Vitamin D Resistance

Our bodies get vitamin D in two ways: from food where the main sources are from cod liver oil, salmon, sun-dried mushrooms, mackerel, canned tuna, sardines. Besides, our bodies also get a small amount of vitamin D from liver, beef and eggs. The vitamin D from food enter the body in the form of vitamin D3 (cholecalciferol) and is obtained from UVB rays in sunlight, which will change the subcutaneous fat layer called 7-Dehydro-cholesterol into vitamin D3, then vitamin D3 will be transformed through the two steps. First it will be converted into hydroxy vitamin D mainly in the liver. Half of this hydroxy vitamin D will degrade within 15 days, making it the appropriate indicator to determine our bodies' vitamin D level. Then, the hydroxy vitamin D will be converted to dihydroxy vitamin D mainly in the kidneys. 

Dihydroxy vitamin D is actually the active ingredient that increase the absorption of calcium from the intestines into the bloodstream, and stimulate bone cells to build bone mass. However, when measuring blood levels of vitamin D, the dihydroxy vitamin D will not be detected, but rather the hydroxy vitamin D instead, as the dihydroxy vitamin D is produced with short half-life; half of them will be degraded within just 15 hours. In addition, the levels of the dihydroxy vitamin D will not easily decline even though the body begins to deplete vitamin D. This is because its’ level are quickly compensated by parathyroid hormone, hence, it is not a suitable marker used to determine the level of vitamin D in the body.

There are two units of measurement for the hydroxy vitamin D which are “ng/mL” and “nmol/L”, where 1 ng/mL = 2.5 nmol/L). To avoid vitamin D deficiency diseases, not limited to cartilages disorder, the hydroxy vitamin D level need to be maintained above 30 mg/mL, which is one time greater than the recommendation by a medical institution.
In case of osteoporosis patient who takes vitamin D3 but the level of hydroxy vitamin D3 has not increased. This can be caused by one of the three reasons below:
1.    Too low intake of vitamin D. As the recommended intake dose of vitamin D according to the American Institute of Medicine (IOM) is 400 - 600 IU per day, but the recent researches has found that it's not enough to treat chronic vitamin D deficiencies. Although given the maximum safe dose recommended by a medical institution of 2000 IU per day, this is rarely enough.
2.    Deficiency of an enzyme that body needs to convert vitamin D3 to the hydroxy vitamin D (CYP27A1). Our body may not have enough enzyme or the enzyme does not work well which may cause by genetic factor.
3.    Deficiency of an enzyme needed to absorb ingested vitamin D into the body. This enzyme in the intestines may not be enough or does not work well.
As for the initial recommendation, you should consult with your doctor regarding recommendation on increasing the vitamin D level. In case that the maximum vitamin D intake has been reached, but the hydroxy vitamin D level does not increased. It is recommended to take the vitamin D in the form of the final active ingredient or dihydroxy vitamin D, a type of vitamin D called Calcitriol; its’ trade name is Rocaltrol® and is more expensive than vitamin D3. Taking this type of vitamin D is to skip the processes occur in skin, liver, and kidneys, as we don't know where about the enzyme deficiency could be. The way to take this vitamin is to take 1 capsule per day, then gradually increase dose by double every two weeks up to the maximum dose of 1 mcg, 4 capsules per day. And once starting this vitamin D intake, calcium supplement should be stopped as dihydroxy will increase the absorption of calcium from the intestines into the bloodstream. Therefore, it is best to get calcium from a natural dietary sources, such as skim milk or soy milk. After three months of taking dihydroxy, the calcium level should be measured. If it is too high, then reduce the dose to 0.5 mcg or 2 capsules a day. There is no need to recheck the level of hydroxy vitamin D as the newly intake is dihydroxi vitamin D which is a different molecule. And as the dihydroxy vitamin D level cannot be tested in Thailand and must be sent abroad to measure its’ level. Apart from vitamin D, calcium, and medications to increase bone mass, another important aspect of osteoporosis treatment is exercise, especially strength training, such as regularly weights training or muscles building exercise.  

Reference: 
1.    U.S. Department of Agriculture, Agricultural Research Service. USDA Nutrient Database for Standard Reference, Release 22, 2009.
2.    Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. Mar 2008;93(3):677-81.
3.    Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press, 1997.
4.    Bischoff-Ferrari HA, Giovannucci 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 Jul;84(1):18-28. 2006.
5.    Vieth R, Bischoff-Ferrari H, Boucher BJ, Dawson-Hughes B, Garland CF, Heaney RP, et al. The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr 2007;85:649-50. [PubMed abstract]
6.    Yetley EA. Assessing the vitamin D status of the US population. Am J Clin Nutr 2008;88:558S-64S.
7.    Holick MF. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes 2002;9:87-98.
8.    Cranney C, Horsely T, O'Donnell S, Weiler H, Ooi D, Atkinson S, et al. Effectiveness and safety of vitamin D. Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235.
9.    Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669-83.
10.    Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr 2008;88:582S-6S.
11.    Ganong, WF. Review of Medical Physiology 18 th ed. 1997; p 359-371.