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.
- Plotknioff at VitaminDWiki 1116 items as of Oct 2017
- Cadavers with good skeletons had 30 ng of vitamin D – Feb 2010
- Vitamin D Webinar - Plotnikoff - Feb 29 2016 latest webinar
- Great Vitamin D webinar for doctors - Plotnikoff Nov 2013 Excellent - the same as the author of this editorial, 1 image follows
- Is 50 ng of vitamin D too high, just right, or not enough
- Evidence that the minimum vitamin D blood level is 30 ng – Grant Nov 2012
- Vitamin D Recommendations around the world - IU and ng
- Incidence of 30 health problems related to vitamin D has doubled in a decade
Vitamin D also low in Europe
- 25 experts recommend vitamin D level of min 30 ng – Nov 2009
The MINIMUM recommendation = 30 ng was higher than the IoM = 20, or UK = 10
Cadaver error - shown as a chart
Proof that Vitamin D Works has the following summary
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|Reduction by Vit D|
click for details
|RCT = Random 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 %||12000 kids, 2000 IU|
|Diabetes Type 2||T||62 %||RCT* CRP reduction, 4000 IU|
Injection is far better - RCT *,
|Back Pain||T||95 % |
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, 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|
|TB||P||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 %||RCT, 4000 IU 1 year 2nd RCT: 2000/800 IU|
3rd RCT 20,000 IU weekly
|Lupus||T||zero flares||Loading then 100,000 IU monthly, RCT too|
|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 Disease||T||Stabilized||RCT, 1200 IU/day|
|Multiple Sclerosis||P |
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|
|Gingivitis||T||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 taller||Benefit||1 cm tall||RCT, 50,000 IU weekly, 8 weeks|
|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
|Low vitamin D |
|P||All infants > 20 mg||RCT, 5,000 IU|
|Fibromyalgia||T||Half of many still has Fibro||RCT, 30-48 ng||RCT 50K IU/week|
|Hives, Chronic||T||Reduced 40%||RCT, 4000 IU added|
|Cholesterol||T||Reduced 4 mg||RCT, 400 IU + Ca|
|Weight Loss||T||lost 5 more lbs||RCT, 2000 IU +diet +exercise|
|Gestational Diabetes||P||40%||RCT * , 5,000 IU|
|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 Patients||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 state in abstract|
|Hepatitis-C||T||Enhanced conventional drugs||RCT 2.000 IU|
|Chron'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|
|Lupus||T||Pain reduced||RCT 4,000 IU|
|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|
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, given to all |
2nd study, similar results
|Osteoarthritis pain||T||60% decrease||50,000 IU/weekly - NOT RCT, given to all|
|Amyotrophic Lateral Sclerosis||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, given to all|
|Metabolic Syndrome||P||reduced 44% when VitD |
increased by 30 ng
|NOT RCT, given to all|
|Hay fever||P||reduced 48%||1,000 IU for 30 days RCT|
|Preeclampsia||P||Recurrance cut in half|
3.6 X less likely if > 30 ng
|50,000 IU every 2 weeks RCT |
4,000 IU daily RCT
|Blood cell cancer|
|T||Survival 90% vs 50%||10,000 IU/week|
NOT RCT, given to all
|Irritable Bowel Syndrome||T||Reduced||3,000 IU spray RCT|
|Urinary Tract Infection||P||50% reduction||RCT 20,000 IU weekly|
|Mite Allergy||P||5X reduction||RCT 2,000 IU preg, 800 IU child|
(depression near birth)
|T||50% reduction||RCT 2,000 IU for just a few weeks|
|Vaginosis||T||10X reduction||RCT 2,000 IU|
|Eczema||T||Reduced||2 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|
|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||Vitamin D & DHA RCT|
|Fatigue||T||Reduced||100,000 IU single dose|
NOT RCT, given to all
|Sleep Disorders||T||Nicely treated||50.000 IU bi-weekly RCT|
|T||Death rate cut in half||300,000 IU injection RCT|
|Infertile males||T||birth rate doubled||300,000 IU + maint RCT|
|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
|T||Reduced||3,000 IU for 12 weeks RCT|