This is from WesonAPrice.org. To see charts go to the link.
As always, if the font is too small, you can use “control +” to increase its size.
In the last several weeks, two momentous occasions have occurred in the world of vitamin D.
First, the Institute of Medicine (IOM) released its new report. It tripled the recommended intakes, doubled the upper limit, and commissioned researchers to go forth and test the effects of intakes higher than the upper limit, as this would be safe under proper supervision and provide valuable information.
This sucker is 999 pages long. When I finish reading it, you can look forward to one heck of a blog post on the matter. Stay tuned, folks.
The second momentous occasion occurred two days ago (Tuesday, December 14, 2010) when bestselling business author and tango champion Tim Ferriss released The 4-Hour Body. Tim’s last book, The 4-Hour Workweek, was number one on the New York Times,Business Week, and Wall Street Journal bestseller lists and has been translated thus far into 35 languages. In his new book, he discusses my research on the interactions between vitamins A, D, and K, and gives the following warning:
Supplemental vitamin D increases your need for vitamin A, so don’t forget the aforementioned cod liver, which includes both.
Hooray! It’s wonderful to see someone with this type of reach get this information out there.
When I wrote these articles, all the most compelling research I had was from animal studies. I wish that when I wrote them I had known that proof of principle for vitamin A-and-D interactions had already been experimentally demonstrated in humans. This revelation, however, had to wait for my 2009 Wise Traditions lecture, Cod Liver Oil: Our Number One Superfood. (You can get the DVDhere). Spiesman treated 54 individuals who suffered from frequent colds (five to seven colds per winter) with massive doses of either vitamin A alone, vitamin D alone, or vitamins A and D together. He treated them during the winter, for as many as three years, with a dosing schedule reaching a maximum of 40,000 IU for vitamin A and 300,000 IU for vitamin D.
Spiesman found that vitamins A and D only reduced colds when fed together:
Likewise, he found that vitamins A and D were only safe when provided together:
This study is not perfect. As you can see from the numbers on top of the bars in the second graph, there were far fewer people in the groups receiving either vitamin alone than in the group receiving both vitamins together. Spiesman reported that this was because it was difficult to get people receiving no benefit to continue the study for very long. It makes the study more difficult to interpret. On the other hand, given the toxicity figures in the second graph, we can be happy for safety’s sake that so few people were given massive doses of one or the other vitamin alone.
It would also have been better to have had a vitamin-free control group. And it would have been better to see the effects of more realistic doses of vitamins.
Nevertheless, the study quite clearly provides proof of principle in humans that vitamins A and D are most beneficial and safest when provided together, just like in the animal experiments.
Several commenters on this blog and on my Facebook Fan Page have provided testimonials about their negative experiences with vitamin D supplementation that support the protective effects of vitamins A and K: Cynthia Frederick, March 2010 I, and many others I’ve met on forums, have adverse reactions to Vit D3, even the lower amounts of 2,000 IU/day and even though we were tested and were deficient. And we do not have the conditions that would make Vit D contraindicated. . . . I’m waiting for the long-term effects to take place in people taking these higher amounts who are not simultaneously increasing their Vit A and K levels. In 10 years I wager we will be hearing about the negative effects that the higher doses of this ‘miracle nutrient’ have had on those taking it. . . [in a later comment] As I mentioned before, there seems to be a subset of us for whom even low doses (1,000 IU/day) of Vit D cause kidney stones, chest pain, fatigue, and aches and pains, even though our 25 OH D levels were ‘low’ (23). We get these symptoms as soon as a week after using the D. . . . I saved myself a trip to the ER with the above symptoms by remembering previous articles of yours about balancing the fat-soluble vitamins, and took about 100,000 IU of Vit A from fish oil and 5 mg of K2. Within 1/2 hour ALL the symptoms disappeared. This happened more than once so I know it is not coincidence. You are definitely on to something here.
Lynn Razaitis, June 2010 I certainly know what happens when you get these ratios off. I naively had a vitamin D shot of 200,000 units after a serious viral infection that used up my vit A. I wrecked my kidneys, thyroid and who knows what else. It took 6 months and Chris’s articles to figure out what the heck was going on with me. Within weeks of getting my vit A up with cod liver oil and a ton of liver (and I was thyroid blood testing monthly so I had test results to compare) my thyroid hormones all normalized. It was fairly stunning.
Andrea Schüler, June 2010 I stopped taking D3 because I developed tendonitis, bursitis, tendon calcification and aches and pains. I brought my level from 20 to 50 in the 25 OH test but maybe the 2000 – 4000 IU daily was not good for me or I have not enough A and K. I will test again to see where my levels are after several months without D3 pills. Maybe I should check Vit. A and K levels too.
I have received a number of other testimonials by email from people who have developed problems such as kidney stones and bladder stones after supplementing with “safe” amounts of vitamin D — within the IOM’s new upper limit — and these symptoms quite readily develop in animals fed vitamin D with no vitamin A under experimental conditions. I have not shared these because they were sent to me in private. If you have such a testimonial and are willing to share it publicly, please post it in the comments section.
If you are a blogger or a practitioner and have commenters or patients willing to share these stories, please help me compile them into a single source by posting them here or contacting me privately. So how much do we need of each of these vitamins and in what ratio? I do not know. We do not even know what the ideal vitamin D level is, and all of the vitamin D studies are confounded by their failure to account for the status of vitamins A and K.
Finally, I believe that the presumption of adequacy should rest with vitamin D intakes needed to achieve the serum 25(OH)D values (i.e., 40–60 ng/mL) that prevailed during the evolution of human physiology. Correspondingly, the burden of proof should fall on those maintaining that there is no preventable disease or dysfunction at lower levels. The IOM has not met that standard.
If I had access to Dr. Heaney’s time machine, I would love to replicate this study. All my requests for NIH funding for a time machine have been denied without any reviewer comments on how to improve my proposal. If we cannot measure paleolithic man’s 25(OH)D, perhaps we can study the fossils that his clothing has left behind, or study the residue that the melanin in his skin has left on his bones, or inspect these bones for the fossilized remains of light-absorbing coconut polyphenols from the coconut oil he may have rubbed into his skin.
But alas, I know of no studies that have quantified the decay rate of melanin or coconut polyphenols over a timescale of thousands of years, or determined the effects that sun spots, lunar cycles, planetary arrangements, and innumerable possible climate changes might have on these decay rates.
Dr. Michael Holick has a more conservative opinion. He believes that 25(OH)D should be at least 30 ng/mL. I believe there is more scientific backing for this level, which I’ve expressed in my post, “Are Some People Pushing Their Vitamin D Levels Too High?” But that doesn’t mean we have scientific evidence that higher levels aren’t better, or that they wouldn’t be if people were getting enough vitamins A and K. I don’t see any reason to believe that this is the case, since vitamin A seems to increase the turnover and utilization of vitamin D, which should produce a “low” level despite “high” status, but this is currently in the stage of hypothesis and guesswork.
Stephan Guyenet recently commented that it would be nice to know what the vitamin D levels of Kitavans and members of other traditional, healthy groups are: I don’t know what their 25(OH)D3 status is, but I wish I did. I’d love to know what their 1,25(OH)D3 levels look like too. I agree that it’s important to have a baseline for comparison so that we can decide what’s biologically normal. I’ve been looking for data to answer that question but I haven’t found it yet.
Knowing this would help, but there is still the question of the optimal A-to-D ratio, and how this might further be affected by vitamin K status.
A paper that Dr. Holick recently co-authored suggested that ratios between four and eight may be ideal. The lead author, Dr. Linda Linday, had used cod liver oil with a ratio within this range to successfully protect against upper respiratory tract infections. These authors also cited research showing this range of ratios to be ideal in chickens. They also cited Sally Fallon’s summary of my A-and-D interaction work as evidence that there was growing concern among the public about the proper ratio of A and D. Their findings about cod liver oil are somewhat convincing, but they can’t account for the vitamin D the subjects were getting from the sun, and they didn’t test different ratios. The chicken research is more rigorous, but it’s, well, it’s in chickens.
From an evolutionary perspective, the usefulness of data from chickens depends on whether you believe the evolutionary trees (or bushes, if you prefer) derived from morphology, which place birds as closer to crocodiles than to mammals by 65 million years, or the evolutionary tree/bushes derived from molecular biology, which place birds with mammals and not with crocodiles. (See this review.) Or perhaps we should consider binding proteins and enzymatic pathways directly related to vitamin D metabolism. With respect to D2 versus D3, for example, primates are much more similar to birds than to rats. (See this review). Ah, the mired network of divergent and convergent evolution. Perhaps we should follow Setphan’s ingenius idea of studying humans. Living ones.
Paul Jaminet of Perfect Health Diet (here, down a few comments) suggests the ideal amounts are 10,000 IU A and 4,000 IU D. This also sounds quite plausible to me, but again, we can’t say it’s more than a semi-educated guess. This brings us back to Tim Ferris. Ferriss tripled his testosterone by bringing his 25(OH)D up to 50 ng/mL and by following a number of other parts of his testosterone-boosting protocol including getting vitamin A from cod liver oil and eating plenty of vitamin K-rich foods. Ferriss didn’t conduct a dose-finding study on himself, and there’s just about zero reason to believe that the ideal level in Ferriss is going to be the ideal level in anyone else, except that we know that Ferriss is human and will therefore fall within the distribution of human requirements instead of outside of it. But “follow me and do what I do” is not the point of his book. The point of his book is to advocate self-experimentation and to provide a starting point for each individual from among his massive audience based on his own self-experimentation.
We should still do the science, but it’s going to take a long time, folks. The best thing to do now is to eat a well rounded whole foods diet and experiment with the levels of cod liver oil and/or vitamin D supplementation that make you feel the best, resolve your symptoms, increse your performance, and normalize your clinical tests if they’re out of whack or don’t throw them out of whack if they’re normal.
And share your results with the rest of us!
26 Responses to Is Vitamin D Safe? Still Depends on Vitamins A and K! Testimonials and a Human Study
1. BillS says:
Chris, what do you think of Dr. Cannell’s argument that Vitamin D3 is more comparable to beta carotene than to pre-formed Vitamin A since Vitamin D and beta carotene are precursors that the body transforms into the active forms (calcitriol and Vitamin A) as needed. He seems to believe that for healthy people at least it’s quite safe to consume large quantities of the precursors but playing Russian Roulette to take large quantities of the active forms and thereby bypass the body’s normal mechanisms for tightly regulating the levels of the powerful active forms. Accordingly, he advocates eating large amounts of colored vegetables containing beta carotene and either sunlight or D3 supplements as needed to provide sufficient Vitamin D stores. But as you know he strongly discourages supplementing with pre-formed Vitamin A, from either supplements or cod liver oil, or, of course, with calcitriol unless you need it due to kidney disease. Do you think his arguments make any sense?
Every time a “miracle” nutrient comes along people take it and run with it upping its consumption to levels uncharted and unknown. It is a very disconcerting practice and, for some people, downright dangerous.
[i]Ah, the mired network of divergent and convergent evolution. Perhaps we should follow Stephan’s ingenius idea of studying humans. Living ones.[/i]
Why? What possibly could we learn this way? 
I read with MUCH interest your blog post on the need for Vitamin A and K, and especially that you are having success with eliminating many of the side effects of vitamin d that I too have found to be present in a certain percentage of people.
I’ve been studying Vitamin D intensively for approximately 3 years, use it in clinical practice with real people on a daily basis and have answered well over a 1000 questions from people about their vitamin d experiences on my website.
Interestingly, I’ve been able to prevent and/or reverse the exact same symptoms that you are finding by always dosing with magnesium at the same time as giving the vitamin d.
If someone has these reactions, I’ll have them stop the vitamin d and do an intensive magnesium replenishment program for about a week before they start taking it again and, voila, no more issues with chest pain, anxiety, insomnia, jitteryness, kidney stones, etc.
I have found that these symptoms are rampant in the general population and are symptoms of magnesium deficiency in and of themselves. There is also quite a bit of evidence that Vitamin D depletes magnesium, and so I find these symptoms are an ‘induced’ magnesium deficiency in those who are already ‘borderline’ magnesium deficient.
When queried after the fact, I find that almost all of these people with these severe reactions had many of the symptoms of magnesium deficiency before they began taking vitamin d, but that these symptoms went unrecognized and undiagnosed- in part because magnesium blood testing is worthless.
I’d be interested in finding out about the relationship between Vitamin A, K and magnesium. I always try to tell people that vitamins are not drugs and don’t work alone in a vacuum. They work together as cofactors in relationships that science may not understand yet. This seems like a perfect example of those relationships.
Kerri Knox, RN
Interestingly enough, after I starting taking an Rx dose of D2 of 50,000 IU’s daily for 3 months, I started to develop severe knee pain and a “hardness” in my knee tendons that became and still is excruciating.
My D levels were as high as 140 for a short time. I also started to develop right thumb pain and a doctor said I had developed spurs.
I do have severe arthritis in my knees so it could be coincidental. I eat a lot of fish and take a quality multi-vitmain that does not have vitamin A or K though I do add these into my diet usually.
I wonder if my A and K intake was too low for the time I spent taking the high dose D?
Also, is it cod liver oil or any fish oil that will up the A in the diet?
I think another possible example of this interaction effect is that of the traditional Greeland Inuit, whose diet was rich in A and D. Among other things, the rate of heart disease among them was remarkably low:
6. Cynthia Fredrick says:
I have always taken magnesium daily for many years, mag glycinate specifically. 200-400mg/day. And I know others who have problems with Vit D take it regularly also. All I know is the symptoms always resolve after taking good doses of A, E, and K.
That argument makes sense in that it is safer to take vitamin D3 than to take calcitriol, the hormone form, but the analogy to beta-carotene does not make sense. Vitamin A and vitamin D are both converted to their active, hormone forms in a two-step enzymatic process that looks like this:
(A) retinol–>retinal–>retinoic acid
(D) cholecalciferol–>calcidiol–>calcitriol
So I think that vitamin D3 is clearly analogous to retinol. In any case, beta-carotene has been very clearly shown to be very toxic at excessive doses, so I don’t think the analogy, whether right or wrong, is particularly important.
Michael, true on both points. Let’s just look at fossilized chicken poop all day and say “wow, man, this like, looks cool and stuff.”
Hi Kerri, that’s very interesting. It’s of course difficult to interpret because magnesium is basically needed for EVERYTHING in the body, so it’s impossible to make these observations and formulate a very specific hypothesis. But it definitely deserves some intensive research!
Fred, it’s possible that you were low in A and K. On the other hand, I would recommend avoiding the doses you were taking like the plague, and I’m not sure why anyone would believe such doses to be safe. Perhaps if you were also megadosing A and K, but 50,000 IU/day? I’d consider that a highly experimental treat-at-your-own-risk disaster-prone type of treatment. Cod liver oil and liver are the best sources of vitamin A. Liver is even better if your D levels are still toxic.
Cynthia, while your experience is awful and deeply lamentable, I’m very glad you have so much information to share about it. That you were supplementing magnesium provides very important information in light of what Kerri has observed.
Hmm, was it D2 or D3 Spiesman used (I can’t look at the paper)? If D3, it was a disproportionally high dose, yet with a lower rate of toxicity (as you mentioned though, too few people).
I tried a K2 supplement (K2 Complex from Life Extension) about a month ago and got a cold after about a week.
[quote]We should still do the science, but it’s going to take a long time, folks. The best thing to do now is to eat a well rounded whole foods diet and experiment with the levels of cod liver oil and/or vitamin D supplementation that make you feel the best, resolve your symptoms, increse your performance, and normalize your clinical tests if they’re out of whack or don’t throw them out of whack if they’re normal.
Sounds like you are advocating that we rebuild our shared, cultural wisdom with trial and error and not wait around for science to resolve all of our issues. I like it!
My numbers:
22 ng/ml after extended daily consumption of recommended daily dose of green pastures fermented CLO
46 ng/ml after adding 5000 IU D3 to the CLO listed above
38 ng/ml after dropping the 5000 IU D3 during the summer but continuing the CLO
11. RobF says:
Have you learned more through your studies on fat-soluble vitamins on how retinoic acid side effects might play into this? It seems on the face of it that D might be able to resolve issues with retinoic acid, but in my experience, large dosages of vitamin D are counterproductive and vitamin A, by itself or combined with D, seems to resolve some issues while exacerbating others.
Very nice summary of the situation! We really do need more data, and can only make educated guesses at this point.
One brief comment: people have asked me about the Linday-Hollick paper that suggests an A to D ratio of 4-8 to 1, while I recommend more like 2.5 to 1 as you note. The Linday-Hollick ratio was from diet/supplements alone, and didn’t include D obtained from sunlight. My lower ratio includes all sources of D. So these numbers are more consistent than they may appear.
13. Jack Kronk says:
just a note that green pastures fermented cod liver oil / high vitamin butter oil blend is a 5 to 1 ratio. Recommended dose of half teaspoon provides 3000A and 600D.
Great article, Chris. Can you elaborate any on your comment about high amounts of beta carotene being toxic? I regularly eat around a pound of sweet potatoes daily, plus a lot of carrots and winter squash in the fall and winter. Could this lead to beta carotene toxicity, and what are its symptoms?
15. The Primalist says:
My understanding is that it’s D3 that we should be supplementing with?
Also, I’ve read that D3 is found in animal sources whereas D2 comes from plants? So where does such a high level of vitamin D come from in the cod liver oil?
I try to eat natural / whole food sources of vitamins rather than supplements, which is why I like the idea of cod liver oil – I was just surprised about the D2 and am trying to get a better understanding.
Thanks.
John, it just says “calciferol” from Mead and Johnson Company. You could probably dig up what they were selling as “calciferol” back then, but the name could mean either D2 or D3. I oppose the LEF supplement because of its 1 mg of K1, and everyone who has asked me I have told them to stay away from it or use one capsule/day max.
Tim, cool, thanks for the info!
Paul, thanks! Good point. I made that point in this post, too, although I think the ratios actually come from the chicken studies, which probably took light into account much more effectively.
Jack, thanks for the info.
Mike, 30 mg/day beta-carotene supplements were shown to kill people in huge randomized controlled trials and the trials were therefore terminated early. Many people say this is because it was isolated beta-carotene or because the population was exposed to smoke or asbestos, but Wang’s group at Tufts showed, using a ferret model, which is very similar to humans with respect to responses to beta-carotene and cigarette smoke, that 30 mg/d beta-carotene alone is more harmful than 1 pack/d cigarette smoke. However, 6 mg beta-carotene seemed helpful, and it’s possible that coadministration of vitamins C and E would have made the 30 mg/d safe. Some of the toxicity in the Spiesman paper above was actually due to beta-carotene. In any case, you cannot get 30 mg/d from food, so I would not worry about consuming beta-carotene from food.
The Primalist, I don’t know the answer and I think there are many unresolved questions about the vitamin D’s in marine oils. Obviously it’s false that D2 comes from plants and D3 from animals, as fish are animals (though this may be accumulated from plankton or other non-animal sources). I think it’s important to realize that we don’t know the biochemistry as much as the hysteria-driven vitamin D movement maintains that we do, and therefore we should look at clinical effects of foods, and not try to extrapolate from specific chemical forms in foods or rely too heavily on 25(OH)D levels in and of themselves.
Chris
Thanks for mentioning and posting the link to your article, “The Pursuit of Happiness.” I’m surprised I haven’t seen it before; I had been bouncing back and forth on that very topic. My mention in the previous comment about feeling good when I ate liver every day seems to make sense.
Hot off the presses:
19. Lillea says:
2 questions:
1. To test for vitamin A levels, is there anything special we need to ask for, or is the standard test sufficient?
2. What is an optimal vitamin A level to shoot for? Or is that in question too?
3 years ago my test results for vitamin A were: 1.8 umol/L
(the lab’s reference range: 1.2 – 2.8 umol/L)
If vitamin D increases your need for vitamin A, the reversed scenario must also e true, or what?
Vitamin A increases your need for vitamin D?
This would somehow explain my reaction to vitamin A. Whenever I have tried to supplement with vitamin A, I get extremely dry eyes and dry skin that gets thin and breaks easily. When I stop it goes away. On my lab test it shows I am relatively low in vitamin D.
Would this mean I would benefit from ONLY supplementing on D3 and possibly K?
21. Monique Verdin says:
I was reading an excerpt from Nourishing Traditions the other day by Weston Price where he said that children should not be given cod liver oil for an extended period of time, as it can cause toxicity. My four-year-old has been taking it since he was about a year old. He also takes the butter oil. Is this true? I thought it was good to give him cod liver oil.
I had recently tracked my dietary intake for 3 days and my average A intake was 19167 IU (RAE of 2336.57, if it matters. I take a 5000 IU vitamin D at least 6 days out of 7…can you see any need for me to take additional A?
23. devil says:
[b]if vitamin d is produced in the presence of uv light is it safe to go to tanning salons?i would preffer to that beacause i’d get the tanning bennefits[/b]
24. Jay says:
I was about to take 10,000 IU of vitamin A and 4,000 IU of vitamin D until I read this newsletter:
It is referenced with studies of people taking high amounts of both vitamin A(retinol) and vitamin D. Anyways, after reading the newsletter and checking the studies I decided that I will only take around 3,300 IU of Vitamin A from animal products. Am I being too fearful? Where these studies cherry picked?
We shared Chris’ article with our readers (with permission from WAPF) and received this feedback from someone. Does anyone have any knowledge/expertise on this? . . .
Since you are advocating the use of cod liver oil, I thought you may want to know in case you didn’t already know that Dr. Jonathan Wright of Health e-Tips Newsletters has repeatedly written that Vitamin E as mixed tocopherols should be taken with any intake of fatty essential oils. This excerpt below is taken from Q & A with Dr. Wright section of the Health e-Tips Newsletter dated Thu, March 25, 2010 6:14:53 AM:
“Fish oil is the best way to increase your intake of omega-3 essential fatty acids. I recommend 1 tablespoon of cod liver oil and 1,500 milligrams of DHA daily. And remember, whenever you take any type of fatty acid, you need to take vitamin E as well (400 IU of vitamin E as mixed tocopherols). Vitamin E helps keep the fatty acids from breaking down too rapidly in the body.”
26. Alobar says:
it is stated:
A few weeks ago, the British Medical Journal published a remarkable paper, remarkable that it studied more than 500,000 subjects, remarkable that it had 56 (fifty-six) authors, remarkable that it confirmed low vitamin D levels obtained in the past are a risk factor for developing colon cancer in the future. However, the most remarkable part of the paper is that the 46 scientists minimized the true significance of their own research. They found that vitamin A, even in relatively low amounts, appears to thwart vitamin D’s association with reduced rates of colon cancer. it is stated:
Spiesman treated 54 individuals who suffered from frequent colds (five to seven colds per winter) with massive doses of either vitamin A alone, vitamin D alone, or vitamins A and D together. He treated them during the winter, for as many as three years, with a dosing schedule reaching a maximum of 40,000 IU for vitamin A and 300,000 IU for vitamin D.
Spiesman found that vitamins A and D only reduced colds when fed together:
So, it seems to me that *some* vitamin A is needed along with D3, but not too much. Any rule of thumb about how much vitamin A to take with D3 supplementation?
