The Glitter and Glitz of High Dose Vitamin D – Is a One Pill Solution the Panacea Promised? Part 1
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Dr. Sarah LoBisco, ND

Part 1

Per Oxford Dictionaries online, the definition of panacea in English is as follows:

panacea

A solution or remedy for all difficulties or diseases.

‘the panacea for all corporate ills’

‘the time-honoured panacea, cod liver oil’

Why do I make this connection of a perceived panacea to Vitamin D? Well, first its due to the massive amount of research available exalting Vitamin D’s powerful influences on our physiology. Try this little experiment: (1) Type in “Vitamin D” in google or another internet search box. (2) Notice. What results did you get? Your results are probably even more inspiring than my “About 56,300,000 results (0.48 seconds)” done a few weeks prior to this article’s release.

The second reason for vitamin D’s superpower status is the fact that it’s difficult to find more than a handful of respected integrative practitioners who do not include this vitamin/hormone in their healing protocols. This is for good reason. Many of them have become familiar with the plethora of studies and media headlines that support a connection to vitamin D levels and disease outcomes. For example, studies support its association with bone mineral density (BMD), risk of falls, cancer prevention, cardiovascular health, frailty, pregnancy outcomes, diabetes, obesity, all-cause mortality, immune responses (e.g., inflammation, autoimmunity, asthma, allergies), hormonal balance, neurological support, mood, nutrient interactions, musculoskeletal responses, bowel health, and many more. Overall, the relationship appears to be that a higher level of vitamin D is related to better outcomes for health. This is often cited with a caveat of honoring a sweet spot to prevent potential overdosing.1-13

Impressive.

Why then do I state a “perceived panacea?”

The conclusions above are mostly based on epidemiological and observational studies reporting on these beneficial associations (as measured by serum levels of 25(OH)D levels). We have been taught as physicians that we cannot confuse an association between an event with its cause. (Just because Johnny was at the party, doesn’t mean that he was the one that brought the alcohol.)

It’s only been more recently that randomized trials with vitamin D being tested as an intervention against a control have been reported on. 1-7These studies move beyond correlating levels of this nutrient to disease risk and assess disease outcomes of taking vitamin D. This sounds more like what suggestions should be based upon, correct?

However, there are some issues with conclusions of many of the randomized studies that make me hesitate to jump blindly on the vitamin D bandwagon. Besides the authors’ conflicting statements of efficacy, there are also the following factors that bias results: generalizability to the population based on subjects’ characteristics in the study, baseline vitamin D levels are often missing, interfering factors of the subject relating to absorption, availability, cofactors, and ability to metabolize a fat soluble vitamin were often not accounted for, quality (e.g. fillers, contamination) and dosage of supplements used in the studies differ,1-7 problems with reliability and validity of different laboratories used,8-10study design differences, and lack of long-term trials.1-13

For example, a 2012 trial of 77 healthy overweight and obese women were randomly allocated to 25ug/d cholecacifeol (vitamin D3) or placebo for 12 weeks. Cardiovascular measurements were compared as well as physical activity and dietary intake. The researchers concluded, “The findings showed that supplementation with vitamin D3 can significantly improve HDL-cholesterol, apoA-I concentrations and LDL-cholesterol:apoB-100 ratio, which remained significant in the multivariate model including anthropometric, dietary and physical activity measures.” 11

“What’s the problem?” You may ask

No problem really.

It’s just we can’t base decisive conclusions for the whole population on a study with overweight women which measures laboratory values over clinical markers and disease endpoints. Furthermore, the study was only three months in length. Many people are on supplementation much longer than this. What we can say is that this study added to the evidence that vitamin D seems to improve lab values associated with cardiovascular health in overweight women, for the short term. Catch my drift?

Another concern I have is that researchers, practitioners, and public health officials can’t seem to agree on an optimal dose or level to aim for. This leaves doctors to decipher for themselves what dosage to give their patients. This is a big job with room for many errors due to the massive amount of literature and clinical opinions. For example, here’s an abstract that is basing recommendations based on associative relationships of vitamin D levels to health outcomes:

Recent evidence suggests that higher vitamin D intakes beyond current recommendations may be associated with better health outcomes. In this chapter, evidence is summarized from different studies that evaluate threshold levels for serum 25(OH)D levels in relation to bone mineral density (BMD), lower extremity function, dental health, risk of falls, admission to nursing home, fractures, cancer prevention and incident hypertension. For all endpoints, the most advantageous serum levels for 25(OH)D appeared to be at least 75 nmol/l (30 ng/ml) and for cancer prevention, desirable 25(OH)D levels are between 90-120 nmol/l (36-48 ng/ml). An intake of no less than 1000 IU (25 mcg) of vitamin D3 (cholecalciferol) per day for all adults may bring at least 50% of the population up to 75 nmol/l. Thus, higher doses of vitamin D are needed to bring most individuals into the desired range. While estimates suggest that 2000 IU vitamin D3 per day may successfully and safely achieve this goal, the implications of 2000 IU or higher doses for the total adult population need to be addressed in future studies.12

However, as you will see next, there are issues with basing conclusions on this rationale.

Measuring Supply Rather Than Function

A third point that makes me a bit weary on prescribing vitamin D based on current understanding is using a measurement of supply without assessing for function or need. In a 2011 article from the Mayo Clinic Proceedings, the authors explain this current measurement as follows:

Determination of vitamin D status is not based on measurement of serum 1,25(OH)2D concentrations. Vitamin D status is assessed by measuring the prohormone 25(OH) D, which is an indicator of supply rather than function. The most stable and plentiful metabolite of vitamin D in human serum, 25(OH)D has a half-life of about 3 weeks, making it the most suitable indicator of vitamin D status. In the past, vitamin D deficiency was identified by the presence of bone disease, either rickets or osteomalacia. Bone disease caused by vitamin D deficiency is associated with serum 25(OH)D values below 10 ng/mL (to convert to nmol/L, multiply by 2.496). More recently, the term vitamin D insufficiency has been used to describe suboptimal levels of serum 25(OH)D that may be associated with other disease outcomes. Precisely defining vitamin D deficiency or insufficiency on the basis of 25(OH)D values is still a matter of much debate. A useful but rather simplistic classification of vitamin D status is shown in theTable. A cutoff value of 30 ng/mL is sometimes used for optimal vitamin status. On the basis of measured concentrations of 25(OH)D, many patients are given a diagnosis of vitamin D deficiency or insufficiency when most have no evidence of disease.13

The authors then describe the pitfalls of this cutoff value which is not evaluating for individual variations:

This is the rationale for selecting 30 ng/mL as the cutoff value for defining optimal vitamin D status. However, this definition represents an average value at a population level but does not account for the wide variation in the 25(OH) D level that represents adequacy at an individual level. Many patients have very low 25(OH)D values without evidence of increased production of PTH, and conversely, 25(OH)D levels greater than 30 ng/mL do not guarantee PTH suppression. Another limitation of this definition is that, in children, an elevated PTH level does not indicate inadequate vitamin D status and has been associated with increased calcium absorption.13

The article further goes into various other methods to determine measuring function of vitamin D, but they too have their caveats. Finally, the researchers discuss the factors that influence vitamin D levels such as race, intake, weight, age, physical activity, vitamin D receptor variants and response, dietary calcium, sunshine exposure, liver and kidney function, and absorption. These are often not considered in studies.

Therefore, they suggest evaluating the need for supplementing with vitamin D in studies based on the following criteria:

  1. Was the study design observational, which can only demonstrate associations and is subject to confounding, or was it an RCT that generally balances unmeasured confounding variables?
  2. How was the intake of vitamin D measured? Was the serum 25(OH)D value considered a proxy measure of vitamin D intake?
  3. What outcome was measured to assess the benefit of vitamin D? Was it the achieved 25(OH)D level or a specific clinical outcome that matters to the patient? Was assessment of the outcome the primary aim of the study?
  4. Is 25(OH)D the most appropriate biomarker of vitamin D status in all situations?13

In other words, doctors must play detective to determine if a study touting vitamin D’s prowess is relevant to their clinical population. This is because evidence based on observational and epidemiological studies make it hard to tease out confounders and prove causality. Still, the authors do make some conservative generalizations and cautions:

On the basis of the current data, it seems prudent for persons older than 60 years to take a vitamin D supplement of 800 to 2000 IU/d to reduce the risk of falls and fractures. These recommendations are consistent with the recently released report of the Institute of Medicine, which recommended that healthy adults take 600 IU/d to maintain skeletal health and also concluded that information about the health benefits beyond bone health could not be considered reliable.93Dark-skinned infants who are exclusively breast-fed are at greater risk of rickets and should receive 400 IU/d of supplemental vitamin D. Vitamin D supplementation in these ranges is likely to prevent bone loss, may improve bone density, may reduce fractures, and appears to reduce falls. Although vitamin D intoxication has been associated only with intakes of 50,000 to 1 million IU/d over the course of months or years,7the potential risks of kidney stones, vascular disease, and fractures with high-dose vitamin D regimens are unclear. Until more data from RCTs are available, a healthy dose of skepticism should be maintained regarding the other health claims for vitamin D.13

In Part II, I will go on to further detail a review on the caveats of prescribing vitamin D for conditions associated solely relating to higher levels of this nutrient and conclude with some suggestions for patients and doctors on prescribing and taking vitamin D.

LoBisco005Sarah Lobisco, ND,  is a graduate of the University of Bridgeport’s College of Naturopathic Medicine (UBCNM). She is licensed in Vermont as a naturopathic doctor and holds a Bachelor of Psychology from State University of New York at Geneseo. Dr. LoBisco speaks professionally on integrative medical topics, has several journal publications, and has completed her postdoctoral training as a certified functional medicine practitioner. Dr. LoBisco currently incorporates her training in holistic medical practices and conventional medicine through writing, researching, private wellness consultations, and through her independent contracting work for companies regarding supplements, nutraceuticals, essential oils, and medical foods.  Dr. LoBisco also enjoys continuing to educate and empower her readers through her blogs and social media. Her recent blogs about living naturally in our complex world and on the applications of essential oils can be found at www.dr-lobisco.com and at www.saratoga.com/living-well. Her new book BreakFree Medicine is now available on Amazon and Barnes & Noble’s. More information can be found at http://dr-lobisco.com/dr-sarah-lobisco-breakfree-medicine/

References:

  1. Shipton EE, Shipton EA. Vitamin D Deficiency and Pain: Clinical Evidence of Low Levels of Vitamin D and Supplementation in Chronic Pain States. Pain and Therapy. 2015;4(1):67-87. doi:10.1007/s40122-015-0036-8.
  2. Wagner D, Trudel D, Van der Kwast T, Nonn L, Giangreco AA, Li D, Dias A, Cardoza M, Laszlo S, Hersey K, Klotz L, Finelli A, Fleshner N, Vieth R. Randomized clinical trial of vitamin D3 doses on prostatic vitamin D metabolite levels and ki67 labeling in prostate cancer patients (abstract). J Clin Endocrinol Metab (online). 2013 Apr;98(4):1498-507. doi: 10.1210/jc.2012-4019.
  3. Putman MS, Pitts SAB, Milliren CE, Feldman HA, Reinold K, Gordon CM. A Randomized Clinical Trial of Vitamin D Supplementation in Healthy Adolescents. The Journal of adolescent health : official publication of the Society for Adolescent Medicine. 2013;52(5):592-598. doi:10.1016/j.jadohealth.2012.10.270.
  4. Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D Supplementation during Pregnancy: Double Blind, Randomized Clinical Trial of Safety and Effectiveness. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2011;26(10):2341-2357. doi:10.1002/jbmr.463.
  5. Dörr J, Ohlraun S, Skarabis H, Paul F. Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial. Trials. 2012;13:15. doi:10.1186/1745-6215-13-15.
  6. Diamanti AP, Manuela Rosado M, Laganà B, D’Amelio R. Microbiota and chronic inflammatory arthritis: an interwoven link. Journal of Translational Medicine. 2016;14:233. doi:10.1186/s12967-016-0989-3.
  7. Ghishan FK, Kiela PR. Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases. American Journal of Physiology – Gastrointestinal and Liver Physiology. 2011;300(2):G191-G201. doi:10.1152/ajpgi.00496.2010.
  8. Mayo Clinic. Vitamin D Testing: The Mayo Medical Laboratories Difference. Mayo Clinic Web Site. Available at: http://www.mayomedicallaboratories.com/articles/vitamind/. Updated September 2013.
  9. Goff CL, Cavalier E, Soubebielle J-C, Gonzalez-Antuna A, Delvin E. Measurement of circulating 25-hydroxyvitamin D: A historical review. Practical Laboratory Measurement. August 2015. 2:1-14.
  10. William B. Grant, Spyridon N. Karras, Heike A. Bischoff-Ferrari, Cedric Annweiler, Barbara J. Boucher, Asta Juzeniene, Cedric F. Garland, and Michael F. Holick. Do studies reporting ‘U’-shaped serum 25-hydroxyvitamin D–health outcome relationships reflect adverse effects? Dermato-Endocrinology. 2016; 8(1).
  11. Salehpour A, Shidfar F, Hosseinpanah F, Vafa M, Razaghi M, et al. Vitamin D3 and the risk of CVD in overweight and obese women: a randomised controlled trial. Br J Nutr.2012; doi: 10.1017/s0007114512000098
  12. Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol. 2008;624:55-71. doi: 10.1007/978-0-387-77574-6_5.
  13. Thacher TD, Clarke BL. Vitamin D Insufficiency. Mayo Clinic Proceedings. 2011;86(1):50-60. doi:10.4065/mcp.2010.0567.
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