What is Driving the Vitamin D Epidemic? (More Testing)

AA Kerber et al. J Pediatr 2021; 239; 212-218. Stable Rates of Low Vitamin D Status Among Children Despite Increased Testing: A Population-Based Study

Methods: The Rochester Epidemiology Project (REP) was used to identify Olmsted County, Minnesota residents aged <19 years who had 25-hydroxyvitamin D [25(OH)D] levels measured between January 2, 2002 and December 31, 2017.  Using each patient’s first 25(OH)D measurement during this period, patients were categorized as vitamin D deficiency/insufficiency if Vit 25(OH)D level was <20 ng/mL.

To convert nmol/L to ng/mL= nmol/L x 0.401 OR nmol/L =ng/mL x 2.496

Key finding:

  • There was a 42-fold increase in the proportion of the county’s pediatric population tested each year, starting at 3.7 per 10,000 persons in 2002 and increasing to 156.1 per 10,000 persons in 2017
  • During the 16-year period, the incidence of vitamin D deficiency/insufficiency (per 10,000 persons) increased from 1.7 in 2002-2003 to 19.9 in 2016-2017, but the proportion that were tested and had vitamin D deficiency/insufficiency remained stable –rates of 21.9% in 2006-2007 and 18.5% in 2016-2017
  • There was a higher rate of Vit D deficiency/insufficiency in females (22.8%) vs males (16.9%) (P<.001)
  • There was a significant association with obesity and Vit D deficiency/insufficiency (32.7% with moderate and 32.9% with severe obesity). It is unclear whether this is a causal link or an association (perhaps associated with less outdoor activity)
  • Limitation: Study was performed in Olmstead county which is 90-95% white; this limits generalizability (though other reports have noted increased testing rates as well in other locations)

My take: Clearly more kids are being screened for vitamin D deficiency. More data is needed on whether this results in any meaningful improvements in outcomes and the associated costs. In addition, it is important to recognize that vitamin D levels can be inversely proportional to inflammatory conditions and can improve without supplementation by addressing these disorders.

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Poorly-Conceived Allergy Testing Can Lead to Unnecessary Diet Restrictions and Complications

As noted in previous blog posts (see below), allergy testing can lead to unnecessary food restrictions which can in turn lead to numerous subsequent problems. Case in point: YV Virkud et al (NEJM 2020; 383: 2462-2470) report on A 29-Month-Old Boy with Seizure and Hypocalcemia

This boy presented with severe hypocalcemia, rickets, and seizures one year after allergy testing led to additional dietary restrictions. Also, his mother was a vegetarian. At time of allergy testing, IgE testing suggested allergies to milk, cashews, pistachios, egg whites, almonds, soybeans, chickpeas, green peas, lentils, peanuts, and sesame seeds. Many of these foods caused no symptoms with food challenges.

Besides working through the potential reasons for hypocalcemia, the authors make several key points:

  • Nutritional rickets is NOT a historical relic. Vitamin D deficiency appears to be increasing in high-income countries despite food-fortification strategies.
  • There are frequent misdiagnosis of food allergies. “Clinical and laboratory testing is severely limited by poor specificity…approximately 20 to 25% of children have positive IgE blood tests to specific food allergens, even though the true prevalence of IgE-mediated food allergy is likely closer to 6 to 8%.”
  • Avoid indiscriminate use of IgE blood testing. Allergen panels are “particularly problematic, because they often uncover false positives and lead to unnecessary food avoidance.” Individual IgE testing can be used to help confirm a diagnosis after an allergic reaction to a food trigger.
  • The most accurate diagnostic tool is an oral food challenge.
  • In children with food allergies, supplements are often needed to avoid micronutrient deficiencies and a low threshold is needed for involvement of dieticians.
  • Early introduction of foods can reduce incidence of allergies and periodic reassessment is needed to determine if a child has outgrown an allergy.
Xrays show generalized demineralization. The metaphyses show flaring (dashed arrow) and cupping (arrowbead). The physes are radiolucent and widened (asterisks).

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

How Important Is It to Correct Vitamin D Deficiency in a Critically-Ill Patient?

According to a recent study (NEJM 2019; 381: 2529-40), correction of vitamin D deficiency in critically-ill has NO significant effects on mortality and other non-fatal outcomes.

Link  to abstract: Early High-Dose Vitamin D3 for Critically Ill, Vitamin D–Deficient Patients

The article notes that observational data have indicated that Vitamin D deficiency is common in critically ill patients and has been associated with longer lengths of stay, prolonged ventilation and death.  However, “vitamin D level is considered a marker of coexisting conditions and frailty, and residual confounding may drive theses associations.”

Methods: a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D–deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo.


  • A total of 1360 patients were found to be vitamin D–deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population.
  • The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group
  • The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, −2.1 to 7.9; P=0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points.

My take: Correction of low serum vitamin D levels did not improve outcomes.  This likely indicates that low vitamin D levels are often an epiphenomenon of critical illness and not a contributing causal etiology.

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Why I Don’t Check Vitamin D Levels During IBD Flare-ups

A recent study (C Striscuiglio et al. JPGN 2018; 67: 501-6) helps explain the role of inflammation on vitamin D levels in pediatric patients (n=51) with inflammatory bowel disease (IBD).

Key findings:

  • The free/total 25-OH D ratio was higher in patients with newly-diagnosed IBD compared to healthy controls (P< .001)
  • A significant direct correlation was found between free/total 25-O D ratio and the activity index of disease (P= .01)
  • While there was frequent deficiency in total vitamin D levels,  the free 25-OH D which is the active form of vitamin D was normal or elevated in patients with newly-diagnosed IBD; this, in turn, was due to a decrease in vitamin-D binding protein which is related to inflammation. The authors hypothesized that at the cellular level in the intestine, there may be peripheral resistance due to inflammation and even supratherapeutic levels of free vitamin D could be needed to produce the active form (1,25-OH D).

My take: This study shows that 25-OH D levels (total) have almost no value at the onset of IBD.  Even normal or elevated free levels of 25-OH D which were found in this study does not preclude the potential need to supplement with vitamin D according to the study authors. In addition, as noted in previous posts, Vitamin D levels can normalize without supplementation when the patient’s IBD responds to therapy.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Dangerous animal –seen on our hike to the tea house, Banff

Understanding Why Vitamin D Deficiency is Not So Common Afterall

An excellent commentary (JE Marrison et al. NEJM 2016; 375: 1817-20) throws a bunch of cold water on the idea that there is a massive vitamin D deficiency pandemic.  The main contention of the authors is that physicians, and by extension patients, focus too closely at specific thresholds which are poorly understood.

They explain the term “Estimated Average Requirement” (EAR) which is the median of the distribution of human requirements.  Whereas, the RDA or recommended daily allowance “reflects the estimated requirement for people at the highest end of the distribution.”  So, at least 97.5% of people will have a requirement below the RDA.  However, due to Vitamin D’s importance, particularly with bone health, “the EAR is set at 400 IU per day for persons 1 to 70 years of age and 600 IU per day for persons older than 70.”

Other key points:

  • The EAR and RDA assume minimal to no sun exposure.
  • The RDAs of 600 IU/day and 800 IU/day correspond to 25(OH)D level of  16 ng/mlL and 20 ng/mL.
  • “A common misconception is that the RDA functions as a ‘cut point’ and that the entire population must have a serum 25(OH)D level above 20 ng per millimeter to achieve good bone health.”
  • “Approximately half the population has a requirement of 16 ng per milliliter (the EAR) or less.”
  • “Many studes establish ‘inadequacy’ using the RDA, though it is actually at the upper end of the spectrum of human need.” Thus, most people who are labelled as deficient are misclassified.
  • Using correct methodology, the authors assert that 13% of Americans 1-70 years are ‘at risk’ and <6% are deficient (with 25(OH)D < 12.5 ng/mL.

The problem with excessive Vitamin D testing and excessive treatment:

  • If 97.5% of the population has levels of Vitamin D exceeding 20 ng/mL, there are likely to be adverse effects in addition to increased costs of testing/treating.

Who to screen?

  • Those with risk factors for vitamin D deficiency: osteoporosis, osteomalacia, malabsorption, medications that can affect vitamin D metabolism (eg. anticonvulsants), or institutionalization
  • “For healthy patients, routine screening is not recommended by most medical organizations.” Though, the authors do recommend that “the RDA will nearly always meet the needs of generally healthy people.”

My take: This article makes a good argument for less testing along with avoidance of overprescribing vitamin D.  Nevertheless, for healthy people taking the RDA for vitamin D is quite sensible.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Victoria Chimes -Maine's Ship on their state quarter

Victoria Chimes -Maine’s Ship on their state quarter

Vitamin D and IBD, More Data

Another large study (Kabbani TA, et al. Am J Gastroenterol. 2016;doi:10.1038/ajg.2016.53) links low vitamin D status with worse outcomes in IBD.

An excerpt from summary from HealioGastro: (Low vitamin D linked to higher morbidity, disease severity in IBD)

Binion and colleagues identified 965 IBD patients (61.9% Crohn’s disease; 38.1% ulcerative colitis; 52.3% women; mean age, 44 years) with up to 5 years of follow-up data in University of Pittsburgh Medical Center’s longitudinal IBD natural history registry…

At enrollment, 8.9% of patients were vitamin D deficient and 33.1% had vitamin D insufficiency vs. 4.9% and 23.6%, respectively, at the conclusion of the study period. Among patients who received vitamin D supplements, 67.9% achieved normal levels by the end of the study…

Overall, patients with low vitamin D levels required significantly more steroids, biologics, narcotics, computed tomography scans, emergency department visits, hospital admissions and surgeries compared with those who had normal mean vitamin D levels (P < .05). They also had worse pain, disease activity scores and quality of life (P < .05).

“More importantly, correction of vitamin D deficiency was associated with overall improvement in clinical status,” Binion said.

My take: Vitamin D levels are often low when patients are acutely ill and can improve without supplements in many; this accounts for some of the association with worsened outcomes.  True vitamin D deficiency and insufficiency does have negative physiologic effects and should be treated.

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Gibbs Gardens

Gibbs Gardens


Get Here If You Can: Improved Vitamin D Status

“I don’t care how you get here
Just get here if you can”

–Oleta Adams, “Get Here”

A recent study (Kugathasan et al. JPGN 2016; 62: 252-8) reminded me of the aforementioned song lyrics. (Full lyrics: Get Here)

This randomized pilot study comparing two regimens for low Vitamin D levels (serum 25-OH Vit D <30 ng/mL). During a treatment period of 6 weeks, patients were randomized to treatment with Vitamin D3 (cholecalciferol) at 10,000 units or to 5,000 units per 10 kg per week.  The maximum weekly dose in the first group was 50,000 units (IU) and the maximum dose in the latter group was 25,000 IU.

Both treatments were associated with improvement; in the higher dose group the mean serum level reached 49.2 whereas it was 41.5 in the lower dose group.  Of note, this repletion effect was nearly lost by the 12-week followup.

Other points:

  • This study used Vitamin D3 (cholecalciferol) which has greater bioavailability than Vitamin D2 (ergocalciferol).
  • No serious adverse effects were noted.  The study monitored Calcium, and parathyroid hormone concentrations.
  • The authors did not report any correlation with CRP values.   This is important because other studies (Why Adding Vitamin D May Not Help IBD | gutsandgrowth)
    have shown improvement in Vitamin D levels without vitamin D supplementation when underlying inflammation has been treated.

My take: This study shows that supplementation with Vitamin D is associated with improved levels  –one can ‘get here’ with either regimen the authors studied.  In those with low levels (not due to inflammation), it is likely that maintenance Vitamin D supplementation will be needed.

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Michigan Union, Ann Arbor

Michigan Union, Ann Arbor

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Single High-Dose Oral Vitamin D Therapy (Stoss) for Children with Inflammatory Bowel Disease

A retrospective study (D Shepherd et al. JPGN 2015; 61: 411-14) shows that a single high-dose oral vitamin D3 therapy can be effective for 6 months.  This study involved treatment of 76 children between 2006-2010.

Stoss vitamin D dosing used in this study:

  • < 3 yrs 200,000 IU
  • 3-12 yrs 400,000 IU
  • >12 800,000 IU

Followup levels of Vitamin D (25-OH) and calcium were checked at 1 week, 4 weeks, 3 months and 6 months..

Key finding:

  • 25-OHD >50 nmol/L (=20 ng/mL) was seen in 96.6% at 3 months and 76.4% at 6 months.  63% had a level >75 nmol/L (=30 ng/mL) at 1 month.

Bottomline: Authors noted: “Stoss therapy safely and effectively achieved and maintained a level of 25OHD > 50 nmol/L during 6 months in these children with IBD.”

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Atlanta Botanical Gardens

Atlanta Botanical Gardens

Vitamin D in Preterm Infants

Vitamin D has garnered a great deal of attention due to concerns that deficiency worsens the outcomes in so many different conditions, including respiratory tract infections, inflammatory bowel disease, diabetes mellitus (type 1), multiple sclerosis, colorectal cancer, schizophrenia, depression, cardiovascular disease, hepatocellular carcinoma and other conditions.  However, evidence of causation is typically inconclusive.

For preterm infants, a study (Onwuneme C, et al. J Pediatr 2015; 166: 1175-80) notes an association between 25-hydroxy vitamin D (25OHD) levels drawn at 24 hours of life and acute respiratory morbidity.

In this study, levels were also drawn at the time of discharge in the 94 preterm infants.  In addition, maternal 25OHD) levels were checked 24 hours after delivery. These preterm infants were either <32 weeks gestation or <1.5 kg.  The study population was predominantly Caucasian.

Key findings:

  • 92% had 25OHD ≤20 ng/mL (=”<20 group”)
  • 64% had 25OHD ≤12 ng/mL (=”<12 group”)
  • Levels of 25OHD ≤12 ng/mL were associated with increased oxygen requirement (P=.008) and greater need for assisted ventilation (P=.013).  The odds of requiring assisted ventilation were approximately 3-fold higher.
  • The authors state that the baseline characteristics for the <12 group were similar to the <20 group.
  • There was statistical difference in the rate of NEC (Bell stage ≥1) based on the 25OHD levels (P=.048)

The authors note in their discussion that they favor supplementation with 400 IU/day which is in agreement with the American Academy of Pediatrics.  Previous ESPGHAN recommendations were 800-1000 IU/day for infants.

The authors note that 25OHD did not affect sepsis outcome.  In addition, antibiotics during labor was virtually identical between the two groups.  However, no data on CRP values were provided.

Bottomline: This study shows an association between 25OHD values and several important neonatal outcomes.  Whether 25OHD is a marker (eg. epiphenomenon) for these outcomes or whether low 25OHD contributes to these outcomes remains unclear.

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John Snow and Hepatology Potpouri

If you mention the name “John Snow,” I bet most people would think about one of the characters from Game of Thrones.  However, a more important John Snow is referenced in a recent Hepatology review (Hepatology 2014; 60: 1124-25).  “In 1855, the physician and epidemiologist John Snow used the technique of medical geography to stem the cholera epidemic in London.  By mapping the number of choleras case and the local water supply, he found that the Broad Street pump station was responsible and after the pump handle was removed, incident cases declined.”

Hepatology 2014; 60: 1150-59, editorial 1124-25.  Using spatial (clustering) epidemiology, the authors show that parenteral antischistosomal therapy (PAT) alone cannot explain the high HCV prevalence in Egypt.  Other iatrogenic exposures and poor infection control are likely contributing factors.

Hepatology 2014; 60: 1222-30, editorial 1130.  In a prospective study (western Europe), the authors show that vitamin D (25-OH) levels were inversely associated with the risk of hepatocellular carcinoma (HCC).  What is remarkable about this study is the levels were obtained on average 6 years before HCC diagnosis.  Also, this study uses tertiles -comparing those in the top third to those in the lowest third.

Hepatology 2014; 60: 1399-1408.  More data showing injury from Herbals and dietary supplements.  Liver injury caused by bodybuilding herbal supplements (often anabolic steroids) were typically less severe than liver injury induced in non-bodybuilding herbals (predominantly middle-aged women). Table 3 identifies by name many of the herbal supplements/dietary supplements associated with death or liver transplantation.  “Contrary to popular belief, this study demonstrates that HDS products are not always safe.”