The Law of Leptin

I’ll never forget the day I first heard about Prader-Willi Syndrome.

I was in the Neonatal Intensive Care Unit (NICU) at Strong Memorial Hospital in Rochester, New York. My twin babies Alexis and Zoe had just been born prematurely, each weighing less than one pound, seven ounces. There was a 4% chance that they would both survive and grow up without any disabilities. David and I were essentially living in the NICU, staring through the fiberglass of the Isolettes at our tiny, ET-like daughters, whispering prayers through the peep-holes.

In those infinite hours that now seem like they existed in a different Universe, we became very close with the parents of the other premature babies in the same small pod as Alexis and Zoe. The D2 pod.

One day, one of the D2 moms came back from a meeting with the Attending Physician looking hollow and tortured. She and I linked arms and walked over to the private pumping room to pump some breast milk, more out of habit than necessity—neither my twins nor her daughter could tolerate actual breast milk. It all got frozen for some sunny future time when we might get to bottle feed it to our hopefully-then-healthy babies.

I asked her what the doctor had said.

She said he’d told her that her daughter may have Prader-Willi Syndrome.

What’s that? I asked.

She described a rare condition marked by cognitive deficits, short stature, behavioral challenges, and a driving, all-consuming motivation to eat, leading to extreme morbid obesity and early death.

They say I’ll have to padlock my refrigerator door, she added.

I let it sink in.

I gave her a hug.

Then it dawned on me that her baby was currently struggling to eat anything at all…that was the biggest challenge she was having.

Yeah, she said. It starts out that way. Then in a few years the nonstop eating will kick in.

My own eating was under control by then, and had been for several years, but it did dawn on me that I could relate to her poor baby girl. Once upon a time, my refrigerator wasn’t safe in my presence, either.

My musings, it turns out, may not have been so very far off the mark.  A recent New York Times Magazine article on Prader-Willi Syndrome paints the picture of a continuum, with insatiable Prader-Willi eating on one end, regular each-bite-brings-you-closer-to-full eating on the other end, and the eating of most overweight and obese folks somewhere in-between, but maybe a bit closer to the Prader-Willi end.

It turns out that Prader-Willi Syndrome is caused by congenital abnormalities on chromosome 15 that lead, in some yet-to-be-discovered way, to the brain not being able to process leptin.


Once again, it all boils down to leptin.

Leptin is the “I’m not hungry and I feel like being active” hormone.

If we all had plenty of leptin circulating in our blood, and our brains could actually register it properly, everyone would be slender, energetic, and upbeat.

With leptin on board, we naturally stop eating because we feel full. Our metabolisms rev, and not only does this make us thin, it literally leads to a feeling of happiness.

In short, leptin makes us happy, thin, and free.

But without leptin on board, we become the human equivalents of the mice that first led scientists to discover leptin, just over 20 years ago.

“Positional cloning of the mouse obese gene and its human homologue”
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J (December 1994)
Nature372 (6505): 425–32. DOI:10.1038/372425a0. PMID 7984236

Those mice were missing the gene that makes leptin, and therefore they had none at all.

They practically never moved.


They just sat by the food trough and ate all day long.

And even though all they had to eat was generic rat pellets, they grew to be very, very fat.

The only way to get those mice to move was to switch the location of the food trough. Then they would waddle, slowly, over to the new location, and plop down and eat.

You could come back a week later and they’d still be there.


Were those mice morally defective?



Nah. They just needed some leptin.

And sure enough, given a few leptin injections, those mice lost interest in food, started voluntarily climbing into the hamster wheel, and got skinny again.


You know, I really wish I could have been a fly on the wall when the news of leptin first made its way into the boardrooms of the big pharmaceutical companies. I can just imagine the melee.

After all, hormones are easy to put into pills.

(Just think, “the pill.”)

And, just like with the pill, leptin could theoretically be manufactured in nearly endless synthetic configurations.

Each totally patentable.

And each worth billions. Maybe trillions.

But as fate, or biology, would have it, the celebrations were premature.

“Leptin resistance – or why leptin fails to work in obesity.”; El-HaschimiK., Lehnert H.
Experimental and Clinical Endocrinology & Diabetes 2003 Feb; 111(1): 2-7. DOI: 10.1055/s-2003-37492.

We all found out pretty quickly that leptin, in pill form, doesn’t make an overweight person lose weight.

Direct leptin injections don’t even make an overweight person lose weight.

Why not?

Well, generally speaking, people are not overweight because they are missing the gene that makes leptin. We don’t have the same problem that those mice did. They had no leptin at all. We do.

In fact, it turns out that overweight people have lots of leptin circulating in their blood. Even more leptin, ironically, than skinny people.

“Serum immunoreactive-leptin concentrations in normal-weight and obese humans”
Considine R, Sinha M, Heiman M, Kriauciunas A, Stephens T, Nyce M et al. (1996)
N. Engl. J. Med. 334 (5): 292—5. DOI:10.1056/NEJM199602013340503, PMID 8532024

This stands to reason, actually, because leptin is produced by fat cells.

Leptin is the feedback mechanism that evolved to keep the weight of a human being in equilibrium.

After an especially abundant harvest and several days of unrestrained eating (leading to a bit of weight gain), leptin is the signal that would kick in and say, “You don’t need to eat anymore right now. Ugh! That’s enough food! But wow, I feel great! Maybe I’ll go build a hut! Or find a mate! Or kill a wildebeest!”

So why isn’t the leptin feedback mechanism working today? What’s causing the malfunction of this finely-tuned system?

The general answer to this question has been known for many years, but the deeper, underlying cause was only discovered very recently.

The general answer is that people today are becoming leptin resistant. Their brains are not registering or “seeing” the leptin that’s circulating in their blood.

“Advances in understanding the interrelations between leptin resistance and obesity”
Haitao Pan, Jiao Guo, and Zhengquan Su
Physiology & Behavior (130)2014). 157–169. DOI:10.1016/j.physbeh.2014.04.003, ISSN 1873-507X, PMID 24726399

And hence, they sit on the couch every night and eat.

But what’s the underlying cause of leptin resistance?

This, my friends, is the holy grail of obesity research.

Solve the puzzle of leptin resistance, and you’ve cracked the code of the obesity pandemic.

And just recently, it happened.

Researchers at UCSF medical center discovered what’s causing widespread leptin resistance.

The cause is INSULIN.

Yup, insulin.

Insulin is blocking leptin in the brain.

“Fat Chance: Beating the Odds Against Sugar, Processed Food, Obesity, and Disease”; Lustig, Robert H.
Plume: New York, 2012, page 47.

Where does this happen?

Well, it used to be thought that it happened in the hypothalamus, which governs most eating behavior. But more recent research shows that the blockage may be even deeper, down in the brain stem.

So rising insulin levels are a key cause of the obesity pandemic we’re now faced with. And it’s affecting us very early in life. Research on overweight kids has shown that their average insulin levels rise 45% from grade school to high school. They’re being set up for a lifetime of obesity by the rewiring of their brains that happens with every bite they take.

And note that we’re talking about “average” insulin levels. We’re not talking about the insulin spike cause by eating some one-off snack out of a vending machine.

So what’s the treatment? What can we do?

Clearly, we have to lower insulin levels. And not right-after-eating insulin levels, but 24/7/365 insulin levels.

But why have our insulin levels gotten so high in the first place?

I have two words for you.

You guessed them.


The average American is consuming 152 pounds of sugar and 146 pounds of flour each year. That’s nearly ONE POUND of sugar and flour per-person EACH DAY.

(And some of us don’t eat any sugar and flour, so some folks are eating way more than that, to round out the average.)

Sugar and flour aren’t foods, my friends. They are toxic drugs.


That’s not an opinion, that’s a scientific fact.

The technical description for sugar is a “chronic, dose-dependent, hepatotoxin.”

That’s “toxin” as in “poison.”

Sugar is a “hepatotoxin” because it’s made up of fructose, which, in high quantities, specifically damages the liver.

Flour is a “chronic, dose-dependent toxin” because its toxic affects aren’t limited to the liver. Flour is made up of glucose, which is processed everywhere, so at high levels, flour damages every cell in the body.

Wheat flour concentrates the complex carbohydrate amylopectin-A which is digested to produce glucose. It spikes blood sugar more than other starches. Willam Davis, Wheat Belly: Lose the Wheat, Lose the Weight, and Find Your Path Back to Health (New York: Rodale, 2011), p. 33.

What can we do when the foods we’re eating are poisoning us?

And what about our kids?

What can we do when the foods our kids are eating, in school, at camp, in restaurants, and at home, are threatening their lives?

That’s exactly the question that every parent of a child with Prader-Willi Syndrome has to face.

So, not surprisingly, we can learn a lot from the treatment of Prader-Willi Syndrome.

There aren’t a lot of inpatient treatment centers for Prader-Willi, but one of the best is the Center for Prader-Willi Syndrome at the Children’s Institute of Pittsburgh.

How do they handle food at the Center for Prader-Willi Syndrome when their patients have been known to lie, steal, and even break into neighbor’s houses to get food? Some patients are so obsessed with eating that if they get their hands on an unlimited supply of food they might literally eat until their stomach linings rupture and they die.

Not surprisingly, the inpatient clinic has developed some pretty great strategies for feeding their patients.

And they work.

Funny enough, their approach dovetails nicely with Bright Line Eating™, especially the Bright Lines of MEALS and QUANTITIES.

At the Center for Prader-Willi Syndrome, nobody eats anything outside of meal time. All food cues have been removed. In fact, food is not even on the floor that houses the patients. Food arrives on trays right at meal time, and then everything is taken away. Quantities are weighed and measured.

Do the patients lose weight? Of course they do.

But what happens to them psychologically when they are cut off from access to the food they crave so much?

Can they withstand the torture?

Well, just like anyone who does Bright Line Eating™ will tell you, it’s hard for them at first, but it doesn’t stay that hard forever.

In fact, after a brief adjustment period, they’re not tortured at all.

They’re happy.

And what about the rest of us?

It turned out that my friend’s daughter didn’t have Prader-Willi Syndrome after all. And Alexis and Zoe hit the 4% miracle jackpot and are growing up happy and healthy.

All three of them dodged those early bullets. But they have now been released into the general population, where insulin levels are rising, poisons are peddled as treats, and moms and dads are left to scramble and do their best to figure out how to serve their kids real food.

Is my friend’s daughter better off? Without question. But I have to say that my heart warms when I think of the patients at the Center for Prader-Willi Syndrome at the Children’s Institute of Pittsburgh. The Bright Lines around food that the Center diligently maintains are keeping them happy and safe. If you ask them, they’ll tell you that they are getting to live in the only environment they have ever known where they can finally stop thinking about food and start living life.

With love,


P.S. — As always, I look forward to reading your comments. Scroll down and share your thoughts!


  1. Tatia Nelson

    I love this! It explains how the product Skinny Secret works! The product has ingredients that lower insulin and others that raise satiety. It gives the recipient a window of time for their brain to recognize Leptin. This effectively helps them avoid food for an hour. Many feel creative or a desire to be active during this time.
    I really love your description, it helped me understand why this works so well!
    Thank you!

    Reply ·
  2. RachealQBabcock

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    Reply ·
  3. Cheryl

    Thanks for all your research and trying your best to inform us on living a healthier life style. There are probably many skeptic people. That goes with anything people can research their selves. This summer (July) I started the starch solution dr. Mcdougall. This really changed my life. I lost over 30 pounds. I told my chiropractor who started me on this diet plan. He gave me other recipes. He gave me plantkatie and straightupfood. What a change in my life I feel great! I have a question? What about the recipes that Dr. Mcdougal uses with flour? Do you recommend we continue to use. I have stop using flour Swansea January when I started a more plant base diet. I started losing again. Sorry I missed the registration for bright line eating. Look forward to next one!

    Reply ·
    1. Susan Peirce Thompson, Ph.D.

      Hey Cheryl,

      Registration is going to open again soon. Keep an eye out, and be sure to open emails from me in the coming days! Good things come to those who wait!!!


      Reply ·
  4. Oak

    So when you are asked for evidence you failed to produce any, could you please follow up with some real science? You said “Ha! You got me. I started looking up the references for things, found two, and couldn’t easily put my fingers on the other ones ” then failed to even link those two. You also said the volume is huge, but if it was then it wouldn’t be hard for me to google the science yet I cannot find anything to back your claims.


    Reply ·
    1. Susan Peirce Thompson, Ph.D.

      Hi Oak,

      Thanks for your patience with me. The Bright Line Eating Boot Camp was just launching and I was tending to 353 newly-registered Boot Campers from all around the world, plus teaching 4 college courses and mothering my 3 small children. I wasn’t intending to be dismissive with my “Ha! You got me” but definitely hand-wavy, as I knew it might take some time before getting the references posted rose to the top of the to-do list.

      And actually, it was a good thing, because it spurred the creation of the Research Department for Bright Line Eating Solutions.

      It did indeed take a while to get all the citations linked. They are there now if you want to check them out. Been there for many weeks, actually.


      Reply ·
  5. Carrie

    Wow! I just watched your 2nd video and I am so blessed to have found this. While I am not obese or even overweight, I have found that I have an unhealthy addiction to food. I never knew why I was tired all the time, never felt like exercising, and eating way more than I told myself I would. What you said makes so much sense to me.

    This problem has kept me from truly reaching the body I have always wanted because of my lack of energy. Something that also confused me is that my husband doesn’t seem to have this issue which makes sense he would be less susceptible to it. I believe the only reason I’m not obese is the fact that I’m young with a semi-fast metabolism and we adopted a vegan diet about a year and a half ago.

    I will definitely be cutting those foods out of my diet for good. Thank you so much for this information, I am so grateful.

    Reply ·
  6. Roxanne B Sukol MD

    Let’s add each other to our blogrolls — wonderful and complementary info. Best wishes for your continued good health and good work. Roxanne Sukol @roxannesukolmd

    Reply ·
  7. Dane Rogers

    Yes, as Roberta and Debbie requested, please post published scientific references supporting your assertions. Thanks Much!

    Reply ·
    1. Susan Peirce Thompson, Ph.D.

      Hi Dane,

      In case you never went back to check, just wanted to tip you off that citations have been posted.


      Reply ·
  8. Mark Fleischman


    Bravo! This really took a lot of time and effort to type-out all of this, not to mention putting together all of the information in such a wonderfully coherent and easy to read way. I got a lot out of this and I do have a question.

    We all know that bread is made of flour and that we should stay away from it. However, flour from sprouted whole-wheat has its benefits, i.e., higher protein content. Do the benefits of flour from sprouted whole-wheat make it safe, safer or not safe when it comes to the spike of insulin when eating regular bread. Also, how about brown rice cakes/crackers (the round kind, one inch or so thick — know what I mean?)?

    Thank you so much,


    Reply ·
    1. Susan Peirce Thompson, Ph.D.

      Hey Mark,
      Your question about flour from sprouted whole wheat is a great one. The answer is that it helps a lot that it’s not in a highly processed form. The release of glucose into the blood stream will be much slower, which will mitigate many of the damaging effects. For some people, bread or other forms of sprouted whole wheat products will be a perfect addition to a healthy diet. But for people whose brains and bodies have been damaged and addicted already, these foods will probably still be too triggering. It all comes back to the Susceptibility Scale…the scale that measures how susceptible someone is to the addictive properties of refined foods.
      Does this help?

      Reply ·
  9. Eric

    Thanks for the great blog, Susan. Although I first became familiar with leptin from reading Jon Gabriel’s book The Gabriel Method, you provide a lot of detail and history I never knew before, and you describe it in a way that is easy to understand. Thanks for all of your posts!

    Reply ·
  10. Debbie

    Susan, thanks so much for this blog. It is one of the clearest & most engaging explanations of leptin and the leptin/insulin connection that I’ve read. As Roberta mentioned, references would be great to help explain it to others. And thanks for letting us know how all the babies turned out!

    Reply ·
    1. Susan Peirce Thompson, Ph.D.

      Hey Debbie,

      Citations have been posted for a while now…check them out!


      Reply ·
  11. David

    Very interesting, Susan!!!!!

    And, too, the whole world….”celebrates” birthdays/weddings and other special occasions most notably with Sugar accepted toxins/and generally in massive doses. Just thinking about how many bakeries there are/and Panera Surely, I have succumbed on far too many occasions/thinking/among other things/when I did think about it, that I could work it off……/food colorings and all. Thinking of Starbucks….Bakers Square…family gatherings….. It has been decades ago, but I can still remember walking about in Luxembourg and smelling the sweet bakery smells as you walk along…../some of which I am sure is planned/with well placed fans.

    As he is quoted so often/having a rather substantial “stage”/as Michael Pollan purportedly said: “Eat F O O D, not food-like substances.” And as they say/stay away from the center of the grocery store.

    By, as often as not, “Crowding out” – “that stuff” by consuming from the amazing array/numbers of plants that God has given to us/it is and can be such a wonderful and pleasurable journey of discovery…..fruits/nuts/seeds/…and hundreds of turnips/varieties of potatoes and yams/varieties of grapes – that so many miss….just is not even in their purview/just don’t look for/nor see it…..

    And I love the whole idea of “Mindful Eating”…..NOT sitting in front of the TV or Computer finding a place to focus on THE FOOD…..enjoying the way it looks/the smell/the flavors and taking T I M E to eat it so that one thing doesn’t just bump in to the next ….and you really don’t know of what you have consumed.

    Eating should be pleasurable/among the very greatest of life’s pleasures/and it should be fun!!!!!! A celebrations of God’s great bounty/all of the varieties that we can avail ourselves of/that comes to us from all over this great planet.

    F O O D….just thinking…is a four letter word. Maybe we should come up with some new words/and/or focus on the essence of sustenance, nourishment…….

    Thanks again for all of your insights and helpful thoughts.

    I am, having read this, SO VERY VERY VERY thankful and GRATEFUL that all the babies turned out/doing well/and the Mother’s doo!!!!!!

    Happy February/Valentine’s Day
    I can imagine Valentine’s Day is vary special in your household for many reasons.

    Reply ·
  12. Linden Morris Delrio

    Love the info on both flour and sugar being toxins!

    Reply ·
  13. Joseph Fleischman

    Susan, what a great blog! I think you outdid yourself on this one, which is no easy task. I have questions regarding a passage and although I imagine that you are quite busy, I wonder if you have time to respond. You wrote that “Flour is a ‘chronic, dose-dependent toxin’ because its poisonous affects aren’t limited to the liver. Flour is made up of glucose, which is processed everywhere, so at high levels, flour damages every cell in the body”. I wonder if you could elaborate on that point, and specifically, please respond to the following related questions: how does flour damage cells, and on average, what is the quantity of flour that triggers the damage?
    I love your blog! Please Keep it coming.

    Reply ·
    1. Susan Peirce Thompson, Ph.D.


      Flour is glucose, which causes insulin to be released and leads to weight gain…a small amount will be metabolized by the liver mitochondria for energy (people with huge energy needs, like kids, can eat a lot of glucose with few repercussions…they burn it up right away….that’s why I don’t worry so much that my kids eat a lot of pasta and crackers). But in adults, excess glucose gets will be converted to triglycerides and will promote cardiovascular disease. Glucose also binds to proteins in the cell, making them less flexible and promoting rapid aging, and releasing free radicals, also causing aging and tissue damage.

      The damaging dose depends on the person. In general, before the body is damaged through chronic exposure, the safe dose of sugar & flour is about half of what people are eating today. But once the blood sugar regulation system and the dopamine receptors in the nucleus accumbens get damaged through overexposure, that body/brain becomes trigger sensitive to further stimulation. So the safe dose for one person isn’t safe for another person.

      Hope this helps,

      Reply ·
  14. Roberta Joiner

    Great information in your blog, Susan! Would it be possible to have the citations for the research to share with friends who like to “see the evidence”? Reading this shows us that, if people with a genetic defect can regulate their eating and lepton levels through BLE, there is hope for the rest of us! Thanks!

    Reply ·
    1. Susan Peirce Thompson, Ph.D.

      Hi Roberta,
      Ha! You got me. I started looking up the references for things, found two, and couldn’t easily put my fingers on the other ones (I read so many things as a professor and also a consumer of popular books and blogs…I try to flag things that catch my attention, but still the volume is so huge, it can be hard to track down the right thing at the right time.) I’ve just released the first video in a 3-part free video series on the psychology and neuroscience of sustainable weight loss and nearly 3000 people have seen it and are sending me comments and questions, so my bandwidth to chase this down is a little limited right now. When I catch a breath I will backtrack and post the links to the sources.
      Thanks for your patience,

      Reply ·
    2. Susan Peirce Thompson, Ph.D.

      Hey Roberta,

      The citations have been posted for a while now, but I forgot to go back and reply to your comment to tip you off. If you want to re-read this blog and then get armed with the citations, now’s your chance. 😉


      P.S. — Thanks for your patience! With the Boot Camp happening and my professorship in full swing (teaching 4 classes), it took me a while to track down every last reference. There were a lot of them. Thanks, also to Dr. Nathan Denkin, head of the Research Department for Bright Line Eating Solutions. His help was invaluable.

      Reply ·
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