JAMA Jumps to Conclusions About Vitamin D

A recent experiment published in JAMA, one of the most prestigious medical journals in the world, found that giving people a very large dose of Vitamin D (100,000 IU) once/month did not prevent colds, even though it greatly increased blood levels of Vitamin D. This finding supports my view that it is important to take Vitamin D in the morning. (Because a study in which this wasn’t done found no effect.) My view implies that blood levels may not matter — you can get high levels of Vitamin D by taking it at what I consider the wrong times of day. The usual thinking about Vitamin D has been that blood level is all that matters.

The editors of JAMA considered the Vitamin D study so important that they asked someone (Dr. Jeffrey Linder, associated with Harvard Medical School) to write a commentary — an associated editorial that puts the new finding in context.

Linder’s commentary (might be gated) is important because (a) it is a kind of random sample of how top research doctors think (he was selected to write it) and (b) he completely fails to grasp that the time of day Vitamin D is taken might matter. Colds, the immune system, sleep, time of day — it’s not far-fetched. When you do an experiment to see if X causes Y, and find no effect, I believe that there are usually many possible reasons other than X never causes Y.  Something was wrong with the equipment, something was wrong with your X (e.g., it was stale), something was wrong with your measurements (e.g., ceiling effect), and on and on. Linder did not see it this way.

The 2011 IOM report called for additional research to determine whether vitamin D therapy reduces the incidence of respiratory tract infections. The VIDARIS trial [= the new study] has rigorously addressed this question. Results suggest that vitamin D should join the therapies listed in the Cochrane reviewsas being ineffective for preventing or treating upper respiratory tract infections in healthy adults.

He seriously thinks one null result proves something. Sure, the new study is “rigorous” in certain ways. But it was far from exhaustive. It did not explore the many ways Vitamin D may be given, for example. It did not consider the possibility that blood levels don’t matter. Linder’s combination of (a) interest in rigor and (b) failure to understand the importance of exhaustive reminds me of a friend. When she was in 1st grade she had a pile of pennies. She knew how many she had — she had counted them. However, she did not know how to subtract. When she spent some of her pennies, to find out how many she had left she had to count them all over again.

My friend had half the skills an accountant needs. Linder’s commentary reflects only half the skills a scientist needs. To the extent that he is representative of top research doctors, this is shocking. It is as if most accountants at Arthur Andersen didn’t know how to subtract.

I have asked Dr. Linder if he has any response. If he does, I will post it.

10 Responses to “JAMA Jumps to Conclusions About Vitamin D”

  1. LemmusLemmus Says:

    What reasons are there to believe that it might matter when you take vitamin D?

    Seth: I believe this because (a) I never noticed any effect of Vitamin D until I started taking it early in the morning and got the dose right (a weaker dose had no clear effect), (b) cases where people changed the time of day they took Vitamin D and noticed a big change in sleep (Tara Grant’s original observation), (c) cases where people started taking Vitamin D in the evening and their sleep suddenly got worse, (d) cases where people started to take Vitamin D in the morning and their sleep suddenly got better, and (e) persistent failure of big Vitamin D studies that do not control time of day to find effects of Vitamin D. Five sorts of findings.

  2. Glen Raphael Says:

    Lemmus: As I understand it, the reason people thought of taking D at all is that exposure to sunlight boosts Vitamin D. Humans mostly evolved before electricity and cars and artificial light so we’re used to regularly getting a big pulse of Vitamin D at a specific time of day, every day, which then tapers off at night. That pulse (it is thought) helps set the rhythm of our body clock – when we feel tired, when we feel awake, how our mood and body temperature change through the day.

    So the initial idea behind taking Vitamin D was that if people who spend all day indoors and a lot of their time under artificial light get depressed or have trouble sleeping especially in the winter, they might be missing that daily pulse of sunlight. if you give them back a big pulse of Vitamin D *as if* they were getting lots of morning/midafternoon sun, they might get back on track. Like a pacemaker. Feel more awake in the morning, feel more tired around bedtime, sleep better through the night.

    Lots of anecdotal evidence (and a few studies) suggest this actually works – that people who take a daily dose of D early in the day sleep better and feel better and get fewer colds. But if it works, the expected mechanism is that the *timing* of the D improves your sleep quality and quantity, and we know that people who sleep well have a stronger immune system and get fewer colds or recover faster from the ones they get.

    One massive *monthly* dose of D does NOT simulate what the sun does to us, so it doesn’t fit the pattern that is thought to improve sleep/mood/immune system response. Nor does D taken in the evening, or taken at random times.

  3. Chuck Says:

    It seems to me that the Pharma/Medical industry want so badly to prove that non-pharmaceuticals are ineffective, they will design their trials to fail. They are not impartial or unbiased. We don’t know if there were trials that indicated taking Vit D was effective. It could be the reverse of pharmaceutical trials where they hide the failures – in this case, they hide the successes.

    Bio-hacking, self experimentation, what ever you want to call it, may have some of the same biases (placebo effect), but not as likely (you may think something worked, but not long after discover maybe not, and try something else). After all, it’s your health you’re tinkering with, not some abstract population.

    Cheers

  4. Arthur Says:

    Does not seem a very good post to ask for a response. You probably should have talked about your evidence that the time of day matters, instead of just linking to other posts. He will probably not click the link, and respond to you like you were a nutjob, or simply not respond.

    Seth: My criticism is reasonable whether or not my idea that time of day matters is true or supported by evidence. It surprises me that a serious scientist would take one null result as seriously as Linder does, not recognizing that there are dozens of possible explanations of that result that do not assume Vitamin D is worthless.

  5. Chuck Says:

    Ok, this is the part of the trial I find incredible: There were 322 participants and during the nine months of the trial, there were a total of 1,204 reported incidents of upper respiratory tract infection – 1,204 UTIs in 322 people in 9 months!

    I think I could walk down the street and randomly select 322 people who, over the next 9 months, would not have 1,204 incidents of UTI. That is just a crazy number.

    I think there were some not so healthy individuals in the trial who skewed the numbers in both groups. I wonder if the incident of UTI per individual participant is in the report? Not just the average per all participants. Did everyone contract 3 UTIs? Or, half contract 6, and the the other half none? Or, a third 9?

    I would also like to see the serum Vit D levels of each individual participant, so you could compare those who contracted a UTI versus those who didn’t, those who contracted more than the average versus those who contracted less than the average. Averaging everything out skews the effect, one direction or the other.

    Think of all the people you know and work with, are they really sick more than 3 times a year? From any cause, let alone UTI? I’m not buying it. I can’t remember the last time I had a UTI, let alone 3 or more in 9 months. I’ve been taking Vid D regularly for over 4 years, and haven’t had a single cold, or the flu.

    This calls for Raspberries, instead of Cheers

  6. MikeW Says:

    Dr. Linder’s eagerness to close the book on D supplementation isn’t shared by the study authors themselves. The last paragraph of the JAMA article makes it clear they realize the narrow scope of their findings:

    “In conclusion, we report that monthly administration of 100 000-IU doses of vitamin D3 did not reduce the incidence or severity of URTIs in healthy, predominantly European adults with near-normal vitamin D levels. Further research is required to clarify whether there is benefit from supplementation in other populations and with other dosing regimens.”

    The authors acknowledge that in another recent randomized controlled trial, Mongolian schoolchildren lowered their RTI incidence by 50% with only a 300 IU daily supplement. In that case, the D3 was added to milk served in school – whether that was first thing in the morning or later in the school day, I don’t know.

  7. Chuck Says:

    Well, I found it – 13 of 322 participants did NOT contract a UTI. 13 out of 322!

    What this tells me, is New Zealanders are not very healthy people, and must have very compromised immune systems. Or, do I just hang around a healthier bunch of people?

    This study proves nothing, one way or the other, to me. I’ll keep taking my Vit D every morning. I use the Carlson’s drops – might try putting it on my skin, in the crook of my elbow, instead of orally. Heard this might be more beneficial. I need to think about how to test this before I start though.

    Cheers

  8. David Johnston Says:

    I’ve been on A, D3 & K2 at ~7.30am for about half a year. It has without doubt improved my sleep. My family is currently in the middle of a shared cold with sneezing and stuffed sinuses, except for myself. I thought I might have mild symptoms two days ago, but it passed without incident. Before taking the morning vitamins, I would have expected to share in their joy.

    I was similarly immune when I used to travel internationally for work about once a month, to diverse places around the world. I did this continuously for about 4 years. After an initial breaking in period, I found I was broadly resistant to colds. My guess is that my immune systems was being exposed to a wider variety of bugs and so was better primed. The hell of permanent jet lag is not worth it though.

  9. charlie Says:

    @chuck; that is a pretty normal rate.

  10. David Says:

    As far as offering useful guidance to the average person deciding if they should take vitamin D supplements, it is useless:

    1. All subjects had normal vitamin D levels, not so for the average person
    2. Monthly dose is exactly the opposite of how an average person would take vitamin D
    3. As mentioned, it doesn’t rule out benefits, seen in other studies, by not even attempting to follow previously used successful protocols