Saturday, December 4, 2010

Meeting the Choline Requirement -- Eggs, Organs, and the Wheat Paradox

by Chris Masterjohn

In several recent posts, I argued that most of us aren't getting enough choline, and that the disappearance of choline-rich foods like liver and egg yolks from the modern diet is likely responsible for the silent epidemic of fatty liver disease that may be afflicting 70-100 million Americans.  If you missed them, you can find them here:
In this post, I'll try to outline what we know about how to get enough choline.  And I'll share some surprising insights about the value of spinach, beets, and wheat, with a little discussion of what I'll call "The Wheat Paradox."

Choline in Foods — It's All About the Organs and Eggs

First, let's take a look at where we can get choline from.  The following data is taken from the USDA database (1).  Clearly, liver and eggs top the chart.
Unless stated otherwise, the values are for foods cooked, but without added fat.  Although not shown, most other organ meats probably rank pretty high, especially brain and kidney. 

Interestingly, wheat germ shows up on the list amidst a bunch of animal foods.  This, however, is not the "Wheat Paradox."  It's just the tip of the iceberg.  But more on that below.

Lots of other foods contain smaller amounts of choline.  Here are some of the better ones:


Meats, seafood, and nuts tend to be decent sources of choline, but vegetables are widely variable.  Boiled broccoli, cauliflower, and brussels sprouts have quite a bit of choline, but boiled kale has hardly any. In general, milk and fruit tend to lag further behind the vegetables.  Spices are often decent sources of choline, but are usually used in small amounts.

Clearly, none of these foods come anywhere near organ meats and eggs.  Liver and eggs, for example, have ten times more choline than most vegetables!

By far and away, most of the choline in these foods is found as phophatidylcholine, a membrane-bound phospholipid.  As a result, it's found in the yolk of the egg and not in the white.  A 100-gram serving of egg yolk has 683 mg of choline, whereas a similar serving of egg white has only 1.1 mg.  For an equal amount of each, then, you'd get three times more choline out of your eggs if you threw away the whites.

I haven't found any evidence that heating foods affects the bioavailability of choline.  If you know of any, please post it in the comments section.

Our next question, then is, how much choline do we actually need?  Do we really need to eat egg yolks and liver every day?

The Impossible Question

Unfortunately, trying to estimate how much choline we need is almost impossible for three reasons: 1) there's very little scientific evidence in humans that can be used to justify a particular intake, 2) the choline requirement is dependent on the intake of several other vitamins, 3) the choline requirement depends on certain genetic variations, and 4) the choline requirement is dependent on the intake of several energy sources, such as sugar, alcohol, and fat.  Thus, even if we look to traditional diets, we must attempt to unravel all of these interacting factors.


Nevertheless, there's good reason to think that the choline requirements of both lab rats and humans have been grossly underestimated. 


Lab Rats Are Deficient in Choline




ca. 1976
Gee Brain, whaddya think these pellets are?
I don't know, Pinky. I've never seen them before.
As I pointed out in "The Sweet Truth About Liver and Egg Yolks," choline is capable of completely protecting lab animals against fatty liver induced by sugar, alcohol and fat.  Yet the most common dietary models of fatty liver disease — besides choline deficiency — use high intakes of sugar, alcohol, or fat to induce the disease.  This clearly suggests that choline provided by standard rodent diets is insufficient to allow the animals to deal with these energy sources.




ca. 1993
Gee Brain, what are we going to eat tonight?
The same thing we eat every night, Pinky. Only the sucrose is reduced and the choline is increased 25%!  
The other piece of evidence relates to brain development. As I pointed out in my 2007 Wise Traditions lecture and article on pregnancy nutrition, "Vitamins For Fetal Development — From Conception to Birth," pregnant rat moms fed three times their ordinary choline intake give birth to rat babies with some remarkable lifelong brain-boosting benefits.  They have a 30 percent increase in visuospatial and auditory memory that lasts through their lives; they grow old without developing any age-related senility; they are protected against the assaults of neurotoxins; they have an enhanced ability to multi-task; and they have a much lower rate of interference memory. Interference memory is when a past memory interferes with an immediate memory — for example, when a past memory of where you parked your car interferes with your ability to find it when you exit the store.


The pregnant rat moms consumed this massive dose of choline during the period of gestation in which the choline-based neurons in the brain develop.  In humans, this period of development corresponds to pregnancy and to the first four years of a child's life.  Regardless of whether this enormous brain-boosting effect transfers over to humans, the fact that rats get such a huge benefit from increasing their choline intake so enormously very much supports the idea that current intakes are way too low.


To the Clinical Trial We Go, How Much Choline Humans Need Nobody Knows


For humans, the evidence about our choline requirement was so limited in 1998 that the Institute of Medicine had to set an "adequate intake (AI)" rather than an RDA.  An AI is basically the "let's make a wild guess" version of the RDA.  You can read the report here (2).


The AI is 550 mg/day for men and 425 mg/day for women. It assumes an average male weighs 76 kg  or 168 pounds, and adjusts the male requirement downward for the female requirement as an adjustment for average bodyweight.  It increases to 450 mg/day for pregnant women and 550 mg/day for nursing women.  The increases are based on the typical concentration of choline in a fetus or in mother's milk.  Since there's no reason to think "average" is best, the increases for pregnancy and lactation are basically meaningless.


All these numbers are based on the AI for adult males.  This is taken from a single study (3) that successfully used 500 mg/day to suppress the increase in liver enzymes that occurred in healthy humans eating a choline-deficient diet.  This is almost certainly lower than the true requirement for choline, however.  "Liver enzymes," or aminotransferases, are enzymes that spill out of liver cells into the bloodstream when liver cells start dying.  This can happen as a result of fatty liver, but only when it progresses to a certain stage. 


About 8% of Americans have elevated liver enzymes, roughly a third of which can be explained by known causes such as alcohol, iron overload, or hepatitis viruses (4). But as many as 30% of Americans may have fatty liver (5), and 80% of them have liver enzymes within normal limits (6).  For the final proof in the pudding, out of ten women who developed liver problems when they were put on an experimental choline-deficient diet, nine of them developed fatty liver and only one of them developed elevated liver enzymes (7).


Thus, the choline requirement is almost certainly more than 500 mg/day.  There are virtually no solid studies in the general population, however, that have randomized people to multiple different choline intakes and measured an important health outcome, which is what would be needed to establish a solid choline requirement. 

Once recent exception to this rule (8) showed that 1100 or 2200 mg/day of choline protected against the DNA damage that otherwise occurred in people consuming 300 or 550 mg, but this study was very small and was conducted in men who were restricted to the RDA of folate, and who thus had declining folate status through the study.  As we'll see below, the choline requirement depends on the intake of folate and a number of other nutrients.


The Choline Requirement Is Dependent on Intakes of Folate, B12, B6, and Betaine


Another reason it's almost impossible to come up with an exact amount of choline we should consume is because choline arrives at an intersection in the methylation pathway where it crosses paths with folate, vitamin B12, vitamin B6, and betaine.  Here's a simplified chart showing this pathway:


Abbreviations: SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine

As we can see from the chart, methionine is a critical amino acid used for the generation of SAM, which is in turn used for the methylation of proteins, DNA and other substances.  Methylation is critical to the regulation of gene expression and the stability of our DNA, but it's also the process that we use to make choline!  That's right, the PEMT enzyme uses SAM to make phosphatidylcholine, a choline-containing phospholipid that can later be broken down to free choline.  For more information on the PEMT enzyme, see my post, "Does Choline Deficiency Contribute to Fatty Liver in Humans?"


Whenever SAM methylates another molecule, it generates SAH and then homocysteine.  In all cells, homocysteine can be turned back into methionine to start the process all over again with the help of vitamin B12 and folate.  In the liver, when the methylation process is proceeding adequately, vitamin B6 gets rid of any extra homocysteine by turning it into cysteine.  The cysteine can then be used to make glutathione, the main antioxidant of the cell and one of the liver's principal detoxfication tools.  For more on glutathione, see my post over at WestonAPrice.Org, "The Biochemical Magic of Raw Milk and Other Raw Foods: Glutathione.


The liver and kidney can also use choline to make betaine, which can substitute for folate and B12 in the regeneration of methionine through a completely different enzymatic pathway.  Betaine is also important to regulating osmotic pressure in the kidney. 


Thus, folate, vitamin B12, B6, and betaine can spare choline, but only methionine can be used to make choline.  The B vitamins and betaine can thus fulfill choline's role in methylation, at least in the liver and kidney, but only methionine can provide the choline needed to export liver fat, to serve as a neurotransmitter, or to make our cell membranes work properly.  As I pointed out in "Does Choline Deficiency Contribute to Fatty Liver in Humans?," studies conducted thus far suggest that the vast majority of our population may have at least one not-so-effective gene for making choline from methionine. 

To make even more of a mess of this, the PEMT enzyme actually creates homocysteine in the process of creating choline!  So, if your PEMT engine is running nice and smoothly, you can make your own choline, but you still need more betaine and B vitamins to neutralize the homocysteine that's generated in the process.  If your PEMT engine is working like this, however...



... well, then, you've got another problem.  If PEMT isn't using up your methionine to make choline, the methionine is just going to go further on down that pathway shown above and make more homocysteine anyway! 

Thus, although having a PEMT gene that Uncle Buck would surely envy might lower our choline requirement, consuming lots of methionine won't help us at all.  In fact, extra methionine just gives us more homocysteine and thereby increases our need for choline, betaine, folate, B12, and B6.

As I previously pointed out in my 2007 pregnancy nutrition article, the interplay between all these nutrients as well as some other amino acids is one reason we don't want to load up on lean muscle meats.  Rather, we should balance muscle meats with skin, bones, organs, and leafy vegetables.

While extra methionine isn't such a great idea, studies clearly support an interaction between the B vitamins and choline and show that B vitamins, betaine, and choline can all substitute for each other in order to support the methylation pathway (9, 10, 11, 12, 13). Thus, whether we need to actually eat choline or just eat B vitamins and betaine instead will be largely determined by how great our PEMT enzyme works.

And this, dear friends, leads us to "The Wheat Paradox."

The Mighty Mighty Betaine and The Wheat Paradox

In the comments of "Does Choline Deficiency Contribute to Fatty Liver in Humans?" blogger and commenter Ned Kock suggested that the choline connection may be able to resolve a number of apparent paradoxes.  Indeed, it could certainly resolve contradictory findings about whether common energy stores like sugar, alcohol, and fat are bad for us, since these substances clearly increase the need for choline.  But our buddy betaine is taking a big elephant in the room for a ride, and the elephant's name is Wheat.

We are all, of course, awaiting with baited breath Denise Minger's long-anticipated wheat post, in which she will reveal some plausible mechanisms by which wheat could contribute to the risk of heart disease.  But Denise also uncovered the curious case of the Tuoli, who lived largely off wheat and dairy, but had reasonably low rates of cardiovascular and other diseases.  Likewise, the inhabitants of Crete live largely off wheat and dairy.  Although they do have some heart disease, studies in the 1960s showed that the rates were very low by Western standards, especially for a population where half the men smoked (15).

As it turns out, by far and away the the best sources of betaine (1) are wheat and spinach:

The betaine is especially abundant in the germ and bran of the wheat, but wheat is such a great source that even white bread of all things has a decent amount!  By contrast, virtually every other food has such a puny amount of betaine in it that it couldn't climb onto this chart even if the very existence of the world depended on it.

Clearly, wheat offers a major advantage to someone with a low intake of eggs and organ meats, and spinach would offer a similar benefit on a gluten-free diet.  In fact, spinach is much richer in betaine than whole wheat.

The choline connection may thus provide resolution to a number of paradoxes, including one that Ned pointed out, that the French consume plenty of white bread.  It's the red wine, the red wine, the red wine!  Perhaps.  But eating liver is likely to protect against some of the nasty effects of eating sweets, and even white bread has the surprising saving grace of providing some betaine in addition to the otherwise nutrient-depleted package of toxic junk it provides.

As pointed out above, however, we can't be quick to assume that betaine can replace choline in everyone.  As pointed out above, genetic variation in the PEMT gene will most likely make or break the success of such a replacement.

Genes and the Choline Requirement

As I pointed out in "Does Choline Deficiency Contribute to Fatty Liver in Humans?," studies conducted thus far suggest that the vast majority of people in our population may have a not-so-effective version of the PEMT gene.  Consider this graph from an American study (16):


Even among healthy controls, the prevalence of at least one "defective" version ("defective" compared to the other version) is over 80%.

Such studies (16, 17, 18) have involved anywhere from fewer than 100 people to over 3000 people, have been conducted in North Carolina and Long Island, and have represented Caucasians, African-Americans, Asians, Native Americans, and other heritages.  They have consistently shown the prevalence of at least one copy of the less effective gene in 75-88% of the population.  Nevertheless, there is likely to be considerable variation between ethnic groups, and the high prevalence probably primarily reflects the Caucasians and possibly African Americans that have been represented in these studies to greater extents than other groups.

In the comments of "Does Choline Deficiency Contribute to Fatty Liver in Humans?," Ed suggested that cultures with more plant-based and less organ meat-based diets might have higher prevalences of the more effective PEMT gene. 

There aren't many studies on this available, but there's certainly large variation between populations.  Here's the prevalence found in a recent Japanese study (19):

Whereas most Americans may have at least one copy of the less effective gene, most Japanese may have two copies of the more effective gene and none of the less effective gene.

Similar results were found in a recent Chinese study (20):


Thus, it is quite plausible that some populations have very high prevalences of the "good" version of this gene, which allows them to make their own choline from methionine for the export of liver fat, to use as a neurotransmitter, and to use in cell membranes.  Meanwhile, they could neutralize the homocysteine generated in the production of choline with high intakes of betaine, folate, and vitamins B6 and B12.

Aye! So How Much Choline Are You Saying We Need???

In conclusion, rather than declaring how much choline people need to eat, we can much better support Ned Kock's idea that the choline connection will, when viewed properly, resolve lots of apparent paradoxes.

Not everyone needs a lot of choline.  People with two copies of the awesome 'possum version of the PEMT gene may get by with very little choline but with very high intakes of B vitamins and betaine.  People with one or more of the not-so-hot version of this gene may need lots of organ meats and egg yolks to keep their liver from looking like an Eskimo's dinner. 

In America, at least, it would appear that lots of us need lots of egg yolks and liver.

Read more about Chris Masterjohn, PhD, here.

50 comments:

  1. Interesting, may I assume there is a similar [gene] situation with other nutrients? It would seem so, since, for example, vitamin A intakes can vary about 10-fold across non-industrialized cultures.

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  2. Hi John,

    All nutrients involve genes and all genes involve nutrients, so there is nothing that is nutrition and isn't genetic and there's nothing that's genetic and isn't nutritional. However, I've never seen any convincing data on what traditional vitamin A intakes were. Where did you see this?

    Thanks,
    Chris

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  3. I have 3-4 eggs for breakfast most days (fried in butter), I presume this should be enough? I fear slightly as my lipid profile is shocking (my HDL went from low to really low when I started low-carb, high fat wtf, and my LDL skyrocketed as is to be expected, with only a small decrease in trigs as the diabetes is still taking it's toll) but I don't think at this stage that the eggs and butter are the problem.

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  4. Chris,
    Are you aware of a reasonably priced way for an individual to be tested for the PEMT gene?

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  5. Very interesting Chris. In fact, when I was playing with the China Study II data, I noticed an interaction effect between animal protein intake and wheat that seemed to be significant. I don't remember if it was negative or positive. (I run several analyses, and blogged only about a few for lack of time, with what seemed to be the most interesting results.) If the interaction effect was negative, then it could provide solid support for your main point. Let's see what Denise comes up with. I'll see if I can go back to it later, depending on what Denise unveils.

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  6. According to the chart, there is 250 mg of choline in 100g of raw egg. If this means the entire egg without the shell, one egg weighs about 50 g. So someone would need to eat eight egg yolks a day to get the 1000 mg/day of choline. That's 56 eggs a week.

    That's a lot of eggs!

    Chris, can we supplement choline?

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  7. Might-o'chondri-ALDecember 4, 2010 at 9:19 PM

    Betaine (tri-methyl-glycine)drink:

    1 gallon water (no chlorine)
    1 bunch of red beets (129mg. betaine/100gr.)
    use the roots, not greens
    1 chunk of ginger (41mg.betaine/100gr.)
    ... grate, dice, finely slice all roots ....
    1 handfull milk Kefir grains (rinse,no chl.)
    tied up in cheescloth or old cloth
    1 dried black fig (feeds kefir grains)
    1 to 2 teaspoons molasses (for grains)
    1 big pinch (1/8 - 1/4 teaspoon) baking
    soda (bicarbonate of Na ions for grains)
    ... put all into something you can cover
    with plastic wrap held tight with a
    rubber band (no metal pots)
    ... keep it out of the light, swirl it
    around every now & then
    ... after +/- 3 days fish out bundle of
    re-useable red kefir grains (store cold)
    ... strain & squeeze out solids, refrigerate
    & drink liquid straight or blend

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  8. Hi Chris,

    A paper you referenced had the Inuit at 30,000IU/day of vitamin A (also high D and iron). Stephan estimates the near-vegetarian African farmers and Polynesian islanders have low intakes ["most of them probably didn't get nearly 10,000 IU per day"]. D intakes would obviously be even more difficult to estimate.

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  9. As per Denise's analysis, wheat seems to be associated with more CVD in China, not less.

    Perhaps the french paradox has little to do with wheat and more to do with (i) higher SFA/PUFA ratio and (ii) higher mineral intake, especially copper.

    If Klevay is on to something and copper is a significant factor in CVD, the French paradox may be explained by their high consumption of oysters (highest in the world, AFAIK), liver (e.g., from pate), and chocolate. Those are the 3 (disproportionately) best sources of copper and the French nail all of them.

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  10. Chris,
    Recent trials seem to find that suplemental folic acid causes an increase in cancer. Are you aware of any reason to think that choline could have a similar effect.

    If folic acid does lead to more cancer and if it does so by increasing promoter hypermehtylation, leading to epigenetic silencing of protective gene expression (i.e., p53 or the vit D receptor), perhaps excess choline could have a similar effect? Any thoughts?

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    Replies
    1. Folic acid is a sub optimal source of folate, because it has to be converted to an active form and this process is not effective in everybody and decays as we get older.

      Delete
  11. I take SAM-e, per my MD's recommendation, for low mood, joints, and because "it's good for your liver".

    Am I correct in understanding that SAM-e helps transport fat out of the liver?

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  12. Brilliant article indeed. If you consider that PEMT is regulated by estrogen you have come very close to a metabolic definition of PMS. How do you call a double defective PEMT? Well, my guess is that depending on environmental conditions and choline intake during pregnancy and later in life you would probably call them either ADHD or bipolar, that are in a way diseases of unlucky carnivors on a herbivor highly inefficient betaine-diet.

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  13. Might-o'chondri-ALDecember 5, 2010 at 2:54 PM

    40 years ago I knew a Jamaican Rhodes Scholar whose refrain was "See the eat in wheat."

    Benet was in his mid 60's, slept outside in a lean-to shelter even in 5*Celsius (41*F) on carpets, daytimes (rain or shine) he dressed in short cotton garments with a shawl & kept 2 female mates vociferously happy.

    He ate some clay, drank only bubbly mineral water & consumed wheat berries from a pouch he carried. We can assume that back then it was not our dwarf wheat seed.

    Other grains were O.K. by him, but said they
    pulled him off a steady center. He was thin with a wirey physique & nobody ever guessed his age.

    Also told me that Roman Centurions carried pouches of wheat berries into war. He claimed his study of food led him to wheat, but he had to give his consorts transitional % of other grains too.

    I brought him to my hydroponic greenhouse where had a wheat grass patch grown for him. He chuckled, seeing the square meter sized plot, and said could eat it all faster than I could replant it.

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  14. Wondering why Choline supplements are commonly paired with inositol and why the inositol is usually phytic acid?

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  15. Responses to Andrew and Alice Brown, Jeff, Ned, Jeremy, ...AL, John, Daniel, Jin, and ...AL.

    Andrew/Alice, 3-4 eggs per day should not make HDL-cholesterol levels plummet. This would be a very abnormal reaction. I think you should be concerned about your lipid levels and actively trying to understand what the issue is. A good start would be to get apoB, apoA, and LDL particle size checked to understand lipid levels more comprehensively. What has *improved* since going very low carb?

    Jeff, I don't know if PEMT testing is commercially available. If you or anyone else finds a source, please post it here.

    Ned, thanks for sharing. I'll be interested to see your results when you post them!

    Jeremy, unfortunately it is still a mystery of how much choline we need. The study that found 1100 superior to 550 was done in men restricted to the RDA of folate and their folate levels dropped by two-thirds over the course of the study. What this clearly shows is that obtaining the RDA for both folate and choline is an unmitigated disaster for men. However, there is no reason just yet to think that the RDA for choline is *inherently* insufficient. That said, liver and heart are also quite rich in choline. You don't need to get all your choline from eggs. If you want to supplement, "lecithin" is phosphatidylcholine (although not purely), which is the type we mostly get in food.

    ...AL, thanks for the recipe!

    John, ahh, I see. Well, it's a bit frustrating in that these are just best guesses. For animal foods, this is hampered because vitamin A content may vary widely depending on production conditions. For plants, this is further compromised by bioavailability issues. The Bantu farmers that Price studied seemed a little bit less healthy than most of the other primitives. The plant-based diets that Stephan presented were extremely low in protein. This may reduce the requirement for vitamin A. It also caused them to take an extra ~10 years to reach their full height, although they didn't suffer any loss of maximum height. I suspect that in most cases, traditional diets contained around ~10,000. But that's just a guess.

    Daniel, as per the cautionary notes that Denise has consistently provided with all her statistical analyses, correlations can not be used to support or refute causation. What is of interest in terms of the "paradox" is that the Tuoli were very healthy. It wouldn't be paradoxical if there were no evidence that wheat could be harmful. The copper issue is interesting. I think one could come up with 1001 hypotheses about what, if anything, is "paradoxical" about the French, and 1001 more hypotheses of why the paradox exists. I do think copper is important.

    Daniel again, "folic acid" is not found in the food supply and I would be careful about generalizing adverse effects of "folic acid" to folate. Could you please provide a reference for the folic acid/cancer studies? Thanks!

    Jin, SAM itself is not directly involved in export of liver fat but it can be used to make phosphatidylcholine. It is phosphatidylcholine that is necessary for export of liver fat.

    ...AL, very interesting anecdote. Thanks!

    Chris

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  16. Strange co-inkydink, I have a friend diagnosed as insulin resistant, pre type 2 diabetic & fatty liver now improving with diet modifications. Was researching that & stumbled on a great article re choline on the WHOLE FOODS website, http://www.whfoods.com/genpage.php?tname=nutrient&dbid=50 which inspired me to Tweet about this focusing on cancer prevention aspects of choline as critical to EFA metabolism for cell membrane conditioning: http://www.twitlonger.com/show/77tgsj

    Also replied to some questions on Mercola's website from readers that have NASH including a great USDA nutrient chart sorted by alphabet or nutrient weight I found here: http://www.ars.usda.gov/Services/docs.htm?docid=20958

    Mercola subscribes to the fructose theory of deficiency, linked to his interview with Dr. Johnson. I believe it can be a combination but predominantly a lack of intake due to the popular low fat theory & the egg, red meat, protein & saturated fat scare.
    As you mention, the proof is in the low intake levels of organ meats & public acceptance & adoption of the false dietary theories.

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  17. Another thought, if the following is true: "A 150 lb. person requires a full pound of protein (or 3 grams per pound of weight!) per day for normal bodily processes. Reference: Basic Medical Biochemistry: A Clinical Approach, page 648" then as you say EVERYBODY is deficient in choline because I don't know of anyone that advocates or practices this much daily protein intake. The more commonly seen intake levels are usually between 1/3 and 1/2 a pound.

    But the biochemistry textbook may actually be close to physiologically correct, as 1 pound of protein = 454 grams X 4 calories per gram = 1816 calories, which is not far off the guidelines for an adult male depending on age, height, weight, activity level, etc., and even leaves a little room for a few carbs & fats.

    Now contrast the above with the recommended amounts more commonly seen all over the web, such as these amounts from this discussion on protein intake at Marks Daily Apple paleo diet website: http://www.marksdailyapple.com/dietary-protein/

    "The current U.S. RDA for protein is 63 grams (2.2ounces!) a day for the average sized male, or for your individual RDA, 0.80 g/kg/day. Many nutritionists suggest that athletes and very active people can maintain their muscle mass at 1.0 g/kg/day. Most nutritionists say protein should constitute no more than 20% of your calories each day. (With the rest typically recommended to be carbs, & a little fat. - my comment)

    Now I’ll give you my perspective.

    ...Experts from the Medical Research Council at the University of College London estimate that while the typical Western diet today is composed of 49% carbs, 35% fats and 16% protein, the diet of traditional hunter-gatherer populations included twice the protein intake.

    In keeping with this research, I don’t believe people need to limit their protein intake to 20% of their daily calories. The upper limit of protein recommendations is hotly contested in all circles. I, myself, try to get at least 1 gram per pound of body weight per day (165). I can survive on less, but I’m all about maintaining my lean mass. You can only do that with protein, and I don’t believe the current RDA allows for that, especially in active individuals."

    So if the textbook's one pound of protein per day rule at top is true, then it's no wonder he's lean & ripped (skinny). Mark's 165 grams of protein is only a little over one third of the textbook's stated protein requirement, which if true means he is two thirds protein deficient, and choline deficient as well.

    Now let's play what if again and let's assume that the entire 165 grams of his protein is from the highest choline containing whole food, beef liver, which has 4.18 milligrams of choline per gram according to this chart: http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR23/nutrlist/sr23w421.pdf

    That means Mark's 165 grams (36%, 1/3 of a pound) of beef liver would provide a total of 690 milligrams of choline, just a little over the published Adequate Intake level for males at 550mg. So then if Mark decided to eat only half of that amount as liver and the other half as a protein smoothie he'd only get half the choline, around 275 milligrams, unless he dropped in a couple of raw eggs or yolks.

    Don't forget that as you move down the choline containing foods list, the amount of choline you get in the various foods DROPS depending on food type so that by the time you get down to the 7th spot & salmon you're getting significantly less choline for an equivalent gram weight than that found in liver.

    So, all that considered it's no wonder we're choline deficient, and people that are still eating junk & processed foods & don't often eat any of the highest choline containing foods on that chart are even more deficient.

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  18. Chris,

    Thank you for your responses- thoughtful as always. The results I referred to are below:

    1. http://jama.ama-assn.org/content/302/19/2119.abstract

    2. http://jama.ama-assn.org/content/297/21/2351.abstract

    3. http://jnci.oxfordjournals.org/content/101/6/432.full

    And, another more dubious one:

    4. http://www.bmj.com/content/329/7479/1375.full

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  19. Here's a few non-RCTs finding associations with folic acid (and folate in some instances):

    1. http://carcin.oxfordjournals.org/content/29/9/1765.full

    2. http://www.wjgnet.com/1007-9327/11/3834.asp

    3. http://www.ncbi.nlm.nih.gov/pubmed/15991278?dopt=Abstract

    4. http://www.ajcn.org/content/83/4/895.abstract

    And one more RCT with biomarker (promoter hypermethylation) endpoints:

    1. http://jn.nutrition.org/content/137/9/2114.abstract

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  20. I changed the language to "studies conducted thus far suggest that the vast majority of people in our population may have a not-so-effective version of the PEMT gene" to better express the uncertainty of the actual prevalence in America.

    I also added the following paragraph:

    "Such studies (16, 17, 18) have involved anywhere from fewer than 100 people to over 3000 people, have been conducted in North Carolina and Long Island, and have represented Caucasians, African-Americans, Asians, Native Americans, and other heritages. They have consistently shown the prevalence of at least one copy of the less effective gene in 75-88% of the population. Nevertheless, there is likely to be considerable variation between ethnic groups, and the high prevalence probably primarily reflects the prevalence among Caucasians and possibly African Americans, who have been represented in these studies to greater extents than other groups."

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  21. As I have recently discovered that diabetes runs in my family. I have modified my diet to avoid processed foods and grains. In my seach to find a supplement that might aid in insulin sensitivity I came accross this study which indirectly points to bleached refined wheat as a beta cell destroyer. It seems that the chlorine used in the bleaching process creates alloxin which is used to induce diabetes in laboratry test subjects.

    http://www.hartwick.edu/Prebuilt/BiolJBR3_Niedzielski.pdf

    Your thoughts?

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  22. Daniel,

    Thanks for the references. This should make for a good post in the future when I have the chance to review them.

    Chris

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  23. Stormrunner,

    I consider white flour to be more or less poisonous. I have not looked into this issue in depth and I don't know whether this dose of alloxan is likely to be harmful. Incidentally, saturated fat is extremely protective against alloxan toxicity and PUFA accelerates it, with no protective effect of vitamin E. I have not fact-checked this, but I have also read that white flour is treated with tissue transglutaminase, which is the enzyme that renders gluten immunogenic in the intestine of celiacs! It's used to make the flour stickier. Back circa 1900-1950 they treated flour with nitrogen trichloride, but it was abandoned in the US and UK because it produced hysteria in dogs and there was worry it might contribute to mental problems in humans, and was done away with in Canada for an entirely different reason, that it was highly explosive and a danger to mill workers. I'd stay away from treated flour!

    Chris

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  24. Paul,

    Inositol itself is not phytate. Phytate is the hexaphosphate of inositol, so phytate digestion can yield inositol. I haven't studied this in depth so this information may not be perfect, but lecithin is the phospholipid fraction of whatever it comes from, usually soy, and phospholipids contain phosphatidylinositol, thus the relationship.

    Chris

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  25. Andinla,

    Thanks for your great comments and links. On protein, I think it's patently absurd that anyone needs 1816 calories of protein, but I think you are on very reasonable grounds for trying to get 165 g. In my glutathione post, I referenced some evidence that the glutathione-promoting effect of protein probably maxes out at around 1 gram per kilogram body weight and ~25 mg sulfur amino acids, which is less than half what you are consuming and astronomically lower htan 1816 calories. In general, sulfur amino acids boost glutathione after SAM is already maximized, and SAM is used to make choline. So I don't think you need any more than the RDA for protein to maximize your choline production.

    Chris

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  26. Beef vs lamb liver?
    Got any info?

    I imagine you're citing beef liver since there's more data available for it? I'm currently living in Inner Mongolia, China, where lamb and goat liver are common cold salads.

    How about pig liver? (Common dish for Han culture restaurants, and from what I understand in the south where I plan to travel.)
    Know much about what might cause differences in choline levels of these animals? Is diet a primary factor in choline content of eggs and liver? (grass/free-range fed vs. grain fed for chicken/pig/ruminant)

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  27. Oh! and incredible stuff, thank you sooooooo much:)

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  28. So in summary, no one knows how much choline the average adult human male needs for optimum liver health BUT based on traditional diets, historical eating patterns, including liver and eggs in the diet goes a long way towards providing enough choline to promote liver health...am I right? My mom was taught to feed her family liver once a week. An old pregnancy diet book I have recommends beef liver once a week (3 oz) and my great grandma's cookbook recommends liver once a week. My antique cookbook doesn't even have liver in it! Granted this is all nutritional information from the 20th century (not a great century for nutrition) but still...these recommendations seem pretty reasonable to me. What do you think? 3 oz of liver once a week and eggs 2 or 3 times a week, plus avoidance of fructose and excessive sugars and alcohol might just be a good foundational eating plan, you think?

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  29. Thanks Chris. I my experience, that which is preventative for CVD is generally also preventative for cancer and vice versa. So, if more choline is beneficial for CVD, perhaps abnormal promoter methylation can also be explained by choline deficiency. I don't see the plausibility from a chemistry perspective (i.e., more choline would seemingly lead to more folate available for methylation) but perhaps you see something I don't. In another realm, I know there is a ceiling effect whereby folate (or folic acid) reduces NTDs up to a point, after which more folate is ineffective. As I understand it, choline and B12 raise that ceiling, preventing more NTDs than folate (in any amount) alone.

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  30. So what does this mean for those of us who know we have one of the MTHFR gene mutations? It would be helpful to know what some of the signs/symptoms would be for having MTHFR mutation versus the PEMT mutation. Elevated homocysteine is common with MTHFR mutation depending on which one you have. Some estimate that as high as 40% of the population (US) has at least one copy of a MTHFR mutation (either A1298C or C677T).

    I already take 4mg of folate daily for the MTHFR mutation, and my homocysteine levels are basically nil so something isn't working right, but it's hard to know what considering the genetic variables at hand.

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  31. So how does the Alpha GPC (L-alpha-glycerylphosphorylcholine) form of Choline fit into all this? I've read it's healthy for brain function, but no mention of it as it relates to the liver. Is it a pre-cursor that's more/less readily absorbed?

    Also, what are the signs of choline intoxication? If 550 - 1650 mg/day is the Adequate Intake (AI) range, what's the upper limit on choline (as measured in the blood)?

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  32. Ive read L-Carnitine can help with NAFLD

    How does this fit in with Choline etc
    http://www.nature.com/ajg/journal/v105/n6/full/ajg2009719a.html

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  33. Another one hot off the presses, if you ever do that post on how folate may (seems to IMO) cause cancer:

    http://cancerpreventionresearch.aacrjournals.org/content/3/12/1552.abstract

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  34. Okay, I'm concerned and about to go out and buy a choline supplement. Here's why:

    * My 3-year-old daughter has an anaphylactic allergy to eggs. So we don't have them in the house.

    * Same daughter has celiac, as do I. No wheat in the house.

    * My kids won't eat enough chopped liver to do much for their choline. I've tried. Though I like chopped (chicken) liver, I can't tolerate the taste of beef liver. I've really tried (and I'm a good cook).

    * I'm tied to a low-fat diet due to a weird form of diabetes. Don't try to talk me out of this - I've tried different approaches and my meter doesn't lie - I do better on low-fat than low-carb. This rules out the chicken liver pate for me (which gave me horrendous readings).

    During my pregnancy with twins, I ate two eggs every day (even if I had to choke them down) and was still eating wheat. We all gave up eggs when my allergic daughter was 15 months old. We were still eating sourdough wheat bread a lot. I had had gestational diabetes during pregnancy, but it had resolved. When we gave up the eggs, and, half a year later, the wheat, I started to quickly gain weight on an otherwise WAPF-approved diet and developed mild diabetes. I wonder if this was partly due to choline deficiency (I was still breastfeeding twins 3 times a day).

    My triglycerides were and continue to be low. My liver enzymes are normal. I've since lost the weight, but still worry about the choline problem - plus, my daughters don't have good sources of choline and are getting a bit chub, though they don't overeat and rarely eat sugar.

    In my case, would you recommend a choline supplement? Anything I should be concerned about in taking one? I have to say, a couple of years ago I tried a lecithin supplement, but I think it must have contained a lot of soy oil, as it gave me achy joints almost immediately, and tried a choline supplement, which exacerbated my acid reflux.

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  35. Helen,

    I'm very sorry you are in a tough situation. You could try a choline supplement, or incorporating spinach, which is loaded with betaine.

    Chris

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  36. Thanks for the speedy reply. Will do!

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  37. I'm most intrigued by the wheat validation as my Hindu Ayurveda teachers come from long lineages of whole wheat, raw milk consumption with little egg and no meat - and amazing health!

    www.look-deep.com

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  38. Chris, do you know if betaine has some effect on stomach acid levels? Some people complain of heartburn eating wheat, and I have also read anecdotally that eating a lot of spinach is a good way to increase stomach acid production (no idea if it's true). HCL supplements are usually labeled "betaine HCL". Am I making a confused association? Love the blog btw.

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  39. Cooked or raw: I don't know about from a nutritional point of view, but purely from an eating point of view, liver needs only the lightest of cooking as overcooking can render it like rubber. One might hope that this also reduces nutrient loss.

    I believe that some people recommend eating it frozen and pulverised, but that sounds just a little too-Eskimo-like for my tastes!

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  40. Helen, for the betaine I sprout the wheat so there is no gluten and make it into a smoothie with honey and banana. Once a week I have a raw liver mango lassi which contains one cube of liver (or you could use the whole chicken liver), mango, as many raw egg yolks as you can handle, I use a teaspoon to separate them; much easier than an egg separator, one Tbs raw honey, 1/2 tsp ground cardamom and 1 and 1/2 cups of raw milk and 1/2 tsp sea salt blending the mango and liver first before adding the other ingredients, and enjoy (serves 1 gutsache!!(me)) Hope this helps.

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  41. On NutritionData.com one of the foods that has the highest concentrations of choline is beef kidney. In 3 oz of kidney there is 436 mg of choline--which is also 134 calories. If we assume a daily intake of 2500 calories in an average diet, if you consumed nothing but beef kidney, you would take in 8134 mg of choline a day. I think that gives a ballpark estimate of maximum physiological intake.

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  42. I really wish someone would have answered Yves question about betaine HCL tablets. Also a passing reference to the association of wheat and heartburn would be nice.

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  43. Spinach is VERY high in oxalates...a compound many people can't handle.

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  44. excellent article. thanks chris. my take from this is that vegans are going to have a hard time filling their choline requirement. is there a solution for them? Thank-you

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  45. Nutrient Mixture Improves Memory in Patients with Early Alzheimer’s
    Souvenaid, the mixture used, contains three naturally occurring dietary compounds: CHOLINE, uridine and the omega-3 fatty acid DHA.
    Choline found in meats, nuts and eggs.
    Omega-3 fatty acids are found in a variety of sources, fish, eggs, flaxseed and meat from grass-fed animals.
    Uridine is produced by the liver and kidney, and is present in some foods as a component of RNA.
    We can easily add raw egg yolks to smoothies or put liver into meals more regularly probably as effective and certainly cheaper than Souvenaid.
    It also makes me wonder if one of the reasons Krill oil is beneficial isn't just astaxanthin and the omega 3 it contains but the phosphatidyl choline which is a source of choline.

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  46. I know phosphatidyl serine is similar to phosphatidyl choline and is probably more effective at improving/maintaining cognition, memory... per weight. I've searched your blog for "phosphatidyl serine and no results were found. I suspect more phoshatidyl serine intake may reduce choline requirements...
    Thanks for your interest in this and sharing your knowledge

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  47. Apparently choline is syntesized from serine, you can check this one for validity:

    ARTICLE:
    THE BIOSYNTHESIS OF CHOLINE FROM SERINE AND RELATED COMPOUNDS
    David Elwyn, Arthur Weissbach, Sarah S. Henry and David B. Sprinson
    J. Biol. Chem. 1955, 213:281-295.

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  48. On NutritionData.com one of the foods that has the highest concentrations of choline is beef kidney. In 3 oz of kidney there is 436 mg of choline--which is also 134 calories. If we assume a daily intake of 2500 calories in an average diet, if you consumed nothing but beef kidney, you would take in 8134 mg of choline a day. I think that gives a ballpark estimate of maximum physiological intake.
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    ReplyDelete

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