Leptin Part Deux: Liver

Readers Summary:

  1. Liver is the engine of metabolism and not the thyroid
  2. What does the liver do in normal metabolic conditions and in leptin resistance
  3. Where does cholesterol (LDL subtypes) fit into this leptin story.
  4. How does Metabolic Syndrome commence and why does it happen.
  5. Why your regular labs may be completely normal while you’re slowly dying.

Many people are under the assumption that the thyroid is the real key to metabolism. I can’t tell you how many meetings I have been to and heard this nonsense. It happened today while I was speaking to a dietician and nutritionist in a hospital. It’s just not correct. The liver is the engine of our body’s Ferrari! The thyroid is best described as the gas pedal for the engine and leptin is the electronic chip that controls the entire process. So we need to discuss some biochemistry now. Rub your head a few times before we start to increase your blood flow!

When humans eat a meal about 60% of the calories wind up in the liver to deliver energy to tissues between meals to sustain normal energy production. Another hormone, Glucagon, mediates this release of fuel. The remainder of the energy (40%) is sent packing to the peripheral tissues and the muscles where insulin allows the energy to enter the cells. If those cells are leptin sensitive they use all 40% of the calories with nothing left over. If they are leptin resistant the excess calories go directly back to the liver to be placed into fat storage (or stuck inside the liver cell) in fat cells because of the high insulin levels. The more fat that gets deposited, the higher leptin levels go over time. If the fat gets stuck in the liver it causes a large immune reaction driving up more inflammatory chemicals. When it gets to a critical level (different body fat levels for all people) the fat begins to make the bad stuff. (IL6 and TNF alpha)

At the liver level something new happens though. Because muscles (muscle leptin resistance) can no longer use the calories partitioned to them they return to the liver. Leptin resistance at the liver also down regulates the LDL receptor in the liver. This allows the LDL particle to stay in the blood longer making it more susceptible to oxidation and disease. The liver responds by packaging this fuel into LDL particles to get rid of it. If the meal is high in carbs it makes small dense LDL. (SdLDL) If the calories are high in fat or protein the LDL is intermediate or large fluffy LDL.(ILDL or VLDL) SdLDL is the particle that causes many chronic diseases when it is present in excess chronically. It correlates best with heart disease and stroke risk. This is the most important thing to take away from a lipid panel. You want this number as close to zero as possible. sdLDL also causes high blood pressure and atherosclerosis because it damages the vascular endothelium (lining of artery) and the LDL particle is small and dense so it fits between the endothelial cells and deposited in the arterial wall to make it a lead pipe. Before it gets into the artery wall it usually becomes oxidized (rusted) because it is chemically very sensitive to chemicals that cause oxidation. (IL6, TNF alpha, and ROS are some of these) The large fluffy VLDL are not a problem because they can not fit in vessel walls so most go to our fat under the control of LPL and hormone sensitive lipase. (Estrogen and testosterone levels determine where on the body this fat goes and stays!) This is the real reason why andropause and menopause cause weight gain in specific parts of your body as you age. Your sex steroid status varies with the amount of inflammation present at the cellular level. Understand that the inflammatory chemicals from the fat are what cause this to happen over time.

Having your liver make a ton of SdLDL is a huge problem for health. Eating carbs results in high sdLDL and not fat or protein. Fructose is a special carb that makes more sdLDL than another sugar we have because of how the liver has to handle it biochemically. The large amounts of these particles causes the liver to make a ton of triglyceride particles to store all the sdLDL’s for storage in the bad places like are arteries, viscera, heart or liver.

Key Point: Hepatic insulin resistance occurs when the liver decides all excess calories must be packaged and stored as fat which fuels the obesity. OK, reference point. When the liver is working well and not leptin resistant what does it do? Remember the 60/40 split of calories from a meal we spoke of earlier? The liver should use the stored 60% of those calories to feed the body fuel when we are not eating like during a fast or during sleep. This is done by raising the hormone glucagon to make fuel from the energy depots in the liver. This is how the body works to supply fuel it needs when we can’t eat or won’t eat. The liver is a fuel bank account for use in a rainy day when we are leptin sensitive. This pathway way does not work well at all when we are leptin resistant because the liver is spewing out excess fuel for storage instead of use.

When we are leptin resistant the end result is to package calories to fat in some form of LDL’s. That delivery has to leave the liver because there is a physical limit to how much fat can stay in the liver. If this process of LDL construction is chronic and overwhelms the liver, fat builds up inside the liver cell and causes extreme reactive oxygen species (ROS). Remember The Quilt’s levee number seven? These are the inflammatory chemicals that insidiously kill cells and are at the heart of all chronic diseases you know of. This process is called development of fatty liver or the Metabolic Syndrome. If the liver continues to be clogged with fat it physically grows and your waist size grows with it. This is why physicians are so concerned about your waist size. It also correlates with your blood test called an ultra sensitive CRP! As your waist grows your cardiac CRP goes higher too. But if you are paying attention to the 30,000 foot view here, the growth of your waist size is a very late development in your disease process. If your waist is large, you have been asking your liver work like mad to store this excess fuel for a long time. The end result for the patient is a sign of feeling of chronic fatigue. You also report a loss of energy if you are asked and it occurs slowly over time and nothing the doctor or you do seem to help. All your basal metabolic studies look fine. Your thyroid panel is unremarkable and you tell the doctor no matter how little you eat or as much as you exercise nothing seems to help the process. Does this sound familiar to anyone reading this? This is classic Leptin Resistance at the liver level!

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  1. Patricia Knigge says:

    I'm still with you. You make the complicated understandable. Thanks.

  2. Can fatty liver disease be quantified? Do trigycerides determine how badly you have it? And if so, is there a trig no. that indicates you don't have it anymore? Just curious… am really enjoying your posts. Thank you!

  3. pardon me, but i am so so confused. i thought leptin was in the hands of amylin? when both work the liver works properly.

    you innate leptin fear of resistance has me not wanting to touch food! jk, but i come from an anorexia nervosa past, recently weight restored and am trying to put the pieces of the puzzle together from a NON obese point

    your home page about the meniscus leading to spine trouble made me lose my breath! last year i sprained both meniscuc's and ACL's in bot knees and ever since the weeks of straight casts have had horrible bone/joint and spine trouble.

    if one become osteoporosis, is it possible to not become leptin resistant then>? and is there any help besides expensive leptin injections to help bones/leptin?

  4. @Carol Yes it can be. They way I do it is unusual because I am a neurosurgeon. When I work up my spine patients I always ask the MRI techs to show the abdominal cavity to assess the amount of fat in the viscera and sometimes I get lucky and see the liver and all the fat. Some GI docs will biopsy it. You can ultrasound it too……But the easiest way to assess it is to look at how high your TG level is and how low your HDL level is and how high your cardiac CRP is. If your still unsure after that…..Rarely I might add then you can do a RevT3. Fatty liver always makes you cardiac or HS CRP shoot high. You want your HS CRP as close to zero as possible. You want your HDL if your a women above sixty, and you want your TG below 50. To do that you must eat a paleolithic diet. A ketogenic diet will work but if youre atkinsesque in your approach you will eat too many omega six's and never get where you need to be. I am a huge advocate of Robb Wolf's The Paleo Solution for a diet. I write Rx for it daily in my office. In my view the best book on what to eat…….But not how to eat. That will be covered soon in this blog.

  5. @Mallory Amylin is a small player. I think if you read the blog you got this. You do need amylin to work with leptin to get proper gluconeogenesis and proper hormonal signaling in the gut, brain and from the HPA. I dont wont to get too complex yet……but i promise I will eventually. My goal is to make all this biochemistry clear as day to you. Once you get it you will be better than any dietician, nutritionist or doctor in this area of your health.

    The Meniscus and spine issue are tied together because of leptin. Any process in the body that requires energy is completely beholden to leptin functioning correctly. I tore my Knee Meniscus because my HS-cRP was elevated due to leptin resistance. If the leptin resistance is more chronic it will cause osteoporosis as well because bone metabolism requires unreal amounts of energy. So if you cant harness that energy the two systems that control bone density fail slowly. Those sides are the osteoblasts and osteoclasts. Both cell lines are directly tied to leptin sensitivity. And you can get osteoporosis from anorexia. I have seen that many times as well. It does not matter if you are leptin resistant from obesity or from anorexia…..the effect on your biology is the same. That is the point of levee one in The Quilt. Anything that effects the cellular terroir can determine the ultimate fate of the cell. Leptin injections don't repair it……restoring your leptin sensitivity will. And that is easy to do. You just have to wait until I unless that blog……but its coming. Hope this helps.

  6. Please share this information with your friends on your social networks too. I think this information is important to get out. We can help save people with a thought.

  7. This is great, it is in-line with what I have read before but I simply haven't connected the dots myself. No wonder you're always talking about context, it looks like many of the things that people obsess about are minutiae compared with the inflammatory side of these things. Is sugar bad for you? Yes, but what really causes NAFLD? Leptin resistance and heptatic inflammation/oxidative stress, amongst other smaller factors. Getting that inflammation under control and keeping it under control indefinitely is paramount, I used to try to convey this message to nutrition newbies but it's a bit hard. How do you do it with your patients?

  8. Resurgent says:

    I second Stabby's question.! How does one get this across – From a doctor to a patient, it can sound like a prescription – But to 'Nutrionists' drunk on the CW or AHA or USDA nectar.??

    • Resurg I promise I will tell you……here and at Paleohacks.com Patrik does not want me talking about this kind of stuff over there because he wants his site to run by his game plan and I respect that. I am new to this medium and I do not know the proper protocols. I thought we were all like minded hacks and that information sharing is out MO. I wont over promise and under deliver because the question you raise is the reason I stopped work on my books and decided to go live here and share my theories and my vision for healthcare.

      We can and we will change the world……one person at a time if we must.

  9. Sparkle Lucis says:

    Outstanding post. I was examining regularly this blog and boy, I am love your work! Very useful details, particularly the final aspect :-)

  10. Thanks Jack… I skimmed Robb Wolf's website last week and I looked at his Quick Start Guide…. http://robbwolf.com/wp/wp-content/uploads/2010/09

    It is exactly what I'm eating on the Atkins induction plan… minus the nuts and serving of fruit that Robb mentions.

    I can't see how Atkins increases omega 6s at all. There is no recommendation for nut or vegetable oils, margarine etc. on the plan. Is there something I am missing?

    Thanks again.

  11. Dr Kruse,

    You spoke of leptin resistance being possible for the underweight as well as the over weight.

    One year ago I went low carb paleo (moderate calorie 2700)dropping grains except a small amount of rice, eating mostly meat, eggs, seafood, vegetables very similar to Panu or what paleohacks might endorse. I quickly and ran into problems.

    I dropped weight fast, got really skinny then ran into the "bone crushing" lack of energy you mentioned – good way to put it. Was leptin resistance a possibility?

    I added carbs about 4 months in and things improved until a 2 months ago when I developed right side weakness, limbs, hip shoulder.

    I am now at a loss as to what has happened. Do I have MS, ALS or some other neural condition. Nothing has been diagnosed yet but I have a nerve conduction test next week.

    I have read with interest your thoughts on mitochondria on paleohacks, does this tie in with leptin resistance. My thyroid panel was within limits and of course my Doc did not do reverse T3 even though he said he was. Thankyou.

  12. First, thank you for this blog. You are teaching a lot of people to fish – and I love fish.

    Second, I am confused about how an underweight person can be as leptin resistant as on overweight person. I thought that hormonal resistance developed from overproduction (from eating too much and too many carbs). Wouldn't an underweight person (specifically someone who is not eating enough for their metabolism) be underproducing leptin which would make them super sensitive (once adequate energy is taken in)?

    Third, you may not be at this point yet but here goes – if leptin sensitivity optimizes our metabolism by enabling us to burn fat and not sugar, is it not advisable then to perform glycolytic exercise? Or is that type of exercise a good way to "detox" from the inevitable endogenous sugar we produce naturally?

    • meredith…..anorexia at its core is also an inflammatory condition. When a person starves them selves because their is no food or because they have anorexia the effect is that the thyroid is down regulated to preserve energy by leptin. When this happens chronically it raises a specific cytokine that damages the hypothalamus and causes a positive feedback loop to develop and anorexia is the result of that loop. Biochemically both the obese and anorexic will have markedly elevated rev T3. We also see this same phenomena in patients with long ICU stays. The pathway to get to the reverse T3 is different……but the result is the same. go back and listen to my podcast with Jimmy Moore. I mention this mechanism with him there. Listen for the I 40 reference and going to met Jimmy in South Carolina. I hope this gives some clarity

  13. I'll listen again, thanks so much.

  14. Diane S says:

    Hi Jack,

    Just wanted to say thank you! I lost 7lbs. last week just by getting rid of ALL the grains like you said!Sid just ordered the Leptin Diet book for us. He lost 9 lbs. this week. My question is Sid,Rob & Eli had the runs all week but I haven't,saw on Byron's site today that they are lossing the water retained, due to all the protein we are eating but I didnt have the runs do you know why?

    Thanks for listening!!

    A very grateful sister

  15. The runs are from the leaky gut you have as well. That has to be repaired. To get a head start on this you need to eat sauerkraut, dill pickles, kombucha, and horseradish type fermented veggies. Those foods get modified in your gut to small chain fatty acids called buytric acid. That acid is found in pastured butter. Organic Valley or Kerry Gold. Every veggie you cook should be in this type of butter or extra virgin cold pressed coconut oil. Coconut oil is the best treatment for a leaky gut. Supplementing with omega three fish oil heals this up even quicker. You can not sustain weight loss if you have a leaky gut.

  16. @Perry you definitely need a work up. Several things come to mind. I can not offer you treatment here but I can tell you you should ask and get your rev. T3 and get a salivary cortisol level done, and an omega 6/3 index. I bet those help fix you. I do think you may have a leptin issue and a cortisol one. You can order the labs yourself from LEF.org or ZRTlabs.com Don't settle for less than optimal.

  17. @Carol…..omega six's in ATKINS foods are everywhere. Mostly in the oils they use and the soy the sneak in. Soybean, canola, veggie oils, and most nut oils outside of macadamia nut oils are horrible because of their omega six content. Anything with soy should be avoided. It is my belief that if Dr Atkins were alive today he would strip his foods of the omega 6's. The people running hsi business are no longer physicians. They are businessmen who will use omega 6 oils to drive costs down. That move kills you. Omega 6's are probably the worse thing in the American diet if you ask me. Atkins was a true pioneer who wanted to change the system. The system instead tried for 30 years to destroy him. Here is another thing to realize……most grains and veggies have a 6 to 1 to 10 to 1 omega six to three ratio. High levels of omega six in the body is another cause of leptin resistance that I have not covered yet. Remember anything that increases inflammation can cause obesity……and omega six are metabolized through the Arachadonic acid pathways to lead to inflammatory cytokines that destroy us. I just previewed the ROS levee for you early!!! LOL You can google anything I saw here to check my facts. I want you to be a closet biochemist because then you will not have to rely on anyone to tell you what is good or not for your health.

  18. Diane S says:

    Jack what is the best way for me to build up my spine so that I dont have to go thru the pain of a sugery. I know I need to stop smoking, im trying. I feel good some days and bad others is laying flat a good way for me to stretch my back out, I've been sleeping in a lazy boy cause I cant sleep in the bed.What should i do? It's my L3,4&5 now. Getting worse I guess.

    thanks Eli

  19. I've been "drinking" phsylium husks or chia seeds – are those considered grains?

    I'm going to have a difficult time giving up lentils, what about the fiber needed in our diet, how do we get?

    • Yes they are. Avoid them. There is no need for fiber. More convention wisdom that is a myth. I would recommend you get a copy of Robb Wolfs book so you are straight on the fuel. Its critical. You can eat lentils……if you are ok being OK and not optimal. That is your choice. My goal is to show you optimal. Robb's podcasts are rockstarish too. Sometimes he talks deep like I write but he is so correct its worth it to listen. Anyone who tries to educate the public to me should be supported.

  20. Thanks for writing this entry. I really enjoyed it. Keep up the awesome work, dude!

  21. This is great information. Thank you for putting it into a mostly understandable package. You're knowledge is well above my level, but I have been around the medical/nutrition area enough that I am able to follow along with your easy explanations (car metaphors help this gearhead out, too :-D )

  22. hey dr Jack! i just found your blog…LOVE the leptin posts!!!! thanks for making it easy to understand. i have been diagnosed w/ "low thyroid" and placed on a small dose of armour…but i feel like i am still missing something /low energy — thanks for showing me the right direction via leptin resistance:) Also, any thoughts on what causes/contributes to pre-eclampsia?! i really feel like that "did me in" and things haven't been the same since my twins were born 5 yrs ago. Many thanks!! your site rocks–

    • Thanks…..and yes I think most thyroid problems can be best solved by regaining your leptin sensitivity first. Once you realize that leptin fuels a rise in reverse T3 and this shuts down your thyroid things get easier to manage clinically. Problem arises when you explain this to an endocrinologist who thinks its the thyroid. That gland is in control of nothing. It answers to higher centers of control. It is a foot soldier in the army of metabolism signals.

  23. Mike Ellwood says:

    Dr Kruse,

    For those of us who have been low-carbing and and reading Gary Taubes since 2007, this emphasis on leptin resistance, as opposed to insulin resistance, comes as something of a surprise. I am open-minded and willing to be convinced, but I'm wondering where the evidence is (for example) that leptin trumps insulin. How come Gary didn't find it when he was writing GC, BC, or even WWGF? Leptin gets one mention in GC, BC in the prologue, while insulin is mentioned all the time.

    One could re-write the article above replacing all instances of leptin-resistance with insulin-resistance, and it might read like something that Gary Taubes might have written.

    You have not yet convinced me of the uniqueness or special role of leptin.

  24. Mike if you talk to Jimmy Moore he has spoken to Gary about this issue. It is not Garys goal. His goal is to get people to acknowledge that what is dogma now is not supported by any data. He is not a looking at causation as we are. My point is this to you. For forty years doctors have been targeting insulin for type 2 diabetics. Have we cured them? We now have 60 million and many in my profession believe there are 150 million undiagnosed because the screening tests we are using are archaic. The recent ACCORD trial showed that with the best medical care we can offer these people still die 6 years earlier from their disease. The implications for that data to me were astouding. We no longer can accept treatment of type two diabetes. We need to eradicate it to give them their years back. You can't cure a disease when you aiming at the wrong target in insulin. That is why you have seen no drop in the incidence of DM with treatments we offer. It gets worse every year. The NHANES curves keep shifting every decade and the now the curves are effecting kids. If you solve leptin resistance you can solve diabetes. I know because I have done it to many patients and I am not an internal medicine doctor. It can be eradicated.

  25. @ Mike Leptin was discovered in 1994. When GCBC was published in 2007 there were only 7000 publications on leptin. Gary began writing the book in 2001 so he was not aware of the implications of the research going on then. He knows about it now. I have heard him speak about it recently. In the last five years the number of leptin cites is now over 30,000. Knowledge evolves Mike. Gary could never have written about leptin because there was not much known and how it coupled energy metabolism to the brain. To convince yourself of the leptin link you need to study the ob/ob mice knock out studies they did on leptin and insulin. Insulin showed no control of energy balance centrally in the brain. All insulin does is allow glucose entry into the cells for metabolism. It does not coordinate anything else and has no effect on leptin while leptin has massive effects on it. Google will help you find them.

  26. Hi – thank you so much for giving your time to this worthwhile cause. I plan to spend the next few days reading your blog. May I ask a question please?

    I spent most of my earlier years as a heavy drinker and gained a lot of weight. I quit 5 years ago (best thing I ever did of course) however surprisingly I didn't lose any weight at the time. I later lost weight eating reduced carb, and now eat about 80% paleo. I still carry quite a bit of weight around my middle. Do you think this is related to my past drinking? I will try out your recommendations here, but is there anything further I might do to reduce the middle which I presume is related to liver issues? I am a 48 year old female. Many thanks

    • very well could be because alcohol is an acute cerebral toxin, hence why you get drunk from it fast, but it is a chronic liver toxin. Remember, that the engine of your metabolism is your liver. So if you damaged it (likely) you most certainly will have problems with belly fat. The key for you is to go strict paleo as outlined in Robb Wolf's book but you definitely need a real good supplement plan to augment your liver. I will be talking supplements somewhere down the road because I am a huge believer in the quantified self approach to healthcare. It give patients their control back. What you should do is get a HS cRP and vitamin D level to begin. You goal is to have the HS CRP below 0.5 and vitamin D 70-100 ng/dl. Then you want to add NAC, Fever Few, Resveratrol, quercetin, curcumin, vitamin K2, and a lot of b complex vitamins. Liver patients need a lot of B vitamins but I base that off organic acid tests from the gut work up. Good Luck

  27. Thank you very much for taking the time to reply. I'm off to the shops this morning!!

  28. Mike Ellwood says:

    Dear Dr Kruse,

    Thank you for your two replies. I don't want to waste your time, but I'm afraid you still haven't convinced me.

    By the way, Gary was in an interview on a podcast with Greg Everett and Rob Wolf on (I think) 3rd May 2011 in which he was asked about leptin.

    http://robbwolf.com/2011/05/03/the-paleo-solution

    He still thought it was "downstream of insulin". Of course he "knew about" leptin when GC, BC was published, but he didn't think it was what we should be focusing on, and it sounds like he hasn't changed his opinion much, as of May 3, 2011.

    But fair enough: Gary is a journalist and not a primary researcher. You say there are 30,000 citations on leptin in the literature now (which might just mean it is "fashionable", the latest bandwagon), and ask me (an admitted non-expert) to use google. Certainly I can and will use google, but I just, with great respect, ask you, an expert, who has said with great certainty that it's leptin we have to focus on and that leptin resistance comes before insulin resistance. Perhaps you could kindly point me to at least one of those 30,000 citations that demonstrates this, just to save me a little googling time.

    As far as I can see, you haven't even told us how leptin resistance starts, or is caused. At least Gary has given us a hypothesis as to how insulin resistance starts, and a plausible way of dealing with it, even if it may yet prove to be inaccurate in many details. (I've certainly read some plausible challenges to some of his details, but they don't seem to invalidate the broad picture).

    I know that Wikipedia is not the fount of all knowledge, but it may be regarded as the layman's shorthand to expert knowledge, so just a few excerpts which seem to suggest that all is not quite as certain as you do:

    "Traditionally, leptin has been regarded as a link between fat mass, food intake, and energy expenditure. This link originally arose from animal research findings, but its application to describing human systems has since been challenged.[36] In humans, there are many instances where leptin dissociates from the strict role of communicating nutritional status between body and brain and no longer correlates with body fat levels:"

    "Although leptin resistance is sometimes described as a metabolic disorder that contributes to obesity, similar to the way insulin resistance is sometimes described as a metabolic disorder that has the potential to progress into the type 2 diabetes, it is not certain that it is true in most cases. The mere fact that leptin resistance is extremely common in obese individuals suggests that it may simply be an adaptation to excess body weight."

    "Although leptin is a circulating signal that reduces appetite, obese individuals generally exhibit an unusually high circulating concentration of leptin.[55] These people are said to be resistant to the effects of leptin, in much the same way that people with type 2 diabetes are resistant to the effects of insulin. The high sustained concentrations of leptin from the enlarged adipose stores result in leptin desensitization."

    Wait a minute: I thought leptin resistance was supposed to CAUSE adiposity? That last sentence says that adiposity caused leptin resistance! If the science is really certain, then someone ought to let Wikipedia know about it.

    Regards,

    Mike

  29. @ Mike I answered you on Jimmy's forum. My goal is not to convince you. My goal is to make you think about why people struggle with these issues and you go and do your due diligence on these issues. I am quite confident once you do a light will be shone on this topic. Remain a skeptic but remember biochemistry is fact. Whether you believe it or not matters little because the beautiful thing about science the truth is the truth regardless of belief.

  30. Dear Doctor,

    Do you think that choline and inositol supplementation

    can be helpful in reducing the livers leptin resistence?

    I read from some medical papers these vitamins reduce fatty liver by helping it get rid of cholesterol and fat.

    My liver was slightly enlarged. I also had reactive hypoglycemia and have been cfs for a long time. Normal

    blood tests. Hydrocortisone+thyroid hormone help somewhat,

    but still fatigue.

    Thank you

  31. Dan Han says:

    Hi Dr. Kruse,

    I'm reading through your articles, so I understand omega-6's are bad and often found in veg oils/grains. So can I still eat lots of leafy greens and fresh vegetables? Or non-starchy vegs?

    Thanks!

  32. Hi Dr. Kruse,

    Like Peter, I am also curious about Choline and inositol supplementation? I have problems with a fatty liver also.

  33. @ Dan……great point often lost on many in the vegan community and some of those in the paleo community. I eat veggies but I tend to eat the same ones over and over again. Protein and Fat are my staples.

  34. At Peter I do think those supplements can and do help but I am a bigger fan of choline from foods. Eggs and Offal are the two best sources.

  35. Very interesting read. I got to your site through Art DeVany's blog. I live in Clarksville, TN. Wonder if you see patients for things other then Nuerosurgery. Finding a doctor who knows anything about nutrition and Paleo is very difficult. Mine just has a blank stare everytime I discuss it and ask for various readings he says I don't need in my blood work.

  36. @Ron I do but when I do its late in the day and no insurance. It takes a lot of time to cut through these things.

  37. Do you know of any interns or primary care docs who practice it or use it philosophically in their practice?

  38. @Ron yes I do but they are my referral docs. I am beginning to have an effect outside my sphere of reference because I have been asked to give talks to several PCP's in other states recently and will be doing those talks to help them help patients.

  39. MimiDiet says:

    Dr Kruse, your page on adrenal fatigue sounded EXACTLY like me, and this page on the liver reminded me of how I always have trouble fasting (for religious reasons). It seems I cannot pull stored energy from anyway, and grow so weak, in fact, that I end up on the couch barely able to move. (This has been the case for decades–can't fast!) This sounds like glucagon is not working.

    Is it likely that I am deficient in glucagon, or simply leptin resistant at the hepatic level? I am very hypoglycemic with severe hyperinsulinism documented by bloodwork (currently controlled on the Atkins diet, though I am still TIRED). Do I need to take glucagon or will leptin sensitivity likely solve this?

  40. MimiDiet says:

    P.S. My CMP came back normal, though for decades I had low cholesterol (total = 123). It is currently in the 180s, I think.

    My board-certified, wholistic dr said there is "something wrong with the liver" since I can't maintain blood sugar at all while fasting, but I'd like to to know more.

    I'm also hypothyroid, taking Armour. Each increased dose would help for awhile, but I go right back to tired. Dr now added Iodoral.

  41. @MimiDiet you my dear need to read what i just posted today……it may enlighten you further. http://jackkruse.com/your-vap-brain-love-not-war/

  42. MimiDiet says:

    Okay–interesting reading! So what do I do about this liver & brain involvement?

    I also should mention my C-reactive protein was astronomically high–11! I have chronic neck pain from a car accident almost 30 yrs ago in which I ate the steering wheel. They want to operate (insert a bone chip or something with titanium screws), but in c-7 area, while my pain is in C1-2 area. I say they're not slitting my throat until they figure out what's wrong with the part that hurts, b/c they're not doing it twice. Also not excited about titanium as I've had chronic cold sores for 2 yrs since having titanium dental implants. At any rate, I'm assuming my suddenly-high CRP is from chronic pain. My neck discs are shot.

  43. Federico Womack says:

    Thanks for another informative blog. Where else could I get that type of info written in such an ideal way? I've a mission that I'm just now working on, and I have been at the look out for such information.

  44. Hi, Dr. Kruse, I read the article you recommended, & looked up more info on what VAP is. Learned a lot; however, still not clear on what my issue is with inability to fast, & still tired on Armour thyroid? My TSH has never been high, suggesting secondary hypothyroid.

    Will a leptin reset really be like to fix ALL of this–inability to fast AND thyroid issues?

  45. *likely

  46. Yes. Took me over a decade to figure out that T2 diabetes is a liver disease.

    That's why milk thistle is a standard supp for me… right up there with D3.

  47. Jack, ARE YOU EVER COMING BACK TO THIS PAGE to answer our questions?? :D

  48. @Mimi your questions can only be answered by a doctor who is testing you and treating you. Your issues are too complex for an Internet forum. Can they be solved? Yes. This forum exists to answer questions that have answers in this format. I can't practice medicine for you here,

  49. Jack, when you finish the quilt, maybe you could work on cloning yourself. :) How would I find a doctor who even deals with leptin & adrenal fatigue? I have a board-certified semi-retired physician who deals with the adrenal fatigue (AMA notwithstanding), but not with leptin. I live near Richmond, VA. How do you find such a dr?

    And if my current wholistic board-cert dr is willing to learn about leptin etc, what blood tests should be run?

    • @Mimi We all have to help our doctors change. By you reading this and me sharing what I know you now have the knowledge to know what it is you must have in healthcare. Once you know what it is you seek it…….when you dont find it…….you help your doc become the doctor you always wanted. Its a joint partnership and you must not get frustrated. As you become optimal you doctor will take notice and start asking questions……..that is when you hit them with science. They will eventually change. Science has that kind of gravity . Most doctors dont want their patients telling them anything because the doctor patient relationship is viewed with a certain perception that it should not be looked at. Most Mds dont even know they are doing it subconsciously but ask any patient…….if they do. They do.

  50. Jack,

    On another thread you posted, "In a large clinical trial, a patented green tea phytosome extract produced exceptional weight loss in obese individuals. Supplemented subjects lost almost 31 lbs over 3 months, while controls lost just 11 pounds!"

    Sorry to ask this on the leptin thread but that thread is closed for comments. My question is…are you able to tell us the particular BRAND name/s that actually contain this "patented green tea phytosome?" :)

    • @MimiDiet I do not recommend brands on this site. I would suggest doing your due diligence using consumerlab.com. They check out most supplements to very what is contained and what is not.

  51. Thanks, I'll do that. What "phytosome" are we looking for?

    • @Mimidiet The Phytosome that works well is a highly bioavailable complex of green tea polyphenols with phosphatidylcholine. Check with consumerlabs.com to see who offers this.

  52. Hey there, You have performed a great job. I will certainly digg it and in my opinion suggest to my friends. I'm sure they'll be benefited from this site.

  53. Thanks!

  54. I said in another post, yesterday, that I didn't go to doctors. That is not 100 % true. I do go for blood work about every year or so, but never follower with their advice and have to go to a different doctor every time. You said, that the engine of your metabolism is your liver. This is exactly why I want to put myself on your leptin reset protocol. After reading this article, you confirmed that my intuition was spot on. My liver numbers were the highest they have ever been and I have been keeping track because I was diagnosed with Hep C 15 years ago. I have been one sick puppy. You recommend a number of vitamins and I am concerned over that because I am also homeopathically treated. I do take Vitamin B's and if allowed I would get B 12 shots every 6 weeks, however, no doctor will just give me those without treating other areas of my body so it won't happen. I sleep much better when taking the shots. I prefer getting Vitamin D from a reputable fish oil source because I have read negative things about taking Vitamin D-3. I just wish I knew of a doctor that would allow me to have complete control of own health care, but from my understanding they are not allowed to. I just stay away as much as I can. I am determined to regain my health.

    • @Susan If you build a relationship with the doctor they will help you. I think you should print your comment above and hand it to them……your honesty will touch them and they will try to help you.

  55. http://paleohacks.com/questions/83492/leptin-and-

    This link shows some work that is coming on board about leptin resistance at the liver level. Jeff the thread starter is a nutrition student I met at AHS and he is a great guy. Please read his post and up vote it.

    In animals, this is a rate-controlling step of gluconeogenesis, the process by which cells synthesize glucose from metabolic precursors. The blood glucose level is maintained within well-defined limits in part due to precise regulation of PEPCK gene expression. To emphasize the importance of PEPCK in glucose homeostasis, over expression of this enzyme in mice results in symptoms of type II diabetes mellitus, by far the most common form of diabetes in humans. Due to the importance of blood glucose homeostasis, a number of hormones regulate a set of genes (including PEPCK) in the liver that modulate the rate of glucose synthesis.

    PEPCK is controlled by two different hormonal mechanisms. PEPCK activity is increased upon the secretion of both cortisol from the adrenal cortex and glucagon from the alpha cells of the pancreas. Glucagon indirectly elevates the expression of PEPCK by increasing the levels of cAMP (via activation of adenylyl cyclase) in the liver which consequently phosphorylates the S133 on a beta sheet in the CREB protein. CREB then binds upstream of the PEPCK gene at CRE (cAMP response element) and induces PEPCK transcription. Cortisol on the other hand, when released by the adrenal cortex, passes through the lipid membrane of liver cells (due to its hydrophobic nature it can pass directly through cell membranes) and then binds to a Glucocorticoid Receptor (GR). This receptor dimerizes and the cortisol/GR complex passes into the nucleus where it then binds to the Glucocorticoid Response Element (GRE) region in a similar manner to CREB and produces similar results (synthesis of more PEPCK).

    Together, Cortisol and Glucagon can have huge synergistic results. Activating the PEPCK gene to levels that neither cortisol or glucagon could reach on their own.It is most abundant in the liver, kidney, and adipose tissue.[1]

    Researchers at Case Western Reserve University have discovered that overexpression of cytosolic PEPCK in skeletal muscle of mice causes them to be more active, more aggressive, and have longer lives than normal mice; see metabolic supermice.

    1.Chakravarty K, Cassuto H, Reshef L, Hanson RW (2005). "Factors that control the tissue-specific transcription of the gene for phosphoenolpyruvate carboxykinase-C". Critical reviews in biochemistry and molecular biology 40 (3): 129-54.

  56. Happy holidays to you and your family. I fee in my heart it is a time to slow down, be calm, and ponder on the changes we want to bring about that are important for our life's journey. Thanks for being so charitable to those of us who are in need.

  57. I am 46 year old female, good health and weight When I was in my 20s I could not go more than 4 hours without eating without a crash; usually resulting in irritability (just get me food!) and headaches, sometimes vomitting. My solution was to just eat often. About 10 years ago, I discovered the South beach diet and realized about how the glycemic index of food might be affecting my health. I started upping my protein and decreasing my high glycemic carbs, with some improvement (it helped control my weight with exercise, but I was probably still eating too much carbs). It kind of got me depressed though (probably the low fat thing)

    About 8 months ago, I discovered paleo, (eating 2-4 times daily, which is great for me) and this last summer got a glucose meter to try to get an idea of what was going on inside me. Recently, I attempted a 24 hour fast. (a solidarity thing for the Tar Sands … I am a biology teacher). I ate a fat and protein rich breaky but after 12 hours, I got the crash, blood glucose 2.5 mmol/L (yuck, but now I have numbers to quantify… yeah!). The length of time is better then a year ago, but still worrisome. My liver just seems to be not working right? I feel I am becoming a better fat burner (12 hours instead of 4) but do you think I have permanent epigenetic damage? My mother and sister are hypoglycaemic, so definitely some genetics there. I am wondering if a Leptin reset (I just discovered your blog) will actually make a difference?

  58. Hi doc — The good, bad and the ugly. First of all, I made it to the doctor. She was very understanding and read your testing recommendations and I was tested for everything unless it was very expensive. The T's are good. ; )Just mentioned it because I see it discussed much here. Calcuim was normal and D was good also. My calcium was always high, and so believe I have K2 to thank for the normal testing. Also, no H pylori. Now for the bad news. Hope you don't mind me writing it down.

    HDL 42 L — haven't felt good enough to exercise.

    Homocysteine Cardiovascular 11.9 H

    Creatinine 0.56 L

    Carbon Dioxide 18L

    Now for the really ugly

    AST 138 H

    ALT 154 H

    Hemoglobin A1c 5.8 H – no wonder I feel so crappy

    Red Blood cell count 5.46 H

    Hemoglobin 16.9 H

    Hematocrit 50.9

    Ferritin 247 H

    I have been doing the diet and taking the supplements you suggested. My doctor told me to quit taking everything for now. She is making an appointment with a liver specialist and that is where it stands for now. Really do not want treatment for my liver but will think about it. Might have to if I don't want to continue feeling the way I have for the last few years. I am not 100% on the paleo diet but getting there and eating much better then I was eating. I am able to get grass-fed butter, beef, and Offal. That is a BITE into my yarn addiction. :-)

    I am sorry this is long, but I wanted to ask you why you recommened feverfew to someone with liver problems? And, is there anything else you recommend besides Milk thistle–been there done that –no good.

    If it weren't for finding your blog I might not have gone to the doctor. I really want to thank you for that and everything you do. Susan

  59. Okay, scratch the above post, but will you please tell me why you recommend feverfew for the liver? I just can't figure out why you recommend it. I know there are liver headaches and I am thinking it has to do with those. A sort of constrictive headache at the top of the head. I have already decided I will not go to a GI a doctor because they simply have nothing to offer me but pain. I will do the paleo diet and homeopathy and refuse to take allopathic meds under any circumstances. HOnestly, it is the last question I will ever ask you.

    • @Susan feverfew=sillymarin It helps the liver flyer the blood of antioxidants so that our serum is more reduced than oxidized in the livers portal circulation. You want to improve you liver's ability to filter toxins well before the blood passes from the portal to the general circulation.

  60. Correction on the botanicals –

    Feverfew (Tanacetum parthenium), a member of the sunflower family, has been used for centuries in European folk medicine as a remedy for headaches, arthritis, and fevers. The name feverfew comes from a Latin word meaning "fever reducer."

    Silymarin, the active extract from milk thistle, is a complex of 7 flavonolignans and polyphenols. The most active compound in slymarin is silibinin. It has been extensively used in patients with liver disease. Milk thistle is commonly found growing wild in a variety of settings, including roadsides. The seeds of the dried milk thistle flower are used.

  61. Thanks Liane..I didn't think feverfew had silymarin in it and still not sure what it has to do with liver function. Also, I think Milk Thistle is some kind of folklore and ineffective. Can't figure out why blood work because all is a first for me, with the exception of liver tests. Since I am not going to a GI doctor, then I need to research extensively to find out how to help myself in that area. I now sleep and feel better since not eating grains. Haven't even attempted the Leptin Reset yet, but will when I work it out in my head.

  62. Hello Dr. Kruse, hope all is well with you. I have a quick question. In the past when I ate carrots why does my skin become orange? I have read that their is a liver/thyroid link. In Canada our testing is pretty archaic, so my doc thinks that my TSH of 5.5 is just fine. So I started to take lugols iodine and selenium. I am now much warmer, but still do not eat much in the way of orange food. By the way I am one full week into your leptin rx. Iam eating like crazy within the rules of 2-3 meals and no snacks. 2 days I have been able to go wth 2 meals and a tblsp of coconut oil in between. Last night I slept without waking for 6.5 hrs,got up for bathroom break and went back to sleep for another hour. I am so happy I could kiss you. I have had No stomach upset eating this much food either.Sleep is not over rated. Thanks again for your generosity.

    • @Angela That is front he beta carotene. No worries. IT IS A CO factor in the conversion of LDL cholesterol to pregnenolone sand requires T3 and Vitamin A (beta carotene is converted to it). Dietary carbs like natural sugars can lower circulating free fatty acids, amino acids, and cortisol when the surrounding environment is above 50 degrees and the light cycles are in spring or summer time mode. This might also activating the thyroid to produce more T3. In the winter and fall the cold has the ability to select for a different epigenetic program that requires a very low carbohydrate diet and it will still give you enough T3 to make you conversion. In fact cold increases production of DHEA to a great degree which dramatically lowers IL-6 and improves sleep. This is precisely how mammals hibernate thru the harshest of climates without food and thrive. That program is in us but we rarely use it in this neolithic world because we control our environment to a great degree.

  63. Sorry just need to understand this,"Dietary carbs like natural sugars can lower circulating free fatty acids, amino acids, and cortisol when the surrounding environment is above 50 degrees and the light cycles are in spring or summer time mode." So does this mean that with longer daylight hours,we do better on higher carbs? And we don't want circulating free fatty acids,amino acids, and cortisol during these higher carb times? But in shorter day light hours on a lower carb diet these circulating factors are not such a problem? Sorry, just trying to get it! Thanks again for making sence of this for us.

  64. So to further this concept of light cycles and carbs, how much of a carb increase do you advocate in the summer? And does that mean lowering your protein and fat content in relation to increasing carb content? And by carbs are you referring to increase in starchy veg or increasing fruit consumption? Just trying to figure out my future plan as we exit winter soon. Thanks again, you are way to cool!

    • @Angela……..read my blog. This laid out in excruciating detail. Go read the Leptin Rx and the Post Leptin Rx blogs. Most people who are LR start with the Leptin Rx……….and then move to the next one. I been post reset now 5 yrs. I eat totally tied to light and temp cycles.

  65. Thanks Dr. Kruse. Have a sunny day.

  66. Wonderful site! Thanks so much for sharing all your knowledge.

    I went Paleo 2 years ago and 6 months ago went very low carb while doing some pretty regular/intense exercise. I’ve been suffering from fatigue, insomnia, low body temp, very low blood pressure and a number of other adrenal/hypothyroid type symptoms. Going the adrenal fatigue route, I’ve tried a number of support supplements, ashwanganda, adrenal complex (bovine), licorice root. All seem to make me feel good at first but eventually overstimulate and lead to headaches and very bad insomnia.

    Your post makes me think that maybe I’ve just become leptin resistant (which has been causing blood sugar issues similar to adrenal fatigue) due to low carb/caloric restriction and too much exercise which completely overstressed my system. Do you think I might be on to something? I tried introducing more carbs thinking that maybe going low carb was the culprit and that it would help (trying to get 100-150/day), but that seemed to exacerbate blood sugar issues and insomnia.

    So, I’m going to take 4-6 weeks off from any exercise (aside from walking) as you suggest and follow the diet you recommend, 50g protein in morning, less than 30g carb/day and eating to satiety. Anything else you recommend to help support my liver? Interestingly enough, on a biofeedback test I did at my naturopath’s office just yesterday, it did show my adrenals at 80% and that my iodine levels were low. And on my intake symptom survey it had poor liver function listed as the 2nd highest scoring problem…

    Any other feedback you have would be great. I’ve spent all day reading your posts and info on your website. Awesome stuff!

    Thank you!!

  67. Hi Dr! So I'm on day 6 of the Leptin Rx + CT and feel amazingly better already! I can't thank you enough. There was such a dark cloud over me for the past few months and it has almost completely disappeared. Finally feel like my normal self and no more insomnia!

    Although still early in the protocol, feels like I still have low blood pressure (was 95/50 when checked two weeks ago) since I still get light headed occasionally. Any advice here besides adding more sea salt? Or do you suspect it will eventually improve? Would being deficient in iodine have anything to do with it?

    Thank you thank you thank you!!

  68. Ok i’ll just keep on then doing what I’m doing, thanks again!! :)

  69. I think I may have caused some liver damage from taking too much kelp powder for iodine along with some other supplements bc I also had insomnia for a while. I would have flushed hands and face after meals along with a very strange ringing sensation throughout my body and noticed I started not being able to digest fat very well. most of these symptoms have improved significantly since following a more simpler, paleo diet and timing meals to circadian but was curious if CT would be harmful to or hard on an already stressed liver or system. Is there ever a time when you would postpone CT? Or would it be beneficial to start sooner than later?

Trackbacks

  1. […] leptin resistant because the liver is spewing out excess fuel for storage instead of use." Leptin part deux………..the Liver. – Jack Kruse Dx. 12/2003 B.G. 126 – Hba1C 6.3 2009 – 5.7 2010 – 5.6 No Meds-Many Supplements Reply […]

  2. […] total energy balance in the body.  This maybe a good time and go back and re read Leptin part 1-3 blog posts.  (each link is embedded with a different leptin […]

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