Here is a music selection for the Sunday morning reflective crowd: Chopin's Ballade No. 4
And let's just get it over with: Vitamin D Supplementation and Depression in the Women's Health Initiative Calcium and Vitamin D Trial.
Okay, HUGE double blind randomized controlled trial. Over 36,000 women, randomized to placebo or 1000 mg calcium + 400 IU vitamin D3 daily for 3 years. Depression scores were measured via questionnaire (one I've never heard of, the Bernam scale) and antidepressant use (maybe problematic because different classes of antidepressants have varying uses, for example, TCAs are prescribed for migraines and chronic diarrhea, and SSRIs are used for anxiety) at baseline and several follow up points. In addition, a subset (828 women) actually had D levels measured during the trial. Beginning average level was 52 nmol/L which is about 20.8 ng/ml in the units I will typically see on a lab report form. After two years (and measuring a separate group of 400 some-odd people), the average level in the supplemented group was 28% higher than those who were not supplemented. (Assuming a similar 20.8 ng/ml starting point, two years of D supplementation increased levels to 26.6.)
Kinda scary that the average level of these women at the beginning is just a tick north of absolutely deficient even according to the conservative Institutes of Medicine. 400IU does seem to prevent rickets, and it is similar to the amount of oral vitamin D one might be expected to get from eating cold marine animals. But it certainly doesn't make up for recommending the entire population avoid the sun at all costs.
In the end, supplementation with 400IU Vitamin D3 (and calcium) was associated with an increased chance of reporting depressive symptoms (the odds ratio was 1.16, though, not too terribly exciting) and not associated antidepressant use compared to placebo.
I'm not surprised, and I'm somewhat annoyed with vitamin D studies and depression at this point. Studies tend to use teensy levels or enormous ones (and please see that link for a round-up of the relevant D and mental health studies.) Why don't we find a middle ground between 400IU and 500,000IU (literally)?
I'll share my clinical experience, which, being anecdotal, may not be worth much. I've been more aggressive about measuring vitamin D in the last few years (as have the internists I work with), and I would say roughly 1/3 of the folks I measure (or have had a D measured in the past year by the primary care doctor) are absolutely deficient. Meaning below 20 ng/ml. Levels between 10-15 are common, but I've seen 4s and 8s as well. The super low folks have tended to have a "sick" look: pale, circles under the eyes, bloated, tired. (Though not everyone who is pale and tired has a low D by any means!) If I had to guess from just looking at them, I would think they might be fighting a cold or were hypothyroid. Most of the time, the thyroid function is absolutely normal.
Most of the folks I see have depression, and typically some sort of resistant depression, and I would say 99% of people come to me having already been put on psych meds of some kind. It's a bit hard to generalize, each patient has his or her own particular circumstances, character strengths, education, and external stressors… but I've figured out that some long-term patients with ultra-low vitamin D finally responded to all the psychiatry mucking around (bolstering supports, lifestyle interventions, therapy, medication adjustment) after the D was corrected. Shorter term patients have looked better and done better since getting D out of the basement. I've never attempted an isolated D intervention (which wouldn't be standard of care by any means).
So, while resistant depression generally requires a lot of adjustments in different areas of life to get trending a better direction and to get people more functional and happier, I surmise that replenishing super-deficient vitamin D may be one of those adjustments that ought to be done and likely won't hurt, and seems to be a piece of the puzzle out of place in resistant depression. Knowing the role of vitamin D in the nervous system so far as inflammation reduction and neuronal repair, there's a sensible mechanism at play as well.
Another interesting bit to the D replenishment story… in the past two years, four of my patients have developed high calcium with adequate D supplementation to bring the levels above 20 ng/ml. Three of them were found to be hyperparathyroid, and parathyroid tumors were found and later removed, resolving many of the original psychiatric complaints. The fourth patient is still undergoing a work-up but since a lump was palpated on the parathyroid, it is likely she has a tumor as well.
When I was in medical school, surgeons absolutely loved parathyroid cases because they were relatively rare. I don't know if four patients in two years is another anecdotal anomaly for me, but I do measure calcium along with vitamin D, and if the calcium pops above 10.2 with supplementation, I'm very quick to refer the patient back to the primary care doctor for further work-up. Having seen so many cases so recently, I wouldn't recommend supplementing a super-low D (particularly below 20, which is low enough that hyperparathyroidism can be masked by the low D level) aggressively without measuring calcium along with it. If you have normal levels (say 30 or above) moderate supplemention of 1000-2000 IU daily is probably fine, because if you had hyperparathyroidism, you would already know it, but keep measuring.
According to UpToDate.com, the psychiatric symptoms of hyperparathyroidism "...include lethargy, depressed mood, psychosis, decreased social interaction and cognitive dysfunction." This seems consistent with your experience.
ReplyDeleteEven in sunny Arizona, I pick up many cases of vitamin D deficiency. The dermatologists have scared us away from the sun.
-Steve
What is interesting to me was that the mnemonic for hypercalcemia is, of course, "stones, bones, groans, and psychiatric overtones." Therefore I attributed the psych symptoms (I've seen very prominent attentional difficulties, fatigue, irritability, and depression) to the hypercalcemia, which those with low D are protected from (can't get calcium out of the bones without D and PTH). But it would make sense that a hormone like PTH might cause symptoms all on its own.
DeleteCorrelation does not equal causation!!!!! The kidneys set the blood levels of Vitamin D. Low levels of vitamin D could signify widespread soft tissue calcification as happens with people who cannot adequately rid their body of phosphorous. Phosphorous then gets in the tissues and magnetizes calcium to it and then there is too much cellular calcium which interrupts mitochondrial production of ATP causing fatigue and also the excess calcium makes nerves and muscles fire at too high an electrical charge which causes pain (fibromyalgia) and too much firing in the brain (sleep disturbance). People need to give the body/kidneys some credit for knowing what its doing. White people have been bred for thousands of years to survive for six months in darkness in high latitude areas. Now white people live in latitude areas too low for their ability to expertly absorb vitamin D, and hence they absorb too much calcium and with the particularly acid diet consumed today which brings excess calcium into soft tissues, there is widespread danger of soft tissue calcification. Low Vitamin D is indeed associated with depression, but that is because, low vitamin D is an indicator of widespread soft tissue calcification. The kidneys are excreting extra D and keeping the blood levels low on purpose, because the more D you have, the more calcium you absorb and if your tissues are almost dead from too much calcium inside, the kidneys keep it out of the blood to save your life. People, please read up on soft tissue calcification. Also, the D absorbed from the sun needs magnesium to convert it into Cholecalciferol (D3), so a low level of vitamin D could also indicate a severe magnesium deficiency which is all too common in cultures where not enough vegetables are consumed. And here in the US, with corporate farming, even if enough veggies are consumed, one could still be magnesium deficient as most of the magnesium has been leached out of the soil through corporate farming practices and the vegetables grown here are deficient in this very important mineral that performs over 400 enzymatic reactions in the body. Magnesium also produces Calcitonin a hormone that keeps calcium in the bones and prevents it from getting into the soft tissues where it should not be.
DeleteSo if there is low D, it is probably supposed to be low. Muscle weakness can be caused from too much calcium in the cells which interrupt mitochondrial ATP production. Thank you Emily Deans for pointing out that low D protects people from hypercalcemia.
Studying for step 2 now, so a good time to review PTH, Vit D, etc. From my exposure to MD blogs, many docs are on the same page regarding the levels used in this study. Can't wait for some more reasonable dosing data to come out!
ReplyDeleteYeah, no kidding. The largest observational study done so far was the Cooper clinic study (earlier this year or last year). But observational ain't all that helpful. I was looking into the low D/high PTH connection… turns out with inc. PTH and calcium the body may convert more 25-0H vitamin D to other forms to reduce calcium uptake from the gut, so hyperparathyroidism seems to cause low vitamin D3 when measured as 25-OH (standard). Therefore it would make sense that a population with low vitamin D will have, statistcally, a few more hyperparathyroid folks in there. But 4 in two years seems excessive (I think I might have had one person before??). And, actually, just remembered a 5th patient who just showed me the second set of labs… D went from 12 to 32 or so with 4000 IU daily in 3 months, but calcium went from 8s I think to 10.7.
Deleteand good luck on the step2!
DeleteIn my opinion, D3 should not be given to patients without some K2 Mk4 too. Not K1 or K2 Mk7 (found in fermented foods), but the Mk4 form in particular, because that form is the only one that tells calcium to go to the right places to the body, and not the arteries or anywhere else. There was another research published recently whining that D3 creates arteriosclerosis because of calcium, but in reality, Western people are simply deficient in K2 Mk4 (mostly found in any large quantity in insects that we stopped eating eons ago). I personally get my D3 with K2 Mk4 for that very reason. Might be something to look at.
Deleteeat gouda and Edam cheese or Natto. All are high in K2. Gouda and Edam cheese taste better and are easier to find than the Japanese Natto.
DeleteIn my practice I have also seen more thyroid and parathyroid issues than earlier in my career.
ReplyDeleteThyroid and parathyroid issues may also be increasing due to the more frequent use of dental X-rays. Vitamin D may just be a confounder!
It would make sense that dental x-rays could be causative of thyroid/parathyroid issues (I'm assuming you saw the meningioma study earlier this year?) despite the low dose… I'd love to see some data. Most autoimmune conditions have increased since the 1960s, as far as I know. Dental x-rays may be one factor, but there may be others, like general use of tylenol, increases in vegetable oils (speculation only!), reduced exposure to our "old friends" the helminths, commensals, and pseudocommensals.
DeleteThe meningioma study claimed that routine bitewing radiographs were associated with a higher tumour incidence than panoramic radiographs.
DeleteFirst off it relied on the patients' memories. This is as reliable as the dietary studies wherein people report how often they've consumed, let's say, spinach on a weekly basis over the previous 20 years. In fact, that information would possibly be more accurate than remembering what sorts of radiographs were taken at a dental office.
I would give an educated guess that intra-oral films of which bitewings are an example, are inherently more uncomfortable and memorable to a patient than extra-oral radiography, namely the panoramic radiograph.
Secondly, a panoramic radiograph requires a huge field of exposure. The film (because this was a retrospective study, pre-digital) is large and the entire lower head is exposed to radiation.
Bitewing radiographs are tiny by comparison, comprising only of the upper and lower posterior teeth in occlusion.
At first I thought someone had made a huge typographical error. Maybe they did.
One's retrospective memory of having x-rays might, indeed, be affected by the fact that you've been diagnosed with a brain tumor, of course, leading to substantial recall bias. It would be nice to see some prospective data but who is that organized. Sweden, maybe?
DeleteAgree entirely on the issue of the range of Vitamin D used for supplementation. I think that it is fairly obvious that the experts on Vitamin cannot even agree on the MDR at this point despite many large studies. I started checking Vitamin D levels about 15 years ago after I encountered a case of spontaneous fracture of his hip due to Vitamin D deficiency in a person drinking large quantities of Vitamin D fortified milk. My experience with it over the years suggests that independent of sun exposure there is a wide (order of magnitude) difference in response to supplementation and that is probably the reason for conservative recommendations. It is also the reason why supplementation without levels (recommended by some health plans as a cost saving measure) – is a bad idea.
ReplyDeleteI couldn’t think of a possible brain mechanism that Vitamin D that would treat depression unless we are talking about the chronically ill appearing folks who are clearly in the deficient range. I even read through Feldman, Pike, and Glorieux’s tome on Vitamin D. I recently came across this interesting blog post on Vitamin D receptor, the renin angiotensin system and reactive oxygen species suggesting a possible immunological/inflammatory response:
http://www.nephronpower.com/2012/08/topic-discussion-vitamin-d-receptor-and.html
I think that there is a also a statistical problem when looking at a very prevalent condition like Vitamin D deficiency and suggesting that it correlates with any other condition with an even moderate prevalence like depression. The science looking at that association has to be very sound.
Yeah. I've had an older patient develop kidney stones on 1000 IU daily. I agree that supplementing without levels is shooting in the dark, though if you rely on sun alone you are probably fine. Since I mix up some very mild sun exposure in the summer with supplementation in the winter, I do check my levels. Agreed about matching up prevalent conditions, but now most of the obervational studies have shown a consistent trend, including the rather large Cooper clinic one.
DeleteFrankly when I read some of these NHS and WHI studies, I'm always amazed at some of the backflipping they do to get data all over the place. It's as if a lot of it wasn't planned out before, but they grabbed random data when they could and come up with papers about it after the fact.
Two years ago I started supplementing with 5000 IU of Vitamin D per day. As of last week, my blood level was 41. Prior to starting the D supplementation I had been on over a dozen different antidepressant meds for dysthymia for the last 30 years - they would work for 6 months and then stop. It went away with adequate D, along with my chronic joint pain, chronic diarrhea, bleeding gums (my toothpaste would be pink every night), chronic sinus infection, and the dozens of various sized lipomas that had appeared over the years have reduced in size by 1/3 to 1/2.
ReplyDeleteI had been taking daily multivitamins with the homeopathic dose of 400 IU for decades.
In due respect, it seems that you are confused by the word "homeopathic"! This study has NOTHING to do with homeopathy. Nothing at all.
ReplyDeleteVitamin D is a vitamin. Legally speaking, homeopathic medicines are drugs, primarily OTC drugs.
To learn something about homeopathy, I invite you to my website at www.homeopathic.com and to an additional collection of articles I've written at the famed Huffingtonpost: www.Huffingtonpost.com/dana-ullman
It's possible you don't understand sarcasm.
DeleteZing!
DeleteAlso, despite my sister being a card-carrying homeopath (don't know if they actually carry cards), my mother managed to birth an equal and opposite skeptic in myself...paindatabase.com/homeopathy
The cards are very very small. It's easy to miss them.
DeleteThey are in fact just a card wallet that carries the 'essence' of the card.
DeleteJust a counter anecdote.
ReplyDeleteI have a friend who is diabetic and quite fat. He got himself tested for a few things including Vit D and Thyroid panel. His Vit D is 4 and TSH is 6.1. The FreeT3 and T4 are around the middle of the range.
After reducing his carbs a bit, he has improved on his lethargy etc, and now he feels energetic. His liver is also in a bad shape. He says that he has the Gilbert Syndrome.
With all that I would have expected him to be very tired all the time and get infections frequently. But he reports that he hasn't been sick a day for at least last two years.
I don't know how to explain this :-). Anyway he is going to supplement 60000IU Vit D weekly to get his level to 30-40 on my recommendation.
The diabetic's D is probably low because he is suffering from magnesium deficiency and has soft tissue calcification. Diabetics, of course have higher blood sugar than normal and that causes an acid condition in the body which is buffered by pilfering calcium from the bones since calcium is an alkaline mineral, so soft tissue calcification is very common in diabetics. Your diabetic friend should be taking magnesium supplements (mag chloride or mag citrate/ mag oxide is only 4% bioavailable) and as I mentioned earlier, w/o magnesium, vit D absorbed by the sun can't be converted into the cholecalciferol (D3) version that gets put in the blood. So magnesium supplementation will help with vitamin D absorption and also help prevent soft tissue calcification which causes high blood pressure, hardening of the arteries/arteriosclerosis/atherosclerosis, heart attack, kidney stones, stiff joints, neuropathy pains and numbness (too much calcium gets into the small vessels in the toes and causes too high electrical firing which causes pain and then the calcium finally packs in the cells so much that it cuts off all electrical firing altogether and then their is numbness. With diabetics, you should worry about getting them magnesium supplementation (600mg/day) and not worry about vitamin D or calcium. I should know, I have had type 1 diabetes for 32 years and I supplement with A, B complex, C and Magnesium Citrate. I have very low D levels, but I have no muscle weakness and walk 2-4 miles every day. In fact if I take any amount of D or calcium or dairy products at all, I get sick and have bad muscle pains and become restless and cannot sleep. Vitamin D is not good for everyone. Also I am very white with very light blue eyes. I am genetically engineered to maximize my D and calcium absorption. How do you think people lived up in Scandinavia for thousands of years w/o all these supplements???? D and Calcium are at best overrated and at worst causing health problems that cause the early deaths of thousands and thousands of people. The two supplement cornerstones of good health for most people are Magnesium Citrate or Chloride and Vitamin B complex. Without these two, you cannot absorb/metabolize the rest of the supplements anyway.
DeleteEmily, nice to hear new experiences from D3 correction, I remember you answered me earlier that D3 had no use in depression in your practice. It seems D3 can exarbate certain underlying med conditions too, like probably magnesium deficiency as well adding to your parathyroid experiences.
ReplyDeleteMatthew, I had similar experiences with bleeding gums, joint pain and even with Crohn's disease. Getting 25(OH)D into 40 ng/ml range basically cured my autoimmune condition for the most part, though it took some time. Not only inflammation in colonoscopy and obvious GI symptoms, but also lessened food intolerances too.
As I'm probably having 2000-4000 IU a day for some time to come, all knowledge on long term usage is very much appreciated.
In due respect, the above study has NOTHING to do with homeopathy or homeopathic medicines. I have no idea in what way you mean "homeopathic", but I can guarantee it is not the real or correct use of the term. It is a tad strange that you chose to use it and more strange that no one else above seemed to notice it.
ReplyDeleteA well known vitamin D researcher (who's name I am currently blanking on, doh,) uses the term homeopathic to refer to 400 IU doses of Vit. D to signify that it is a laughably small or inadequate dose. If you read a few articles at the Vit. D council you will run across it.
DeleteDr. Deans,
ReplyDeleteI first just want to say I really enjoy reading your blog. I work in psychiatric research and have a very holistic/nutritional based view on mental disorder as well, which is hard to find in this profession! So thank you.
I found this post very interesting as I was just recently diagnosed with a Vitamin D deficiency (who isn’t, right?) I’ve been searching for an explanation (or at least a partial one) to years of depression, anxiety, and increasing muscle pain and weakness, and when I got tested for this I was hoping it could be an ‘Aha!’ moment for me. However, I’ve been having great difficulty taking Vitamin D supplements. My doctor gave me prescription D2 (50,000 IUs), but after researching how D3 is a more bioactive form thought I could get my levels up quicker, so I bought an OTC supplement. My problem is I can’t take Vitamin D without getting terrible headaches. No matter what the dose, different brands, with or without food, with magnesium (which I’ve researched can cause the headaches as Vitamin D uses magnesium, but the mag irritated my stomach so probably wasn’t on it long enough to notice if there was a benefit.) I can’t seem to find any research linking Vitamin D supplementation and headaches (if anything, research shows the opposite) and my doctor can’t seem to make sense of it. I wasn’t sure if you have any insight on this matter.
California Dreamer, your vit D is low on purpose!!! Your kidneys are making it so, because you already have soft tissue calcification which is dangerous, so your kidneys are excreting any D so you don't absorb more calcium which can kill your cells and kill you! that is why you are having headaches. Taking the D causes you to absorb more calcium and you already have too much in your system. The calcium causes too high electrical firing in the cells and contractions in the muscles and voila a bad headache. I have the same problem and I avoid D and calcium and dairy products like the plague. Stop taking the D!!!!
Deleteand when you take magnesium (get the book, the Magnesium Miracle by Dr. Carolyn Dean), take either Solgar brand Magnesium Citrate (each tablet is 200mg), but I suggest letting your body get used to it by taking 1/4 (50mg) to 1/2 tablet per day to start, sort of like how you gradually warm up a person who has hypothermia (you don't take them to 98.6 immediately because it will shock the system/ even if thats the right temp for them eventually) so take a very small amount for a few days then gradually work your way up to 400mg day of magnesium which is the RDA for normal people. If you have a chronic illness and /or are diabetic, then the RDA is 600-800mg. Also when you have more stress, you can take more, or if you eat a lot of meat, as meat requires extra magnesium for metablolization.
Another good magnesium to use to start out with really small doses is Trace Minerals Research Ionic Magnesium. Its liquid magnesium that you can put in orange juice or other juice (it tastes bad). 1 dropperfull equals 100mg, so you can start by putting in just a few drops and really control how much you take if you are sensitive to begin with. This formula is Magnesium Chloride solution and very easily absorbed by even the most sensitive of stomachs.
Another type of magnesium to try is transdermal magnesium which you rub on your skin (and DO NOT eat) Ancient Minerals is the best brand of transdermal Magnesium oil.
You can also take Epsom Salt (magnesium sulfate) baths (2C to a bath for 30 min) which is a good quick way to start getting magnesium in your body.
Good luck and stay away from vit D, calcium and dairy products until you have all the excess calcium cleaned out of your cells.
You might also try reading two good books on soft tissue calcification. One is called "Calcification: The Aging Factor" and the other is called "The Calcium Lie"
Good Luck!!!!
I'm lucky here; before I supplemented Vit D3 I had an optic twitch that went away in midsummer, was worst in late winter.
ReplyDeleteIt went away when I supped D3, came back eventually whenever I stopped.
That twitch is my spirit guide in the Vitamin D quest.
I want one of those Vit D spirit guides. Who wants to pay to get lab work done all the time?!?
DeleteThe title of this blog post, btw, is the best. Homeopathic indeed. I want someone to make some better rules about who gets to study what and get paid for it.
Hi Emily. So I met you AHS 2012 and came up to see you after your presentation. So my wife lowered her dosage to 25mgs of Zoloft. We're trying to get her off of it before we conceive. I started reading up on this program called The Road Back. It's basically a program (Online Book) that helps patients detox with "Natural Supplements" from taking a variety of different drugs for depression and anxiety. They recommend taking JNK, Relax Day and Relax Night with Melatonin. I have her supplementing with 5000iu's of Vit-D for the time being and it's only been 2 days. She's mos def deficient in Vit-D. I'm not even sure if you can even recommend anything due to legal constriants but I would love to hear your approach if you were to try and detox someone from taking Zoloft for 11 years! Any info is GREATLY appreciated!
ReplyDeleteYou need to get your wife on B6. Zoloft is an SSRI Serotonin Specific Reuptake Inhibitor. It keeps Serotonin in the synapse between brain cells (neurons) so there will be more of it for the cells to have. This would suggest a serotonin deficiency which can occur with not enough B6 since B6 is one of the main things used to produce serotonin and dopamine. But since all Bs in nature are found together and taking one without taking the others will cause a deficiency in the others, it is best to take a good B complex vitamin. I recommend Country Life Co Enzyme B Complex. Its a highly absorbed vegan capsule. It is usually sold at stores for around $50 for 240 (you take 2/day so this is a 4 month supply), but you can get the same bottle for around $30 on Vitacost.com.
DeleteHow is your wife supposed to have enough serotonin in her system if she is deficient of the chemicals (B6) needed to make serotonin????
I would also suggest 10,000 IU vit A (which is the RDA), 500mg 2-3x per day of Vit C, and 400mg/ day of Solgar brand Magnesium Citrate (400mg is the RDA, but slowly build up to it). In the book, the Magnesium Miracle by Dr. Carolyn Dean, it says that magnesium helps with anxiety/depressive disorders and also helps to prevent cerebral palsy from occurring as Magnesium deficiency in mothers has shown to be linked to increased births of babies with cerebral palsy. Also magnesium supplementation helps prevent preclampsia (high blood pressure in pregnant women)
I have Genetic weepy Depression since long, I am taking Cipralex 20 mg
ReplyDeletemy Questions 1. which product of Vit D 5000 IU will be beneficial 2. which product in Magnesium will be best besides this which supplement will be better 3. I have Gas ie Flatulelence so what supplements will be better is this causes Depression?
Thanks for your help Awaiting Your kind Advice.
MSK