Category Archives: cmasterjohn

When SAMe Helps, Consider Magnesium and Your Metabolic Rate

I have written quite a bit recently about the methylation cycle and its relation to nutrient balance. At Wise Traditions this November in Anaheim, one of my three talks will expand these ideas to include targeting methylation nutrition to individual needs based on genetics and health status. Here, I’d like to chip away at oneContinue Reading

7 Responses to When SAMe Helps, Consider Magnesium and Your Metabolic Rate

  1. D. Smith says:

    Several years ago I tried to use SAM-e because it was recommended to me for help with anxiety. This supplement was not that expensive at the time so I tried it for about 1 week and discovered it made my anxiety even worse, and also created a new problem – panic attacks. What type of methionine rich snacks are you referring to in your article?

    I have had homocystein checked (only once about 6 years ago) because my doctor’s office will not test for it, they do the useless cholesterol testing. I do not have a family history of cholesterol type issues, so to me that’s a useless, non-indicative “test”. But homocystein is different. Mine was perfectly normal at that time. I use magnesium in various ways (oils, soaking in epsom salt baths, Mag Asporotate capsules, etc) so I think my mag levels are adequate, but my metabolism is extremely slow. I’ve done the basal body temp testing many times and it shows no issues should be present. My sleep cycle is bad – I’m awake more than I’m asleep ever since menopause.

    We eat pasture raised meats, very little chicken however because we don’t have access, but we do consume pastured chicken eggs often. We drink good water, have only occasional alcohol, take few supplements, and we try to eat “organic” as much as possible, although the status of organic foods is up for debate. I try to grow a garden but for the past three years we’ve had such different weather patterns in this area and such a short growing season we’ve had little to no garden fresh homegrown veggies, so we must depend on farmers markets (also questionable) and food co-ops. Still, we try.

    Do you have any suggestions as to why my metabolism might be slow or my sleep cycle always being interrupted?

  2. Luis Martinez B says:

    I have solved my cold intolerance and low Matabolism . 3 changes have done. 1.- TS Supplementation from Dr. Wilson, 2.- HGH Glandular Stimuli via Peptides, Sermorelin and CJC No Dac ( females use with Dac..). And the inclusion of Nat’l Dissecated Thyroid extract Armour plus my 20 years levothyroxine supp. ( Actually I have dimiinished my levo dose due to higher metabolic rate…? ) LMB ( mexico) forgive my spelling. From the three factors I guess the most important is the first one, it took about 2 months to be felt but the change in body temp. was very noticeable…

  3. Allan says:

    Such a treat indeed to read an article that is able to blend complicated and vital science and nutritional issues together in understandable language that gives us useable and beneficial health information. SAMe does indeed carry a top shelf price, and it is pleasing to know that we have viable alternatives.
    Even though genetics is probably the most complex of sciences, we have learned more in the past few years that all that was ever known by humans. Genetic sciences are still in their infancy and there is little we can do now to intervene with genetic disorders, However, that is about to change in extraordinary and profound ways in the very near future (More on that later).
    Regarding relevant supplements and whole food suggestions, please consult your primary care provider before eating or drinking anything.
    For those of us who are cost conscious, research dug up some interesting facts:
    Magnesium: 400mg $.06 ea.
    D3 2000IU $.02 ea.
    K – K2 complex $.09 ea.
    A (as beta carotene from marine algae Salina) $.10 (every other day)
    A and E Red Palm Oil 1 tsp. $.10
    (Sources: Vitacost, Cosco, Sprouts, WalMart)

    For those of us who prefer AU-NATUREL :
    With a juicer/extractor, make two or more gallons (for less than $25) of super concentrated whole juice mix containing mixed berries, asparagus, brussel sprouts, broccoli, beets with tops, carrots, red cabbage, black grapes, kale, spinach, mushrooms, red bell peppers, tomatoes, and anything else you like.
    This concoction provides copious amounts of fiber, micronutrients and carbohydrates, all in the best whole foods form possible, and it forms the basis of a novel and extraordinary diet spawned from deep research that is a hybrid mix of the best parts of the paleo and Mediterranean diets blended with the dietary recommendations from the Weston A. Price Foundation’s Wist traditions…
    (More on this later)

  4. Oya Paugh says:

    Hi Chris,
    excellent information. Thank you. The most practical and cheapest way to check for basal body temperature that I know of, is to check basal temperature before getting up in the morning with a thermometer. Do you feel that this is a reliable way to determine basal body temperature? I am familiar with Broda Barnes’ work but wonder if you have any more information about this?

  5. Yinai says:

    Another approach to all of this is to consider that certain types of foods will lead to imbalances and thus problems with methylation etc, instead of saying that people are different. Yes, people are genetically different, and the bodies of people that are sick, aged etc may be less efficient in doing various processes, but people also eat differently.

    Today the average American probably eat around 150 gm muscle meat and 50 gm cheese. He eats less egg yolks, drinks less milk, and eats less organ meats than in the past.

    For example while 75 gm misc organ meats + 75 gm muscle meats plus 500 ml whole milk can provide 4 mg vitamin B5 and 400 mg choline, 150 gm muscle meats plus 50 gm cheese may provide just a little over 1 mg b5 and 100 mg choline.

    In other words vitamin B5 is a nutrient we should investigate more. It is related to all these things; metabolism, fatty liver, high LDL cholesterol etc. High doses (pantethine) seems to be able to help fix these things, but smaller amounts found in natural foods along with other co-nutrients (like choline) may be more effective, and there will be synergy effects.

    While human milk is low in folate, b12, methionine etc, it is relatively higher than other vitamins vs the RDA for choline and b5 (as well as for vitamin C and vitamin A).

    I think there´s a case to be made for eating leafy greens, to consider it a special type of needed food, not only a «vegetable» along with all the others. It´s not only because of nutrients like folate and K1, but likely many others, especially perhaps chlorophyll – I think chlorophyll, also related to the detox process, can be considered kind of a semi essential nutrient, that will greatly assist when other processes fails.

    In nature carnivores obtain relatively little magnesium, and often 10-30 times more calcium than magnesium. The human body also has around 30 times more calcium than magnesium. In milk it´s like 10 times more. It is clearly a nutrient related mostly to carbohydrate metabolism, and lots of white sugar should cause a deficiency, and to a lesser extent refined grains, while fruits, tubers, potatoes etc will provide all the needed magnesium (and other nutrients). Whole grains would be rich in magnesium, but not in a very good form, and will miss many other nutrients needed for carbohydrate metabolism, such as potassium. The combination of refined grains and large quantities of vegetables, as in the case of Japanese and Italian cuisine, seems to be fine.

    Anyone living on pizza and soft drinks would obviously get all these problems. Supplementing magnesium will just fix the tip of the iceberg for them.

    It is common to observe that milk drinkers are slim, while heavy cheese eaters are often fat.

    The role of fruit and natural sugar and potassium in metabolism should also be investigated. It´s been shown in some of the paleo diet trials that just replacing whole grains with fruits effectively boost metabolism and leads to weight loss.

    But yeah, eating enough calories and calories is the most essential of all. But in conjunction with the required nutrients in a reasonable balance with each other.

  6. Terri DeCaire says:

    Thank you Chris for sharing such an interesting article. What type of health practitioner could help me diagnose and treat the nutrient imbalances related to the methylation cycle? My GP doesn’t seem knowledgeable about such issues, even though the lab has flagged many problems with my blood work related to folate, B12 etc.

    Kind regards,

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Are Kombucha and Other Fermented Foods Toxic Because of Their Aldehyde Content?

In my last post, I addressed the first of two questions raised by a reader in response to a newsletter circulated by a representative of Biotics Research Canada, citing articles from Dr. Lawrence Wilson and Dr. Mark Hyman. In that post, I addressed the question of whether we should avoid animal protein in order toContinue Reading

8 Responses to Are Kombucha and Other Fermented Foods Toxic Because of Their Aldehyde Content?

  1. Christina Fritz says:

    If kombucha is out, should we consider kefir to be okay or a substitute for those looking for pro-biotics in another form?

  2. So glad that I first read the comments on this at the Daily Lipid as the main retort there gave me a great “heads up” on this article – sparing me from needless anxiety about good old kombucha – a long-time fermented tea drink that I have been making and drinking consistently for over fourteen years with great enthusiasm along with many other blessings!

  3. Jennifer says:

    I make my own kombucha and drink 64 oz a day. It seems to help my digestion. I feel better drinking it.

  4. Tom Jeanne says:

    Chris, I don’t put much weight on the easy-to-find information on the Internet that suggests kombucha is beneficial, but I like the rest of your summary. Your biochemical reasoning is impeccable, though what we still need is empirical evidence of aldehyde content in various formulations of kombucha.

    On that note, given the wonderful wildness of homebrewed kombucha, with local strains of bacteria and fungi playing a role, I worry about fungal toxins. Aflatoxin, which typically is a contaminant of cereal grains in poor storage conditions, is one of the most potent carcinogens known. It doesn’t seem unreasonable to worry about Aspergillus or another toxin-producing fungi growing on kombucha, especially if the initial ferment is in warm conditions. The last few batches I made had various tastes ranging from interesting to alcoholic to weird…. I don’t know if I should try to acquire a taste or dump them–precautionary principle would say the latter, even though I would admit the potential for a high risk toxin is probably low.

  5. WILL BOYDEN says:


  6. Kenny says:

    And he advises drinking dairy products. Pure nonsense from your typical SAD advocates.

  7. Doris says:

    Chris – Thank you so much for the article. Is there any concern with the aldehyde content of raw sauerkraut? My kraut ferments in the high 60’s to low 70’s temperature range of my apartment. I think Dr. Wilson advises minimal to no consumption of kraut. I welcome any insight you might have.

  8. Ken says:

    Excellent information. My wife and I have just starter making kombutcha and drinking it nearly every day. Appreciate clarifying this issue.

    Good job!

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Should We Avoid Animal Protein to Optimize Methylation?

A reader asked me to respond to a newsletter recently distributed through email by a representative of a company called Biotics Research Canada that cited two older articles by Dr. Lawrence Wilson and Dr. Mark Hyman arguing that animal protein should be restricted to optimize a biochemical process that is incredibly important to our healthContinue Reading

3 Responses to Should We Avoid Animal Protein to Optimize Methylation?

  1. Jaron du Preez says:

    Outstanding article! I love the work, effort and research your Foundation does.

  2. Alan says:

    Very interesting subject.

    One little off-track question: I understand that cats have to have Taurine in their diet otherwise they go blind. Is that because they lack the ability to digest plant matter and therefore do not have a source of B6? I think understanding that will help understand the cycle in humans.

  3. Peter says:

    Cats are true carnivores, with a short and acidic digestive system. They lack enzymes to digest plant matter, and their acidic digestion are suited toward animal foods. Their teeth cannot chew, only tear and rip apart animal flesh.

    Cats die from heart failure in taurine deficiency, and doesn’t only become blind. Do a google search on “felines taurine”, and educate yourself.

    Some useful info –

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Did Cod Liver Oil Contribute to the Historical Decline in Measles Mortality and Mortality From Other Infectious Diseases?

Measles has been in the news a lot lately. It therefore seems timely to fulfill my now more than two-year-old promise to write a blog on the possibility and evidence that cod liver oil may have contributed to the historical decline in mortality from measles and other infectious diseases.Continue Reading

One Response to Did Cod Liver Oil Contribute to the Historical Decline in Measles Mortality and Mortality From Other Infectious Diseases?

  1. Robert says:

    But vitamin A looks so unscientific and commercial!
    But vaccines are scientific and non-commercial. Unlike with cod liver oil, there are no patents involved with vaccines, and they are always safe to everybody. But cod liver oil comes from the liver, which means it will cause gout. And all fish are full of deadly anisakis.

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An Ancestral Perspective on Vitamin D Status, Part 2: Why Low 25(OH)D Could Indicate a Deficiency of Calcium Instead of Vitamin D

In the first post in this series, I critiqued the “naked ape hypothesis of optimal serum 25(OH)D,” which I believe influences many researchers to interpret uncertainties in the scientific literature in a way that is biased towards recommendations for high intakes of vitamin D that could be harmful to some people, especially without appropriate attentionContinue Reading

21 Responses to An Ancestral Perspective on Vitamin D Status, Part 2: Why Low 25(OH)D Could Indicate a Deficiency of Calcium Instead of Vitamin D

  1. Jeremy says:

    This is an excellent series. I am looking forward to the next parts.

    • Hilary says:

      At last some rationality about vitamin D!

      I have been exasperated by the lack of science behind the support for extraordinary levels of supplementation that are often supported by seeminly intelligent people.

      Measuring 25OHD is just silly. It is a storage mechanism for excess vitamin D because we cannot readily excrete it. Raising levels of this makes no sense.

  2. jesse says:

    Looking forward to part 3. I had a few questions on the calcium and vitD supplementation. Are there downsides to supplementing calcium and vitD together besides the “missed opportunity” of getting the other nutrients that come from the calcium rich foods? Are you mentally differentiating pastured raw milk from factory farmed ultra-pasteurized milk here or is that irrelevant with respect to calcium content? Are all calcium forms equally bioavailable, or are there some forms and co-factors that are preferable?

    I hope this request for slightly more detail doesn’t distract from my appreciation of the information in the current form :)

    Thanks in advance.

    • JP DC says:

      One of the keys to health for the body is, the ease at which it can maintain it’s homeostasis or balance in spite of an ever changing environment. Stress in the form of mechanical, emotional or nutritional/chemical continually challenges homeostasis. Using high doses of any isolated substance challenges this balance. One reason drugs have side effects is because they challenge the homeostasis, or in other words they make certain organ systems work hard at detoxification (which uses up valuable resources) but also detracts the organs from contributing to maintaining balance. The drug is a stress to the body which makes it work harder. High dose supplements are also a stress which makes it work harder (just not as hard as a “drug”). The key to health is to make the body’s job easier not harder.

  3. Gary Ogden says:

    Do you think taking cod liver oil/high vitamin butter oil through the winter for A/D/K2 is sufficient to maintain good status of those vitamins, in a dairy-rich and nutrient dense diet? What about the necessity of taking them during the summer? BTW your Foreword to “Death…” is a fine piece of writing. I had no idea you had literary talent. (You do) Also, I liked the natto in Atlanta, but don’t plan to make a habit of it.

  4. Hi Dr. Masterjohn, many years ago I wrote and article on my my website regarding the issues with oral vitamin d supplement and it role in calcium metabolism. While all my assertions where about the basic calcium metabolism it definitely raises the questions about oral supplement issues. When I saw your series on Vit d I was excited in that I knew it would go way more in depth than my article. Thanks so much for doing this series. Here is the link to my article that explains the potential pitfalls of oral Vit D.

  5. Mary E says:

    The above is consistent with my experience. I get vitamin D from the sun and cannot tolerate D from supplements or UVB lamps. The amount I get is consistent every year. My 25D usually quickly jumps up to the high 40’s ng/ml from sun exposure. Last summer it was only at 26. I had occasional carpopedal spasms suggestive of tetany, and my parathyroid hormone was below the reference range (I believe from supplementing vitamin A for dangerously low vitamin A per blood test). My 1,25D was at the top of the reference range, 60.5 pg/ml–way too high. I lowered the vitamin A amount, and parathyroid returned to normal. (Never toxic on A per blood tests.) I experienced similarly elevated 1,25D several years ago for another reason, and my 25D was again in the 20’s rather than the usual 40’s.

  6. Jacquie says:

    This is a terrific series, Chris. It’s personally relevant and I’m very interested in learning the other potential causes for low Vitamin D levels. I especially appreciate the effort you make to explain these topics in a way that is understandable to a non-scientist such as myself.

    A couple of years ago, my 25(OH)D level was measured at 11 ng/mL, despite my taking 2000 IUs of D3/day during the two or three years preceding the test and getting weekend sun exposure. (My doctor thought that amount of supplementation was too much and wanted to make sure my D level hadn’t gone too high.) At the time, I was eating dairy, sardines or salmon with bones, and plenty of calcium-rich vegetables daily.

    But I was also eating a lot of raw seeds and nuts, particularly almonds. Almonds look to be a decent source of calcium, but I’m guessing the calcium and other minerals were less available — or not available at all — due to their phytic acid content. I’ve since taken to soaking and then drying almonds and sunflower seeds in a low heat oven, a la Sally Fallon, in an effort to decrease phytic acid and increase mineral availability.

    What I’d like to know, though, if you have the opportunity to respond, is whether the phytic acid and/or other anti-nutrients in grains, nuts, legumes, etc., not only interfere with the bio-availablity of the minerals in those items, but also in the absorption of the minerals in foods eaten along with them?

    For example, would eating oatmeal along with sardines keep some or all of the calcium in the bones from being absorbed? Or the calcium in cheese mixed with whole wheat pasta? If that’s the case, then I’m probably not getting nearly as much (absorbable) calcium as I thought I was and the daily menus will have to be adjusted accordingly.

  7. Mike says:

    Very interesting, I also once wondered whats up with vitamin d and animals that never go into the sun or eat any vitamin D like bats or deep water fish. Its seems bats are vitamin D deficients but not mineral deficient.

  8. Rs711 says:

    Hi Chris,

    Have you seen this study discussing 25(OH) Vit. D’s apparent anti-carcinogenic effects in vivo (in rats)? Considering how widely useful calcitriol/25(OH) Vit  D are in many many metabolic processes – shouldn’t we expect the level(s) to change significantly depending on metabolic issues that may be present?

    Looking forward to the rest of the series!


    [1a,25(OH)2-Vitamin D and a Nongenomic Vitamin D Analogue Inhibit Ultraviolet Radiation–Induced Skin Carcinogenesis

  9. David I says:

    Hey, Chris–

    A bit off-topic, but your mention of cruciferous veggies and their downsides raised a question in my mind about preparation. All the info I seem to find on vitamins and antinutrients seem to be on steaming vs boiling vs microwaving.

    Where does roasting fit into all this? My favorite method for brussels sprouts or cauliflower is 350 F for 20-40 minutes. That to raise the internal temp quite high, but doesn’t drain anything away via cooking water…

    Any thoughts?

  10. Patrick Taylor says:

    Thanks for your excellent work.
    I just got some lab results. My 25(OH)D is a bit low (it’s 22). However, my calcium was also measured and is well within normal range (it’s 9.3 mg/dL). Is that calcium measure a reliable indicator that my calcium intake is probably sufficient and is unlikely the cause of my low 25(OH)D?
    Thanks again,

  11. Jack Cameron says:


    The information you have provided debunking the “naked ape theory” of vitamin D has clarified the findings of a couple of studies on vitamin D levels and mortality that found the lowest CVD and all cause mortality at vitamin D levels that are much lower than vitamin D levels widely promoted by the “experts”.

    A 2010 study, “Plasma vitamin D and mortality in older men: a community based prospective cohort study”, found the lowest hazard ratio of mortality and cancer incidence when the range of vitamin D was between 18 and 37 ng/ml

    A 2008 study “25-hydroxyvitam D levels and risk of mortality in the general population” found the lowest ratio of all cause and CVD mortality in the quartile of vitamin D (3rd highest quartile) with vitamin D levels between 24.4 and 32.1 ng/ml.

    The two aforementioned studies kept me from being concerned about achieving the high Vitamin D levels that have been widely promoted. Your explanations given in the series have been very reassuring

    • Josefina says:

      Then there is the study about breast cancer and vit D status showing those with the highest concentration were more likely to survive. The last study you cited says that women are more likely to have low D levels.

  12. Gary Via says:

    I’ve had a comment “awaiting moderation” for nearly a month (posted on Dec. 31).

    Do you find my question threatening? Is Trevor Marshall’s work (right or wrong) being censored on your site?

    If censorship is not your goal, what exactly is the problem with my comment?

  13. Sara says:

    Chris, will topical application of coconut oil on the skin block UV, necessary for Vit D sythesis? thanks

  14. Lauri P says:

    2 weeks before I gave birth to my daughter I started shuffling my feet when I would get up. I had terribly stiff joints. Moving on to 2 years later I had 3 episodes of pseudo gout and a frozen shoulder due to calcium deposits the Dr. said. Continue with heavy leg symptoms, stiff joint and joint pain. then kidney stone (biggest one they ever saw) Finally found out I was low Vit D at 22. Took supplements felt better, winter came started to have joint pain and hurting legs again and found out back to low D at 25. On supplements again. Any ideas to guide me to what the problem may be?

  15. Hank says:


    I haven’t found a proper forum in which to ask this in yet, so I hope it’s okay that I ask the question here:

    I’ve been trying to follow a diet of traditional foods for about 3-4 months now and I think I have the most crucial parts down.

    You see in Sweden, where I live, proper “oldschool” food is kind of hard to come by. (What with the lobbyism of dairy companies and so on.) But I’ve managed to secure the things that I have found to be the most important.

    Now, i eat the same lunch every day because I really don’t care about it, I just want the nutrition. Proper nutrition. It consists of the following:

    Natrol Multivitamin (It seems to be the most natural supplement for multivitamins.)
    Carlson Labs CLO gelcaps. (Can’t really afford the green pasture CLO Butteroil blend)
    Now Foods Vitamin K-2 (Again, can’t afford the butter oil)
    Garden of life expeller pressed coconut oil.
    Raw Multiple (Compound of dried organs, can’t stand eating liver or brain)
    Braggs ACV.

    Those are the supplements I’m taking. Now on to the smoothie:

    Organic raspberries, frozen.
    Organic raw eggs.
    Organic Kefir (Not homemade, haven’t found kefir seeds that I want to try yet.)
    Raw milk (Managed to find, after 10 hours of searching, an organic dairy farm willing to sell)
    Raw honey, locally produced (also very hard to find)

    For extra safety of the milk I blend the other ingredients first, then add the milk in a shaker.

    Oh, and I shouldn’t forget to tell you. I eat no breakfast, I keep a 12-8 pm (16/8 diet) eating schedule, so I take Garden of Life Primal Defense ultra probiotics in the morning. I do drink coffee every morning at 10, and it’s my only real health crime in the morning.

    Now, as I can’t afford the pricier CLO+Butteroil blend, I can’t afford eating only pasturized grass-fed cowmeat, so the dinners are usually just normal, but with low carbohydrate intake. I try buying all the things that aren’t that much more expensive when bought organic (cream, vegetables and so on.)

    Is there something crucial I’m missing? I’m a student now which limits my funding for food, but when I start earning money it will get better. So for now, just something that I’m missing.

    Also, I have to say, I’m doing this for the future, not because I have any certain issues right now.


  16. cristina says:

    All the vitamins are very important for our body to make it healthy. i respect your thought and the way you share this with all of us thanks for sharing this blog with us.

  17. Dr. Masterjohn, Thank you for this excellent article on calcium deficiency as a cause of low 25(OH)D. I look forward to future articles about other potential causes of low 25(OH)D besides poor vitamin D exposure. We sorely need a systematic approach for interpreting the likely cause of low 25(OH)D. You may be interested to read our paper “Inflammation and Vitamin D: the Infection Connection” which was recently published in Inflammation Research.

  18. Chuck Stackhouse says:

    Regarding butteroil. I make raw butteroil for myself from jersey cows eating only grass (30-40 different types of grass from May 1 to the end of June). I get 5-6 ounces of pure butteroil from one pound of butter and its bright yellow. I have found there is approximately 7-8 ounces of butter wax in a pound of butter and the rest is milk solids. I don’t heat the butter. Why do I make my own butteroil? I purchased a jar of butteroil from GP and found it taste like wax and was almost pure white. So, I took an 8oz jar of it and put it though my process and found it to be approximately 75% butter wax. In my area you can buy raw spring butter for $7.00 per pound and get 5-6 ounces of butteroil out of it. Or three spoons of raw butter is the same as one spoon of butteroil.

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An Ancestral Perspective on Vitamin D Status, Part 1: Problems With the “Naked Ape” Hypothesis of Optimal Serum 25(OH)D

It has become increasingly common for health enthusiasts and now even typical patients in the doctor’s office to have a lab estimate their vitamin D status by measuring serum 25-hydroxyvitamin D, abbreviated 25(OH)D, and use vitamin D supplements to bring this value into the “sufficient” range. While even this basic practice is problematic, the extraordinaryContinue Reading

17 Responses to An Ancestral Perspective on Vitamin D Status, Part 1: Problems With the “Naked Ape” Hypothesis of Optimal Serum 25(OH)D

  1. Interesting.

    So in practice, one should really measure:

    1. 25(OH)D3
    2. 1,25(OH)2D3
    3. PTH
    4. Blood calcium
    5. Urinary calcium excretion

    To get an idea of vitamin D status in a more functional manner?

    Also, you might find it of interest, that Dr. Henrik Hey her from Denmark, has done some interesting studies on vitamin D.

    He is of the basic opinion, that a lot of people are in some stage of insufficiency and correcting that will improve individual well-being and public health.

    However, supplementation is not the only way.

    He did one study of school children, where they found that when the kids are healthier overall (exercising more, eating more vegetables, fruits, whole grains as opposed to refined grains, getting more sun, more sleep etc). they 25(OH)D2 levels improved.

  2. Thanks a lot Chris!

    This is awesomely brilliant! I appreciate your honest and humble approach that is the hallmark of a true science researcher. Can’t wait for the next episodes of this series.

    Regards from France.

  3. Cat says:

    Thanks for the great article, Chris!

    I was going to ask what you think about mid-day being when the UVB/UVA ratio is optimal, given your points about how humans and other primates all seek shade mid-day, but I assume you will address that in your how-to guide. Can’t wait!

    Totally agree on different optimal serum Vitamin D levels between different groups. That actually makes more sense than treating humans as genetically homogeneous, which general public health recommendations always unfortunately seem to do.

    I wonder about the lifeguards who didn’t get kidney stones; it would have been great if there was a dietary analysis so we could see if they had a different diet: more vitamin A? more citrate? The synergy angle is really interesting.
    An anecdote: I remember reading your articles on balancing Vitamin A and D, but whenever I increased A I would have an increased frequency of colds unless I really ramped up the Vitamin D as well. Recently I started eating oysters a couple times a week, and now I can eat liver once a week without any ill effects. I thought only Vitamin A and D influenced each others’ tolerances, but zinc seems to have that effect for me at least. (I will try with some actual isolated zinc to see if it’s actually that, but it seems plausible.)

  4. Kathleen says:

    Thank you! So interesting and quite coincidental, as I was reading my daughter’s blood work just as the post arrived. Her one low result was vitamin D. I look forward to the next posts.

  5. Lynne says:

    Excellent – thank you.
    Looking forward to further posts and your conclusions.
    Important work as we are all carried away on the wave of high vitD recommendations in pursuit of better health.
    Kindest Regards
    Lynne (UK)

  6. Gary Ogden says:

    Fascinating. Makes excellent sense. It seems to me to be a near-universally normal human (and animal) behavior to seek shade during the hottest part of the day. Thank you so much for sharing your good work with us.

  7. Colleen says:

    Interesting analysis. One reason I like it is that it reinforces the notion that popping a bunch of pills (here a vitamin) isn’t the answer to health.

  8. newbie says:

    As usual, your thought processes as you dissect a topic are so well articulated – looking forward to your series.
    Looking for your comments on the following – In Ontario, Canada, the normal range for 25-OH Vit D is 75-200 nmol/L (30-80 ng/ml), so our bottom end is your max zone. We are told a value of 175 is great, especially if it comes without supps, and other indices are normal – ie PTH, urine and serum cal, PO4, Zn, Mg. The only time we are allowed to run this test is in the context of osteoporosis investigation, I say this to explain why the other parameters are also being measured, as your first comment referred to these tests. We actually encourage people to get their numbers high, I’m wondering if we are doing people a disservice. I look forward to your future analysis and explanations.

    • Thanks Newbie.

      I don’t consider 30 ng/mL a maximum, but I think getting over 50 ng/mL or so is really pushing into the potentially dangerous region. Of course this is complicated by which assay you are using and so on, but I’ll try to clarify all this as the series progresses.


  9. Having listened to Vieth a lot, I think you’re missing a couple of his points. One is that dark skin doesn’t actually reduce the amount of vitamin D that people can synthesize — it just makes it so that you need more sun to synthesize that amount. That is because after a certain point, the vitamin D precursors that are generated by ultraviolet light start being broken down by ultraviolet light. People with white skin hit the maximum pretty quickly, but even with dark skin, if you’re running around in the sun all day (or even a good fraction of the day), you can easily max out, at least on the portion of your skin that is uncovered. (And I’m prepared to believe an argument that humanoids a hundred thousand or a million years ago likely had and used furs, but that they routinely covered most of their skin, in the daytime in Africa, seems quite implausible.) The vitamin D maximum about coincides with the “minimal erythemal dose” — the dose that just produces a hint of sunburn; and if primitives were using oils or other substances as sunscreens, they likely were doing so to prevent the serious sunburns that result from going far beyond that dose. That wouldn’t detract much from their vitamin D production.

    Also, Vieth’s hypothesis, the last I heard, is not that humans evolved a biochemical dependence on vitamin D sometime in the last two million years, but rather that it’s something we inherited from monkeys. Fur-bearing animals, he argues, get vitamin D largely by secreting the precursors into their fur then licking the fur. I haven’t looked into this in any detail myself, so can’t defend it; but Vieth has been known to participate in informal online discussions in the past, so if you give him a heads-up, he might comment.

  10. Lava says:

    In the “Problems with the Latitude Hypothesis” paragraph above, you contradict yourself.

    First, you say Caucasians far from the equator *decrease* 25OHD. The next sentence, Caucasians there have *higher* levels of 25OHD.

    • Hi Lava,

      I’m sorry if the way I wrote the sentence was in any way unclear, but there is no contradiction. Caucasians far away from the equator have lower 25(OH)D than Caucasians living close to the equator but higher 25(OH)D than non-Caucasians close to the equator.


  11. sara says:

    Chris, thanks for the great information. Read part 2 also and looking forward to future series info. So based on this information, is it best not to apply coconut oil topically on the skin if one only gets out 30-60 minutes /day for best Vit D production?

  12. Ev says:

    “During the evolution of our species, requirements for vitamin D were satisfied by the life of the naked ape in the environment for which its genome was optimized through natural selection.” – how any theory based on the theory of evolution can be free of mistakes is unclear – if there is no one solid piece of an evidence to support Darwin theory? – and what is most amazing that organization like Weston Price or Paleo movement in general are – they are trying to figure out our past in order make our future better still refer the theory of evolution as reliable base for understanding of human beings and developing new theories – it is very very very strange situation!!!

  13. Ron says:

    I am 40 years old and of English heritage but tan very easily. Since my early 20’s my calcium has always been around 11.1. It was not until 2008 that I had my PTH taken and its usually in the 90s, sometimes low 100’s but then a few months ago, normal. My vitamin D tends to run low – 30. Supplemental vitamin D does not seem to influence the calcium level in my body and despite my love for the sun, my vitamin D levels will not elevate unless a take a lot orally. The medical community would like to simply explore my parathyroid glands and remove one BUT I refuse to go the mainstream route, especially when my levels are hovering near normal but slightly elevated. I’d like to learn more about the vitamin D gene mutation which I have heard of but no one talks about. I believe I have issues with Vitamin D conversion – I should note I have severe gluten intolerance and poor absorption of minerals. After a few mineral IV treatments, my PTH returned to normal, BUT my calcium still hovered around 11.

    Thanks for any insight.

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Undercarboxylated Osteocalcin: Marker of Vitamin K Deficiency, or Booster of Insulin Signaling and Testosterone?

Osteocalcin is a vitamin K-dependent protein that our bones produce. The job of vitamin K is to activate this protein by adding carbon dioxide to it, which in scientific jargon we call “carboxylation.” Vitamin K researchers widely regard the ratio of undercarboxylated to carboxylated or total osteocalcin as a marker of inadequate vitamin K status.Continue Reading

18 Responses to Undercarboxylated Osteocalcin: Marker of Vitamin K Deficiency, or Booster of Insulin Signaling and Testosterone?

  1. Interestingly, vitamin E elevated undercarboxlated prothrombin, but not osteocalcin, in this human study

    if tocopherol does protect undercarboxylated osteocalcin in rodents, this might explain why it is a fertility factor.

    There are no animal studies in Pubmed and just one other relevant human study:

  2. Chris Heppner says:

    Chris, thanks for a very interesting, though deliberately inconclusive, study. I hope that in the follow-up you will also deal with the issue of arterial and heart valve calcification, since this process seems to be connected with bone mineralization, and K2 has a history (maybe now being questioned) of assisting in directing calcium into bones and keeping it out of arteries and valves.

    There are documented cases of K2 supplementation reversing valvular calcification (from Japan mostly, but William Davis also records a case history of aortic valve stenosis much improved by addition of K2). I have a personal interest here–in 2004 I was found to have a “severely stenotic and heavily calcified aortic valve,” which was replaced by a bioprosthetic valve. As you know, these are also suject to calcification; I have been supplementing K2 (as well as eating a diet rich in K1), and 9 years out my valve is still functioning and looking (on echo) well. I won’t give up my K2 without some more definitive evidence!
    Thanks again, Chris Heppner

    • Hi Chris,

      I think it’s clear that K2 protects against soft tissue calcification and promotes bone mineralization. But that’s mainly the function of matrix Gla protein, not osteocalcin.


  3. rocks2stocks says:


    To what were you referring when you wrote:
    “and a variety of high-dose nutritional supplements, …, could interfere with the process of bone resorption.”

    • Hi Rocks2stocks,

      There are a variety of nutrients that at high doses could inhibit bone resorption, tocotrienols and K2 are among them, but I need to do more research before I conclude anything about it. Coming in the next post!


  4. Erella says:

    It is great to see you reevaluating your older publications and updating it as new information comes out. Your ability to get difficult and convoluted information across to your reader in an organized fashion is without parallel. I am grateful to be a recipient.

    I was not sure in which venue to ask you this question, and I thought that your article today relating to bone health/bone hormones is a good place to post this question.
    Taken from “Why Broth is Beautiful: Essential Roles for Proline, Glycine and Gelatin”- 18 June 2003 – by Kaayla T. Daniel, PhD, CCN
    “You can use the stock as is, or chill to remove the fat that congeals on the top. (There is nothing wrong with the fat, but culinary purists point out the clearest sauces are achieved with stock from which the fat has been removed).”
    Is there any nutritional value in the fat? Are any of the fat soluble vitamins( ?or other nutrients) extracted from the marrow or other fat content of the simmered bones preserved in the fat that congeals when the broth is put in the fridge? If the liquid part of the bone broth does not become jellylike on refrigeration, does that mean that the gelatin was not extracted properly (I cooked the broth for 72 hours)?

    Since vitamins A/D/K are fat soluble vitamins( vs the unstored water-soluble vitamins), would be giving your child liver once per week, as well as full fat yogurt/cheese/sauerkraut regularly be enough, or would you suggest supplementing (eg. with Thorne vitamin K2)? I understand that you don’t have the data, I am asking for your best guess.

    I thank you.

    • Hi Erella,

      Thank you for your kind words.

      I don’t know the answers to any of these questions for sure, but my best guesses are as follows:

      1) All the fat-soluble nutrients in the marrow should be present in the fat. Some of them may suffer some heat damage, however. Also, the fat itself could suffer some heat damage, especially if it is from chickens, which tend to have fat high in PUFAs (though not intrinsically so — see my blog post “Good Lard, Bad Lard” on that topic).

      2) Lack of gelling is probably from insufficient gelatin, or destruction of the gelatin. It may be the case that cooking too short a time or using too few bones or not using any more gelatinous materials like chicken feet is responsible for inadequate gelatin, or that cooking too long a time breaks down the gelatin. Try to find the happy medium.

      3) Liver once a week and yogurt/cheese/fermented veggies should be good, but for vitamin D make sure to get sunlight or use cod liver oil. Overall I think this should be decent for most children without the need for supplementation but there could be individual cases where supplementation is warranted.

      Hope that helps,

  5. David says:

    Here is my anecdote for you: based on my reading of your and Stephen Guyenet’s writings about K2, as well as my own reading of the original journal articles 2.5 years ago, I have supplemented myself and my family with K2, approximately .5mg of MK-4 menaquinone per day per person. I started this when my first child was in utero. My second child has been supplemented since conception. Both are exceptionally healthy, quite lean, and certainly don’t show any signs of insulin insensitivity. We didn’t have any trouble conceiving the second child while I myself was supplemented.
    As a younger man I had a poor diet and occasionally suffered some mild post-meal hypoglycemia, so I feel I’m pretty aware of my blood sugar. I think it has never been better.

  6. Erella says:

    If I can impose again, from Kaayla’s article –
    “Whatever form of gelatin is used, it should never be cooked or reheated in the microwave. According to a letter published in The Lancet, the common practice of microwaving converts l-proline to d-proline. …..In other words, the gelatin in homemade broth confers wonderous benefits, but if you heat it in the microwave, it becomes toxic to the liver, kidneys and nervous system”

    Do you believe this to be true (in which case I will know longer reheat the mug of broth in the microwave) ?

    • Hi Erella,

      I’m not sure about that one. You might want to ask Kaayla or look up the original study. I haven’t researched microwaves much myself in part because I rarely use them for anything.


  7. Amy B. says:

    My mind is reeling a bit. Very difficult to make sense of this all. Thanks so much for digging into things, Chris. The story of vitamin K is clearly far from being well understood, but your deep-dives into the research and generous sharing of your thoughts with is can only help.

    I wonder what role — if any — these nuances of osteocalcin might play in PCOS:

    “When we consider that these mice have no obvious bone defects yet are fat, infertile, and metabolically damaged, it would seem that in the mouse the primary role of osteocalcin is to regulate energy metabolism and fertility rather than to do anything particular to bone.”

    When I hear “insulin and testosterone,” my mind jumps right to PCOS. The line I quoted above leans in that direction, too. (And also to men with gynecomastia and other feminizing conditions…am I wrong in that insulin upregulates aromatase, leading to some testosterone being converted to estrogen? Elevated levels of both insulin *and* testosterone sounds like it might tip the scales in this direction. Not sure what the effect would be of increased *sensitivity* to insulin, though, which is another effect of the uncarboxylated osteocalcin, right?)

    Lots of questions…few concrete answers.

    True science is a harsh mistress! Thanks for all you do, Chris!

  8. Bill says:

    Interesting to me, as I have a cousin who has been suffering stress fractures (osteoporosis) AND is extraordinarily thin, lacking both lean and fat mass at the extreme of normal human body types, AND seems to have excellent metabolic health without any special attention to diet (triglycerides very low, HDL very high, etc.).

    Of course we know that this body type is considered a “risk factor” for osteoporosis.

    But . . . maybe if your line of reasoning is correct her body type, osteoporosis, and insulin signaling are closely related: maybe her K2-dependent carboxylation is for some reason (genetic; she’s been like this since birth) very weak, leading to extreme leanness, lack of muscle, metabolic health, but, unfortunately, osteoporosis.

    So . . . maybe lots of K2 would move her toward a better balance, with fewer fractures and more body mass she desperately needs. Maybe worth a try?

  9. David I says:

    It sounds as if the mice reseachers may be not only be leaping to conclusions, but leaping in entirely the wrong direction.

    It reminds me of the dialogue in the movie “Top Secret”:

    Doctor Flamand: This giant magnet is capable of removing the salt from 20 millions gallons of seawater every day. Do you understand what that could mean to the starving people of this world?

    Nick: Wow!…they’d never have to buy salt again!

    • David,

      Is this an in-joke between you and yourself? If so, why post it here?

      If it is meant to communicate something, why not communicate your point in a way the rest of us can understand?


  10. Would this also explain a slower growth and later puberty onset among children fed adequate or high amount of dietary vitamin K2 (i.e. diets high in animal produce)?

  11. MIchele says:

    Hi… I have a couple of questions for you.. I am going to get a biologic dentists opinion.. but our 13 year old fell about 4 years ago and now all of a sudden his tooth (chipped) was hurting.. so took him to a regular dentist and he said from the trauma he needs a root canal… I am gonna try raw milk, cheese and cod liver oil.. idk if will heal… Also we have a 16 year old who has not gone through puberty. He does drink raw milk and we eat raw cheese.. He also eats lots of eggs.. just wondering what your thoughts are… thanks. Michele H.

  12. B.S. Bharath Kumar says:

    Dear Chris,

    With respect to the role of undercarboxylated osteocalcin (ucocn) in male fertility, Oury et al. (2011) observed a dose dependent increase in testosterone levels between the doses of 0 and 3 ng/ml of ucocn and a dose of 10 ng/ml of ucocn failed to elicit the increase in testosterone. However, they failed to demonstrate the effect of ucocn between the doses of 3 and 10 ng/ml. Ferron et al. (2010) and Lacombe et al. (2013) observed the normal serum ucocn levels to range between 3-6 and 7-20 ng/ml, respectively. Owing to the normal levels of serum ucocn, it would be presuming to examine for its physiological role in reproduction and the lack of data regarding the stimulatory effects of ucocn between the doses of 3 and 10 ng/ml compels me to agree with you.
    P.S. Kindly forward the references related to normal serum ucocn levels in mice.

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The Scientific Approach of Weston Price, Part 7: Placing Price’s Work in Context

This is the seventh and final installment in a series of posts in which I am laying out the most salient points from my 2012 Real Food Summit talk, “Weston Price on Primitive Wisdom.” See these links for part 1, part 2,  part 3, part 4, part 5, and part 6. How are we toContinue Reading

One Response to The Scientific Approach of Weston Price, Part 7: Placing Price’s Work in Context

  1. Frederik Ackermann says:

    great way to finish up an impressive series!
    – much appreciated

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Does Carnitine From Red Meat Contribute to Heart Disease Through Intestinal Bacterial Metabolism to TMAO?

In April of 2011, I posted a rebuttal of a Nature paper from Stanley Hazen’s group at the Cleveland Clinic arguing that choline from animal foods causes heart disease: Does Dietary Choline Contribute to Heart Disease? Their argument was that our intestinal bacterial convert choline to trimethylamine, which our livers then convert to trimethylamine oxideContinue Reading

80 Responses to Does Carnitine From Red Meat Contribute to Heart Disease Through Intestinal Bacterial Metabolism to TMAO?

  1. A great rebuttal of the danger of partial truths being used to create controversy and fear by anti red meat factions.
    The evidence, when considered as a whole, is irrefutable that red meat, today represented by grass/greens fattened beef is extremely healthy. Not only is it the modern equivalent of wild ruminant big game our ancestors consumed throughout our evolution, but if eaten daily, suitably fattened, gives long healthy life. It is a functional food with Omega 3’s in balance and equal to cod fish, plus the added advantage of other essential nutrients such as CLA and fat soluble vitamins A,D,E, and K. Science indicates we developed our brains from eating it long before learning to fish.
    To deny its goodness is to deny all history, now increasingly supported by balanced scientific enquiry.

    • Angie says:

      Totally agree! Grassfed beef is the only way to go.

    • David I says:

      “Science indicates we developed our brains from eating it long before learning to fish.”

      Highly debatable. Some authorities suspect the distant ancestors of humans may have been littoral dwellers, along the edge of the sea or lakes. In this case, although they may not have “fished” in the sense that Hemingway did, their animal protein and fat intake may have been from shellfish and crustaceans–and possibly grubs and insects as well.

      In any case, we don’t know enough to make blanket statements. All we really know is that our distant ancestors were extremely versatile omnivores, and that it is silly to condemn any of the foods they were likely to have eaten.

    • vaclav nikdo says:

      We are always comparing ourselves to our ancestors of the remote past in terms of the diet we should follow. This is good but it only can be taken so far. We are trying to find a diet that helps us maintain a healthly life into our 80’s and beyond. These ancestors didn’t live much past 30. Before 30 most of us can eat all kinds of junk and feel fit. I think looking at how our biochemistry developed around food sources is great, but evolution doesn’t care if we develop deseases in our later years, we have already passed our genes on, they are real focus of biological evolution. What we are looking for, in my opinion, is a diet that takes us beyond what biological evolution has created. Some focus on early diets is educational but it has limits in directing us toward a goal for which is there is little precident in nature, to go beyond our evelolutionary blueprint.

      • Sorry I initially read your comment in a different interface and thought you were replying to the article rather than the above comment, so I left a comment that didn’t make much sense, which I’m deleting now.


      • Polo says:

        I’m not sure that there is no evolutionary advantage to old people being around. They carry knowledge and techniques which they transfer, they have experience, and they are more prudent, keeping people social and civilized, and crime lower:) Communities with old people possibly allowed younger people to eat better, stay healthier, and reach reproduction age.

      • Heather says:

        No they didn’t live until 30 and then drop dead. It’s an average age. You are comparing the hostility of two environments. In 1900 the average lifespan was 40. Infant mortality dropped and the average lifespan increased.

  2. Excellent post Chris. Especially the points about gender and TMA>TMAO. The idea of looking for toxic bacterial metabolites (or at least eliminating them as causes of disease) is a good one (shades of Elie Metcnikoff) but someone appears to have hijacked this study and ridden off to Crazytown.

    “An analyte with identical molecular weight and retention time to
    l-carnitine was not in the top tier of analytes that met the stringent
    P value cutoff for association with CVD. However, a hypothesis-driven
    examination of the data using less stringent criteria (no adjustment for
    multiple testing) revealed an analyte with the appropriate molecular
    weight and retention time for l-carnitine that was associated with cardiovascular event risk (P = 0.04).”

    A vegan ate a steak? No wonder this story was big news. I hope he’s OK.

  3. Robert Klosa says:

    Reading your commentary after the original paper felt like the reveal at the end of a mystery novel . Somehow all the clues where there but darned if I could see them… Thanks for connecting the dots.

  4. Steven says:

    Excellent analysis Chris. The real question is of course: ‘will supplemental carnitine increase CVD?’. Without an RCT its unknown but seeing as there are many studies which find benefits of carnitine after a CV event, it’s unlikely that carnitine promotes carnitine.

    There are other instances of carnitine being therapeutic. The combination of carnitine and alpha-lipoic acid increases mitochondrial biogenesis and reduces the symptoms of neurodegenerative diseases.

    Seeing as mitochondrial function is probably an important part of CVD, and carnitine improves outcomes following CV events and increases mitochondrial biogenesis (with ALA), my hypothesis would be that carnitine is therapeutic for CVD.

  5. Rob says:

    Thanks for all of the time you put in to these articles, Chris.

  6. Dimezzano says:

    what about “The China Study ?”

    • China study keeps coming up amongst our converted vegan now beef eating customers who, convert for health challenge reasons. I even wasted time checking it out this red herring only to discover the same quantum leaps of interpretation as in the Cleveland study.
      Please Google rebuttals to it and dig down into, what becomes biased interpretation of partial truths. I thought all with open minds now give it the negligible weight it deserves.

    • Leaf Eating Carnivore says:

      Go read Denise Minger’s excellent dissections of this really stinky dead mouse.

      The studies were generally so bad that (even before I found her analyses) I ripped up the book and threw it away – a lifetime first for me.

      And I’m not even a biochemist.

  7. Tim says:

    Thank you very much Chris, for this supreme work of deconstructive diligence. It really has a sobering effect on ones to give any bias to a study depending on the journal it is pulished in…

    I have just one question left unanswered: if and I repeat, if LMAO would have any effect on atherosclerosis in wild-type humans :D, there would be much more reason to be concerned about carnitine and coline salt supplements than about red meat (excluding fish which I consider absolved by epidemiologcal evidence).

    As I have no access to the 1999 study, could you give the excretion levels for the supplements administered in that study too? I would like to see how they compare to the foods you have shown in the diagrams.

    • Hi Tim,

      It’s tough to say because the methodology and reporting was somewhat different in the 1999 study between the supplements and the foods. There were three trials per person with 24-h urine collection for the supplements and one trial per person with 8-h urine collection for the foods. They reported that ~30% of a 15 mmol supplement was converted to TMA+TMAO over 24 h. If excretion in urine is constant over 24 h, this yields 1500 umol/8 h, which is comparable to some of the lighter seafoods. However, the dose is very large (~2.4 g, about 13 servings of steak).


      • Tim says:

        Hi Chris,

        thanks for giving those numbers. It’s interesting that even such a large dose of pure carnitine doesn’t seem to cause more LMAO excretion than fish does.

        I guess the only possible loophole for the authors’ hypothesis that elevated TMAO promotes atherosclerosis could be found in the time domain – if dietary LMAO would be rapidly excreted in contrast to endogenously produced LMAO from carnitine or choline. Thus the gut bacteria would create some “slow-release” TMA over a long period of time, resulting in chronically elevated TMAO levels, while oraly ingested TMA(O) would cause only a rapid spike in blood levels. I don’t know if this loophole-hypothesis makes any sense though.

        • Tim says:

          PS. Some short in my orthographic neurons apparently caused me to write TMA(O) instead of LMA(o) 😉

        • The 1999 paper I cited “assumed” that 50% of TMAO is metabolized by gut bacteria to TMA and reoxidized to TMAO in the liver, so probably in both cases TMA is being generated. They didn’t have quantitative data on that though. Anyway, it seems pretty implausible to me that the TMAO is going to have a different half-life in the plasma depending on where it comes from. If it does, that does not salvage their hypothesis. It’s a different one. Thanks for your comments!


  8. Tom says:

    Well done – a well-written and considered article. My only quibble with it, and your previous, related one on choline, is your comment that seafood “…is generally contaminated with some trimethylamine….”. In fact, fresh saltwater fish do not contain much, if any, TMA. However, they do contain large amounts of TMAO that they use as an organic osmolyte. In caught fish this is rapidly reduced by bugs to TMA – hence the need to keep fish chilled. When fresh fish is eaten the TMAO can be reduced back to TMA by some classes of gut microbes that use TMAO as a terminal electron acceptor in anerobic respiration.

    Also, I’m not sure that the male-female difference in TMA-(FMO3)->TMAO is observed in other species other than mice (probably making the mouse a poor model for these experiments). Male mice lack FMO3 in the liver as they excrete TMA as a ‘chemosignal’ (see PMID:23177478). Rats don’t show this sexual dimorphism.

  9. Jeff says:

    i had scribbled a post last night – tracking on some of the same things you highlight – although i’m more focused on the microbial issues. will post 2day. had a quickQ: on the 1.3% carnitine supplement in the mice, you mentioned that it was administered in water. i had been looked throughtout the article and supplement info to try and estimate dosage as well – but could not find a reference to water – only that the chow was spiked. thanks, jeff

  10. Kenny says:

    Chris, can you tell us the magnitude of the supposed increased risk of CVD, PAD, and CAD?

    I looked Figure 4’s Forest plots of odds ratios and couldn’t understand it.

    Can the increased relative or absolute risk be quantified?

    • An odds ratio of 2 means twice as likely. An odds ratio of 1 means no difference in likelihood. If the error bars cross the vertical dotted line extending from one, it means the difference is not statistically significant.


  11. Thanks for this great review. I would normally dismiss this out of hand, especially given it’s informercial title, but, as you say, “parts of this study are very well conducted, providing insights into metabolism that should fascinate anyone who loves biochemistry” although I never thought of it as “meandering down rabbit holes.” Well, maybe that means Wonderland. You saved us all a lot of time.

    One thing on the figure labeled d is that the errors are worse than you say. It might be worth pointing out that all the figures in the paper, like so many in the literature report SEM (standard error of the mean) which, for readers who are not familiar is a way to determine statistical significance but can drastically visually obscure the real spread in the data. Much better (I think should always be used) is the standard deviation, SD. To convert the SEM to SD you multiply by the square root of n which in this case is about 2.2 so the terrible spread in error in the figure is even worse.

    In the end, there’s something sad about all this. This was a lot of work and well designed with some sound logic but by trying to make the point about heart disease they gave it a phenomenological character along the lines of somebody’s description of high-school science fair projects: “I poured salt on it and it died. “

    • Hi Dr. Feinman,

      I see your point that standard error bars make the variation look smaller than would standard deviation bars, but I don’t agree that SD should always be used. In my opinion, SEM was appropriate here because the purpose was not to provide general descriptor of a set of data but rather to provide the basis for comparing one group to another. SEM is the measure of statistical precision used for that purpose. So, in my opinion, SD should be used when the purpose is simply to describe the spread of the data and SEM should be used when the purpose is to compare one group to another. It’s a way of tying the graphical depiction to the intended statistical test and the P value reported.

      I definitely agree that this good work ruined by the agenda promoted.


      • SEM is correct for demonstrating that the groups are statistically different and that should be done. The purpose of a figure is to transmit information to the reader and SEM obscures that.

        But really, what’s wrong with showing the data points? Any statistical measure reduces information. If you check out Basu (Lustig’s paper in PlosOne), he shows all the data points. In the comments with link to annotated figure, I point out that this allows you to see how much variability there is and how inappropriate the conclusion is. That may be why people resort to group statistics.

  12. Sean P. says:

    Out of curiosity, why did you choose to use a linear dose conversion when adjusting for body weight between mice and humans when trying to determine the human equivalent dose of carnitine used in this study? Shouldn’t you use an allometric scaling conversion? So the mouse dose would be 3,250mg/kg carnitine (assuming 20g mice and 65mg carnitine dose) which would only be 263.5mg/kg in humans (HED = 3,250(mg/kg) x 3 (mouse Km) / 37 (human Km)). For a 70kg adult human that would be 18,446mg of carnitine per day or 80 half-pound steaks per day (at 454mg carnitine per pound of steak) instead of a “thousand steaks per day.”

    Still, the caritine dose is ridiculously high and no human can even come remotely close to consuming anywhere near this much, but i think the distinction/correction is still important (80 vs 1000 is a pretty big difference).

    • Hi Sean,

      I chose it mainly because it was simple. I don’t think it’s really “correct,” but I don’t think it’s possible to make a “correct” conversion without understanding the mechanism better and quantifying the relevant variables in humans compared to mice. There are a lot of ways to make the correction. Another could be calorically. The ideal would be based on the pharmakokinetics of the relevant metabolites, but we don’t have that information in enough detail to my knowledge.

      In any case, I’m familiar with the concept of allometry, but I don’t understand your calculation at all. Where do the 3 and 37 come from? What is being measured in kilometers?


    • I ran the calculation through this calculator with a recommended mouse-to-human exponent of 0.8, and I got a little over 40 steaks:

      But I still don’t understand the principle here. It makes no sense to me that the pharmacokinetics of all compounds could possibly have the same ratio between humans and mice, or could possibly be directly and primarily related to some anatomical factor. Particularly in this case, where the active component is supposed to be an enzymatic metabolite of a microbial metabolite.


      • Sean P. says:

        Km in this case refers to the conversion factor for converting mg/kg dose to mg/m^2 dose. Km is equal to the body weight of the species divided by its body surface area. In this case, mice have a BW of .02kg with a BSA of .0066m^2 which gives a Km value of 3; humans have a BW of 60kg and a BSA of 1.6m^2 which gives a Km value of 37. You then divide the 3 (mouse Km) by 37 (human Km) to get the appropriate conversion ratio, which is 1/12 or roughly .08. Using allometric scaling is typically more accurate than using isometric scaling since BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. See “Dose translation from animal to human studies revisited”: and “Animal Models in Toxicology” page 839-849

        It’s obviously not “perfect” but this method of scaling is a good starting point without having additional data points.

        Either way, 60 steaks or 1000, no one is ever going to get close to consuming this much carnitine.

        • Thanks Sean. I’ll put an edit in the article linking to your comment. Since neither are going to be perfect (and I’m really not confident in one or the other), I’ll reference both. For what it’s worth, based on my data in rats, it seems like isometric scaling is more appropriate to compare the dose of vitamin D and its effect on 25(OH)D levels.


  13. Nathan McCorkle says:

    Thanks for the great teardown and background. My one criticism/opinion is that your ‘clean’ version was a bit long-winded and watered down. I read most of the article afterwards because the ‘clean’ version wasn’t convincing. I was convinced by the end, so I guess I’m just saying you can improve your writing style a bit. More facts, less opinion in the ‘abstract’ section would have allowed me to skim to the interesting details faster, etc.

    Thanks again!

    • Hi Nathan,

      Thank you for your comment. I don’t really understand it though. What was watered down about the “clean” version? What details should I have left out? You read my article or the Nature Medicine paper? You were convinced by what? My post or the Nature Medicine paper? I don’t know what you mean by “opinion in the ‘abstract’ section.”


      • Nathan McCorkle says:

        Hi Chris, I guess generally I just felt the section before ‘Why Single Out Red Meat’ (the intro section) could have acted more like a journal article abstract. Facts I found quite important were not in that section, these are the facts I found most impressive/telling of the ‘research feel’ of the paper. Things like ‘To take the most extreme example, halibut generated over 107 times as much TMAO as red meat.’ and ‘Adjusting for body weight, this is like a human eating a thousand steaks per day. This is beyond the capacity of even the most die-hard meat-lovers.’

        This one is quite informative too:
        “While it is possible that intestinal flora accounts for the difference, it is disappointing that the authors did not consider other possibilities, such as differences in the activity of the enzyme that converts trimethylamine to TMAO. For example, vitamin B2 is the main cofactor for the enzyme, and vegans are three times as likely to be deficient in vitamin B2 as vegetarians and omnivores.”

        These are the points I’ve been mentioning to people when they mention the Nature article.

  14. Andy says:

    Another great post along with Mr. Kresser’s.

    It would be wonderful if mainstream media would widely publish a review of this study along the lines of what you have done. Sadly though, since your review is not have a “black and white” outcome, it is not interesting or simple enough to generate interest in the general public. Not to mention it doesn’t demonize red meat, and what else is our society good at if it is not inaccurately chasing any and all reasons to prove that red meat is bad for us.

    Love the posts!

  15. Studies show that humans that consume certain types of fish do not get heart disease, while humans that consume red meat do. No amount of testing on animals or humans can change that observation. Perhaps there are some synergistic effects involved, but that does not change the bottom line. Eat like people who die a particular way and if you live long enough you will die from that cause, too.

    • Hi John,

      Thank you for your comment, but I don’t think you understand how science works, and I don’t think you’re familiar with the present observations either. There are no studies showing that people who eat certain types of fish don’t get heart disease. Of course there are studies showing that people who get red meat die of heart disease. That is because people who eat anything often die of heart disease. You seem to be confusing statistical correlations with absolutes. There are studies that, on the balance, show that people who eat fish are less likely to die of heart disease than people who don’t (or who have a negligible intake), but that is very different from showing that anyone who eats fish does not get heart disease. Regardless, it’s a basic rule of science that correlation doesn’t show causation. It’s just a false statement that because “people who do x are more likely to die of y, you should not do x or else you will die of y.” Shoe size strongly correlates with reading skill, especially among children, but you’re not going to read better by buying bigger shoes, for example.


  16. Sean P. says:

    Have you seen the recently published study, “Supplementation with High Doses of Vitamin D to Subjects without Vitamin D Deficiency May Have Negative Effects: Pooled Data from Four Intervention Trials in Tromsø,” yet? If you don’t have any future subject material lined up already, I’d be very interested in reading your thoughts/analysis of this study’s findings.

  17. tomas says:

    Hi Chris,

    don’t you know when exactly was the time interval between the last shot of antibiotics and the post-ATB challenge?

    Because we know that ATBs suppress bile salts, we could speculate that this might have influenced conversion of TMA to TMAO – FMO3 seems to be dependent on the status of bile salts.

  18. Chris,

    I am not an expert on the biochemistry of all of this, so your input would be much appreciated. Regarding the study you cite showing that fish increases urinary TMAO… what about serum TMAO? Isn’t that more relevant as far as the carnitine study? I’m not sure of the relationship between serum and urine TMAO, but knowing that beef doesn’t increase excretion of TMAO doesn’t seem to prove anything. What about TMAO in the serum?

    • Hi Brendan,

      So far no one has shown that beef or any other food increases total TMAO in the blood. For whole foods, we only have urinary excretion. The TMAO has to enter the blood to exit into the urine, so we know any food that raised urinary TMAO increased the flux of TMAO through the blood, but we don’t know that entered the blood quickly enough and exited it slowly enough that had venous blood draws been taken, the increase in total TMAO would have been of sufficient magnitude to be of statistical significance or potential clinical relevance. Based on the data of Zhang et al., it would appear that fish and shellfish but not the other foods are the foods we could expect to be candidates for raising plasma TMAO. With respect to the hypothesis of the Hazen group, they do not postulate that beef raises TMAO by inhibiting its excretion into the urine. Their hypothesis is all about generation. So with respect to their hypothesis, in evaluating the objectivity of their approach, and in the absence of contrary evidence, it is quite reasonable to assume that the half life and fractional excretion of plasma TMAO derived from beef is the same as that from fish. For it to be otherwise would mean that these foods contain substances that have quite powerful effects on those parameters, which no one arguing from any angle has postulated. For example for beef to raise plasma TMAO but not urine TMAO, while halibut led to a 107-fold increase in urine TMAO, would mean either that beef is not a substantial source of plasma TMAO or that beef is a similar source of plasma TMAO as halibut but contains something that decreases its fractional excretion 107-fold. It’s a much more parsimonious interpretation to tentatively conclude what is rather straightforward when one considers that fish contain TMAO itself, which is that fish but not beef are major sources of TMAO. And again, no one has shown that beef *or* fish raises blood TMAO. Make sense?


  19. NH says:

    “Some Pacific Island groups that subsist largely on seafood, such as the Kitavans, appear to be free of heart disease”

    Way to skew things in your favour.

    Kitavans eat mainly root vegetables like sweet potatoes and starches. Considering that fish are around 50% fat, 50% protein, and Kitavans ate less than 20% fat a day, coconut making up the majority of fat. The Kitavans ate very little fish.

    Which means your “subsist largely on seafood” claim is bullshit. Which you probably already knew.

    • I suppose “largely” wasn’t the best word, but in the context I think it is fairly reasonable in the sense that it is their main animal food, which is the sense in which I was thinking of it. Lindeberg (AJCN 1997) estimated they consume about 5% fish by calories. It would have been better if I’d written, “who consume seafood regularly.”


      • david says:

        There is no context, even one which requires anyone reading your words to be a mind-reader in order to divine that sense in which you meant it, in which “subsist largely on seafood” has the sense of consuming an amount of fish that would make up 5 percent of calories.

    • Hi NH,

      I changed it to “regularly.” Thanks for pointing that out.


  20. Brian Self says:

    Hi Chris:

    It is clear you did the real scientific and unbiased research on this. Thanks for taking the time to be so thorough and deliver this info to our community.

  21. Blaine Kennedy says:

    Prevotella bacteria seem to be the inciting agent of TMAOs, yet the study done does not focus on pre-existing infection with the organism, and the sources thereof. Im not a microbiologist, but it seems that people have the bug in their oral cavities, just ask a dentist. The study did not examine patient exposure or risk factors for Prevotella exposure, such as dental disease and stomal infection. Perhaps there is a difference between vegans and omnivores in the oral bacterial population, and the gut flora develops in omnivores from chronic seeding from the oral cavity.

  22. Markus says:

    And the craze goes on. Now the group is demonizing eggs over the same mechanism, just published yesterday @ NEJM.

  23. Windy says:

    Would Citicoline [stabilized CDP Choline (cytidine 5’diphosphocholine)] be considered a salt of free choline that would generate TMAO? And if so, would that increase heart disease risk? I take a choline supplement of citicoline and do not want to take it if it might increase the risk of heart disease.

    • Hi Windy,

      No I don’t think so, but I’m not sure how it’s metabolized. It depends where it’s absorbed. If it’s efficiently absorbed in the small intestine, it should be safe, but if a substantial portion reaches the large intestine, it could generate TMAO. That said, I’m not convinced that this increases the risk of heart disease.


    • Noah says:

      Sin entrar en la pole9mica sobre la uditilad real de los probif3ticos actuales o del Lactobacillus patentado por Danone, mi impresif3n es que esto variare1 de unas personas a otros, dependiendo precisamente de la composicif3n de la flora intestinal de cada uno. Pero claro, no hay estudios al respecto Lo que sed se desprende de todo esto es que deberedamos evitar el exceso de lecitina, que -por cierto- es el nombre comfan que se da a la fosfatidil-colina , un ledpido que este1 en la membrana de las ce9lulas, y que se utiliza tambie9n como emulsionante en algunos alimentos. Es muy frecuente que te intenten vender la lecitina (de soja, sobre todo) como ff3rmula me1gica para bajar el colesterol malo y subir el bueno , pero las evidencias cientedficas al respecto son me1s bien escasas

  24. steve naples says:

    Chris, I’ve never written into a blog. but I found you analysis thoughtful and interesting. I lost my grandfather, Dad and Brother to sudden death from heart all at 57. So at 52 I am very interested maybe too much, in this topic. I’ve looked at Macro biotic, vegan, vegetarian Palao, etc. I presently eat a 80 percent plat based diet. anyway, I was wondering. has anyone ever looked at the fact that alcohol drinkers (alcohol at most meals like the French) may work as an antibiotic on the Lecithin, and L carnitine. to basically render it harmless in the creation of TMAO? Thoughts? Thank you

    • Hi Steve,

      I’m not convinced that TMAO is harmful, but that’s an interesting idea and I’m not sure the answer. Thanks for writing! If you find anything interesting on it, please let me know.


  25. Mike says:

    Hi,Chris. I am probably one of many folks who check this site regularly to see if you are going to critique last week’s egg/tmao study. I hope you do. As someone who eats a lot of fish, eggs, peanut butter, red meat and cabbage, I seem to have a vested interest! After reading Hazen’s meat study, where he categorized into 4 groups based on whether their carnitine was high or low and whether their TMAO was high or low, and then described how only 4 of the 53 subjects had the prevotella predominance, I wondered if maybe only a very small percentage of people actually have “dangerously” high TMAO assuming Hazen’s theory is correct. But last week’s egg study actually broke the TMAO levels into equally divided quartiles, which suggests either that an extremely high percentage of people with the highest levels within the top quartile had heart problems, or roughly 25% of the population has “dangerously” high TMAO. Also, I was confused by the fact that the omnivores in the meat study had roughly a 45% higher baseline TMAO. Does this 45% higher level fall within the top quartile in the egg study? Or is it just that 25% of all us, ominvore or not, are “unlucky” enough to have “dangerously high TMAO and the rest of the ominvores have harmelessly higher levels of TMAO than the vegitarians? It was hard for this nonscientist to try to compare the numbers between the two studies. It does make me want to become a scientist though:) On behalf of the many readers who trust your take on these types of reports more than anyone else’s, I hope you give us your take. Thanks. Mike

  26. Simon Reves says:

    Hey Chris, we’ve never spoken before, but I’d like to say that your articles are extremely detailed(!) and that I really enjoy the reads. :) Felt a bit like Robert commented; as though you’re making the pieces of a “mystery novel” fit together for all of us out there that don’t have the time to sit-down and thoroughly analyse a study like this.
    I find it striking, though, how much analyses of the same data can differ so much – take a look at Dr. Michael Greger’s (not surprising) point of view, for example – Who thought the media didn’t go far enough with pushing “cartinine –> atherosclerosis”.

    Thought it was brilliant of Mark (Sisson) to link to the caritine supplimentation study by James J. DiNicolantonio et al. weekend following all the fuss.

    I like, though, that he (Greger) takes the time to present the data of actual studies to support his opinion(s), but I feel that there is a lot of epidemiology, and occasionally really irrelevant emphasis on the findings of certain trials, in the mix. Take for example the studies that found that saturated fatty acids help along LPS-tranlocation – would it not be relevant to mention that the storage proteins of some grains would be able to do the same ? Or that, despite increased LPS, inflammation (as a measure of TNA-alpha) was no higher in the group fed the cream than dextrose?
    And that endotoximia occurs as a result of intense exercise as-well?

    On that note, is there any chance you can cover/have covered whether the relationship between dietary choline and prostate cancer risk + advanced prostate cancer risk is casual or causative in nature. Of all people, you seem to be the choline “expert”, so I figured you’d be the one to ask.
    Could there perhaps be sense in telling men with advanced prostate cancer to lay of the eggs and get their choline from vegetable sources of betaine / suppliment betaine, or even reduce all forms of choline + predecessors?

    It’s articles like yours that gets me extremely skeptical towards conventional ways of thinking. I like that you always take a broader perspective than the reductionist point of view of most nutrition (e.g. fish is good for it’s long-chain n-3’s). But I suppose, on the occasion, conventional knowledge gets to be right sometimes. So if you ever get the time: Choline and cancer – what’s the connection?


  27. Theresa says:

    I am looking for information/research in choline levels in people with paeudocholinesterase deficiency. Are you able to help me out?
    I find your articles about choline very informative and easily understood. Thank you.

    • Hi Theresa,

      Unfortunately, I don’t know anything about that condition at the present time, but perhaps if you have very specific questions about interpreting whatever you find, I could try to answer them if I can find the time.

      Good luck and take care,

  28. Paul M says:

    I once wished that every medical school would make it a requirement for their students to read Now I wonder if it would it do any good anyway.

    I just got done watching a contributing physician today on Foxnews using the Koeth RA, Nat. Med. carnitine study as definitive proof that vegetarians live longer than people who regularly eat red meat.

    I also recently had a physician friend turn completely vegan based on this study. He had been contemplating going vegan for a while, despite my objections and continued references to this site. It wasn’t until he saw the carnitine study that it nailed his decision down for him.


    Keep up the great work you’re doing Dr. Chris Masterjohn.

  29. TH says:

    > As I pointed out in my last post on this topic, lots of foods seem to increase TMAO in humans and red meat does not stand out among them.

    Hazen’s work is intended to demonstrate that TMAO levels are correlated with past eating habits. Unless you can clearly disprove that (and you seem to avoid saying you have done so), prior studies that do not control for the eating habits of the participants– vegan, omnivore, etc.– shouldn’t be taken as evidence against his thesis.

    > red meat should be no more dangerous than potatoes and carrots and the real killer should be seafood.

    Without knowing the eating habits of those 6 volunteers in the 1999 study, we shouldn’t conclude anything about potatoes and carrots relative to red meat.

    But as for seafood, suppose the Hazen hypothesis is correct. That means excessive dietary carnitine/lecithin nourishes TMAO-generating bacteria in the gut, causing future meals containing carnitine/lecithin to impose an extra TMAO load on the cardiovascular system. That could be like eating fish 3 times a day every day. I doubt any studies show that eating fish that frequently is healthy.

  30. dahlia says:

    Wow- I wish I could analyze studies the way you do. Thank you so much.

    Could you address carnitine supplementation- we recommend it to cardiac patients quite a bit- in hefty doses along with CoQ 10 and d-ribose. What is your opinion now about doing that?


    • Hi Dahlia,

      You’re welcome and thanks! It appears to be beneficial from what I have seen. If I have a chance in the future to review the literature on it more thoroughly I’ll write something on it.


  31. David I says:

    Excellent article.

    On behalf of the Cartilagenous Fish Anti-Defamation League, however, I feel it necessary to point out that skate are not invertebrates.

    They should not be grouped of mollusks, crustaceans, octapods, and decapods. They belong with sharks and rays.


  32. Zenaida Zody says:

    Carnitine plays a critical role in energy production. It transports long-chain fatty acids into the mitochondria so they can be oxidized (“burned”) to produce energy. It also transports the toxic compounds generated out of this cellular organelle to prevent their accumulation. Given these key functions, carnitine is concentrated in tissues like skeletal and cardiac muscle that utilize fatty acids as a dietary fuel “-..:

    All the best

  33. Phil Nicols says:

    if vegan or vegetarian was bad for us, then all the vegans / vegetarians would be dead by now.. or at least sick.

    instead, we have gold medal olympic athletes, top MMA fighters, boxers, football players, extreme sports competitors, bodybuilders…. in fact the strongest man on earth today is vegan. If its “good enough” for them, then its good enough for the average keyboard warrior.

    2) its not all about me.. it takes 25 times as much land to feed cattle as it does to feed people, then after the cattle is brutally slaughtered, only 35% makes it back to the tables of humans.

    3) besides land, it takes immense amounts of water and energy to do this.
    2500 gallons of water = 1LB of meat
    750 gallons of water = 1 quart of milk
    55sf of rainforest = one 1/4 lb burger pattie
    we lose 65 acres of rainforests every minute of every day due to factory farming alone
    10 years ago it was estimated that we only have 50 years of rainforests left.
    rainforests act as the liver of the earth filtering out toxins that we pump into it daily…. pollution is going up and our natural defense against this is going down. without a liver, earth gets “liver failure”

    4) then theres the horrific cruelty. there is no such thing as humane slaughter. if there is, would you trade places with a cow pig, sheep, cat, dog, or anything else thats on the menu these days?

    we lose nothing by making some different choices in life but we help the big picture.

  34. sharonrays says:

    Very informative post.Thanks.

  35. James says:

    The food we take constitute mostly to our health condition.Our health is determined by the food we ingest. Heart disease is not an exception. Thanks for creating awareness.

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Thyroid Hormone and Vitamin A Protect Against Vitamin D Toxicity in Cows

I recently came across several papers published in The Veterinary Record in the 1960s documenting the efficacy and risks of injecting cows with a mega-dose of vitamin D just before calving to prevent “milk fever,” which isn’t a fever at all, but is a mix of clinical symptoms including weakness, loss of appetite, and inContinue Reading

14 Responses to Thyroid Hormone and Vitamin A Protect Against Vitamin D Toxicity in Cows

  1. Awesome as usual! We may have to look twice regarding the vitamin D hype and be sure to back up any supplementation with blood work. Do you think the usual toxicity threshold for blood vitamin D (around 100 ng/mL) is safe? Or is it possible that the calcification process occurs at lower dose?

    • Hi Laurent,

      Thanks! I think the risk of harm begins at much lower levels than that. I’ve never suggested any such level as a threshold and I can’t understand on what basis anyone would do that.


      • Thanks for your answer Chris! In France, when you ask for a lab test on your serum vitamine D, the optimal “zone” is set between 30 ng/mL and 100 ng/mL, hence my question.

        • Hi Laurent,

          I think having the upper limit that high is pretty reckless. I think harms from vitamin D can come at almost any level of 25(OH)D, in part because the point isn’t how much vitamin D one has in one’s system, but it’s interaction with these other factors, and in part because 25(OH)D is not a specific marker of vitamin D status. I plan to write a blog series on that latter point soon. All that said, I think the risk of harm becomes much higher when you get past 50 ng/mL, which is where you start to see some specific ill effects in the epidemiological literature, such as bone resorption. Total mortality is lowest at a considerably lower 25(OH)D as well. So I think the main focus should on getting all the synergistic partners. As a secondary point, I think 30-50 ng/mL is a much safer range than 30-100. I see no reason to push25(OH)D above 50 ng/mL unless someone has a genetic resistance to vitamin D of some sort.


  2. Norm Haight says:

    Thanks so much for providing us all with a front row seat to your cutting-edge research. Just from observing the people close to me, it sure appears that vitamin D supplementation is becoming imbalanced.

    I’m interested in how a person can have access to better nutrition in a cost-effective way and have been making sauerkraut and raw milk kefir, mainly for their probiotic benefits. I’d like to quantify and possibly enhance my efforts from a vitamin K2 standpoint and am wondering if you think it’s practical, cost wise, to have some individual foods tested. If so, please recommend a lab.

    I’ve been involved with market gardening for several years and would enjoy seeing firsthand the affects that changing soil fertility, season and various fermentation processes have on nutrition, particularly the various isoforms of vitamin K2.


    • Hi Norm,

      I’m glad you’ve found the writings helpful. Setting something up “in-house” for testing fat-soluble vitamins in foods is a major goal for WAPF right now, but I anticipate that taking another year or two to get going. Currently I don’t have a specific lab to recommend, but I would recommend using a lab that is very upfront and open about their methods/testing protocol.


  3. Travis Culp says:

    Thanks for the work, as always.

    I’ve found that, for myself at least, 2-3000IUs of D3 maintains my sun-induced summer 25(OH)D level of 40-50ng/mL. It would appear that the body uses about that much per day. If my cursory research is correct, the body also uses about 4-5000IUs of vitamin A per day, so I’m fairly certain this dose would maintain a desirable serum level.

    The only problem is that I have no idea what a desirable serum level is. If we move vitamin D higher in the acceptable range, do we then need to do the same to A? I wonder if something like 80µg/dL is desirable in that case. Have you ever come across anything that might indicate what an optimum level is?

    As far as I can tell from the cancer incidence studies, around that level appears to be desirable without much in the way of vitamin D. It would seem that in the absence of vitamin D sufficiency, one has to choose between cancer and fracture.

    • Hi Travis,

      Vitamin A blood levels seem to be less related to vitamin A status outside of extreme deficiency or excess than 25(OH)D is to D status. I’ll try to write more about this in the future though.

      Thanks for your comments,

  4. Wilfrid says:

    Hi Chris,

    Why don’t using vitamin A/D/K on skin rather than by mouth?
    It should at least minimize largely the toxicity.
    I think that the work of Sobel and Al on transdermal vitamin therapy could justify that kind of utilisation for liposoluble vitamins.

  5. Wilfrid says:

    I would like to add that of course absorption would be less efficient….
    But using around 50000 UI of A with 20000 UI of D and around 5mg of K will probably be a safe bet and more safe in the long run.


  6. Count Iblis says:

    The question is then how high calcidiol levels would interfere with the processes that are regulated by calcitriol, which are tightly controlled. If I read this paper:

    I don’t get a lot concerned with my intake of about 7000 IU/day and my calcidiol level of around 200 nmol/l. It could be that problems start to occur on the long term in the gray area between 250 nmol/l and 750 nmol/l, but I find it difficult to understand how natural levels of 250 nmol/l or lower could be dangerous.

    We have to also consider that until very recently not a lot was known about natural calcidiol levels. While one could have known that the 10,000 IU/day that you can naturally get from the Sun suggests that 150 nmol/l is more natural than, say, 50 nmol/l, the medical establishment was still surprised by this result:

    And later the same team performed more such measurement, they even found a pregnant women with a calcidiol level of 263 nmol/l.

    Thing is, after her baby is born, her baby gets enough vitamin D via her breast milk, while here in the West, we need to give our babies vitamin D supplements.

    • The epidemiological evidence suggests that harm, such as bone resorption, kidney stones, and heart disease, might occur at levels considerably and in some cases far less than 250 nmol/L. Same for total mortality. The sun does not provide 10,000 IU/day. It may for a single dose for the first day in an unexposed person with light skin, but long-term studies suggest that people with very high sun exposure have levels closer to what someone would get from supplementing with something closer to 3,000 IU for the coldest six months of the year in a temperate area. I’ll be blogging about this a bit more in the future. In any case, thank you for your comments.

  7. Spokes says:

    Interesting article. I use vitamin D3 supplementation, it’s been very effective in managing some of my mental health issues (I can’t rule out placebo, but it’s worked better than other things I also believed would work). It’s not like I get a lot of sun, but I became more cautious of it’s use because of headaches. I will remain cautious of its use, especially after this examination of the stuff, but I will also consider it in more in the context of other factors. I did try a cod liver oil purported to contain A and D in good ratios, but I didn’t get on well with that at all.

  8. Alex Lorin says:

    I have recently been diagnosed as having hypothyroidism as well as a vitamin D deficiency (as well as an iron deficiency). Since I have been on supplements and Synthroid I can say that my mood and general state have improved. I will be sure to stay up on blood testing and watch for other changes. Thanks for the interesting (and maybe a little above me) read.

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