Vitamin D Deficiencies: from Rarity to Public Health Concern
By Jesse Davis, DC

Vitamin D research papers indexed in Pubmed Central have more than tripled from 2002 to the year 2012,[1] far outstripping the growth of other micronutrient-focused research. First discovered in 1913 by E.V. McCollum and others, its existence and actions has been hypothesized since ancient times.[2] Today, despite a growing understanding of its many activities in the body, Vitamin D deficiencies have actually increased in many populations overall the last few decades. In fact, according to the Mayo Clinic in 2011, “Vitamin D (VD) deficiency has re-emerged, after more than hundred years, as a public health problem worldwide.”[3]

Vitamin D was originally understood in its relationship to the prevention of rickets in children and osteomalacia in adults. Vitamin D has had its RDA values for intake from food tied to prevention of these disease states in the past, and now to bone health in general.[4] Its role in bone health is due to its function in increasing absorption of calcium, where it is the primary mode of increasing intestinal uptake, as well as phosphorus.

Sources of Vitamin D

woman-in-sun.pngSources of Vitamin D in the body are from production initiated in the skin through UVB exposure, and also intake from food sources, fortified foods and supplementation. Food sources are few and mainly limited to fatty fish such as salmon followed by sardines and mackerel, as well as cod liver oils, and mushrooms and egg yolks (if the latter two have substantial exposure to sunlight). Fortification of vitamin D in the US food supply occurs primarily in dairy products, and also some juices such as orange as well as breakfast cereals.

Sunlight is the other primary source of Vitamin D in the body, breaking down 7-dehydrocholesterol (proVD3) in the skin, that is then subsequently further broken down in skin by heat and then converted to active forms by liver and kidney.[5] Experimental evidence has pointed to the amount of vitamin D produced by UV exposures. Since different skin types are capable of producing at different rates, the measurements of this have been made in minimal erythemal dose (MED), or the time required to create mild pinkness in skin (being set to 1 MED for the individual). One full body exposure at one MED is believed to produce between 10,000-25,000 IUs of vitamin D3, while “one-quarter of personal MED on one-quarter of skin area (hands, face and arms) yields a dietary equivalent vitamin D dose of about 1000 IU.” [6] The Norwegian Institute of Air Research (NIAR) has a publicly available web calculator to determine an approximation of production of vitamin D in skin based on the input of necessary factors. It can be found at this link.

Research found that outside the windows of between 10am to 4pm during the day, and between November and February, the UV light content of sunlight is low enough in UVB to be relatively ineffective at making vitamin D, at the latitude and altitude in Boston, MA. Therefore, other modes of intake must be sought at times when an area is incapable of supporting vitamin D synthesis.

Tested supplementation strategies have been found to be effective at raising the rates of vitamin D levels in the blood.[7] Other research has been highly favorable in regards to vitamin D supplementation and its ability to successfully support proper vitamin D levels. “Supplementation with VD has been estimated to prevent VD deficiency in approximately 98% of the general population.” JCOT 2015

In addition, “seasonal variation in serum 25(OH)D was greatly diminished in supplement users”[8] according to an Australian study of elderly adults. The RDA for various ages and demographics can be found here.

Deficiencies

There has been a new category of vitamin D level created this decade that is called insufficiency, to distinguish an amount higher than deficiency, but not be optimal for health. According to the Mayo Clinic (2011): “Vitamin D deficiency, which classically manifests as bone disease (either rickets or osteomalacia), is characterized by impaired bone mineralization. More recently, the term ‘vitamin D insufficiency’ has been used to describe low levels of serum 25-hydroxyvitamin D that may be associated with other disease outcomes.” The distinctions are below:

Vit-D-Table

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012634/table/T1/

Source: Mayo Clin Proc. 2011 Jan; 86(1): 50–60.

The Endocrine Society has produced an alternative cutoff, “defining insufficiency as lower than 30 ng/mL and normal as higher than 30 ng/ mL.” EMCNA 2013 Reasons for the various viewpoints are below.

“Reliance on a single cutoff value to define vitamin D deficiency or insufficiency is problematic because of the wide individual variability of the functional effects of vitamin D and interaction with calcium”[9] (Mayo Clinic 2011) as well as other nutrients.

“Because of the wide inter-individual variation, the one-size-fits-all approach does not work with vitamin D supplementation, and it is imperative that clinicians take those factors affecting the response to vitamin D supplements into account and individualize their strategy.” Nutrients. 2015 Jul; 7(7): 5111–5142.

“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.” Mayo Clinic 2011. It has been suggested by some inadequate calcium intakes over time can cause 25(OH)D levels to appear low as the precursor is used up in efforts to raise serum calcium levels.[10]

Non-Musculoskeletal Impacts

When it was discovered that vitamin D receptor (VDR) exists in nearly all cell types, new research avenues emerged. Prior to this, it was believed that vitamin D had impacts on calcium metabolism only. Combined with certain observations about geographic location and disease risk, an expanded paradigm emerged.

“That vitamin D might confer benefits beyond bone health was first suggested by ecologic studies showing lower cancer and cardiovascular mortality in regions with greater exposure to solar UV-B radiation (associated with greater cutaneous synthesis of vitamin D). [11]

Telomeres and Aging Associations

tablets.2.pngThere has been an association found between vitamin D levels and telomere length, a molecular genetic marker for how cells have aged. According to the original paper in the American Journal of Epidemiology,

“We found that a higher plasma 25(OH)D level was significantly associated with longer leukocyte telomere length, with evidence of a dose-response relationship. Our finding is consistent with that of Richards et al. (10), whose study was also conducted in a cohort of only women. In that study, 25(OH)D level was found to be negatively correlated with C-reactive protein, suggesting that vitamin D reduces systematic inflammation. In addition to reducing inflammation, vitamin D is also known to reduce cell proliferation (1, 2). Because inflammation from tissue damage and enhanced cell proliferation accelerate telomere shortening (46), vitamin D may reduce telomere shortening through both anti-inflammatory and antiproliferative mechanisms.”

However, the authors are careful to note that the measurements were of a single time point and not reflective of a long term state of patients’ serum vitamin D levels. In addition, they note that there is plausibility of mechanism but no clear causality, as well as being limited to the study population (in this case, Caucasian women).[12]

Cancers and Association with Vitamin D Levels

This last point of causality is an important one in looking at the various recommendations. The following two quotes discuss the nature of the existing evidence on vitamin D, and in this case cancer incidences.

From the publication bearing the newer intake guidelines had the following: “After careful consideration of the evidence, the Committee concluded that bone health was the only outcome that satisfied criteria for use as an “indicator” whereby causality was established and the available evidence on dose-response was sufficient to support its use for DRI development” JCEM 2011

However, others have felt that this was not “A recent article concluded that evidence of a beneficial role of vitamin D in reducing the risk of cancer incidence and mortality is not impressive, in part because of a lack of good randomized controlled trials (RCTs).1

They went on to say “No mechanism other than vitamin D production has been proposed to explain the correlation with or effect of UVB doses on cancer risk in well-conducted ecological studies.

Further support for the beneficial role of vitamin D in reducing the risk of cancer is that an individual and group index of high solar UVB irradiance and incidence or mortality rate of non-melanoma skin cancer is often inversely correlated with the incidence or mortality rates for other forms of cancer. In an ecological study in Spain, the mortality rate of non-melanoma skin cancer inversely correlated with mortality rates for 15 types of cancer after adjusting for the smoking index.”

“A comprehensive method to evaluate the evidence for a natural compound such as vitamin D is by applying Hill's criteria for causality in a biological system. The primary criteria are strength of association, consistency, biological gradient, plausibility (mechanisms), experimental verification (eg, RCTs), and accounting for confounding factors. These criteria were evaluated for cancer and found to apply well for breast and colorectal cancer and reasonably well for 9 other types of cancer.7[13]

In fact, this research is ongoing and we should hear more on this story. “The Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH) leads and sponsors

Population Groups at Highest Risk

The factors that affect the ability of the body to create active vitamin D lead to some groups being at higher risk of deficiencies. These factors include melanin in the skin (which absorbs greater portions of UV), sunscreen use, as well as older age and obesity. Due to this, ethnicities with darker skin types, the elderly and the obese are the most prominent groups most likely at risk.

Darker skin types can produce up to six times less vitamin D in the skin than pale types.[15] Nutrients 2010 It is estimated that on the Indian sub-continent, deficiencies are widespread due to many factors including decreased production from sun exposure. “VD deficiency prevails in epidemic proportions all over the Indian subcontinent, with a prevalence of 70%–100% in the general population.” JCOT 2015

The elderly have a decreased vitamin D synthesis in the skin due to decreased 7-dehydrocholesterol levels present and a decreased conversion on exposure to light. The elderly also have several other related factors decreasing overall vitamin D related function, including decreased calcium absorption (for a given vitamin D level) by intestinal resistance of calcium absorption to circulating 1,25(OH)2D, decreased levels of vitamin D receptors, and decreased renal production of active vitamin D.[16] All of these factors lead to a recent 2015 publication stating “The prevalence of vitamin D deficiency among seniors is high.”[17]

Obesity also has a profound impact on vitamin D levels. “A number of studies have shown that obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, is associated with low serum 25(OH)D levels”[18]

Possibilities of Excess

However, like nearly all things, vitamin D also has risks at higher intakes. While some have promoted very high levels, there is reason for pause to avoid excess. “A U-shaped relation has been found in several cohorts, with elevated risk for adverse outcomes – including CVD and all-cause mortality – at not only low but also high levels (>50-60 ng/ml of 25[OH]D).” JAMA 2015 Studies of lifeguards (as a population with high UV exposure levels) found populations may experience health impacts regardless of skin-related concerns, including changes in parathyroid hormone and an increased incidence of kidney stones.[19] In addition, as with other fat soluble vitamins, vitamin D is not quickly cleared from the body.

While balancing strategies for patients, the details of the patient’s particular situation and strategies to ensure sufficiency should match. And these are worth re-visiting over time. In fact, while things like sun exposure, seasonal variations and even eating patterns can change over weeks to months, so can the internal circulating levels. According to Mayo Clinical Proceedings research, “The most stable and plentiful metabolite of vitamin D in human serum, 25(OH)D has a half-life of about 3 weeks.”

References:

  1. [1] http://www.vitamindwiki.com/Expodential+growth+in+vitamin+D+publications
  2. [2] Raju Vaishya, MS et al. Resurgence of vitamin D: Old wine in new bottle,J Clin Orthop Trauma. 2015 Sep; 6(3): 173–183.
  3. [3] Douros K, et al. Does Vitamin D Deficiency Epidemic Parallel with Allergy and Asthma Epidemic? Mini Rev Med Chem. 2015;15(12):967-73.
  4. [4] Ross, C et al. The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know. J Clin Endocrinol Metab. 2011 Jan; 96(1): 53–58.
  5. [5] reported previously 2
  6. [6] Engelsen O. The Relationship between Ultraviolet Radiation Exposure and Vitamin D Status. Nutrients. 2010;2(5):482-495. doi:10.3390/nu2050482.
  7. [7] Mazahery H, von Hurst PR. Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation. Nutrients. 2015;7(7):5111-5142. doi:10.3390/nu7075111.
  8. [8] Pittaway JK, Ahuja KDK, Beckett JM, Bird M-L, Robertson IK, Ball MJ. Make Vitamin D While the Sun Shines, Take Supplements When It Doesn′t: A Longitudinal, Observational Study of Older Adults in Tasmania, Australia. Smith B, ed. PLoS ONE. 2013;8(3):e59063. doi:10.1371/journal.pone.0059063.
  9. [9] Thacher TD, Clarke BL. Vitamin D Insufficiency. Mayo Clinic Proceedings. 2011;86(1):50-60. doi:10.4065/mcp.2010.0567.
  10. [10] Weston Price Foundation, An Ancestral Perspective on Vitamin D Status, Part 1: Problems With the “Naked Ape” Hypothesis of Optimal Serum 25(OH)D, http://www.westonaprice.org/blogs/cmasterjohn/an-ancestral-perspective-on-vitamin-d-status-part-1-problems-with-the-naked-ape-hypothesis-of-optimal-serum-25ohd/
  11. [11] Manson J et al. Vitamin D Research and Clinical PracticeAt a Crossroads. JAMA. 2015;313(13):1311-1312. http://jama.jamanetwork.com/article.aspx?articleid=2165869
  12. [12] Liu JJ, Prescott J, Giovannucci E, et al. Plasma Vitamin D Biomarkers and Leukocyte Telomere Length. American Journal of Epidemiology. 2013;177(12):1411-1417. doi:10.1093/aje/kws435.
  13. [13] Grant WB. Weighing the Evidence Linking UVB Irradiance, Vitamin D, and Cancer Risk. Mayo Clinic Proceedings. 2011;86(4):362-363. doi:10.4065/mcp.2011.0020.
  14. [14] National Institutes of Health, ODS Vitamin D Initiative, https://ods.od.nih.gov/Research/VitaminD.aspx
  15. [15] as previously reported 5
  16. [16] Gallagher JC. Vitamin D and Aging. Endocrinology and metabolism clinics of North America. 2013;42(2):319-332. doi:10.1016/j.ecl.2013.02.004.
  17. [17] Brouwer-Brolsma EM, et al . Relative importance of summer sun exposure, vitamin D intake, and genes to vitamin D status in Dutch older adults: The B-PROOF study. J Steroid Biochem Mol Biol. 2015 Aug 11. pii: S0960-0760(15)30045-5.
  18. [18] ICipriani C, Pepe J, Piemonte S, Colangelo L, Cilli M, Minisola S. Vitamin d and its relationship with obesity and muscle. Int J Endocrinol. 2014;2014:841248. doi: 10.1155/2014/841248.
  19. [19] Advances in Experimental Medicine and Biology Volume 128, 1980, pp 467-472 http://link.springer.com/chapter/10.1007/978-1-4615-9167-2_51 +davischiropracticofmelrose@gmail.com

 

 

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