPAR gamma, mitochondrial signaling, and hormonal regulation of metabolism.

66e6b190e62fb3bcf42d4c60801c7bf6

(12407)

on April 27, 2011
at 01:38 AM

Thank you for your comments, dr. So, if a person is trying to lose bodyfat, do they still keep carbohydrates low or does cycling carbohydrates a la a cyclical ketogenic approach more conducive to making one more leptin sensitive? also, what do you think about the "set point" theory?

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 27, 2011
at 02:27 AM

Amgen's trials on their synthetic leptin drugs have completely changed the way research scientists are now looking at leptin function and signaling. As Dr Rosedale speaks of it appears after someone has lost a ton of weight normally or via bypass surgery their response to infusion of leptin is paradoxical and we believe now it has to due with the context of receptors and the IGF 1 pathways and the interaction at PPAR gamma with hormonal influence and biochemical signaling of the mitochondria and the state of backround inflammation in the cytosol and leakiness of the first cytochrome.

4
47a42b6be94caf700fce9509e38bb6a4

(9647)

on April 25, 2011
at 11:06 PM

Yes, it appears leptin regulation trumps insulin regulation, but if we don't know what causes leptin resistance then it's not really very helpful to know this. I'll attempt to explain what I mean.

If (barring massive and conscious overeating) we are obese if and only if we are leptin resistant, then our being leptin resistant doesn't tell us anything helpful. All we have done in that case is to rename obesity. It would be like this: "Why am I obese when I never gain weight and never lose weight?" "Well, you have leptin resistance." "What's leptin?" "It's a messenger hormone that operates on a negative feedback loop. The more fat mass you have, the more leptin you produce, which is a signal to your body to eat less. But if you have leptin resistance then you're producing plenty of leptin, but your brain is resistant to its effects, so you keep eating." "OK, so you're telling me that I'm obese because my brain doesn't recognize the hormone that tells me not to be obese." "Yes." "So how is that helpful?"

And if the response is instead: "well, there are methods that are shown to decrease leptin resistance," then my response would be: good, but if there's no obesity without leptin resistance, then you're just telling me, effectively: "there are methods that are shown to decrease the fat mass setpoint." In which case ... Please do tell me about them!

If (notice I said "if" from the very beginning) it is correct that we are obese if and only if we are leptin resistant, then it is obviously a good thing to be aware of that fact, especially if you're an obesity researcher; you can look at the various things in the body that interact with leptin, etc. So it will help get you on the right track. But if what we laypeople are interested in is what we should eat and how we should exercise to stay thin -- that is, what we can actually do about it -- then I don't see how knowing about leptin helps us.

We have our suspicions about what causes obesity. One possibility is fructose. Lots of evidence for that; might do something to the liver, etc., etc. Another possibility is fructose + high PUFA. This one seems to work well with lab mice; in fact if you need to get your mice fat that's a pretty reliable way to do it.

Maybe when Stephan comes out with his grand theory (and I am pretty excited) he'll be able to account for all of the different causes of obesity (and, along with them, the different causes of weight loss). I would bet that the last few phrases of the theory will be: ".... which causes leptin resistance, which means the brain isn't getting the message that it has body fat to burn, which means a high body-fat setpoint is retained." That will be the last part of the theory -- but it's what comes before it that interests me.

3
40c6ba923990736e21efd26cbcb2fcba

on April 25, 2011
at 07:20 PM

Acupuncture is not pseudoscience. People's interpretation can be flawed but acupuncture is a physical therapy sometimes it works and sometimes it doesn't. No different than another modality.

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 25, 2011
at 10:27 PM

Lots of stuff I have done did not work.....and its called medicine. This is a problem patients have......medicine is an art meshed within a science. Not all we do works and not all we dont do does not either.

2f54dbe892ec89b12d1db686568e885a

(919)

on April 26, 2011
at 08:41 AM

it works on racehorses - no placebo effect at work here

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on April 25, 2011
at 10:26 PM

i refer patients out for accupuncture and I dont think its pseudoscience. If it helps it helps.

4781cf8ae1bfcb558dfb056af17bea94

(4359)

on April 25, 2011
at 08:05 PM

I don't know how you could prove that results are not due to a placebo since patients obviously know when they are being stuck and when not. Or is the theory that it matters precisely where you get poked not only if you get poked? If so, are there randomized placebo trials where some people get poked in the wrong spot. are there trials in unconscience people? If not, it's kind of hard to falsify... Doesn't make it pseudoscience per se but makes it hard to believe.

06d21b99c58283ce575e36c4ecd4a458

(9948)

on September 07, 2013
at 01:28 AM

The only true criteria for acupuncture is...does the patient feel better?

0
8f4ff12a53a98f3b5814cfe242de0daa

(1075)

on April 25, 2011
at 07:16 PM

It does not have to be an either/or. Everything in your body has some modest amount of coordination. Insulin and leptin could have a strong physiological link.

(Not to use the above to endorse any pseudoscience craziness like acupuncture, just speaking to areas where a physical connection can be made).

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