Vitamin D Benefits: Hope or Hype?
By Michael Smith, North American Correspondent, MedPage Today
Published: November 27, 2011
Vitamin D is good for what ails you. Or at least that's what patients and doctors might conclude if they read only the headlines.
In the past few months, deficiency in the substance has been linked to chronic obstructive pulmonary disease, tuberculosis, spinal inflammatory diseases, age-related macular degeneration ... and the list goes on.
On the other hand, taking high doses of vitamin D didn't help patients with multiple sclerosis, MedPage Today reported, and it was of no benefit in reducing left ventricular mass in patients with chronic kidney disease.
But overall, vitamin D gets pretty good press. The trouble is that hard evidence to back up the vitamin's benefits is lacking, according to Clifford Rosen, MD, of the Maine Medical Center Research Institute in Scarborough. "There's no data," Rosen told MedPage Today. "It's all weak association studies."
Benefit Beyond the Bones
At the American Heart Association meeting earlier this month, several studies suggested associations between low vitamin D and various aspects of heart disease.
But as one observer said at the time, there are no clinical trials yet that show improving vitamin D status does anything to reduce cardiovascular risk.
One study, the Vitamin D and Omega-3 (VITAL) trial, may shed some light on the issue. It is a randomized trial that is enrolling some 20,000 patients to see if daily vitamin D supplements prevent cancer and cardiovascular disease.
It will be one of the few randomized trials — if not the only one — to look at the issue directly, according to JoAnn Manson, MD, of Brigham and Women's Hospital in Boston, who is the principal investigator.
Although other randomized trials have produced evidence for a vitamin D benefit in several important clinical categories, Manson told MedPage Today it was mostly as an afterthought.
"Many of the randomized trials people have heard about were trials designed to look at the effect of vitamin D on fractures and falls," she said, with other effects as secondary outcomes.
It's in the nature of statistics, she pointed out, that if researchers look at enough outcomes, some will be significant just on the basis of chance.
The vast mass of the evidence for any kind of nonskeletal benefit is observational, and therefore suspect until confirmed by a properly designed, randomized trial, Manson said.
Among other things, a host of confounding factors — obesity, poor nutrition, lack of exercise — might play a role. No matter how carefully an observational study is done, she said, confounding is always possible. "Correlation does not prove causation," Manson reminded.
She noted that randomized trials have demolished observational evidence many times in the past, notably in the cases of such former fads as beta-carotene and selenium.
According to Rosen, there is reasonable evidence that improved vitamin D status leads to better bone health and some evidence that supplements reduce all-cause mortality in elderly women.
For almost everything else, he said, hard evidence is missing.
Biologically Active D
Measuring exposure to vitamin D is relatively easy — it's a simple matter of serum levels of a compound called 25-hydroxyvitamin D, or 25(OH)D, Rosen said.
But the relationship between circulating 25(OH)D and the active form of the vitamin, 1,25-dihydroxycholecalciferol, is not clear. It's entirely possible, he said, to have low levels of 25(OH)D and yet have a perfectly adequate amount of the hormonally active form.
Indeed, Manson said, the Institute of Medicine (IOM) recently estimated that the average requirement of 25(OH)D is really only 16 nanograms per milliliter — a level that would in most cases ensure adequate amounts of the active vitamin.
"It's extremely variable," she noted, "and there is much that isn't known about vitamin D and metabolism."
"So the tissues and cells may be seeing adequate amounts of biological active vitamin D and adequate stimulation of the vitamin D receptor even in those who have lower blood levels," she said.
So the question of how much vitamin D is enough is a vexing one. But doctors and their patients still want an answer.
The IOM last year released new guidelines for vitamin D, which say that healthy people should aim to have at least 20 nanograms of 25(OH)D per milliliter of serum.
That can be achieved, the IOM said, by taking 600 IU a day of a vitamin D supplement if people are between ages 1 and 70, and 800 a day if they are 70 or older.
Manson, who along with Rosen was part of the IOM panel, said that "relatively modest amount" of vitamin D will keep 97.5% of the general population in good bone health.
And, she noted, the IOM really was only concerned about bone health, because there's such a dearth of evidence for benefits in other areas.
But even if there's no evidence for a benefit, is there any harm in taking a bit extra? Well, possibly.
One of the functions of vitamin D is to regulate calcium and phosphorus; too much can lead to hypercalcemia. The IOM set the tolerable upper limit at between 2,500 and 4,000 IU per day, depending on age.
The institute also cautioned, Manson said, that there is some evidence of a U-shaped curve for vitamin D — too little is bad and so is too much.
In particular, the IOM reported that, although the evidence is weak, more than 4,000 IU a day of the vitamin might increase the risk of cardiovascular disease, some cancers, and all-cause mortality.
"There's no evidence that more is better, so why use more?" Rosen asked.
On a day to day basis, most people can ensure they have enough vitamin D by eating certain foods – fatty fish like salmon, for example – and taking a multivitamin, Manson said.
But there's no need to screen the healthy population for vitamin D levels at least until there's more evidence that it matters, the IOM concluded.
On the other hand, the Endocrine Society has called for regular screening for groups at risk for vitamin D deficiency such as the obese, African Americans, and pregnant women.
- - - Interesting comments by readers, many of whom are Doctors - - - - - - - - - - - -
margaret swartz - Nov 28, 2011
Interesting that nothing was mentioned about D being the answer for many misdiagnosed "depressed" individuals, nor that RARELY is anyone getting an "overdose" of D, and most individuals are very deficient. Also, if the Journal of Orthomolecular Medicine was indexed and referenced, you'd find that most-if not ALL-vitamins and minerals, plus hundreds of supplements have already been clinically proven for efficacy for years.
Bonnie Camo MD - Nov 28, 2011
I am glad to see that the Vitamin D and omega-3 VITAL trial will be using Vitamin D3, the effective form of the vitamin, in a significant dose, 2000 iu, unlike the study allegedly showing vitamin D was of no benefit in reducing left ventricular mass in patients with chronic kidney disease, which used a synthetic version of the much less effective form, Vitamin D2. How many other useless trials have been done using ineffective forms of vitamins so that it can be claimed that they have been tried and found useless? For example, the recent study claiming to show that Vitamin E causes prostate cancer, which used synthetic dl-alpha tocopherol. Vitamin E consists of 8 different compounds, including d-alpha tocopherol. (The "l" part of synthetic dl is useless.) Previous studies have shown that it is gamma tocopherol, not alpha, which has an anticarcinogenic effect. Giving massive amounts of synthetic dl alpha tocopherol is known to actually deplete the body of gamma tocopherol, thus producing the predictable rise in prostate cancer, not caused by "Vitamin E".
Frank James, MD - Nov 28, 2011
As one of the investigators in the SELECT trial I must say that this article is wise in it's perspective. SELECT was a large (35,000 person) long (over 10 years) study to evaluate the effect of antioxidants on prostate cancer. There had been many small observational studies that supported the connection between vitamin E or Selenium in reducing cancer. There were some large well designed studies that also showed possible benefit but where design was for a different endpoint. The most difficult thing in recruiting participants for the study was in getting them to stop the current Vit E they were taking and be randomized into the study, many taking twice the dose that the study was to evaluate. The conclusion of the $117 million study are now well known, vitamin E dose not reduce prostate cancer and may increase it. Had I asked my grandmother before we did the study she would likely have said that to give people something they are missing may help but to use a vitamin in pharmacological doses rather than the dose we know to be needed physiologically will surely cause more problems than it solves. And she would have been right. Vitamin D levels look like a powerful predictor of disease, my own physician has me taking it, but honestly as pointed out here, the data is not in, the real studies to look at causality have not been done and the massive enthusiasm by both the public and many physicians is misplaced for anything but some well designed and financed studies of large enough populations for long enough to see if the impacts are useful and healthy or just more loss associations that generate vitamin sales without real evidence of benefit.
john simms - Nov 28, 2011
It is likely that vitamin D level is inadequate in most of the over 70 segment of the population. It may well slow the development of Parkinson's Disease by acting as an antioxidant when it is used at above about 1200 units/day. I look forward to the results of the double blind study. Until then it would be prudent to take about 2000 units of vitamin D a day and to monitor the concentration in the blood. The cost/benefit is likely to be favorable. By the way, who is benefiting from the vitamin D "Hype"? Not the drug companies or the medical profession or the multivitamin suppliers.
KWightman, ND - Nov 28, 2011
On average, while measuring Vitamin D3 in employee populations in the southern tier of states, I have noted they are at least 75% deficient in Vitamin D3. Meaning, their serum D3 levels were below 30 micrograms/mL. Some people were as low as 8 ug/mL. Relating this to clients in my practice, I recommend at least 5,000 IU D3 daily. This helps bring their serum D3 levels up to at least 70 ug/mL. At this level problems with immune function, glucose metabolism, stress handling, depression, and bone resorption all improve. As the article represents, this is all part of a whole body approach that includes a balanced diet, exercise, and other more targeted nutritional therapies. All of the research published on D3 can be found listed on http://www.vitamindcouncil.org . The pharmaceutical companies will never fund the type of research referenced in your article because that would result in a drastic loss of revenue as people change to a vitamin or prohormone over something like Prozac. The industry has stepped up its attacks on the efficacy of D3 supplementation directly proportional to the huge increase in the public's awareness of the benefits achievable from D3. If I had the time to waste, I would research the MD's and researchers referenced in your article to see who supports their research and who donates to their hospitals.
Anon, MD, MPH - Nov 28, 2011
No randomized controlled trials for cigarette use either.... "just weak association studies." Perhaps we should back off on our recommendations not to smoke as well. Since a couple of hours of sunshine cause our bodies to produce 20,000 IU of Vit D, and ours is the first generation of sunscreen wearing cubicle creatures, and in some studies 80% of those in the US are Vit D deficient, it seems premature to sound a warning about Vit D supplementation. __Perhaps the decreased BP in people on Vit D and Calcium threatens the antihypertensive medication sales of your advertisers._
m t cicero - Nov 28, 2011
Dr James, Your insights are much appreciated. Unfortunately you face an uphill battle against the 'alternative medicine' crowd. These latter day alchemists will never be dissuaded from their faith in the strictly anecdotal.
carol houde - Nov 28, 2011
It certainly seems to live up to the hype at least anecdotally. My sister who works indoors all year, and covers herself when she is in the sun is likely Vit D deficient. She always complained about being tired, and so did her coworkers. Certainly, they have stressful jobs and they hardly ever saw the sunlight. When I suggested they try Vit D, they did. ALL of them exclaimed how much better they felt after just a few days. Could that be placebo effect? Maybe so. They still take it and feel fine.
margaret swartz - Nov 28, 2011
Great post! I concur completely!!
Dr. Dean Raffelock - Nov 28, 2011
The research on D3 by Michael Holick, M.D. looks quite good. The way detractor studies are put together these days wreaks of a concerted effort to try to demonize vitamins and minerals but give many dangerous or unnecessary drugs a free pass. In this case, recommending D3 levels far below a range that would elevate D3 into the mid to upper normal lab ranges seems reckless. Go to John Cannell's Vitamin D Council website for more reliable information. It seems ignorant to take evidence that D3 helps to prevent many disease processes and then expect D3 to CURE the disease. Nothing scientific about that...just an effort to discredit vitamins until Big Pharma can pay off enough corrupt politicians to help it take over and control the industry. Then Voila! new studies will be revealed showing the marvelous effects of these same vitamins and minerals.
Dr. Dean Raffelock - Nov 28, 2011
Just like in the ridiculous "Did Alternative Medicine Kill Steve Jobs" article, the title of this article is similarly biased and histrionic. As a clinical nutritionist for the past 35 years, I can tell you that the average Therapeutic daily dosage for D3 in patients not receiving much sunshine is in the 6000-12000 IU liquid drop range not 600 IUs. This is often enough to help patients who averaged 2-4 bouts of colds and flus per year have none. I certainly don't need yet another study for me to know that. What's next? D3 is discredited because it can't reverse highly advanced glioblastomas?
Narayanachar S. Murali, MD, FACP, FACG - Nov 28, 2011
Time and better research will show that low Vitamin D is a very reliable marker for both acute and chronic inflammation. It is a negative acute phase reactant. Outside the setting of true deficiency states, giving Vitamin D as a standard of care whenever low levels are detected may not help and is a simplistic approach to treating a host of chronic inflammatory states. At best you may improve blood levels of Vitamin D! The Vitamin D supplementation in high doses as a panacea has truly become a cult thing now!
toni bark MD LEEDap - Nov 28, 2011
it's unfortunate that Clifford Rosen has major financial conflicts of interest on this one along with many of those on this IOM panel. It used to be that the IOM was one place where there were no COI, but this has changed greatly over the last decade. when those on a panel to assess vitamin D, a non-patentable item, is on the payroll for industry making either patentable osteoporosis drugs or patentable synthetic forms of vitamins, their legitimacy is squashed.
Lin Memm - Nov 28, 2011
I am heartened by the responses to this misleading headline. It seems no matter how many "studies" come out that try to discourage the use of vitamins so that big Pharma can prevail, more and more people are not buying into the propaganda. There is no supplement that has undergone more testing than Vitamin D. In case after case, it has been proven that people with higher vitamin D levels not only have more energy, but they have less disease. And I am not sure where how they made the conclusion that Vit. D does not help MS patients. I have a friend with MS who got her life back after she ditched the drugs and opted for high doses of supplements, including Vit D. It was not a placebo effect. She even has brain scans that show a vast improvement.
tom hennessy - Nov 28, 2011
One curiosity no one has been able to explain is WHY when there is increased iron there is decreased vitamin D but when one treats the iron by removal the vitamin D is NOW normalized ? In age-related iron accumulation one can assume the SAME thing would happen ? Logic. "The results reveal that the low serum 25-OHD concentration in patients with hemochromatosis is directly related to the extent of iron loading and it is improved by venesection therapy." "Evaluation of Growth, Puberty and Endocrine Dysfunctions in Relation to Iron Overload in Multi Transfused Indian Thalassemia Patients." "92.8% had low levels of Vitamin D"
rachel higgins - Nov 28, 2011
What is the relationship between Vitamin D and Crohns disease? I have heard that you need 10,000 units per day to help crohns
SDRInc, md - Nov 28, 2011
I made a file of this excellent paper by Dr. Caroline Wagner from University of South Carolina regarding the effects of Vitamin D in pregnancy for mothers and their baby. i would like very much your thoughts or the bloggers opinion on this paper. Thank you. http://www.medpagetoday.com/tbindex.cfm?tbid=19847
bert kummel - Nov 28, 2011
The "experts" obviously have not read the European literature and the importance of PTH determination. About one third of my patients have elevated PTH levels and "normal" (per Institute of medicine) D2 levels.
Karen Vaughan, L.Ac., Registered Herbalist (AHG) - Nov 28, 2011
The problem with the recommendations of 600-800 iu per day is that it only correlates to bone health, not the more significant uses: cancer, diabetes, cardiovascular health, lower complications of childbirth, type 1 diabetes when given to children. It takes ridiculously little to prevent rickets, but higher levels to prevent recurrences of cancer. I rarely find that you can budge 25(OH)D levels under 10,000 a day iu- and that is based on sending my patients for blood testing. The lab looks at serum levels of 25(OH)D between 50-100 as optimum. In trying to get my on levels up, 10,000iu daily doses for 6 months failed to get me above 32 ng/ml. I had to go on 50,000 iu daily to get into the low 50s. That is twice the physiological dose (25-30k)that the body would make in a couple of hours near the equator. But I both sequester and use more D than many, so the right question isn't how much people should take but how much it takes to maintain their blood levels.
Anon, MD, MPH - Nov 28, 2011
SDRInc,md.. Excellent RCT reference with a dose response... could it be that Dr. Clifford Rosen stated that "There's no data" but didn't bother to do a literature search even within Medpage Today? hmmm. For yet another RCT... (and there are quite a few): Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586-91. On this issue the so called "alternative" crowd will be proven correct. I would caution my fellow MD's to make certain that they are well-read before taking a dismissive stance.
milton hare - Nov 28, 2011
I believe the medical-pharmaceutical alliance is going to resist the mounting evidence that Vitamin D reduces the symptoms of auto-immune diseases, cancer and other infectious diseases simply to protect its investment in much more expensive approaches to treating those same symptoms. The pharmaceutical giants in particular are loathe to admit that high doses of Vitamin D3 alone, administered with or without a prescription, can lower blood pressure and blood sugar, eliminate the pain associated with rheumatoid arthritis and slow a number of cancers to a crawl. This approach to treatment costs a few pennies a week, but the pharmacies will never sell their proprietary medications less than a dollar a pill. They do not benefit from Vitamin D3, but the patients certainly do. And the costly studies suggested? Who will fund them? Study up on D3 and you'll save your patients' money, and, their lives.
Dr. Dean Raffelock - Nov 29, 2011
Hot off the presses: http://newhope360.com/news/new-research- finds-optimal-vitamin-d-levels-reduced-risk-diabetes-52? cid=nl_npi_daily Gotta love the arrogance of m t cicero who thinks anything he doesn't agree with is anecdotal.
D. Hayden-Hixson - Nov 29, 2011
My mother suffered from Rickets as a child, scoliosis in her teens, preeclampsia and Vitiligo in her 20s & 30s, followed by Sjogren's, alopecia & Rheumatoid Arthritis after menopause. My reading of the Vitamin D literature leads me to believe my mother either inherited a mutant VDR gene or was always severely vitamin D deficient. Personally, as her daughter who also suffered from Rickets, scoliosis and preeclampsia, I suspect the first possibility is more likely. For the ~25% of people who inherit a mutant VDR, very different questions need to be asked about how much vitamin D is enough. In my opinion, this MedPage article is almost as damaging to their health as the IOM's recent report on Calcium & Vitamin D.
Harvey Grove - Nov 29, 2011
I am a patient of Dr. Holick for a long time (before Forteo). I am 84. I was referred to him with osteopenia. He ordered fosamax plus Ca 600 mg w vit D 400 iu, bid and rocaltrol 5,000 iu every 2 weeks. When Forteo was released it was added and fosamax was DC. I stayed on this regimen for 2.5 years. Then Forteo was DC and I remain on the Ca w Vit D and rocaltrol. All this time I also was on Omega-3, 1200mg qd. I know Dr. Castelli of the Framingham heart study and this August he suggested adding Vit K2, 100mcg qd after one of his patients went from osteoporosis for years to osteopenia after adding K2 to the Ca 600mg w Vit D 400m IU and Omega-3 1200mg qd. I have bone density pictures every year all these years. The K2 was added a short time ago (Aug, 2011) with approval of Dr. Holick. No bone density pictures were done since I started K2. I have no idea if there is any evidence of this on a bone density study as there have been none since about Mar of this year. I discovered my Omega-3 had a familiar odor that turned out to be COCONUT OIL. The company was called and they admitted it was in their Omega-3. As this is SLUDGE for the heart, I have no idea what this did to my heart. There is no FDA supervision of OTC products Dr. Michael Kline, cardiologist at BU Med Ctr (trained at the Brigham) now Chief of Coronary unit at BU says, at 84, I have the ECG of an 54 year old man. He followed me since I was 40 yrs old. He told me I was unusual as reading these ECGs is his speciality and he reads them ALL DAY LONG and teaches this subject.
Dr. Dean Raffelock - Nov 30, 2011
Interesting that Manson is the main expert quoted in this piece as she was part of the IOM committee that produced the new extremely conservative vitamin D guidelines. She also was recently seen in an on-line video cautioning against the use of all dietary supplements: http://vimeo.com/2771699 , and quoted in others such as Consumer Reports: http://www.consumerreports.org/health/natural-health/top- selling-vitamins/overview/index.htm.
Why people who have no training, knowledge, or clinical experience in the clinical nutrition area are quoted as experts is beyond me.
Except for most likely being paid by forces who hate the $ competition.
After all, why take an inexpensive nutrient when you can take an expensive drug.
Manson’s previous hard-line and tragically biased positions on nutritional supplements across the board creates high suspicion for bias at the outset, as she is the PI of one of the trials cited in this article.
It isn’t too hard to guess which way she hopes it comes out now is it?
Also of note is her quote, “It's in the nature of statistics, she pointed out, that if researchers look at enough outcomes, some will be significant just on the basis of chance.” Interesting that the sword never seems to cut both ways in how the media and the orthodoxy present the data on nutritional supplements. Apparently, if a “positive” or “useful” association is found in these outcomes it is likely just due to statistics and looking at enough outcomes. However, if the association is a “negative” one, then it must be “real.” Sometimes "double-blind" just means blind in both eyes.
LMyers - Dec 01, 2011
Life is short, art is long (Hippocrates). Physicians make decisions everyday that are not scientifically sound. To wait for science, is to often wait for a very long time. Many of us will be dead before that time. Science is great but too often an anchor preventing good medical judgment.
duewood ray - Dec 16, 2011
Epidemiology studies indicate vitamin D may help prevent Breast cancer.