The Sweet Truth About Liver and Egg Yolks — Choline Matters More to Fatty Liver Than Sugar, Alcohol, or Fat

Visit Us
Follow Me
In a recent post, I pointed out that perhaps as many as 100 million Americans have some degree of fatty liver disease.  Why?  Alcohol has been blamed since the 1800s, but we currently have an epidemic of nonalcoholic fatty liver.  Some researchers, such as Dr. Robert Lustig, are making the case against fructose.  Naturally, the nutritional establishment and the media will blame anything on saturated fat, and fatty liver is no exception, even when the “saturated fat” is corn oil.

After studying the relevant literature and tracing it much further back in time than anyone else ever bothers to, I've come to the conclusion that neither fat nor sugar nor booze are the master criminals here. Rather, these mischeivous dudes are just the lackeys of the head honcho, choline deficiency.  That's right, folks, it's the disappearance of liver and egg yolks from the American diet that takes most of the blame.

More specifically, I currently believe that dietary fat, whether saturated or unsaturated, and anything that the liver likes to turn into fat, like fructose and ethanol, will promote the accumulation of fat as long as we don't get enough choline. Once that fat accumulates, the critical factor igniting an inflammatory fire to this fat is the consumption of too much PUFA (polyunsaturated fat from vegetable and perhaps fish oils).

Choline protects against fatty liver disease.
Choline (Chloride) — Is his deficiency a villain or just the absence of his superhero-ness? An irrelevant question for people who philosophize too much. Read on to find out why choline is awesome.

Most reviews about nonalcoholic fatty liver disease (NAFLD) trace the disease back to a 1980 paper published by Jurgen Ludwig and several of his colleagues from the Mayo Clinic (1).  But Ludwig's group never claimed to have discovered NAFLD.  On the contrary, they simply came up with the name nonalocholic steatohepatitis, which they abbreviated “NASH.”  They took credit for achieving three things by inventing this new word (2).  First, NASH is really easy to say.  It only takes one syllable.  Second, giving a convenient name for the disease encouraged an organized approach to researching it.  Third, it stopped physicians from assuming their patients were lying about not consuming alcohol just because they had an inflamed liver.

As Ludwig's group acknolwedged, Samuel Zelman had produced the first case series of obesity-associated NAFLD patients back in 1952 (3).  Zelman launched his investigation after observing fatty liver in a hospital aide who drank more than 20 bottles of Coca-Cola every day.  This was before the days of the obesity epidemic, so it took him a full year and a half to find 20 obese people who weren't alcoholics.  All but one of them had some indication of liver damage, and about half of them had pretty substantial NAFLD.

But fatty liver goes back even further than that.  According to one paper I found, fatty liver had been identified in type 1 diabetes at least as far back as 1784 (4).  By the 1930s, some physicians recognized fatty liver as a common occurrence in severe cases of diabetes and it tended to spontaneously resolve when they treated the patients with insulin and a low-carbohydrate diet that included 100 grams of bread and 100 grams of fruits and low-carbohydrate vegetables, with the remainder of energy requirements coming from fat (5).

Severe type 1 diabetes is quite a special case and it is likely that in these instances it was the severe metabolic derangement causing the fatty liver.  This, however, quite clearly cannot explain why as many as 100 million Americans or more currently have the disease.  Nevertheless, it was the study of type 1 diabetes animal models that led to the discovery of the critical role of choline in preventing and curing fatty liver.

Diabetes and Choline

Physiologists first identified the role of insulin deficiency in type 1 diabetes by studying the disease in dogs.  In 1889 they produced diabetes by simply taking out the whole pancreas from these dogs and, after scrambling for a couple decades to identify the active component, they cured the diabetes with insulin in the early 1920s (6).  As cured as their diabetes was, the insulin-treated dogs nevertheless developed severe fatty liver degeneration and ultimately died of liver failure.  Adding raw pancreas to their diet, which was composed of lean meat and sucrose, cured the problem.  As researchers attempted to discover what it was in raw pancreas that cured the disease, they found in the early 1930s that egg yolk lecithin, which is abundant in choline, could cure it (7).  And then they found that choline alone could cure it (8).

It later turned out that the dogs became deficient in choline and methionine without a pancreas because they weren't producing the digestive enzymes needed to free up those nutrients from the foods they were eating.  Thus, simply providing them with the digestive enzyme trypsin could cure the fatty liver (9).

We now know that choline is necessary to produce a phospholipid called phosphatidylcholine (PC).  This is a critical component of the very low density lipoprotein (VLDL) particle, which we need to make in order to export fats from our livers.  The amino acid methionine can act as a precursor to choline and can also be used to convert a different phospholipid called phosphatidylethanolamine directly into PC.  Thus, the combined deficiency of choline and methionine will severely impair our abilities to package up the fats in our livers and to send them out into the bloodstream (10).

High-Fat Diets and Choline

In 1932 a group of researchers decided to replicate the fatty liver seen in depancreatized dogs in a nondiabetic rat model.  What better way to stuff their livers with fat?  Feed them fat!  Seemed simple enough.  And, in fact, it worked.  Althogh they had trouble reproducing the fatty liver with different colonies of rats or during the summer heat, they produced fatty liver in certain colonies of rats during the winter by replacing 40% of their ordinary cereal-based diet with beef drippings.  Lecithin derived from egg yolk or beef liver (11) or simply choline itself (12) cured the disease.

These experiments were back in the day, before researchers realized that methionine would be able to indirectly cure choline deficiency.  Another group of researchers had the bright idea of trying to replicate this experiment in a group of rats who were consuming sufficient protein to maximize growth.  So they fed them 40% beef drippings but replaced another 20% of their cereal grains with the milk protein casein.

Lo and behold, these researchers discovered a now well known phenomenon that occurs during the process of scientific discovery called the “epic fail” (13).

Proteine protects against fatty liver disease.All of the groups had average levels of liver fat under 7% and could hardly be said to have gotten fatty liver of any sort.

So the researchers had an idea.  Perhaps it was the casein they fed them that was the problem.  And indeed, their hypothesis turned out to be correct: on a choline-free, 40% beef dripping diet, reducing the casein from 20% to 5% doubled the level of fat in the liver (14).

Those of you who have been reading my blog for the past few months may remember that in the wake of Denise Minger's shredding apart of the China Study's epidemiological data, I dug deep down into the buried secrets of Dr. T. Colin Campbell's rat research, and found that he attributed the “protective” effect of 5% casein diets to the massive fatty liver that the rats developed.  As described in “The Curious Case of Campbell's Rats” and the associated addendum, the membrane containing a drug-detoxifying enzyme that he blamed for liver cancer got stuffed with 3-4 times more fat, which may have clogged up the enzyme and stopped it from working.  Well, it turns out that others had shown a similar effect of such a diet on liver fat decades earlier.

Back to the 1930s.  So these researchers repeated their experiment with the different fats, this time using 5% casein.  Ta-da!  The experiment worked much better (13):

Fat causes fatty liver disease when the diet is low in protein.The butter produced the worst fat accumulation, where almost a third of the liver was fat!  The animals taking cod liver oil tended to eat a bit less food than the others, which undoubtedly confounded the results at least to some degree, but it still seems from this graph that the more saturated the fat and the longer-chain the fat, the worse the fatty liver was.  In fact, if we blow up the graph, we can see this more easily:

Dietary fat caused fatty liver in rats fed low-protein diets.

Whoa!  Hold your horses, you might be thinking.  Mr. Masterjohn, haven't you been telling us that saturated fat protects against fatty liver disease?

Well, yes I have, and I stand by that.  But it appears that things are a little more nuanced than they first appeared.  As it turns out, saturated fats increase the choline requirement a bit more than PUFAs do.  Take a look at the results of this 1957 paper that tested the effect of butter and corn oil on the choline requirement (15):

Rats fed corn oil needed less choline to minimize liver fat than rats fed butter. As it turns out, the choline requirement is about 30% higher on a 30% butter diet than on a 30% corn oil diet.  Why would this be?  It's not entirely clear, but I have a good guess.  As I pointed out in my PUFA Report, “How Essential Are the Essential Fatty Acids?”, studies in rats, humans, and other primates show that 18-carbon PUFA are burned for energy at an extraordinarily high rate compared to other fats.  In rats, 60% are burned for energy, 20% are broken down into basic building blocks to make more saturated fatty acids, and most of the rest are secreted into the fur.  They do accumulate over time at a slow rate, but the body seems to sense that these fatty acids are an unnecessary oxidative liability and tries to get rid of them however it can.  Thus, perhaps saturated fats require more choline to get them out of the liver because they don't scare the liver into burning them for energy so quickly.

In any case, the clear picture that is emerging is that dietary fat increases the choline requirement, and that high-fat diets promote fatty liver only when the level of choline in the diet is insufficient to meet the extra demand for it caused by the increase in fat.

Fructose, Sucrose, Ethanol, and Choline

The buzz is all about fructose nowadays, but the role of fructose in fatty liver has been known since the 1930s, just like the role of fat.  It also played a critical role in the modification of the AIN-76A standards for purified lab rat diets to the AIN-93 standards in 1993, when sucrose was switched to corn starch, like I explained in “They Did the Same Thing to the Lab Rats That They Did to Us.”  Fructose can be provided in the diet as free fructose or as sucrose, which is half fructose and is the type of sugar found in refined, white table sugar.  Fructose is different than glucose in that it goes straight to the liver rather than dispersing throughout the body; thus, the liver converts much of it to fat, sending the fat back into the bloodstream — providing it has enough choline.  Ethanol, the type of alcohol we get drunk from, is metabolized similarly (16).

The first studies showing that fructose played a role in fatty liver disease developed out of the discovery of the essential fatty acids.  I've recounted the history of this discovery in my recent article, “Precious Yet Perilous — Understanding the Essential Fatty Acids.”  In 1924, George Burr joined the laboratory of Herbert Evans, where Evans and Katherine Scott Bishop had recently discovered vitamin E.  Evans and Bishop were having trouble reproducing their vitamin E-deficient diet, and Burr helped them develop a highly purified diet based on reprecipitated casein and recrystallized sucrose.  The new diet produced a deficiency that vitamin E couldn't cure, which Burr and his wife Mildred later identified as essential fatty acid (EFA) deficiency.

Observing that the annual per capita consumption of sugar in the United States had tripled over the preceding decades from 38 pounds to 115 pounds, Clarence Martin Jackson conducted a comprehensive analysis of the anatomy and tissues of rats fed Burr’s EFA-sufficient, 80% sucrose control diet and compared them to rats fed 45% sucrose or 45%  corn starch (17). Neither the 45% sucrose diet nor the 45% starch diet produced fatty liver, but the 80% sucrose diet produced moderate to severe fatty liver with flattening and displacement of nuclei within the liver cells.  Jackson warned that the liberal provision of cod liver oil, dried yeast and wheat germ satisfied the nutritional needs of the rats in all treatment groups, and that smaller amounts of sucrose may contribute to fatty liver in humans consuming nutritionally deficient diets.

This is rather remarkable, because much lower concentrations of sucrose started spontaneously producing fatty liver disease in lab rats in the late 1970s and early 1980s once the American Institute of Nutrition set standards for purified rodent diets that relied exclusively on isolated vitamins and minerals rather than whole-food supplements like cod liver oil, yeast, and wheat germ.  We'll never know exactly how much choline was in Jackson's diet, but purified diets with 0.3% methionine and 0.8% choline, though to be adequate in these nutrients, produced moderate fatty liver when the sucrose concentration was increased from 20% to 25-35% (18).

Physicians and researchers had started pinning the blame on alcohol abuse for fatty liver back in the 1800s, so while research was first highlighting the role of sucrose in fatty liver, other research was doing the same for alcohol.  In 1949, however, researchers showed that sucrose and ethanol had equal potential to cause fatty liver and the resulting inflammatory damage, and that increases in dietary protein, extra methionine, and extra choline could all completely protect against this effect (19).

Conversely, much more recent research has shown that sucrose is a requirement for the development of fatty liver disease in a methionine- and choline-deficient (MCD) model.  The MCD model of fatty liver disease is the oldest and most widely used dietary model.  The MCD model produces not only the accumulation of liver fat, but massive inflammation similar to the worst forms of fatty liver disease seen in humans.  What no one ever mentions about this diet is that it is primarily composed of sucrose and it's fat is composed entirely of corn oil!

In methionine- and choline-deficient rats, sugar must replace starch to produce fatty liver disease.As you can see here, the MCD diet resulted in only the most miniscule increase in liver fat when it was composed of starch (column 4 vs column 2), but when it was combined with sugar (green bar) it produced a massive increase in liver fat. The researchers also found that the MCD-sugar diet led to full-fledged inflammation, while the MCD-starch diet had no such effect (20). They found that on the sucrose diet, the fructose component led to the synthesis of fat in the liver, and because the choline level was deficient, the liver could not export that fat.

The picture that is clearly emerging from all of these studies is that fat, or anything from which fat is made in the liver, such as fructose and ethanol, are required for the development of fatty liver.  But in addition to this some factor — overwhelmingly, it appears to be choline deficiency — must deprive the liver of its ability to export that fat.

Oxidative Stress May Impair Export of Liver Fat

An interesting test tube study using isolated cells found that incubating liver cells with PUFAs would suppress export of fats while incubating the liver cells with saturated fats, vitamin E, or a chelator of free iron would improve the export of fats.  The results indicated that lipid peroxidation, that is, the oxidative destruction of PUFAs, causes liver cells to degrade their VLDL particles before they send them forth into what would be the bloodstream if the experiments were conducted in a live animal.  They also provided preliminary evidence that this occurs in live animals by directly infusing their bloodstreams with DHA (21).

While it seems possible that excess PUFA might interact with iron overload, ethanol, or some other type of toxicity in order to impair the export of liver fat in the absence of choline deficiency, it nevertheless seems unlikely that excess PUFA in and of itself causes enough oxidative stress to make this happen, because even rats consuming 30% corn oil mentioned above fared fine if they were given enough choline.  However, as we'll see below, excess PUFA are required for the inflammatory part of NAFLD.  And, moreover, in humans there may be many interacting factors that “activate” the ability of excess dietary PUFA to suppress the export of fat from the liver.

MCD-Sugar Sets the Kindling, Corn Oil Lights the Fire

MCD formulas containing 20% fat as either lard or olive oil produce equivalent levels of NAFLD, suggesting that changes in the ratio of saturated to monounsaturated fats is not important (22).  Substitution of carbohydrate, coconut oil, or beef tallow for corn oil similarly offers no protection against accumulation of fat in the liver nor on the injury to liver cells that causes increases in liver enzymes; all these substitutions, however, dramatically decrease lipid peroxidation and and the resulting inflammation (23).  Corn oil probably promotes inflammation both by increasing vulnerability to lipid peroxidation because of its total PUFA content and by decreasing tissue levels of DHA because of its high omega-6-to-omega-3 ratio.

Choline is King!

I have to conclude from all these studies that choline deficiency plays a role in virtually every type of diet-induced fatty liver model.  The fat has to be provided to the liver through either dietary fat or dietary lipogenic substrates like ethanol and fructose, and the fat has to be trapped by impaired export of fats from the liver.  And choline deficiency seems to be the preeminent cause of this.

So does fructose cause fatty liver?  Kind of.  I'm not suggesting fructose is harmless or that you should go out an eat a bowl of fruit loops with your liver and eggs, but the loss of cholesterol-rich foods like egg yolks and organ meats as a result of cholesterol paranoia seems to be at the bottom NAFLD thus far.

There's just one question.  Leptin deficiency and leptin resistance both cause fatty liver.  And obese people are leptin resistant and the majority of obese people have fatty liver.  Can fatty liver or choline deficiency cause leptin resistance?  Or does leptin resistance cause cravings for choline-poor, fatty, and fructose-rich foods?  Here's a web I'll try to untangle in future posts!

Join the Next Live Q&A

Have a question for me? Ask it at the next Q&A! Learn more here.


Subscribe or upgrade your subscription here.

Masterpass members get access to premium content (preview the premium posts here), all my ebook guides for free (see the collection of ebook guides here), monthly live Q&A sessions (see when the next session is here), all my courses for free (see the collection here), and exclusive access to massive discounts (see the specific discounts available by clicking here). Upgrade your subscription to include Masterpass membership with this link.

Learn more about the Masterpass here.

Take a Look at the Store

Visit Us
Follow Me

You may also like


  1. […] Chris Masterjohn has written extensively about choline deficiency and its relationship to fatty liver disease which affects as many as 100 million Americans and is often attributed to excess alcohol and sugar consumption by conventional practitioners. After a review of the literature, Masterjohn concludes that choline deficiency plays a role in virtually every type of diet-induced fatty liver model, and that adequate dietary choline is essential for proper liver function. He also suggests that high consumption of dietary fat, including saturated fats, increases the amount of choline required to prevent the accumulation of fat in the liver. (6) […]

  2. Can someone help me understand this study that was listed in Chris’s article here. I clicked on it and this is what I found. Also, I tried a mild keto diet and it helped my muscles a bit, but eventually where my liver is, it HURTS daily. I have been diagnosed in the past with fatty liver and Gilbert’s syndrome-hyperbillirubanemia. I have also develped an ulcer. I notice fatty foods make everything hurt more on the right side and my muscles have gone back to having so much pain, so quit the high fat diet. My gallbladder checked out perfect on both blood and ultrasound. Since the new pain under rib cage I haven’t had a test. Hoping I can figure it out before I go back to the doctor. I get tired of all the tests. I have mast cell activaiton, so I get overwhelmed with health issues. But I found this article and it confused me. This is from the article attached to this article of Chris’s.
    Hyper- Number bilirubinaemia*
    Period of tests
    No. %
    Year. No. of tests. No. %
    1926 130. 34 26.1% Lowcarbohydrate-highfat**
    1935 500 74 14.8 % Firsthighcarboydrate-lowcalorie*t
    1936 3000 232 7.7% First modification of high carbohydrate-low calorie
    (between-meal feedings of 10 gm. carbohydrate)t
    Total 2226 156 7.0% Secondmodificationofhighcarbohydrate-lowcalorie
    New 692 108 15.6 %. (between-meal feedings of 20 gm. carbohydrate)tt
    Old 1534 48 3.1%

    Since I have fatty liver and Gilbert’s (hyperbilurubinanemia) should I be eating less fat? And. more carbs? I know on Keto, I never had enough energy but after a carb snack I could feel better for a few hours.

    1. See here on fatty liver:

      I suspect the ideal diet is a protein-sparing modified fast based on lean protein, 1-2 servings of liver per week, 2-3 whole eggs per day, and a high volume of low-calorie vegetables with low-fat and low-carb, if one is overweight, and continue weight loss until reaching ideal weight. If not overweight, I’d make up the rest of the calories with starch.

      1. I have done Keto and Carnivore ending up making my fatty liver worse. Ill be following your advice above with TUDCA and Black Cumin Seed oil to hopefully see some results. Its basically whats called a cutting diet in body builders universe. Low carb. Low fat. high lean protein and plenty of veggies. Your adding the choline which is excellent.

  3. I have lost about 20 pounds in 2 months. 2 boiled eggs and about 4 oz beef liver with dark chocolate coffee and I don’t get hungry for up to 12 hours. Iced green tea unsweetened with lemon juice has become my other sipping beverage of choice. I try to include 8oz canned black beans with a tsp of Cumin every other 12 hours meal and 8 oz Spinach or other canned greens. I have resistance band around towel rack waist high in kitchen. Grab handles lean back and do curls till my biceps and shoulders hurt every time I wait on microwave, Is toning my whole body. The eggs and liver are the thing. I am missing my broiled fish, chicken and Maitake shrooms from my secret White Oak till later. Thanks. 71 and becoming ATLAS.

  4. So, after much research and reading volumes of research dogma. the practical diet that I need to buy and eat boils down to what is again not said. Organ meat such as beef liver in moderation, eggs daily with beans such as black beans and greens such as Spinach or Collards. Highly dose the beans with Cumin to enhance weight loss. Ground Rosemary and/or ground Celery seed are good healthy salt substitutes.
    I crave beef liver but you can tone it down by mixing it with ground Chicken, Turkey, Rabbit, Sausage or Chuck along with the Cumin, Rosemary and Celery seed. The research behind it all is fine, but I should not need to read volumes to have practical answers just to buy groceries. Thanks for this valuable info. My liver thanks you too.
    When I eat out, I find a good salad bar and order Jumbo Shrimp Ala cart.

  5. In a study published in the April 8, 2017 edition of the World Journal of Hepatology (PMID 28443155), Zeinab Mokhtari et al. , concluded that participants who consumed two to three eggs per week were 3.56 times more likely to have NAFLD than those who consumed less than two eggs per week, after adjusting for other risk factors.

    1. Then I guess we can agree that Iranians who eat 2-3 eggs per week are screwed 🙂 This kind of questionnaire-based correlation doesn’t teach us anything about NAFLD except that 2-3 eggs per week neither prevents or cures the disease in the population that was included in the study. It is also interesting that the conclusion omits any mention of the study group who consumed 4+ eggs per week.

    2. Question is do most people in this study cook with vegetable oils high in PUFA’s or do they cook with lard/butter/water? I’m guessing its the former.

      Correlation based studies are pretty much a shot in the dark and are the reason why it seems all foods are unhealthy nowadays.

    3. Yeah, great study there Bruce. Note that almost NINETY percent of the fatty liver patients were SMOKERS, compared to only 18 percent of those without fatty liver.

  6. If Choline deficiency presents with lowered TG and Cholesterol levels in serum, then how do you reconcile the fact that NAFLD patients normally have elevated levels? Wouldn’t it be hard to have elevated serum lipids without sufficient choline to transport it?

  7. […] In the past, choline was considered a part of the Vitamin B family, but today you will most likely only find it as a standalone nutrient. Choline is extremely important for liver and brain health. It is a precursor to acetylcholine, a neurotransmitter involved in the function of our memory. Our liver uses choline to process fats. Choline also impacts our levels of LDL cholesterol, and getting enough choline can help to prevent fatty liver. It was proven that choline deficiency is a major contributor to fatty liver disease. […]

  8. Wow! We definitely need to take care more about the amount and quality of nutrition. Thanks for such detailed article and for sharing these useful information’s!

  9. Omg! Please tell me there are other ways to get choline in my diet. Liver blah, egg yokes blah… Help! I have to help my big ol fatty liver ASAP! Do egg whites have choline? Thanks!

    1. I make Jiffy corn muffin mix with 3 egg per box and bake in pyrex pie plate 35 min at 350. Mix 1 lb. liver with 2 lb. ground chuck and bbq. Beans/cornbread and a burger loaded What’s not to like.

  10. I was diagnosed of Chronic Obstructive Pulmonary Disease (COPD) in summer of 2014, my symptoms started out with shortness of breath and chronic cough. The pulmonary disease specialist prescribed me some medications to help my symptoms however the medications did no good and their side effects were too severe. In May 2016, i started on NewLife Herbal Clinic COPD Herbal formula treatment, i read alot of positive reviews on their success rate with the COPD Herbal formula and i immediately started on the treatment. Just 11 weeks into the Herbal formula treatment I had great improvements with my breathing, there is no case of dyspnea and chest tightness since treatment, visit NewLife Herbal Clinic official website www. newlifeherbalclinic. com or email info@ newlifeherbalclinic. com. This treatment is incredible!

    Shirley Heche

  11. Hi Chris,
    What happens if a person already has fatty liver and cholesterolosis? I was just diagnosed with slight fatty liver a few days ago and diagnosed with cholesterolosis a year ago, would the same diet that you mentioned i.e. eggs, and I assume keto or low carb diet with good fats included. Would this help both conditions or stop them getting worse?
    If the liver is exprting or getting rid of fat thats great but where does this fat go? I fear it goes into the gallbladder and I worry that too much cholsterol/bile/fat gets excreted into my gallbladder which is already suffering from too much cholesterol/bile/fat etc being pumping into it, cholesterolosis = polyps of cholesterol in the gallbladder wall.
    I thought I eating a vegan diet and juicing but then realise after reading this article that I may be making my problems worse by eating sweet veggies and friuts as juices especially like carrot/apple/pineapple etc are all sweet, beets are sweet as well but are supposed to be great for the liver, I dont get it.
    I suppose I could do green juices like cucumber/celery/lettuce/spinach/kale etc?
    Instead of eating eggs (I have stopped eggs since the cholesterolosis diagnosis a year ago) couldnt one supplement with Choline? I am taking soy lecithin granules now is that okay or does one need a specific type of choline?
    Im just stuck between eating Vegan and going low carb or keto and infact frightened eating fats especially when I have conditions in my Liver/gallbladder that are to do with accumilating cholesterol/fat.
    I havent always eaten vegan or done low carb, tried to eat healthy, have gluten and dairy intolerance so stopped those but the gluten free cakes, bread etc are full of sugar its unbelievable so I stopped those as well now.
    I have been taking Prilosec for Hiatal Hernia/GERD and Paxil for depression for 20yrs and so drugs could have a hand to play in my liver function and fat accumilation, so my next goal is to taper off these drugs AND lose weight, so I will exercise daily now not ony to lose weight to my ideal weight but also to keep healthy.
    Is vitamin D3 good for reversing fatty liver?
    Anyone who can help I will apreciate any advise that can help me reverse this, thankyou.

      1. Eve, where is the study or reference backing up your claim that glucomannan ‘gets fats out of the liver’?

  12. ^Also, on the subject of bile's effects upon gut health, in "Red meat and colon cancer:
    Should we become vegetarians, or can we make meat safer?" it's claimed: "Dietary fat increases bile acids secretion inside the gut, andthey act as aggressive surfactants for the mucosa thus increasing cell loss and proliferation (Bruce, 1987)." Could you please comment on that?

  13. Hi Chris, could you please comment on Don Matesz's claim in his recently-released eBook Powered by Plants that high bile content in the colon (from a high-fat diet) would promote colon cancer given the "cytotoxic, genotoxic, mutagenic, and tumor-promoting effects on colon tissue", citing "The role of bile acids in carcinogenesis" from _Mutation Research_ and "Role of bile acids in colorectal carcinogenesis" from _European Journal of Cancer_?


  14. Awesome site Chris, so much useful health info, thanks! I now understand why choline is essential especially for people like me eating a high saturated fat/low carb diet. And thanks Anonymous, that is good advice about the caviar! I work on a fishing boat where the roe fish (mature females) are frozen and sent overseas to Japan. If only we Americans knew how good it was for us! Time to start getting my homepack together… 🙂

  15. Choline or Lecithin, as the names have been intentionally made interchangeable by those seeking to confuse the population and profit from that confusion, is "The Key", "The Missing Nutrient" and many other names it's been referred to by throughout history. Why do I say, "throughout history"? Remember the parable of the mustard seed in the Bible? Is it just a coincidence that, aside from soy beans, which weren't a Biblical crop, mustard seeds are the richest source of Choline in the plant kingdom, followed by wheat, which is also mentioned all throughout the Bible… ? Is it also a coincidence that "true" Caviar, prized by the wealthy who are now the only ones who can even afford a small amount, is the richest natural source of Choline on Earth… ? Lecthin, obtained from plant sources like soy, sunflower, etc is a plant version of Choline… but it isn't the same, as we've been led to believe. Unlike animal Choline, plant Lecithin is not heat stable so when you heat it, it becomes altered, just like any plant derived oil or fat aside from Coconut. Cocunut is "good" but again… it isn't the same, as we've been led to believe. Why do you think Caviar (fish eggs) and the yolk of any egg is the richest source of Choline on Earth? Choline is required to protect the sperm cell, which fertizes an egg… any egg… even human eggs. Egg yolks are used as "semen extenders" for transporting frozen semen used for artificial insemenation in animals. Semen is the only substance on Earth with the unique combination of spermine + choline. Think about this… every human and animal is nothing more than a full grown sperm cell. Just as it was crucial for your survival as a sperm cell… it still is now. As a child, humans are higher in their Choline content. As they age, their Choline content decreases. Choline is an emulsufier. Just like dish detergent, it allows water and oil/fat to mix, dissolve and be washed away. Choline is what emulsifies oil/fat in your body, dissolves it and allows it to be flushed out. Without Choline, that same oil/fat slowly hardens, calcifies and becomes plaque. Now, if you wanted to make billions each year off the sale of pharmaceutical drugs, what would be the most effective way to accomplish that? Create a Choline deficiency by warning people not to eat the very foods that are high in choline, wait for all the symptoms to become "national epidemics", give each symptom a name and call it a "disease", "syndrome" or "chemical imbalance" and keep coming up with new drugs to treat the symptoms… that you yourself are causing.

    Oh yes, the rabbit hole is deep… far deeper than you can possibly even begin to imagine. 🙂

  16. Hi,
    Would citcholine be of worth for averting fatty liver? What about choline salts (citrate, bitartrate) ?


  17. Hi Chris!

    Thank you for a fantastic post, you're by far my favourite diet-researcher. I have a quick question, do you think it's possible to replenish choline-levels with Dimethylaminoethanol (DMAE)?

  18. and sorry Chris, I meant to delete the last sentence which I cut and paste from a previous post I did. Obviously, you are a real researcher. :]

  19. Both of my parents are poorly controlled diabetics on insulin. I should say "were" poorly controlled, because 1176 mg of Choline per day (in the form of choline bitartrate) has dramatically improved their blood sugar control before and after meals and especially morning glucose. The effect was completely unexpected and occurred immediately. These are people in their late 60s that have had excursions of glucose into the 300-400 mg/dl range at times. They have literally halved their insulin dosages!

    The only explanation I have is that the increased methylation from the choline has acted as some sort of epigenetic switch on hepatic gluconeogenesis. This would explain the vastly improved morning sugars. One of them now routinely has sugars in the 60-70 range in the mornings while the other is around 115. Even after meals they dont shoot as high as they did previously.

    Truly amazed by this and have called Linus Pauling Institute and LEF to try and get somebody to follow up on this with addtional research. Have not been able to find anything on PUBMED about this kind of effect.

    Any ideas on how to get the word out to some serious researchers?


    1. It is interesting, but if it was indeed immediate, then I would look for a common mechanism, not A->B->C

      The choline could be both reversing the fatty liver and lowering blood sugar. If there is a metabolic issue, caused or exaggerated by a choline deficiency, shouldn't adding choline improve both? Blood sugar might have to drop first, so the liver can release fat.

    2. My thought exactly but in that case this is a huge discovery. I mean their blood sugar levels have dropped by a hundred points at least. Meanwhile the Pharms are all pumping out DPP IV inhibitors (sitaglipin and ilk) that cost a fortune when plain old choline can do the same job with no side effects for $8 a bottle!

    3. I don't see why the blood sugar would drop first. High blood sugar is likely a consequence of liver energy overload. I don't know how long it takes to correct fatty liver, but you can't store glycogen in a cell that's loaded with fat, so reversing fatty liver should cause an immediate and proportional improvement in blood sugar regulation.


    4. I don't have an exact mechanism in mind either, but I don't think the liver can dump enough fat in a day to drop blood sugars really quickly. I am just speculating based on the word "immediately."

      I would expect it to be proportional to the loss of fat in the liver, so the blood sugar should drop steadily, not precipitously. That is why I am thinking of a common mechanism. Again, speculating, that the blood sugar could cause the fatty liver, and so the drop in blood sugar could allow the liver to release fat over time. Without exact blood sugar numbers at several points in each day as it dropped, including the all important morning reading, and some type of imaging/biopsy of the liver while it was happening, it is all speculation.

      With fatty liver/high blood sugar we could be looking at a chicken/egg thing. And likely in different people different things will come first.

    5. I agree that this is pure speculation and that there might not be a one-size-fits-all explanation for the sequence of metabolic abnormalities and their reversal, but I think in general, high blood sugar is not something that causes fatty liver but rather the opposite. High postprandial blood sugar in a type two diabetic is primarily coming from insufficient glycogen storage.

      This being the case, it seems a rather simple explanation to me that if you have a glob of fat in the cytosol of a hepatocyte where glycogen is usually stored, you don't have any room for glycogen. I'm not wedded to the idea that the choline's first impact would be to remove fat from the liver — though in someone who was quite choline deficient this seems like it could have a substantial and rapid impact — but there is no alternative hypothesis yet.

      Alterations in gene expression shouldn't happen "immediately," either, though everyone has a different definition of "immediately" I'm sure. An effect on post-translational modifications like phosphorylation state would be much quicker.
      But VLDL assembly might also be pretty quick. Quicker than regulation of gene expression.


    6. I defiantly agree that most methylation-dependant changes in gene expression are slow. I, even with my bias as a geneticist, don't think this is a genetic thing. What I really would want to see is replication and data. (Have to rule out the random factor, it gets us in trouble sometimes.) It is likely that taking choline was not the only change, even if people think they don't change their diet or habits, they often do. And when starting a new drug or supplement this can definitely happen.

      It is possible that both people were very deficient, married couple often eat together, and the same foods. This is probably more likely then they both having some weird genetic difference that causes them to need really high amounts of choline to maintain a normal metabolism.

      I usually think that it is a combination of things. Maybe the liver could store more glycogen with the increase in choline, even if it was still full of fat. Maybe the choline gave the person more energy and they worked off some of the blood sugar. Maybe the choline had a direct effect on blood sugar that was not tied to liver fat levels. Possibly several of these.

      And in this case there was both high postprandial and high morning sugar. This would point to insufficient storage and excess release. If the choline simply let the liver take up and hold on to more, it would drop the sugar quickly. But there is a limit, the rest of the body would also have to take up more as well. What do you think the effect choline could have on overall insulin resistance? Or possibly a quick effect on liver glycogen storage, and the lower blood sugars could help somatic insulin resistance?

      I keeps on coming down to the fact that I want more data. But if it had this good of an effect in a couple of people, and has a low chance of harm, it is another tool in the chest.

    7. I agree with everything you said.

      But yes, my thought was along the lines of the scenario you describe. Make a little room for glycogen storage and you take some burden off the rest of the body. Meanwhile, still taking the choline makes a little bit more room for glycogen storage. Of course there is a limit to glycogen storage, but whatever the normal limit is allows for normal metabolism. So it's a matter of the rate at which room is made. Like you said though, a lot more data is needed!


    8. The mechanism involved is inhibition of INS/IRS SREBP-1c pathway thru increase of the methyl donor
      S-adenosylmethionine (SAMe) involved in Methylation and critical for synthesis of phosphatidylcholine (PC), as described in

      Ohh, and talking of mechanisms, dear Chris, let's not forget that choline is actually an alcohol, so you can go way back in time and check on that long forgotten discussion about SCD and alcohol as I pretty well remember I mentioned inhibition of SREBP-1c and lipogenesis de novo long time ago. Cheers, mate.

    9. Thanks for your comments Ilya. That's not a dietary choline paper. A paper that I discussed in this original post showed that dietary choline increases lipogenic gene transcription:

      I don't think it's helpful to reduce biology to mRNA expression. As that paper shows, what occurs with mRNA expression can be contradictory to what happens at the levels of protein and substrate. In general, I think it's good to try to connect gene expression back to the big picture by asking, "Why?" Since choline plays such a critical structural role in lipid transport, it makes sense to try to connect its role in gene expression to its structural role. So, choline increases lipid synthesis and transport, perhaps acting as a signal that it is present in sufficient amounts for its structural support.

      So, as Karstyl and I were just discussing, you could have multiple mechanisms acting in concert — perhaps they are not coincidences. Perhaps you have choline a) providing structural support for immediate removal of lipids and b) having short-term and long-term increases in lipogenic gene transcription that enhance this effect.


    10. Not to be anal but it sounds and looks as dietary choline intervention to me: "To determine whether rescuing PC production would reverse SBP-1-dependent lipogenic events in sams-1(RNAi) nematodes, we provided excess dietary choline. Strikingly, dietary choline supplementation completely rescued accumulation of lipid droplets corrected overexpression of the SBP-1 transcriptional targets fat-5, fat-6 and fat-7 in sams-1(RNAi) worms (Figure S3A,B and data not shown). These results support our hypothesis that decreased levels of PC[choline, my edit] in sams-1(RNAi) worms may be directly linked to the increased SBP-1-dependent[SREBP-1c, my edit] lipogenesis." Not picking long-forgotten fights but you can trust me next time (as you can trust me that ethanol does not cause AFLD despite the name). My pleasure and let's drink to that.

  20. Bravo! This is a marvellous article! I believe you are on to something that the majority of people should pay attention to.

  21. New Protocol for Insulin Resistance, Part 3

    It was after reviewing their blood tests over and over again that I realized I was seeing a pattern, and one that had left them undiagnosed for insulin resistance/Metabolic Syndrome for years, despite the fat gain and complaints. We who have MSXX do not fit the MS category — at all. We have high HDL and low TG. We have normal blood pressure. We have normal TSH, and rising but still normal A1c and fasting insulin (most of the time; hyperinsulinemia is seen in 100% of women who took HCG injections). Yet we are fat. We are tired. We are cold and we often offered tranquilizers for our clearly deluded minds.

    In MSXX however, the symptoms are quite different from those in MS. With MSXX, the particular flavor of IR is PCOS, regardless of age, regardless of menstrual regularity or ability to get pregnant. Unschooled doctors often insist that PCOS isn't there when it is. Insulin levels are usually normal, but insulin in MSXX is bone-ass lazy. It just can't do the job. Thus, 1-hr PP's are often lower than 2-hr PP's – a major MSXX symptom.

    Gluconeogenesis is out of control. We are exquisitely sensitive to Cortisol. As a result, when *we* do "Body By Science" workouts, we may put on muscle — but we *always* put on fat around the middle. Impossible, but true. The slightest amount of excess protein sends sugars way up, despite eating no carbs but veggies. Reverse T3 is enormous. Free T3 and Free T4 are in the basement. Temps are incredibly low, and energy is negligible. It's very difficult for women with MSXX to achieve lipolysis, despite very low calories and carbs. One symptom of untreated MSXX is water loss and gain of the same 2 – 5 pounds, over and over and over again.

    The Protocol treats and reverses all that. All of it. Although for the most resistant cases, Metformin is necessary. In fact, in helping so many women with it, I finally had to ask myself if female obesity and male obesity are somehow different. My answer now is: Yes. This helps explain why so many women follow Taubes, Groves, Lutz, and Attia to no avail. What those men, who I greatly respect, know most about is male obesity, and their advice seems to work wonderfully for men. For women, it's hit or miss. For women with MSXX, it's always miss. Especially if they go VLC for an extended period, which invariably shuts down their metabolisms with massive thyroid hormone problems.

    Once again, a long post, and I thank you for your indulgence. I hope you will take a look at some of the articles, journals and data on my blog, and I especially hope any reader who thinks they might have MSXX will read it. I suspect a lot of light-bulbs will go off, despite the fact that I'm neither a doctor, nor brilliant like you and Peter of Hyperlipid. I've plodded along doing theoretical research for years, but I have tested my theories in the real world with real people, and have had real world results. If Taubes and Attia ever get their Research Foundation up and running, I'd love to see a Female/Male Obesity study in the works.

  22. New Protocol for Insulin Resistance, Part 2

    I did it. Not just for me, but in the last year for many women.

    I decided that what MSXX requires is a brief (2 weeks, no more) kick in the pants with a low-calorie, modest fat, modest protein, modest carb semi-fast of one main meal and one light meal a day. And then, before the brain can cry "Starvation Mode" — four to six weeks of enormous, fat-laden calories in Maintenance. Followed by one or two more weeks of Protocol, followed by higher fat, higher calorie, four to six weeks of Maintenance. And so on. Success in the Maintenance phase is defined as no weight or inch re-gain of Protocol losses. The body's true acceptance of lower set-point. Over and over and over again, until fat loss goal is achieved. Then you can stay in a high fat, high calorie Maintenance phase forever.

    After it worked so successfully for me, I believed it could work for others. That's when I began my blog:

    I started with the first (and only, as far as I know) scientific debunk of Simeon's HCG Protocol, "Pounds & Inches." I then enlisted several HCG users in a real-time experiment, to prove once and for all that HCG does nothing to non-pregnant users except give them extra adipose fat cells. All that is on the blog. Then other women began to come, women who had tried and failed at everything — including HF/LC — to lose and *keep off* pounds and fat. They too underwent metabolic blood testing, were given their Protocol ratios, and began to post blood sugar readings, food, ketostix, and weight stats daily for months. On Monday they report measurements. The success of these women, who not only lost weight but who have now kept it ALL off, has been astounding. As have been their normalized blood sugars and other metabolic indicators.

  23. New Protocol for Insulin Resistance, Part 1

    Hi, Chris – long time, no talk. 🙂 While doing research into choline, I came across this page and found my long series of posts (as awriter) and your replies. A lot has happened since then, all good, and a lot of (what I believe is) important data has accrued that I hope you and your readers can use.

    Since last I wrote, I've lost another two dress sizes (now a size 8), my leptin level is finally true normal (8.5, down from nearly 35 when I began this journey), my TG's are still in the 40's, my HDL in the 90's, my A1c is 5.0 and my average glucose reading is 88-90. My thyroid hormones are great, and my temps average 98.5. That's nice for me of course, but a year ago I stopped being n=1 and became n=many.

    The first thing I had to do was not just diagnose what was wrong (I now have a name for it, seen many times since in very many women: Metabolic Syndrome XX — more about which below), and then create a Protocol to fix it. The usual HF/LC simply doesn't work for women with MSXX. We lose some pounds and inches, then stop dead. We have "plateaus" that last _years_, not weeks or months. And we can eat as LC and as HF as we like; our blood sugars never get down into the true normal range. Nor can we ever eat normally. An ounce of berries gets us a pound gain on the scale.

    Thus my goal wasn't to just lose the rest of my excess weight and fat, it was to truly heal my broken metabolism once and for all. And not just part of it, but all of it: sugars, IR, LR and THR. All proper metabolic hormone signaling restored. I wanted to be able to eat normally again. Not SAD or sugar foods, but bread or potatoes or pizza once in a while if I wanted it. Without gaining an ounce or an inch back. Without raising insulin or blood sugar levels. Berries and dark chocolate, ditto. I wanted my body to know what to do with the food I ate: burn, not store it. And I wanted to be able to get on a scale on Jan 1 of one year, not count calories or food, and weigh just the same on Jan 1 of the following year. In other words, true metabolic stabilization. Brain accepting new weight and fat set-point, not fighting it.

  24. Not sure if you're reading this John, but after 1 year of eating no fruit but cranberries and no vegetables but mustard greens and escarole, I'm back to eathing fruits and veges, due to taking Choline 1000 mg/day. Thanks !!!!! – Kudos, since I learned about choline from you.

  25. My mind goes fuzzy whenever I eat any fruit or veg except for cranberries. Via 3 docs ruled out structural intestine and other issues, My unfuzzy diet is just white rice, potatoes, vitamin,iodine,iron,mustard greens, 1 egg and a bit of chicken. All else doesn't work. Giving choline a try.

    Tracked this condition with a lig for a year now.

    Thanks! Extremely interesting blog and comments.

  26. It is good to read so much about ill health and how it can be fixed.There is no better treasure than good health and therefore diet and medication and exercises are very essential things for life.

  27. Wow! I am so impressed on all the information and comments I have just read. I myself suffer from Fatty liver and am desperately looking for a way to get better as I am 48 years old and feeling tired and depressed during all the day. I am sleeping 10 hours a day and always feel so empty energy wise. I am desperately looking to get better. Thank you!

  28. Sorry, typo. ALT is 89.

    So I guess I should be looking for a new doc soon. I was hoping it could wait until we get back from our long vacation. (Going to NYC for the funeral of my grandmother who lived to 93.)

    For a long time I was eating my eggs by softboiling them very undercooked and eating the barely-warm yolk and whatever little bit of white goo got scooped up with it. Then I got tired of that after about 10 months and switched to undercooked sunny side up, again not eating most of the whites. Last 6 months I have been doing scrambled, so I guess I should go back to undercooked softboiled again.

    I've never been a fan of liver, but I hear that grassfed tastes immensely more pleasant. I'm going to give it a try. If I don't think I can do it, I've heard of swallowing it in small frozen pieces.

    I just "liked" your FaceBook page, so you'll notice me commenting there. 🙂

  29. Hey Leigh,

    I just realized I didn't respond to your food questions. Theoretically, cooking shouldn't interefere with your ability to get choline from these foods. However, I think it is best to eat most foods either raw or cooked gently. I tend to eat liver sauteed in a pan for about 1 minute, and tend to eat eggs by eating the yolks raw and throwing the whites away.


  30. Hi Leigh,

    Liver enzymes are not legitimate means of diagnosing fatty liver as they have little correspondence. Ultrasound, magnetic resonance spectroscopy (similar to MRI), or biopsy should be used. Magnetic resonance spectroscopy is probably best, as biopsy can suffer from sampling error and ultrasound can lose sensitivity when fat accumulation is mild. Biopsy becomes necessary for looking at more advanced stages of disease.

    You have two different values for ALP. Not sure which one you meant. If your liver enzymes are greatly elevated, you should seek medical attention. If they are mildly elevated, you should just monitor them over time. If they are mildly elevated, you might have them retested and find they aren't high anymore.


  31. Hi, I am new here. I just found out today that my GGT is 202, my ALP is 194, and my ALP is 89. I do not have a practitioner to help me navigate, so I am stumbling around myself. I understand that these numbers suggest I have fatty liver. I see that I should be eating liver and eggs, but in what form? I've had 5 eggs for breakfast almost every morning for 18 months. (Scrambled for the past 6 months.) Do the eggs have to be raw? Is it ok to eat just the yolks? Is cooked liver suitable, or does it have to be raw? How much is ideal to eat?

    1. Thank you for this link. It also contains a table at the end from USDA showing choline content of common foods–useful to choose foods to eat to increase choline uptake.
      One interesting not is they state Egg yolk, raw, as having 682. It may be that RAW is the USDA’s preferred state to ingest it, possibly answering the question of one person here on whether cooked or raw changed the amount of choline present in the egg.

      Thanks so much for all the information!

  32. Chris,

    Short of having a biopsy, what would be the tell-tale signs of a fatty liver? Would it be fat around the waist ("apple shape"), as I have seen suggested, or are there other signs? Can you have fat around the waist and not have a fatty liver?

    How did doctors in those early reports you mentioned diagnose it, and how do modern doctors diagnose it?

    Sources of Choline: from the point of view that we should try to eat as much like we did in what we might simplistically call our evolutionary period, I am wondering if our ancestors would have had a ready supply of eggs, and wonder if they would have had to depend on organ meat for their choline and other nutrients.

    On a lighter note: protection from ethanol (and fructose) by choline: I wonder if this (in some kind of folk memory sense) is the origin of consuming raw eggs after a night of alcoholic excess? 🙂

    Mike Ellwood

    p.s. Thank you for your well-written and comprehensive articles.

  33. Severe type 1 diabetes is quite a special case and it is likely that in these instances it was the severe metabolic derangement causing the fatty liver. This, however, quite clearly cannot explain why as many as 100 million Americans or more currently have the disease. Nevertheless, it was the study of type 1 diabetes animal models that led to the discovery of the critical role of choline in preventing and curing fatty liver.

  34. Chris

    Thanks so much for your quick response. Sorry I was not able to get back to this till now.

    Does it not seem strange that someone so insulin sensitive should be unable to drop any weight at all? I have started on Vitamin D and A and some iodine and in the last few weeks have started to feel better, and my fasting insulin is back at 6 for the first time in years.

    I'm wondering if there is anyone else who seems to be gaining/unable to lose weight with such low fasting insulin, and what the reason for it might be?


  35. Anonymous,

    Why do you think you are insulin resistant? It is possible to go insulin resistant and then to suffer beta-cell burnout where you cannot make enough insulin, but usually this is associated with diabetes and high fasting blood sugar. Normal fasting blood sugar with low fasting insulin would seem to indicate you are very insulin sensitive.


  36. This is very interesting. I am not overweight, but have suffered thyroid and adrenal problems for the last few years, and am trying to sort it all out. i have about 10lbs or so which i put on during this period,and which i can't shift in spite of a very healthy diet. have tried low-carb, normal carb whatever, it just doesn't go. one thing no-one has been able to explain to me is why my fasting insulin (6 when i first checked about 5 years ago when all this started) is now less than 2. my fasting blood sugar is normal at 80 – 90, so i must be making enough insulin to clear it, and yet it always tests so consistently low. is it really possible to be insulin resistant and yet have such low fasting insulin?

  37. Part IV

    You may see this type of insulin resistance as odd, given my fasting insulin
    > and HDL, TG levels — but as any post-menopausal woman who went on Atkins
    > and lost weight — until the day they didn't anymore, or as any woman with
    > PCOS can attest — there's nothing odd about it at all. Unless you're a
    > young man who will never have the same hormonal problems.
    > Sometimes there are more things in heaven and earth, Chris, than are dreamt
    > of in your philosophy. 🙂

    Quite certainly. I'm very sure I know immensely less than 1% of what
    is to be known, probably immensely less than 1% of what is to be known
    about nutrition and physiology. Still, I don't think you can assume
    that you had resolved your leptin issues after the initial decline in
    leptin levels, and I don't think you can conclude that insulin
    resistance was the primary causal driver here, though it was probably
    present to some degree.

    > I hope this long post proves useful to your readers, especially women who
    > may have also tried everything and who, despite eating a very healthy (high
    > fat, low carb) diet have reached a "plateau" lasting years. There are ways
    > to deal with that, first and foremost coming to believe that sometimes a
    > cigar is really just a good smoke — despite other appearances.

    Definitely. Thanks so much for posting your experience!

    > And I hope everyone will wish me luck with Second Chance, since the two
    > finalists will get to present their business plans to the entire NY Angel
    > Investment Group in the Boardroom of the NY Stock Exchange! I'll certainly
    > post here again, with Chris' permission, if I'm one of the two.

    Good luck! Continue to post as you wish.


  38. Part III

    > Put myself on a modified Wilson's syndrome treatment that my research
    > indicated would work, using pure T3, or Cytomel. My TC dropped by _100
    > points in 30 days_ and has continued to drop ever since. After 3 months of
    > treatment my body temp went from 96.5 to 98.6, steady. My RT3 disappeared,
    > and my Free T3 soared.


    > Weight loss during therapy, plus next three months: ZERO
    > Weight gain: 5 pounds — ALL around the waist.

    Interesting. Any thoughts on what happened to your food intake?

    > You know, when something looks like a duck and quacks like a duck — time to
    > treat it like a duck. Despite my high HDL and my low TG's, my FBG and A1c
    > had been creeping up, which Peter over at Hyperlipid has addressed for those
    > who eat low carb and high fat: physiological insulin resistance. It was
    > clear I had it. To quickly test, I asked my endo for a trial injector of
    > Symlin. I injected for two weeks before the pen ran out.
    > Weight loss over 2 weeks: 5 pounds, all from the waist.
    > Weight gain over the next 3 weeks after the pen: 5 pounds.

    This drug is an amylin analogue. According to this abstract, have to
    read the review later, amylin interacts with leptin amd other satiety
    signals in the CNS, including interacting with leptin at the

    > First, I severely cut my protein level. That alone finally stabilized my
    > weight. No loss, but no more steady, creeping gain! Then I discovered that
    > metformin not only stops excess gluconeogenesis in its tracks, but deals
    > with high cortisol levels too. And increases the efficiency of insulin. My
    > insulin wasn't *too* low, but it was clearly and demonstrably NOT working
    > efficiently. If I was correct, metformin treatment should allow me to:

    It is unclear how metformin works. Some refer to it as an insulin
    sensitizer, some as an AGE inhibitor, some as an AMPK activator. It's
    relationship to insulin is mechanistically unclear at this point, so
    while it is clear that you had an issue with elevated gluconeogenesis,
    it is also clear from your experience with symalin that this may have
    been CNS-mediated. Metformin simply acts more directly at the liver,
    whereas leptin and amylin are acting indirectly in the CNS to affect
    gluconeogeneis. Again, it very much seems to me that you never
    resolved your leptin resistance.

    Part IV follows.

    1. as a woman with pcos, yes the hormonal complexities of this is astounding and men should thank their lucky starts theyre male. kudos that the T3 and metformin worked. neither did anything for me, used over a yr. along with lchf, vlc, lifting weights, walking, etc. IFing even.
      Nothing. Works.
      and i gave up a yr ago.
      if im gonna look like i eat crap n sit in front of tv all day then im eating carbs. im happier lol my kids like me baking again too.
      its still sad tho.

      1. i think i decided my insulin istoo high despite nice bld sugars when lchf or vlc.
        changing that is whats stumping me.
        i was hungry in ketosis i finally figured out. i wanted to chew more if you can understand that. so i only did keto less than three months. i think i need a yr of it to heal my whacked out body.

  39. Part II

    >.From the day I returned, despite now being able to walk again (I'd been in a wheelchair for the
    > year prior to surgery) and exercise, I never lost another pound. My weight remained stable for
    > the next eighteen months and then, despite not changing a single molecule of my diet or
    > exercise — weight gain. Twenty pounds over the next two years — all around the waist.

    What was the surgery?

    > First came leptin. Yep, my leptin level at over 32 showed I was LR. My
    > research indicated UDCA to restore signaling. Treatment was successful and I
    > reduced the level by 30% — to 21.9 — in just two months. Six months
    > passed. A new test, after not being on UDCA for the prior three months,
    > showed another tiny drop, to: 21.8

    Certainly you're normalizing something but I don't think this shows
    you eliminated leptin resistance. After all, adipose secretion may
    decline but this says nothing about whether it is reaching the brain
    or having an effect at the hypothalamus.

    > Weight loss during the 6 months: ZERO
    > Weight gain during the 6 months: 5 more pounds

    Doesn't sound like leptin resistance was normalized. Sounds like
    leptin secretion dropped without sufficiently increased sensitivity.
    Or at least that sensitivity and secretion were adjusted in the same
    proportion, leading to no leptin effect.

    > I then moved on to thyroid hormone signaling, which can and often is
    > disrupted in women by V. low calories OR V. low carb for an extended period.
    > Sure enough, my Free T3 was in the basement, my Reverse T3 was sky-high —
    > and despite great HDL and TG's, my TC was 400 and my LDL was 300. Sure signs
    > of improper thyroid hormone signaling to the liver, since the 5' Deiodinase
    > (iodide peroxidase enzyme), present in T3, is missing the _'_ marker in the
    > mirror image Reverse T3. And it is that marker that signals the liver about
    > sufficient cholesterol levels.

    Clear signs of leptin resistance.

    Part III follows.

  40. Hi Lisa,

    Thanks for your detailed reply!

    First, congratulations and GOOD LUCK with the competition!

    I'll respond point by point to make this easy to follow.

    > First, I would posit that it's impossible to become
    > obese (and certainly as morbidly obese as I was: 225 pounds w/ measured 53%
    > body fat), with most of the weight being adipose fat tissue, without being
    > insulin resistant.

    I agree it's pretty likely, but it's very possible to be obese without
    being clinically and pathologically insulin resistant.

    > I do this with a vengeance for 3 years, eating
    > between 1100-1300 calories a day, with V. low fat. An egg didn't pass my
    > lips for years, and heaven forbid butter. But boy did I eat "healthy" carbs!
    > The weight *really* piled up then and by the end I was heaviest: 225 pounds.

    So we have an effect due most likely to menopause, and compounded
    either by calorie restriction or excess carb relative to protein
    and/or fat.

    > Two things happened then. I discovered I needed hip surgery, and I read
    > Taubes. It took 2 years but by cutting carbs and adding fat, I lost 65
    > pounds and went off to surgery.

    Awesome! Congratulations. It's difficult to tell what about the
    protocol worked, mechanistically — unlikely to be spontaneous calorie
    restriction that usually occurs on low-carb because you were already
    restricting calories low; likely to be variations in macronutrient or
    micronutrient intake that affected metabolism, but unlclear which of
    many possibilities.

    Part II follows.

  41. Part IV

    You may see this type of insulin resistance as odd, given my fasting insulin and HDL, TG levels — but as any post-menopausal woman who went on Atkins and lost weight — until the day they didn't anymore, or as any woman with PCOS can attest — there's nothing odd about it at all. Unless you're a young man who will never have the same hormonal problems.

    Sometimes there are more things in heaven and earth, Chris, than are dreamt of in your philosophy. 🙂

    Naturally, once I finally lose the next ten pounds I thought would easily achieve after my surgery — which only took a multi-year detour — I will cut the metformin and keep meticulous notes over the following several months. If I keep losing till I reach my goal — another ten — I will consider my insulin resistance gone and my metabolism healed. If instead I stagnate — or, perish the thought — gain, back on the metformin I will go.

    I hope this long post proves useful to your readers, especially women who may have also tried everything and who, despite eating a very healthy (high fat, low carb) diet have reached a "plateau" lasting years. There are ways to deal with that, first and foremost coming to believe that sometimes a cigar is really just a good smoke — despite other appearances.

    And I hope everyone will wish me luck with Second Chance, since the two finalists will get to present their business plans to the entire NY Angel Investment Group in the Boardroom of the NY Stock Exchange! I'll certainly post here again, with Chris' permission, if I'm one of the two.

    Happy Holidays to all…


  42. Part III

    I couldn't afford to buy the pen, but it was clear now what the problem was. It took a few more months of research to pin down the precise problem so I could find the most effective treatment. That's where I discovered the long-term cortisol effects of major surgery — and the concomitant rise in gluconeogenesis from protein in these people.

    First, I severely cut my protein level. That alone finally stabilized my weight. No loss, but no more steady, creeping gain! Then I discovered that metformin not only stops excess gluconeogenesis in its tracks, but deals with high cortisol levels too. And increases the efficiency of insulin. My insulin wasn't *too* low, but it was clearly and demonstrably NOT working efficiently. If I was correct, metformin treatment should allow me to:

    1: Eat a bit more protein.
    2: Eat a bit more carbs (just enough to keep me out of ketosis and thus prevent hypothyroid return)
    3: Lower my FBS
    4: Lower my A1c
    6: Lose weight again — finally– especially from around the waist.

    Over the last 4 years I have kept meticulous records of everything: food, treatments, and even temps, day by day. Same with the metformin. It took a good 2 months to do *anything* but then!

    After 6 months of metformin:

    — A1c dropped 6% — to normal again.
    — FBG dropped 6% — to normal again.
    — TG dropped to 220
    — LDL dropped to 94
    — Fabulous HDL and TG's remained. All Pattern A.
    — Eating more protein and carbs. Staying out of ketosis. No sugar of course, but more fruit (like apples and melons) and starches like potatoes and bread. Had a croissant for breakfast yesterday. 🙂
    — My leptin level dropped *another* 15%!
    — Weight loss: ALL of the regained weight plus another 6 pounds. I am, for the first time, slimmer than I was when I returned from surgery. Then: size 14. Now: size 12.
    — Most of the loss has been fat from around my waist. I've lost 4 inches from around my belly button alone. Big losses on thighs, calves (and around the knees!) and upper arms.
    — My muscles have remained, especially on biceps and quads, and you can see them even better now without all the fat on them.

    Final Part IV coming up.

  43. Part II

    I then moved on to thyroid hormone signaling, which can and often is disrupted in women by V. low calories OR V. low carb for an extended period. Sure enough, my Free T3 was in the basement, my Reverse T3 was sky-high — and despite great HDL and TG's, my TC was 400 and my LDL was 300. Sure signs of improper thyroid hormone signaling to the liver, since the 5' Deiodinase (iodide peroxidase enzyme), present in T3, is missing the _'_ marker in the mirror image Reverse T3. And it is that marker that signals the liver about sufficient cholesterol levels.

    Put myself on a modified Wilson's syndrome treatment that my research indicated would work, using pure T3, or Cytomel. My TC dropped by _100 points in 30 days_ and has continued to drop ever since. After 3 months of treatment my body temp went from 96.5 to 98.6, steady. My RT3 disappeared, and my Free T3 soared.

    Weight loss during therapy, plus next three months: ZERO
    Weight gain: 5 pounds — ALL around the waist.

    You know, when something looks like a duck and quacks like a duck — time to treat it like a duck. Despite my high HDL and my low TG's, my FBG and A1c had been creeping up, which Peter over at Hyperlipid has addressed for those who eat low carb and high fat: physiological insulin resistance. It was clear I had it. To quickly test, I asked my endo for a trial injector of Symlin. I injected for two weeks before the pen ran out.

    Weight loss over 2 weeks: 5 pounds, all from the waist.
    Weight gain over the next 3 weeks after the pen: 5 pounds.

    Continued in Part III

  44. On Dec 2, Chris wrote: "Given that your insulin, glucose, and triglycerides were/are normal, I see no evidence that you had insulin resistance in any form."

    Chris, sorry it's taken so long to get back to you about this, but although I didn't mention it earlier I was selected back in September as a semi-finalist in Sprint's SECOND CHANCE earch for an entrepreneur with a new idea.

    I'm the first person in the country whose figured out a way to make all-natural, artificial-sweetener free sugar free desserts that actually taste good — LOL. The last two weeks I've done nothing but deal with the voting (only the top 2 vote-getters go on to the finals) and set up

    The winner gets $150,000 to start their new business — so wish me luck!

    Now, on to the fun stuff. 🙂

    Let's stand your comment that I show "no evidence" that I am insulin resistant on its head. First, I would posit that it's impossible to become obese (and certainly as morbidly obese as I was: 225 pounds w/ measured 53% body fat), with most of the weight being adipose fat tissue, without being insulin resistant. I'm sure you will agree that I was certainly insulin resistant then. So let's look at all the evidence in a time-line order.

    Youth: Slim. Wore a size 6 to my HS prom.
    Adult: Still slim, but no size 6 after kids, alas. Size 10.
    Post Menopause: Uh-oh. Starting to gain weight around the middle. Doc says eat less and cut out the fat. I do this with a vengeance for 3 years, eating between 1100-1300 calories a day, with V. low fat. An egg didn't pass my lips for years, and heaven forbid butter. But boy did I eat "healthy" carbs! The weight *really* piled up then and by the end I was heaviest: 225 pounds. Size 24 dress.

    Two things happened then. I discovered I needed hip surgery, and I read Taubes. It took 2 years but by cutting carbs and adding fat, I lost 65 pounds and went off to surgery. From the day I returned, despite now being able to walk again (I'd been in a wheelchair for the year prior to surgery) and exercise, I never lost another pound. My weight remained stable for the next eighteen months and then, despite not changing a single molecule of my diet or exercise
    — weight gain. Twenty pounds over the next two years — all around the waist.

    I tried everything. Cut more carbs. Cut fat. Cut calories. Raised fat, raised calories — you name it. Nothing worked, even starting "slow burn" weight training. Turns out I'm a true
    Endomorph — put on muscles easily, but fat just as easily. So I developed biceps you can bounce a quarter on, but also more fat around my waist. Slow burn is so intense, it sends cortisol levels sky-high — as does, by the way, major surgery. And for some people, surgery does long-term damage to the metabolism in several different ways, as you'll see.

    By this time I was desperate to figure out what was wrong, and so began my intense research for causes — and solutions.

    First came leptin. Yep, my leptin level at over 32 showed I was LR. My research indicated UDCA to restore signaling. Treatment was successful and I reduced the level by 30% — to 21.9 — in just two months. Six months passed. A new test, after not being on UDCA for the prior three months, showed another tiny drop, to: 21.8

    Weight loss during the 6 months: ZERO
    Weight gain during the 6 months: 5 more pounds

    Continued in Part II

  45. Thanks Chris for your blog!

    I would like to know your opinion about soy lecithin ( as a source of choline, since it seems an easier source for high quantities than egg yolks. The only think that bothers me is its 30% of soy oil with its high omega-6 fatty acids (I will look for "refined" next time I go shopping for it), but I hope it will be neutralized with enough omega-3 intake.

    As an anecdotal comment, as an infant and a toddler my mum gave lots of "ponches" to me: egg yolk with a cup of hot milk (adults with some sweet wine). Nowadays with the cholesterolphobia it seems that this good procedure has been lost.

    Thanks in advance.

  46. "We've got them just where they want us!" More on how our "obesity epidemic" (leptin resistance ?) is occuring.

    Bacterial varieties in a flies gut cause them to mate (that's right, "cause") with flies having the same type of bacteria. The match up of bacteria is centered around what unique digestive enzymes they have.

    Flies are multi-cellular organisms showing genetic selection occurs to modify and adapt based on both the symbiont (bacteria & their phages) and the host organism.

    Antibiotics break the cycle of "like attracts like" and those same flies will mate without regard to gut biome. But, re-introduce a specific set of gut microbes and those flies go back to mating with just the same gut flora flies.

    We think internet dating is a step above match makers. Those fly dates are so directly simple because different microbial biomes give them distinct sex pheromones to "hook up".

    Human antibiotic use alters the ratios of gut bacteria; even though the treatment was meant to "kill" 1 type for a cure. However, bacteria
    have millions of years jump on us and go into "spore" mode to save their lineage.

    Eventually strains reappear, but hopefully any virulent ones area a minority player. In a sense we become "carriers" who go out to touch
    and mingle bacteria.

    The 24 (known) obesity genes have free range in our global village. Statisticly "like attracts like" is going on; even when we think
    it's free will the way we sometimes "breed like flies".

    Remember, we get genes from mother & father in one nucleus in one cell. Our progeny get a lot of shots at getting obesity genes.

    Each bacteria, with their phage DNA, has multiple nucle-oids with genes. Varieties of E. Coli, for example, aren't mating; so specific strains pretty consistantly do their "own thing" with us.

    Bored or lost, maybe this final bit will satisfy. The bacterial genetic enzyme variation is more precise than does it digest carbohydrate, protein or fat.

    It's for which, among the 500+ bacterial strains in humans, has for an example … amylase enzymes (etc). So a Kitavan on sweet potatoes, a Frenchman on baguette, a Yank on corn, Nubian on millet or Thai on rice would have (in previous eras of social isolation) bacteria with the same name, but with a sub-set of bacterial amylase DNA.

    ((Colonizing people said the natives smelled, but the Indians said the colonizers smelled. Warriors could smell the enemy & hairs would stand up on the back of his neck.))

    Modern diet and the introduction of refined foods to native populations are factors you can read about elsewhere. And just be humble; we have no idea how the "viruses" (phages) got the bacteria "just where they want them" !

  47. Lisa,

    Thank you for sharing your story. Given that your insulin, glucose, and triglycerides were/are normal, I see no evidence that you had insulin resistance in any form. I am open to considering the possibility that you had some type of insulin resistance very different from what other humans typically have, if you have evidence of that.

    There is no consensus about the mechanism of action of metformin, and as such, your story is difficult to interpret. Moreover, it doesn't seem like your story allows us to attribute the effects specifically to metformin given that the other treatments could have taken a while to result in weight loss. Unless you went through the trouble of repeatedly taking yourself on and off of metformin.

    If you have any other observations from your story that may clarify this, I would be interested to hear them.

    Thank you again for sharing your story,

  48. Chris,

    For the last five years my TG's have fluctuated between 42-55. My HDL from 88-97. My last C-RP was .6 and a VAP done six months ago (before Metformin) showed 100% Pattern A. All reasons why the idea that I was insulin resistant was difficult to believe. In fact, it seems to be clear that my particular form of this is what I'm now calling 'inefficient insulin' since that seems to fit.

    I went for my labs yesterday, and should have the results back by the end of next week. I too am curious about how the metformin has affected everything.

    One interesting note. As I continued to eat VLC, my fasting glucose kept rising slightly. Before VLC it was in the high 80's to low 90's. For the last three years it crept up to 101 no matter what I did or what I ate. Peter over at Hyperlipid explains why this is so for HF/LC eaters in a series of posts about "Physiological Insulin Resistance," which he distinguishes from pathological insulin resistance. A HF/LC eater is just in need of a good breakfast (borne out by my PP's in the 80's) . . . whereas a SAD eater with high fasting glucose is a "heart attack waiting to happen."

    My fasting glucose yesterday? 95 — a 6% reduction.

    Al — I agree with your last post, thank you.


  49. Firmacutes are associated with obesity & conversely Bacteriodes with less metabolic syndrome.

    With each of us having over 500 types of gut bacteria, them hosting about 10 phages each that's a lot of potential for viral genomic DNA.

    These bacteria are dynamic; the pictures of rods & cones in books is misleading. This is the 2nd largest "organ", after the liver, in our bodies.

    It tasks our imagination because none of those phages are technically alive (viral DNA is insidious) & they don't all follow one set of rules. They have millions of years of strategic tricks to further their mysterious cycles.

    Please, anyone here, with the most respect for your personal feelings permit me to include this comment.

    It seems that sometimes there is a constellation of problems we track through.
    We want a direct cure for a diagnosed condition. The remedies we find have us wondering if our genetics won't finally let us catch a break.

    A "trigger" is my word for when things go wrong for humans. If it was prophages, phages, plasmids and virion like particles then that was precisely when it started going right for it.

    They even have layers of interrelationship.
    We are not sure of what activation of any one keys another to do. Nor know what it elicits from the 10% bacteria DNA coded into ourselves.

    This is not a touting of pro-biotics & live happy forever. Nor am I insisting that I know we can blame everything on what we host.

  50. Lisa,

    Your story is extremely interesting and may prove useful for unraveling these questions, but certainly it does not invalidate the role of gut flora. Just because gut flora played no role in your particular case — which we are assuming but don't know for sure — that does not mean that it plays no role in every other case. And, in fact, simply putting gut flora from obese animals into the guts of other animals makes them obese. So there is very good reason to think that gut flora plays a role.

    Regarding your own story, what happened to your plasma triglycerides when you went on metformin?


  51. "I believe it is incorrect that the causal pathway is always gut flora —> leptin resistance and never leptin resistance —> gut flora."

    Or perhaps — none of the above. As I mentioned previously, treatment with UDCA lowered my leptin level into the 'normal' range. And I lost some fat. But not enough. Nor was my weight seriously affected. This surprised me because I had lost 65 pounds (and gone from morbidly obese to obese to slightly overweight) while on a VLC diet. When I suddenly stopped losing weight about 20 pounds from goal, I figured I was at a plateau. When the plateau lasted four years — and I *gained* 20 pounds back despite switching from VLC to Kwasniewski — I figured it had to be leptin.

    But lowering my LL and fully restoring proper signaling didn't get me really closer to my goal. Then, reading that long term VLC can (especially in women) cause thyroid *hormone* problems, I had those tested. Sure enough, with daytime temps of 96.3 and a massive Reverse T3 problem, I was indeed hypothyroid.

    I put myself on a modified Wilson's Syndrome course of Cytomel (pure T3) and within six months my average temp was 98.6, my Reverse T3 was gone, my Free T3 was great and all hypo symptoms were gone. And I was off all meds. But . . . not a pound or inch did I lose.

    So, despite having an excellent non-diabetic profile (PP's in the 80's, FG in the 90's and fasting insulin of 4), I concluded that even after fixing my leptin levels and thyroid hormone problems, I *must* be insulin resistant.

    I've been on metformin for 4 months. I've lost the 20 pounds I'd regained — plus 2 more — and three inches from around my waist, still eating a diet that's 75% fat, 15% protein and 10% carbs (just enough to stay out of ketosis and thus to avoid future hypo problems).

    Gut flora? Don't think so. {s}


  52. Response to Jana and …AL,

    Jana, yes that is the point, that eggs and liver are good sources of choline and getting choline is most important when it comes to protecting against fatty liver. Could you make some suggestions about how I could improve the conclusion under "Choline is King!" in order to make it more understandable?


    …AL, I think you are on track and that gut flora does contribute to obesity. However, genetically induced leptin defects still lead to "obesity flora," so I believe it is incorrect that the causal pathway is always gut flora —> leptin resistance and never leptin resistance —> gut flora.

    It's probably something more like

    leptin resistance
    / |
    | |
    | /
    changes in gut flora


  53. Bear with me ….

    Chubby infants are good & active children will grow out of their baby fat. Like diabetes there are probably various leptin resistant scenarios that develop.

    Obese adults have distinct microbial composition in gut than others.It sounds unlikely leptin resistance inside accounts for bacteria varieties taking hold after the fact.

    Gut bacteria are not passive. Some put pilli into the intestinal wall to sample & send. This is not the same as "leaky" gut phobia.

    Bile is part of their world & maybe certain bacterial strains are interacting with fractions of it (analog like the Bear bile fraction. Assumptions about bile salts may not account for all it's involved in.

    Back to childhood for perspective & you can go.

    Kids microbial biome changes & so does their % of white blood cells circulating inside them. This variable may be protective against a trigger event gaining dominance automaticly.

    By time child can run around we are heading to adult blood composition. Used to be leptin resistance was an adult phenomena. Of course we may be breeding bacterial strains that kids get exposed to.

    Some time or other life posits a challenging exposure to a microbe variety that interacts differently with some bile fraction. "Bad" bacteria passes it's differently configured messenger compound into the intestine is my scenario.

    Mast cells, which previously "saw" a benign
    bacterial bile message are altered. The type of virulent input causes the gut's mast cell to incorporate aberrant transcription factors.

    Mast cells go into circulation with these mangled proteins to mess up the genes signalling leptin metabolism. These mast cells can affect the endoplasmic reticulum &/or hypothalmus.

    Does the "off kilter" mast cell transcription "wake up" a viral genome lurking in our DNA inside the endoplasmic reticulum? Some of those prophages will just be plasmids of DNA "lying" apart from our own chromosome.

    This may be why the hypthalmus must be kick started to over-ride phage DNA setting. Likewise our gut bacteria may turn on us because of their own virion like particles.

    (Ex: 136 of 178 Salmonella strains,
    38 of 68 Streptococcus strains & 83 of 107 E. Coli strains release one or more functional phage.

    Rheumatoid arthritis & brain pathology are being suggested as bacterial damage. Some bacteria's endgame is to have us obese for what our intestinal dynamics offer them to thrive. (The cat owns it's master.)

    Once leptin resistance triggered the dietary metabolic conditions exasperate things (tail wags the dog). Feast or famine cultures don't allow the syndrome to develop into a self-propagating state.

    Bear bile fraction chaperoned to hypothalmus sets the leptin function back to more normal with message of "good" bile as input.

    The obese type of bacteria populating the intestine still may be capable of sending their aberrant signal. However, by now the mast cell doesn't over-react so any incorporated transcription factors aren't
    messing up leptin genes.

  54. Sorry, Chris — I don't know it. I have the article itself. I'm sure if you searched pubmed for "Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin Resistance" I'm sure you'll find it.


  55. Chris, great article (as always), thank you. But I believe I can shed some light on your final questions:

    "Leptin deficiency and leptin resistance both cause fatty liver. And obese people are leptin resistant and the majority of obese people have fatty liver. Can fatty liver or choline deficiency cause leptin resistance? Or does leptin resistance cause cravings for choline-poor, fatty, and fructose-rich foods?"

    I have done a great deal of study on leptin resistance, and after reading the January 2010 article on "Leptin Resistance Treatment" in _Cell Metabolism" (among others) came to understand that it is caused by the breakdown of signaling from the adipose fat cells to the hypothalamus. Which itself is caused by endoplasmic reticulum stress. Which can be caused by *many* things — such as diet — including excess or chronically elevated cortisol. Which in turn can be caused by something as simple as major surgery — which I had four years ago, and which coincided with weight gain despite following the Kwasniewski OD, filled with choline-rich foods.

    The question is, can LR be treated? As the *Cell Metabolism* article pointed out, yes it can. Although the article researchers treated mice, I saw no reason not to try their method on myself.

    Basically the researchers believed that although giving leptin injections to LR mice (or people, for that matter) had been clearly shown to be a failure — they thought that if they first *pre-treated* subjects with a 'chaperone molecule' — proper endoplasmic reticulum folding might re-commence — thus allowing existing leptin to leave the bloodstream (where it uselessly pooled) and cross the blood brain barrier. Thus restoring normal leptin signaling to the hypothalamus.

    They tried 2 different chaperone molecules. One had spectacular results: TUDCA (the taurine conjugated form of UDCA, which is available to researchers here in injectable form. Hard to get those mice to swallow pills. ).

    Ten days of treatment with UDCA alone was enough to not just restore leptin signaling (they harvested the hypothalami to make sure), but these mice lost weight AND body fat. A tiny bit of leptin after that (much less than was required with the other chaperone molecule they tried) increased benefits, even though without TUDCA, leptin did nothing.

    After researching UDCA (made from bear bile) and discovering that it is used to treat — guess what? — non-alcoholic liver disease, with zero toxicity, I got my endo to give me a prescription, and figured out what dose to take with a researcher currently overseeing UDCA trials on a wide variety of diseases including Parkinson's.

    A month later I had another leptin serum test. My leptin level had dropped by a full 30% — right down into the normal range. I also dropped a lot of adipose fat (put on despite eating OD long-term). But . . . had signaling actually been restored? I stayed on the UDCA for another month, weaned off and then stayed off for six months. My next leptin test revealed that not only had signaling stayed restored — my LL dropped a bit further.

    BTW, I *never* had any cravings for fructose-rich foods, but then I believe those cravings aren't caused by LR, but are a result of eating a fructose-rich diet to begin with. Which is one of the causes, I feel, of LR to begin with.

    I have a Yahoo group devoted to LR and all things metabolic: If anyone reading this wants to join, please mention this blog in your membership request, and _sign your name_. We have the _Cell Metabolism_ article and a lot more in our group files.

    It's been a year since my last labs, and I go tomorrow for a new set. I expect to see that my leptin level has dropped even further.

    My apologies for such a long post…


  56. Chris,
    Love your blog…but for those of us without a chemistry degree, would you consider putting a recap at eh bottom of your posts in layman's terms. I think what you are saying is that it's healthy to eat eggs and that the lack of choline is one of the causes of fatty liver disease. Eggs are a good source of choline. Am I on track? Thanks for taking the time to do all this research.

  57. Thanks for the great article.

    I have a 13 yo that takes phosphatidylcholine directly and it does wonders for him. We learned of this before we learned that his health issues are due to severe glutamate sensitivity; apparently choline is neuroprotective from glutamate ( We recently made a tentative connection from the glutamate sensitivity to an underlying oxidation/NOS/ammonia issue (I don't really understand it but BH4 -Tetrahydrobiopterin- has been helping immensely) that we are still figuring out (along these lines: Does this spark any thoughts? I'm wondering if you have heard of any connection between choline, glutamate / NDMA receptor sensitivity, and/or BH4 synthesis?

    I did find this google book result and may need to order the book. This page references insulin and choline but I can't really decipher it all. The Role of Nitric Oxide in Heart Failure , pg 58

    Anyway, never mind if this is rather obscure – my main point was actually to point out that supplementing PC, though perhaps not ideal, is an option.

  58. Wonderful article…just made myself a 6 yolk, 1 white omelette, cooked in bacon drippings and a bit of coconut oil.

    I could get used to eating like this. 🙂

    As a 50 year old male, I'm looking forward to future articles on how to adjust my diet to deal with the fatty liver I probably have right now.

  59. Links supplied by Eades in their latest book: Dietary Saturated Fatty Acids Reverse Inflammatory and Fibrotic Changes in Rat Liver Despite Continued Ethanol Administration J Pharmacol Exp Ther November 1, 2001 299:638-644
    Dietary saturated fatty acids: A novel treatment for alcoholic liver disease
    Gastroenterology Volume 109, Issue 2 , Pages 547-554, August 1995

  60. Chris, I have really been enjoying your discussion of choline. It is truly fascinating and this could be a breakthrough in our understanding of metabolic syndrome. I'm very excited to see where you go with this.

  61. Chris,

    Incredible article. Your ability to dig deep into these details already seem inherently genius even as of now, but I believe that this type of research will be viewed as monumentally significant in the years ahead. I think some of the blogospheric health gurus will be seen as the champion pioneers of information that will come to be known as common knowledge of tomorrow. That might sound a bit wordy, but honestly I applaud your diligence to seek out the truth.

    I'm not sure who Ilya is, but maybe he/she just wants to drink a bunch of alcohol or something. I just drank a Stone pale ale and I'm really not worried about it. haha. Anyway I like your style of communication on that 'brief exchange'. Well played.

    Meanwhile, although my brain still hurts from the data, I can go eat some eggs and just take comfort that I am getting valuable choline to help protect against fatty liver. Very nice how that works on an applicable level.

    Thanks again Chris.

  62. Hi Ilya,

    Nothing in my post or that I have said within these comments even made the slightest suggestion that people who drink alcohol have equivalent or shorter lifespans than those who don't.

    Of course such a study did not prove that or anything else, because proof only occurs in a priori sciences and not empirical sciences, and because epidemiological studies are not even capable of providing supportive or refutive evidence for cause-and-effect hypotheses.

    I think your decision to end this brief exchange is probably a good idea, although if you would like to discuss it further in a logical, step-by-step and systematic manner I am open to that.

    Thank you for your contributions,

  63. I beg to differ about the role of ethanol in increasing hepatic lipid and will only say that resistance or rather insensitivity to ethanol is the reason for such an increase. What has bearing to the above is the fact that a 20-year longitudinal study DID NOT prove that people get hepatic steatosis from systemic use of ethanol but it DID prove that they live longer. With this I rest my case. It was pleasure discussing the matter:)))

  64. Ilya,

    I appreciate your efforts to save everyone time. Thank you.

    I did not villify ethanol. I have no idea where you got that idea.

    Of course ethanol can increase liver fat, which is why all the references you've been posting and the references within those references acknowledge as much. How long people who consume such-and-such amount of ethanol has no bearing on the fact that under certain conditions — namely, those that prohibit the liver's ability to properly dispose of the energy it's given to dispose of — ethanol will contribute to liver fat. Any other source of calories can do the same, insofar as a portion of those calories are metabolized by the liver.

    I agree that choline has transcriptional effects. I also think that all transcriptional effects should be viewed in the larger context of why they are occuring, and exactly what signals are being communicated. Ultimately choline's role in the liver has very, very much to do with the fact that it is essential to the secretion of triglycerides.

    Thanks for writing,

  65. I'll put things in a very simple way and will try to save your and my time and that of the people following the blog and will not dig into the too many "I don't understand why". Straight to the essential point:
    "Regardless of whether ethanol increases liver fat by acting as a lipogenic substrate, increasing lipogenesis from other substrates, or decreasing fat oxidation, the export of triglyceride must also be impaired, thus the protective effect of choline."
    ETHANOL DOES NOT INCREASE LIVER FAT by any of the described paths. Evenmore it does not increase liver fat at all. You obviously missed the passage in my lost post which explains what ethanol does but. Ethanol or not, hepatic steatosis develops. Vilifying ethanol is socio-cultural phenomenon NOT scientific, the scientific fact is that Moderate and Hard Drinkers live longer than Non-Drinkers:
    There is pretty sound scientific explanation of the fact and it does not allow frivolous musings. And as I already explained the effect of CHRONIC abuse of ethanol is CONTRARY to that of dose-dependent use and you don't have to hold a Doctor's degree to understand that though it could help.
    The protective effect of choline consists of inducing SCD-1 which as SOD and AMPK has anti-inflammatory and anti-oxidative effect. Choline however is NOT the solution nor its defficiency is the CAUSE for hepatic steatosis. Can't make it more clear than that, I'm afraid. Regards.

  66. Ilya,

    By describing the diet in the Best paper, I am not sure what your intention or point is, as you do not lay it out explicitly.

    Describing the mechanism of an effect is important to understanding it and to generalizing from it, but it is not important to meet the scientific burden of evidence that the effect happens.

    I don't understand your logic in saying that the chronic effects of ethanol abuse are not the result of ethanol. Clearly, if a chronic high intake of ethanol is called "ethanol abuse," then the effects of "ethanol abuse" are the effects of a chronic, high intake of ethanol.

    I don't understand what you think is ridiculous about substituting maltose or other sugars for ethanol.

    I did not say that "ethanol per se" causes hepatic steatosis. In fact, the entire point of my post was that neither ethanol per se, nor fructose per se, nor fat per se cause steatosis but rather that an increase in liver fat without means of exporting it causes liver steatosis.

    You think that an MCD diet, despite causing steatosis, is "NOT causative"? I do not understand what that means.

    I'm not sure why you are capitalizing High Carb Overfeeding, but as the evidence in this post indicates, a combination of a source of liver triglyceride, which could be but must not necessarily be carbohydrate, is essential but not sufficient to cause steatosis.

    Decreases in lipogenic gene transcription do not show that lipogenesis is decreased. See the Pickens study on sucrose being required in the MCD model.

    After reading the response to Lustig's paper, I agree that his presentation of ethanol metabolism was simplistic. However, the paper showing that ~ or < 5% of an ethanol bolus is turned into fat also shows a massive decrease in fat oxidation as it is replaced by acetate:

    They still show most of the ethanol going to the liver, and only 70-80% escaping as acetate. So apparently 15-25% stays behind to, most likely, decrease fat oxidation in the liver.

    Regardless of whether ethanol increases liver fat by acting as a lipogenic substrate, increasing lipogenesis from other substrates, or decreasing fat oxidation, the export of triglyceride must also be impaired, thus the protective effect of choline.


  67. This was Ilya's comment. Not sure why it didn't go through.


    Thanks for answering, Chris. The basic diet used along with ethanol in the 1949 study was:"The basal diet had the following composition, in percentages:
    casein 10, gelatin 5,zein 3, cystine 0.3, salts (Beveridge
    and Lucas, 1945) 5, celluflour 2, sucrose 41.7, starch 10,
    dextrin 10, beef fat 10, corn oil 2, "vitamin powder" 1,
    cod-liver-oil concentrate* 0.015, a-tocopherol acetate 0.01,
    choline chloride 0.05."
    Does this somehow ring a bell?
    Second,"the extremely well known and universally recognized ability of ethanol to contribute to fatty liver" that lays in the name of the syndrome DOES NOT meet the scientific burden of proof as it does NOT reveal the mechanism. On the other hand, CHRONIC abuse of ethanol does bring to desensitizing of hepatic receptors involved in the Fatty Liver Syndrome but this is not the effect of ethanol but rather resistance to it as ethanol inhibits SREBP-1c by lowering plasma pH under 7 and thus has neuro-protective and anti-inflammatory effect (I don't think I have to quote research on this as it is all over the net). Hope I somehow contributed to your post. A good study giving some food for thought is:
    Last study I run across about Fatty Liver Mechanism used maltose as a valid substitute for ethanol diet plus extra sugars in it. I think this is ridiculous. To sum it up: Ethanol per se does not cause hepatic steatosis. Choline Methionine Defficiency causes suppression of SCD-1, a key (enzyme)factor in SREBP-1c, the flagman of DNL (Lipogenesis de novo) and Lipotoxicity and promotes hepatic steatosis but is NOT causative. By which we arrive at the point of High Carb Overfeeding. Hope this settles it. One last thing, not sure, but think that there are quite a few instances when MCD is NOT existent but hepatic steatosis does develop notwithstanding. Regards.

  68. And a thing more: Did the post that I left prior the one about Richard Lustig's article somehow disappear? As I was pretty sure it was online a few minutes ago. Could be just a glitch. Do you want me to repost it?

  69. Oh, and Chris could you, if you have the pdf of Richard Lustig's article and the two comments to it(BTW the very first one questions the very core of his assumption that fructose and ethanol metabolism are similar and which, of course, is NOT true and quite a mis-statement). I'll subscribe to the thread by e-mail too but in case you, or anyone else, decide to help me out with the research email to iberaha at ya-hoo dot com Thanks in advance.

  70. Ilya, thanks for writing. I already did elaborate and provided two relevant references. See reference 16 for a review on the similarities between fructose and ethanol on lipogenesis, and see reference 19 as one instance of the extremely well known and universally recognized ability of ethanol to contribute to fatty liver.


  71. Responses to Ned, Anonymous, Anonymous, Chuck, and Mrs. Ed.

    Ned, thanks!

    Anonymous, you're welcome. I will address the choline requirement and how to obtain it in a future blog post. However, my next choline post will probably deal specifically with fatty liver and it might take me some time to get to a more general choline post.

    Anonymous, I find what you posted to be extremely difficult to read, as if it isn't quite written in English. I'm sorry but that makes it very difficult to respond.

    Chuck, I will try to get to these questions in my general choline post, which will likely be a couple choline posts from now.

    Mrs. Ed., yes, good point!


  72. It's amazing how many of the old sayings turn out to be true. I like reading older books on health and nutrition, it's amazing some of the insight they had that has gotten totally lost today (although they will also have some outdated material too). I just picked up some Adelle Davis books and she mentions the old saying "Eat what ails you" and recommends eating liver for liver problems.

    1. The Chinese had/have a similar view, eat the part that ails you, for example Brain, liver, stomach, feet (Chicken or pigs feet – Trotters) lungs and even penis (really and testes)

  73. So what is a healthy choline blood measurement?

    And assuming levels are low, how many mg a day would you shoot to supplement with?

    Finally, is Alpha GPC (L-alpha-glycerylphosphorylcholine) the preferred form of Choline?

    It seems Alpha GPC is the natural form, also used for brain function, but it doesn't exactly seem like its the same as liver friendly choline.

  74. "Harper's Biochemistry at str.328 to 330
    "The phenomenon is described in one sentence:" The lack of balance between production of triacylglycerol secretion is the cause of fatty liver, "and explanation – two metabolic syndrome (metabolic pathology) due to specific environmental conditions (read: mistakes in nutrition): the first two cases concern a -starvation, the liver accumulates enough power to their own work and 2 – Channel-shaped transition to the diet, when the amount of exogenous fat is from 40 to 60% of the energy of the ration and the second: if there is a metabolic syndrome block the production of plasma lipoproteins – VLDL-u or – no protein packing fraction of triglycerides in the liver – B-100 (as a characteristic example for thick Vegetarian and type I diabetes). And further description of an artificial call this phenomenon (fatty liver) by choline deficiency, caused, in principle, a shortage of methyl groups.
    So described the state has nothing to do with health, and only a description of the pathology and high fat diet does not apply where it is delivered in a ration above 80% energy as fat

  75. Hi Chris…

    Thanks again for all the great leg-work you're doing for the rest of us. I love reading your posts.

    I had a question pertaining to how to best supplement one's diet with choline. Since a large egg contains approx. 115mg, then one would have to consume approx. 5 egg yolks/day just to get the RDA minimum, which you've hinted may even be on the low side. Do you think it would be prudent to take lecithin granules, such as the one being sold by NOW Foods? They have one that is certified Non-GMO and which contains 2.5gms of Phosphatidyl Choline per 1 1/2 TBs. It also contains 1.5gms/TB of Phosphatidyl Inositol to go along with it.

  76. Hi Chris.

    Below are the links to a post on fructose and a few articles that I've been reading:

    The second link, to a study by Nilsson and Hultman, is fascinating. After administration of what seemed to be 5 g of sugar per kg (341 g of sugar for a person weighing 150 lbs), they found that very little was stored as fat (much less liver fat). Most of it became muscle and liver glycogen. I am having trouble getting the full text; I want to see if these health volunteers were fasting or exercised prior to the experiment.

  77. Responses to Tyler, Stephan, Stuart, Ed, Ed, Anonymous, Ed, and Ned. 🙂

    Tyler, thanks! Yes, fatty liver in children is depressing 🙁 I'm glad they are at least removing the soda and hope they get to the liver and eggs next, once we crush the cholesterol paranoia. I find it interesting that Zelman connected fatty liver to soda 58 years ago.

    Stephan, good question. I will try to answer this in my next choline post.

    Stuart, yes indeed, since the AIN-93 supplies 0.1% choline, lower than the choline requirement shown in the above graph from the 1957 study for either corn oil or butter. They are *still* doing the same thing to lab rats they are doing to us. Thanks for the toast!

    Ed, thanks for the link. Ed, I could, but then I'd have to incorporate an estimate of the ideal surface-to-volume ratio of VLDL particles and assume that choline doesn't affect this, then factor in all the things that do, then adjust for intakes of methionine and betaine and folate while making all kinds of assumptions and guesses about their metabolic interactions, and then factor in carbohydrate load and the other things that can affect VLDL size, and I'd wind up with something a bit like the economist who gets stranded on a island with a can of food and says "assume a can opener."

    Anonymous, could you please post the link to the study the Eades discussed?

    Ed, I don't think there are different non-interconvertible forms of choline itself, but it certainly occurs in different molecular combinations in foods and in the body. I have more to learn and will try to incorporate this into my next choline post.

    Ned, thanks! I agree on fructose and there are other things such as exercise and thyroid and oxidative stress that also modulate the lipogenic effect of fructose. I have MUCH more on fructose coming in the future. In the mean time, I know you have done some work on fructose and glycogen. Could you please post the links? Thanks!


  78. Hi Chris.

    If you are on the right track here, this can be potentially huge. I guess I don't have to tell you that.

    A small point. If the liver is low on glycogen (e.g., early morning, after a night fast), it will convert fructose into glycogen, not fat.

  79. The Eades recently stated that when lab animals are given saturated fat in addition to the fructose, the fatty liver will not happen. Is that not true?

  80. I bet you could do a back of the napkin calculation to make a guess as to ranges of choline intake requirements. I.e. If each VLDL requires x choline molecules and your liver needs to export y VLDL particles/day given a diet that has [z] calories of [fat, fructose], then you'll need c grams of choline per day.


    Steven H. Zeisel, M.D.
    November 2009

    Mean choline intakes for older children, men, women and pregnant women are far below the Adequate Intake established by the IOM. Given the importance of choline in a wide range of critical functions in the human body, coupled with less than optimal intakes among the population, dietary guidance should be developed to encourage the intake of choline-rich foods.

  82. Since longer-chained saturated fats increase the initial amount of choline needed to minimize liver fat, and since the mice in the study I mentioned before were being fed a hypercaloric diet (albeit with a bit more of the AIN93 vitamin mixture, which doesn't provide enough choline to minimize liver fat from any substrate anyway), that all fits together very nicely.

    I've eaten 250g of liver and several egg yolks today, and now I raise an ethanol- and fructose-laden toast (cider) to your research skills!

  83. Hi Chris,

    Nice post. What I'm wondering is whether or not choline is limiting in a human diet with a typical protein intake, say 15% of calories. Are humans not as good as rodents at converting methionine to choline, or do we simply not eat enough protein to allow sufficient choline production?

  84. Hi Chris- really top notch data synthesis and connection of ideas. I really appreciate the work you do, can't wait for the upcoming posts.

    Your analysis fits in perfectly with something I learned a couple weeks ago- I got in to a conversation with a diabetes specialist at a health center and she told me that many of the children she sees are developing NAFLD at 5 years old! She went on to say that the single action of removing soda from the diet often results in huge improvements. I wrote a little about our conversation here:

    After reading your post it's apparent that all these kids are probably choline deficient too… no surprise really, you never see marketing for egg yolks and liver.


  85. You're welcome Frosty.

    Phoenix, haha! Thanks!

    Kat, thanks! Good question. I believe cooked choline is ok, even though I eat most of my egg yolks raw. But I will try to post about this in future choline posts; thanks for the idea!


  86. Great post Chris. What about how to prepare liver and egg yolks to get the most benefit from them? Is it best to eat them raw, or for choline does it not matter?

  87. Thanks, Chris. I suspected that there wasn't an exact answer. I'll be looking forward to your choline requirement post. I would be especially interested in what you think the requirement might be for someone to rectify the damage already done versus a young healthy person.

  88. Thanks Chris and Terry! You're welcome Terry!

    Jana, yes there are other foods rich in choline but these two foods are uniquely abundant. I will post more in the future on obtaining choline. should help for now.

    Charles, they are broken down in the intestine, not so much in the mouth. I didn't say there was a large difference — there are some differences, but mostly sucrose acts similarly to providing half its weight in free fructose. However, sucrose and fructose are much different than starch or glucose.

    Frosty, any protein will do. It's primarily a result of the methionine. There is more methionine in animal protein, although I think it is better to obtain choline itself rather than lots of methionine. Folate and betaine also help spare choline. I don't trust that the RDA is sufficient, and again it depends how much sugar, alcohol, and fat you are consuming. But it certainly isn't sufficient for people with very common defects in folate metabolism. Furthermore, the DRI is set assuming some methionine is included, but I do not think there are controlled experiments in humans very clearly establishing choline requirement for a given methionine intake. So, I will try to address the choline requirement more completely in the future but I doubt your question can be precisely answered. Sorry to not be of more help.

    Thanks for your comments everyone!


    1. Hello Chris, new to your site and late on this article, but I'm a bit confused: I eat lots of butter and drink whole milk for breakfast, plus a general run of meat & fish in my diet, eat eggs every morning, however. is there such a thing as too much sat fat??

      So should we eat less saturated fat in general and keep up eating eggs and liver?

  89. Interesting post.

    In the experiment where 20% casein prevented NAFLD, was there something special about casein or was it just because casein is a complete protein? Would other complete proteins do the same thing (I don't tolerate casein very well).

    Also, you mentioned that methionine can be used to cure choline deficiency. Is there a conversion factor of some sort to figure out how much methionine is needed? For example, 12 oz of cooked 80/20 ground beef contains 300 mg of choline and 2.3 g of methionine. How close would that come to satisfying the 550 mg of choline that is recommended for men?

  90. Fascinating! Thanks so much for delving so deeply into this matter Chris.

    I've been enjoying reading your posts. Keep up the great work!

  91. Andras,

    Yes, that's why I said more saturated and longer chain length. MCTs are burned for energy much more quickly than longer chain fats because they do not require carnitine to be shuttled into the mitochondria and because burning them is not suppressed by insulin or carbohydrate.


    Yes, they have a high leptin level, and they seem to be extremely leptin resistant, which is why their enormously high leptin level does not make them lean, mean, not-eating machines.

    See here:


    Thanks! Yes, homeopathic only there is actually liver in the liver. 😉



  92. French popular culture keeps liver health at the centre of attention.

    The 1930's detective writer certainly thought it was part of the French (and Belgian) national stereotype, e.g.

    Hercule Poirot: Hein, the pancreas is nothing. Of the digestive organs, the liver is the key. Look after the liver and life will take care of itself.

    Isn't the idea of eating liver to cure the liver nicely homeopathic?

    Great post, man, you really on a ROLL

    . . . . . .(an egg roll!)

  93. Great Post.
    Just a question.
    Quote: "And obese people are leptin deficient and the majority of obese people have fatty liver."

    I thought that obese people have a high Leptin level = Leptin resistance?

    1. Obese people are leptin resistant. Actually Dr. Robert Lustig says it is because fructose makes people insulin resistant, which makes them produce more insulin, which keeps the body from seeing its own leptin. However, dieting makes an obese person both leptin deficient AND leptin resistant at the same time. Of course, the SAD is both high in fructose and low in choline, so no surprise there is an epidemic of insulin resistance & fatty liver.

  94. This is a truly wonderful post. I have to point out one tidbit:

    coconut is by far the most saturated of all fats in the 30's fatty liver study, yet it is rather in the mid range. Could its being much higher in MCT do something with it?

Leave a Reply

Your email address will not be published.