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Vitamin D Deficiency: Time for Inaction (question mark)– Jan 2014

Vitamin D Deficiency: Time for Inaction?

GLOBAL ADVANCES IN HEALTH AND MEDICINE January 2013 • Volume 2, Number 1
Gregory Plotnikoff, MD, MTS, FACP, United States
Penny George Institute for Health and Healing, Center for Health Care Innovation, Allina Health Care, Minneapolis, Minnesota.
Dr Plotnikoff is an editor of Global Advances in Health and Medicine. Gregory.Plotnikoff at allina.com

In 1998, the British Medical Journal boldly stated in an editorial headline, "Vitamin D Deficiency: Time for Action."1 The urgency was clear: vitamin D deficiency was going undiagnosed and untreated in large numbers of people. Patients were at risk and suffering needlessly. A simple, extremely low-cost, low-toxicity intervention was readily available. All that was required was vitamin D advocacy.

In the 15 years since then, more than 20 000 articles have appeared in the national Library of Medicine database that correlate vitamin D deficiency with adverse health states, increased morbidity, and even increased mortality across the entire age spectrum and across nearly the entire spectrum of human illness. In fact, this pro-hormone called vitamin D is so important in human health that replenishment of vitamin D deficiency is likely to be the single most cost-effective medical intervention in North America and Europe.

Why then the call for inaction? In 2010, the esteemed Institute of Medicine (IOM) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium made the following three assertions:

  • (1) current evidence does not support non-bone benefits for vitamin D,
  • (2) 600 IUs of daily vitamin D3 intake ensures vitamin D sufficiency for 97.5% of the population, and
  • (3) all North Americans, with few exceptions, are already receiving enough vitamin D.2

To further support the call for clinician inaction, the IOM lowered the internationally established normal value of 25-OH-vitamin D from >= 30 ng/mL to 20 ng/mL.

The report's message was a simple reversal of conventional thought on vitamin D deficiency: time for inaction. And since this 2010 report, payers (both public and private) health systems, and subspecialty societies have affirmed the IOM's call for clinician inaction: Some have requested, or even demanded, that clinicians not assess a patient's vitamin D status. Some have blocked recommendations for vitamin D supplementation above the recommended daily allowance. For example, one large Midwestern obstetrics/gynecol-ogy group wrote to its partners,

‘’the protocol committee met yesterday and, based upon the ACOG [American College of Obstetrics and Gynecology] press release [on the IOM report], effective immediately, we will no longer utilize doses of Vitamin D greater than 1000 IU per day.... Patients that are currently on doses greater than 1000 IU per day should be advised to reduce their dosage or given the option to discontinue replacement entirely. Furthermore, Vitamin D levels will no longer be a part of our prenatal screen" (personal communication, July 21, 2011).’’

But are the IOM's recommendations truly evidence-based? Consider the irony that the IOM's recommendations on dosing and on the definition of a sufficient serum level were not based on what the IOM considered evidence: a meta-analysis of randomized, controlled data.

For example, the recommendation for a minimum serum level of 20 ng/mL came from one study of 675 cadavers in Germany that compared the serum level of 25-OH-vitamin D at the time of death to bone strength defined as the ratio of unmineralized to total bone mass.3 "Weak bones" were defined as a ratio of 2 or greater. The authors of this cadaver study concluded that 30 ng/mL (75 nmol/L) was the cutoff for vitamin D sufficiency as this level included no subjects with a ratio of 2 or greater. No subject with a serum level greater than 30 ng/mL had weak bones. The IOM disagreed with the authors and defined the cutoff as 20 ng/mL as only seven subjects with levels greater than 20 ng/mL had a bone mineral ratio greater than 2. The IOM committee argued that seven of 675 subjects is inconsequential. Many statisticians disagreed: they argued that the ratio of seven subjects over the denominator of 28 subjects with serum levels between 20 ng/ mL and 30 ng/mL is anything but inconsequential.

This cadaver study had additional problems: it only correlated a one-point-in-time vitamin D measurement, which can vary significantly over time, with bone mineral status that presumably does not vary significantly over time. This is a classic flow/stock mismatch error. The IOM did not address how this correlation study met their definition of evidence when literally thousands of other correlation studies did not.

At the same time, randomized studies already exist that document that optimal bone density is found at levels much greater than 20 ng/mL.4,5 Furthermore, a dozen studies with more than 40 000 participants have demonstrated that the 20 ng/mL level is not enough to prevent either fractures or falls, but higher levels do.6,7 Despite these studies, the IOM stated that there is no convincing evidence that levels higher than 20 ng/mL confer greater benefits.

The IOM also stated that most North Americans "with a few exceptions" meet the minimal goal of a serum level of 20 ng/mL. Who are these exceptions? The most recent Center for Disease Control and Prevention's National Health and Nutrition Evaluation Survey (NHANES) data demonstrates that nearly 30% of black participants had profound vitamin D deficiency with serum levels of less than 10 ng/mL.8 In a study of 10 646 fully insured healthcare employees (>90% white) in the upper Midwest, 30% had levels less than 20 ng/mL and 6% had levels less than 10 ng/mL.9

Although one IOM leader has put in writing that most people in the United States have a baseline level of less than the 20 ng/mL IOM recommendation,10 she continues to urge clinician inaction.11 The recommendation is that clinicians wait until results of the $20 million National Institutes of Health (NIH)-funded VITAL study (the VITamin D and OmegA-3 TriaL: www.vitalstudy.org) are published. In 2017, this study will report on prevention of cancer and cardiovascular disease after 5 years of daily placebo or 2000 IUs of vitamin D supplementation in 20 000 men (aged >60 years) and women (aged >65 years).

Here is one reason for clinician inaction: this NIH study's success requires clinician inaction. Participants must agree to be potentially randomized to placebo vitamin D for 5 years and to limit any additional vitamin D intake to at most 800 IUs per day. For this study to work, participants must not be tempted to increase dosing on their own. Clinicians must not measure and report on vitamin D status. And any clinician vitamin D advocacy and any positive media coverage are potential threats to the study's integrity.

The IOM report raises three profound political questions for clinicians to ponder.

  • First, are well-documented healthcare disparities due to institutional racism, as many claim, or due to overlooking the impact of vitamin D deficiency in minority populations?
  • Second, who determines public funding priorities?
    The most important clinical research question is this: If I document a nutrient deficiency and replenish it, does that make a clinical difference?
    But schools of public health do not ask this question.
    Even the $20 million NIH-funded trial gives a one-size dose to everyone whether they are deficient or not.
  • Third, when is vitamin D advocacy justified? Should we wait until 2017 and later for clinical trial evidence of a cause-effect relationship?
    Would it harm or benefit our patients to ensure a minimal level of 30 ng/mL?

The bottom line is this key question for each reader: Given the well-documented low levels of vitamin D in multiple populations including symptomatic patients and people at risk, and given vitamin D's low cost, low toxicity, and broad biological activity in every tissue as a pro-hormone, is it time for action or inaction?

Have too many clinicians answered with inaction?

As one wise mentor taught me, "Don't get mad . . . get data!" My advice: conduct "n of 1" clinical trials in your patients. Measure vitamin D status, replenish to at least 30 ng/mL, document any clinical improvement, and share the results with colleagues. Consider what role vitamin D status has on other interventions from acupuncture to Xeloda. We at Global Advances in Health and Medicine invite you to submit your compelling case studies.


  • 1. Compston JE. Viamin D deficiency: time for action. BMJ. I998;3i7:i466.
  • 2. Institute of Medicine of the National Academies. Dietary reference intakes for calcium and vitamin D. http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx. Accessed January 8, 2013.
  • 3. Priemel M, von Domarus C, Klatte TO, et al. Bone mineralization defects and vitamin D deficiency: histomorphic analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res. 2010 Feb;25(2):305-I2.
  • 4. Bischoff-Ferrari HA, Giovanucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006;84(i):i8-28.
  • 5. Bischoff-Ferrari HA, Dawson-Huges B, Orav JE, et al. Dietary calcium and serum 2-hydroxyvitamin D status in relation to BMD among US adults. J Bone Miner Res. 2009 May;24(5):935-42.
  • 6. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomized controlled trials. BMJ. 2009339^3692.
  • 7. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of non-vertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Int Med. 2009 ;i69(6):55i-6i.
  • 8. Ginde AA, Liu MC, Camargo CA. Demographic differences and trends of vitamin D insufficiency in the US population, i988-2004. Arch Int Med. 2009;i69(6): 626-32.
  • 9. Plotnikoff GA, Finch MD, Dusek JA. Impact of vitamin D deficiency on the productivity of a health care workforce. J Occup Environ Med. 20i2;54(2):ii7-2i.
  • 10. Manson JE. Vitamin D and the heart: Why we need large-scale clinical trials. Cleveland Clinic J Med. 20i0; 77(i2):903-i0.
  • 11. Manson JE, Mayne ST, Clinton SK. Vitamin D and prevention of cancer— ready for prime time? N Engl J Med. 20ii; 364-5): 85-7.

See also Vitamin D Life


Vitamin D also low in Europe
from DSM

2009 and later minimum recommended levels

Cadaver error - shown as a chart
IoM error  8% not just 1% see http://is.gd/iomerror8

see wikipage: http://www.vitad.org/tiki-index.php?page_id=2533
derived from Grassroots 2013
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Proof that Vitamin D Works has the following summary
Vitamin D prevents or treats 88 health problems
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Health Problem Treat
Reduction by Vit DRCT = Randomized Controlled Trial
   * = link to additional RCT
CT = Clinical Trial
149 to 142 mm Hg
HT risk reduced 10X
RCT*  *, 2400 IU.  100,000 IU*
When Vitamin D > 40 ng
Cardiovascular after attack T 32 % fewer deaths CT 1000 IU
Diabetes Type 1 P 85 % 12,000 kids, 2000 IU
Diabetes Type 2T 62 % RCT* CRP reduction, 4000 IU
Injection is far better - RCT *
RCT 50,000 IU/2weeks + probiotics
RCT 5,000 IU daily 6 months
Back Pain T 95 %
reduced 50%
5000/10000 IU
60,000 IU weekly
Influenza P 90 % RCT *, 2000 IU
Falls P 50%RCT, 100,000 IU monthly
RCT with Meals on Wheels 2016
Hip Fractures P 30 % RCT * 800 IU
Rickets P 98 % Turkey, 400 IU
NOT RCT, given to all children
Raynaud's Syndrome T 40 % RCT, visual scale, 20000 IU Avg
Menstrual pain P 76 % RCT, 7000 IU Avg,
70% reduction 2018
PMS reduced by half
Pregnancy risks P 50 % RCT, 4000 IU
C-section, unplanned P 50 % RCT, 4000 IU, small study
Low birth weight P 60 % RCT * 1000 IU of D2
TBP 60 % RCT, 800 IU
Breast Cancer P 60 % RCT, 1100 IU (2007)
Rheumatoid Arthritis pain T 40 % RCT, 500 IU, added to prescription
Cystic Fibrosis T 75 %
2nd study improved
RCT, pilot 4X fewer deaths 250,000 IU
RCT, pilot 8,200 IU
Chronic Kidney T 90 to 70 PTH RCT, 3500 IU,
Respiratory Tract Infection P 63 % 3 RCT, 4000 IU 1 year 2nd 2000/800 IU
20,000 IU weekly
Lupus T
zero flares
Pain reduced
Loading then 100,000 IU monthly,
RCT too
RCT 4,000 IU
Sickle Cell T Less pain
RCT, up to 100,000 IU/week
Leg ulcer healing T 4X faster RCT, 50,0000 IU/week, small study
Traumatic Brain Injury T 2X RCT, 20,0000 IU/day with progesterone
Parkinson's DiseaseT StabilizedRCT, 1200 IU/day
Multiple SclerosisP
95% were CURED
RCT, 7100 IU prevent pre-MS ==> MS
20,000 to 140,000 IU/day
Congestive Heart Failure T 90 % RCT, 1000 IU infants (also: Adults, not RCT)
Middle Ear Infection P 30 % RCT, 1000 IU infants
GingivitisT 88 %RCT, 2000 IU
Muscle in seniors T 17 % more muscle RCT, 4000 IU
Antibiotic use when >70y T 47 % RCT, 60,000 IU monthly
Infants tallerBenefit1 cm tall RCT, 50,000 IU weekly,
for 8 weeks while pregnant
Gestational Diabetes T Reduced 3X RCT, 2 doses of 50,000 IU
After Heart Attack T +6% ejection fraction RCT, 800,000 IU one time
Prostate Cancer T Fewer +cores RCT, 4000 IU (2012)
Asthma P   T Reduced symptoms RCT, 60K IU/month;
RCT 50K IU/week
Need good D at 4 weeks into preg.
Depression T Reduced RCT 300,000 IU injection
RCT 1500 IU helped Prozac
RCT 50,000 IU weekly, elderly
Low vitamin D
while breastfed
P All infants > 20 mg RCT, 5,000 IU
Fibromyalgia T Half of many still has FibroRCT, 30-48 ng
RCT 50K IU/week
Hives, Chronic T Reduced 40% RCT, 4000 IU added
CholesterolT Reduced 4 mg RCT, 400 IU + Ca
Weight Loss T lost 5 more lbs RCT, 2000 IU +diet +exercise
Gestational DiabetesP 40% RCT * , 5,000 IU
Chronic Obstructive
Pulmonary Disease
T 17X improvement CT, 50,000 IU weekly
RCT 100,000 IU monthly
Asthma T 1/2 Asthma attacks RCT >42 mg of vitamin D
Quality of Life (QoL) T Nursing Home QoL CT, 4,000 IU in daily bread
Death of Critically Ill
T 20% increase in survivability RCT 540 K IU loading than 90K monthly
Restless Leg Syndrome T Score 26 ==> 10 CT, Vitamin D dose size
not stated in abstract
Hepatitis-C T Aided normal drugs RCT 2.000 IU
Crohn's disease T improved when > 30 ng
2nd study fewer relapses
RCT 2,000 IU
10,000 IU RCT
Pre-term birth P 2.5X decrease, also: fewer
c-section & better Apgar
RCT 2,000 IU India
Cluster headaches T CH eliminated in 60% 10,000 IU, Mg, Omega-3, etc
Autism T 80% improved CT 300 IU/kg/day for 3 months
PreDiabetes T ~20% reduced RCT 60,000 IU/month
Weight loss:
Overweight and Obese
T 12 lbs in 6 months RCT 100,000 IU/month
Sarcopenia = muscle loss T 27% increase RCT 1,000 IU
Growing Pains T 60% decrease ~100,000 IU/month -NOT RCT
2nd study, similar results
Osteoarthritis pain T 60% decrease 50,000 IU/weekly - NOT RCT
ALS T helped 2,000 IU - NOT RCT, given to all
Vertigo T 3X reduction if raised > 10ng 600,000 IU load, then maint.
NOT RCT, given to all
Warts T 80% eliminated injection NOT RCT
60,000 IU/injection
Metabolic Syndrome P reduced 44% when VitD
increased by 30 ng
NOT RCT, given to all
Hay fever P reduced 48% RCT   1,000 IU for 30 days
Preeclampsia P Recurrance cut in half
3 RCT 3.6 X less likely if > 30 ng
50,000 IU every 2 weeks
4,000 IU daily
Blood cell cancer
Multiple Myeloma
T Survival 90% vs 50%10,000 IU/week
NOT RCT, given to all
Irritable Bowel Syndrome T Reduced3,000 IU spray RCT
Urinary Tract Infection P 50% reduction RCT 20,000 IU weekly
Mite Allergy P 5X reductionRCT 2,000 IU preg, 800 IU child
Perinatal depression
(depression near birth)
T 50% reduction RCT 2,000 IU for just a few weeks
Vaginosis T 10X reductionRCT 2,000 IU
Eczema T Reduced2 RCT 1,600 IU
Fatty Liver Disease
T Reduced RCT 20,000 IU weekly
Knee Osteoartiritis T Pain Reduced RCT 60,000 IU monthly after loading dose
Tuberculosis T Faster Recovery RCT single 450,000 IU dose
Stroke - Ischemic T Faster Recovery RCT single 600,000 IU injection
RCT single 300,000 IU injection
Sepsis T Reduce ICU and Hospital
length of stay by 7 days each
RCT 400,000 IU
Trauma deaths T 50% fewer deaths Vitamin D & Glutamine
NOT RCT, given to all
Hemodialysis patients T helped 50,000 IU weekly NOT RCT, given to all
Fatty liver - child T 2 X reduction RCT  Vitamin D & DHA
Fatigue T Reduced 100,000 IU single dose
NOT RCT, given to all
Sleep Disorders T Nicely treated RCT  50.000 IU bi-weekly
T RCT   Death rate cut in half300,000 IU injection
Infertile males T birth rate doubled RCT   300,000 IU + maint
Waist size T Waist size reduced 3 cm 100,000 IU loading + maint for 6 months
for those with Metabolic Syndrome
NOT RCT, given to all
Attention Deficient
Hyperactivity Disorder
T Reduced
RCT  3,000 IU for 12 weeks
RCT  50,000 IU weekly
Alcoholic liver cirrhosis T improved survival1,000 IU of vitamin D NOT RCT
Diabetic nephropathy T Reduced HOMA-IR, FRS RCT 50,000 IU weekly
Ulcerative Colitis T Reduced 60% RCT 50,000 IU nano daily for a week
Obese weight loss T Lost 3X more pounds $10 of Vitamin D added to
  calorie restriction & walking

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