Vitamin D supplementation, and what levels to use are common discussions amongst Nutritional Therapists. I have written a number of commentaries and reviews on this subject over the last couple of years and a recent paper published in the Journal: Joint Bone Spine presents a very interesting take on mega supplementation to restore Vit D status.[1]
Rather than looking at the results as a directive for vigorous upfront Vit D supplementation, as there are obvious considerations that make this as a universal approach very questionable, it remains clinically relevant, and may provide a degree of confidence. What is of greater interest is the rapidly declining levels of serum 25-hydroxy vitamin D (25OHD) after the first month and the differences noted in the weight of the patient.
The author’s state: This protocol was effective in rising serum 25OHD of most vitamin D insufficient patients with a BMI less than 25kg/m(2), but not in overweight patients. As almost one half of our patients had a serum 25OHD level less than 30ng/mL at Month 2, we suggest that regular doses should be started quite soon after this initial supplementation.
The first and in many ways the most significant component of this approach is the use of validated assays, simply assuming deficiency and not assessing outcome would not justify supplementation of anywhere near this initial amount.
But assuming blood tests confirm a deficiency, then, keep in mind the changes achieved in the time frames allocated on the oral dose of 100,000iu (yes you read correctly – one hundred thousand) of Vit D3 every 2 weeks as defined by blood serum at baseline.
The paper can be summarised as follows:
Objectives:
There is no protocol of vitamin D supplementation used worldwide due to a great disparity of vitamin D supplements available in different countries. The aim of this study was to evaluate the efficiency of the protocol most often used in France and in other EU countries to correct vitamin D deficiency defined by a serum 25-hydroxy vitamin D (25OHD) level of less than 30ng/mL.
Methods:
This was a pragmatic multicentric study of vitamin D supplementation in 257 osteopenic/osteoporotic, vitamin D deficient patients who received 100,000IU vitamin D3 vials every two weeks according to their initial serum 25OHD level.
| Vitamin D Baseline status | Oral Vial dose x 100,000iu | Month 1 | Month 2 | Month 3 |
| <10ng/mL | 4 | |||
| 10-19ng/mL | 3 | |||
| 20-29ng/mL | 2 | |||
| Target Level | ||||
| >30ng/mL | 77% (198/257) | 55% (140/257) | 46% (118/257) | |
| BMI < 25kg/m2 | 85% | |||
| BMI > 25kg/m2 | 66% |
Comment:
Whilst the initial dose of up to 400,000iu of Vitamin D3 by Nutritional Therapists standards is extreme, in patients with osteoporosis or osteopenia, these doses are regarded as being valid to return them to levels above 30ng/mL but their serum levels soon drop below Vit D competency without either on-going supplementation or regular relevant sunlight exposure.
The implications are clear, all patients, but especially those with an identified loss of competence in bone metabolism need on-going oral supplementation, and even more so when not experiencing whole body sunlight exposure, this may include oral doses of greater than 20,000iu per day and needs to be calculated based on weight and blood analysis.
The chart below provides sufficiency levels and the two principle measurements for comparison.
| Serum 25(OH)D | ||
| ng/mL | nmol/L | Nutritional description |
| <5 | <12 | Severe Vitamin D deficiency |
| <10 | <25 | Vitamin D deficiency |
| 10-20 | 25-50 | Vitamin D insufficiency |
| 10-30 | 25-75 | Vitamin D insufficiency |
| >20 | >50 | Vitamin D sufficiency |
| >30 | >75 | Vitamin D sufficiency |
| 100-150 | 250-375 | Possible toxicity |
I have previously written on the role of Vitamin A and D in terms of key receptor attachments and it is worth repeating here that these nutrients work in a synergistic manner that single oral bolus supplementation may correct or adversely modify.
Vitamin A can be obtained “preformed” from certain foods such as dairy products, liver and eggs. But another key source is beta-carotene, the orange pigment in carrots, which is converted into the vitamin in the body.
In 1988, an American study found that excessive use of vitamin A during pregnancy was associated with certain birth defects.[2] Beta-carotene, however, was deemed to be safe and this led to the general advice that we should eat more of this nutrient, allowing the body to convert what it needs into vitamin A.
Recently a group from Newcastle in the UK have identified a common gene variant that greatly reduces the body’s ability to convert beta-carotene into vitamin A.[3] Their work revealed that a significant number of individuals are “low-responders” unable to absorb and/or convert provitamin A carotenoids to vitamin A, and that even in individuals who would normally be able to metabolise provitamin A to vitamin A, numerous other common factors can effectively impede this conversion.[4] These include; dysbiosis, alcohol, poor bile acid production, insulin resistance, HCl deficiency, bacterial infection, coeliac disease and others. Even without the additional factors the researchers estimate that as many as 40% of the European population may have difficulty in converting vitamin A due to the gene variants.
Vitamins A and D are notably distinct from other vitamins in that their respective bioactive metabolites, retinoic acid and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), have hormone-like properties . More than 532 genes are recognised as either directly or indirectly regulated by retinoic acid and over 220 by vitamin D.[5],[6]
Retinoic acid and 1,25(OH)2D3 compete for the same nuclear receptor partners; both the Retinoic Acid Receptor (RAR) and the Vitamin D Receptor (VDR) must form heterodimers with retinoic X receptors α, β, and γ (RXRs) to be able to bind to response elements and initiate transcription.[7] For this reason, 1,25(OH)2D3 and retinoic acid naturally moderate each other’s uncontrolled effects.[8] Balanced supplementation or food selection of these nutrients is required for bone health as well as immune tolerance and represents safe supplementation strategies once individual nutrient deficiencies have been corrected.
References:
[1] Rouillon V, Dubourg G, Gauvain JB, Baron D, Glemarec J, Cormier G, Guillot P. Vitamin D insufficiency: Evaluation of an oral standardized supplementation using 100,000IU vials of cholecalciferol, depending on initial serum level of 25OH vitamin D. Joint Bone Spine. 2011 Nov 4 View Abstract
[2] Dickinson A. Vitamin A and teratogenesis: recommendations for pregnancy. J Am Diet Assoc. 1988 Mar;88(3):364. View Abstract
[3] Leung WC, Hessel S, Méplan C, Flint J, Oberhauser V, Tourniaire F, Hesketh JE, von Lintig J, Lietz G. Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15′-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB J. 2009 Apr;23(4):1041-53. Epub 2008 Dec 22. View Abstract
[4] Leung WC, Hessel S, Méplan C, et al. Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15′-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB J. 2009 Apr;23(4):1041-53 View Abstract
[5] Balmer JE, Blomhoff R. Gene expression regulation by retinoic acid. Lipid Res. 2002 Nov;43(11):1773-808 View Abstract
[6] Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, Handunnetthi L, Handel AE, Disanto G, Orton SM, Watson CT, Morahan JM, Giovannoni G, Ponting CP, Ebers GC, Knight JC. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 2010 Oct;20(10):1352-60. Epub 2010 Aug 24 View Abstract
[7] Mucida D, Park Y, Cheroutre H. From the diet to the nucleus: vitamin A and TGF-beta join efforts at the mucosal interface of the intestine. Semin Immunol. 2009 Feb;21(1):14-21 View Abstract
[8] Ertesvåg A, Naderi S, Blomhoff HK. Regulation of B cell proliferation and differentiation by retinoic acid. Semin Immunol. 2009 Feb;21(1):36-41 View Abstract
