Vitamin-D Deficiency: A Global Health Problem


Vitamin D deficiency: a global health problem


Nowadays, hypovitaminosis D represents a global health problem, affecting over a billion people worldwide. Vitamin D is a fat-soluble vitamin and a steroid hormone that plays a pivotal role in the regulation of calcium-phosphorus metabolism and bone homeostasis. There are two forms of vitamin D: vitamin D2 (or ergocalciferol), derived from a common plant steroid named ergosterol, and vitamin D3 (or cholecalciferol), produced from the precursor 7-dehydrocholesterol in animals. Anyway, if we define a vitamin as a required substance that is not endogenously synthesized, vitamin D does not meet the criteria. In fact, only 20% of vitamin D is guaranteed by nutrition, with the remaining 80% of requirements secured by sunlight exposure through UVB-mediated conversion of 7-dehydrocholesterol (present in keratinocytes) to vitamin D3. Once produced in the skin, vitamin D3 is transported to the liver, where a hydroxylation at C25 position occurs, leading to production of 25-hydroxyvitamin D3 (25-OH-vitamin D3), the major circulating metabolite of vitamin D, even considered the best biomarker to define the vitamin D status, due to its long circulating half-life (2-3 weeks). A further hydroxylation at C1a position is then required to synthesize the metabolically active form of vitamin D, also known as 1,25-dihydroxyvitamin D3 (or calcitriol or 1,25(OH)2-vitamin D3). The proximal renal tubule is the main site of action for the above-mentioned process, catalyzed by the enzyme 1a-hydroxylase. Bone, kidney, intestine, and parathyroid glands represent the classical target tissues for calcitriol peripheral actions. Under physiological conditions, vitamin D acts promoting renal calcium reabsorption, increasing calcium uptake by small intestine and stimulating calcium absorption and mineral deposition at bone level; meanwhile, in the parathyroid glands calcitriol inhibits parathyroid hormone (PTH) synthesis. As a consequence, vitamin D deficiency can impair calcium-phosphorus homeostasis and bone health through reduction in bone mineralization and increase in bone resorption (due to the   consequential rise in PTH serum levels), thus leading to rickets in children and osteomalacia/osteoporosis in adults and in the elderly.

Despite there is no univocal consensus on 25-OH-vitamin D3 thresholds for defining vitamin D deficiency/insufficiency, there is enough support for using the following benchmarks:


  • Deficiency: serum levels of 25-OH-vitamin D3 less than 20 ng/mL (equivalent to serum levels less than 50 nmol/L, according to the International System of Units)
  • Insufficiency: serum levels of 25-OH-vitamin D3 between 20 and 29 ng/mL (equivalent to serum levels between 50 and 75 nmol/L, according to the International System of Units)
  • Sufficiency: serum levels of 25-OH-vitamin D3 ≥ 30 ng/mL (equivalent to serum levels ≥ 75 nmol/L, according to the International System of Units)


Some of the risk factors for vitamin D deficiency include lack of sun exposure, latitude of residence, aging (the capacity of the human skin to synthesize cholecalciferol decreases with age), limited dietary choices, use of certain drugs (i.e. anticonvulsants or glucocorticoids), obesity (vitamin D is “sequestered” in body fat and its levels are inversely related to body mass index), reduced exercise opportunities, skin pigmentation (melanin is an efficient blocker of UVB radiation), and malabsorption syndromes (i.e. Crohn disease or celiac disease). Therefore, an adequate screening for vitamin D deficiency should be guaranteed especially in these individuals, keeping in mind that recommended daily intakes to prevent bone complications of hypovitaminosis D substantially depend on age and can be summarized as follows:

–     14-18 years: 600-1000 IU*/daily

–     19-70 years: 1500-2000 IU*/daily

–     > 70 years: 1500-2000 IU*/daily

*IU: international unit; 1 IU is the biological equivalent of 0.025 mg cholecalciferol or ergocalciferol.

It is worth noting that in individuals diagnosed with vitamin D deficiency/insufficiency an appropriate vitamin D supplementation should be promptly started, aiming at the achievement and maintenance of optimal vitamin D serum levels (25-OH-vitamin D3 ≥ 30 ng/mL).

Of note, vitamin D also regulates several processes involved in cell growth/differentiation and exerts pleiotropic effects on extra-skeletal target tissues, such as immune and  cardiovascular system, muscle, adipose tissue, and pancreatic endocrine cells. With this regard, different studies support that vitamin D deficiency may result in several pathological conditions other than bone disorders, including autoimmune diseases (i.e. type 1 diabetes mellitus, multiple sclerosis, Hashimoto’s thyroiditis), obesity, hypertension, depression, and neurodegenerative diseases. Vitamin D deficiency may even contribute to the development of cancers, especially prostate, breast and colon cancers. This is the reason why vitamin D supplementation could be beneficial in such conditions. For instance, recent data suggest a potential role of high-dose vitamin D therapy in halting progression of autoimmune diseases, such as type 1 diabetes mellitus or Hashimoto’s thyroiditis.

In conclusion, vitamin D deficiency still represents a growing and ignored epidemic. Hence, long term strategies to address this global health problem should include public education of potential deleterious skeletal and non-skeletal consequences of vitamin D deficiency, along with health policies for screening, prevention and treatment with vitamin D supplementation.

Marco Infante, MD

General Practitioner, Italy
Clinical Resident in Endocrinology and Metabolic Disorders

Curely link:

1.  N.J. Bosomworth, Mitigating epidemic vitamin D deficiency, The agony of evidence. Can Fam Physician. 2011 Jan; 57(1): 16–20.

2.  Caprio M, Infante M, Calanchini M, Mammi C, Fabbri A. Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects. Eat Weight Disord. 2017 Mar;22(1):27-41.

3.  Zahid Naeem, Vitamin D Deficiency- An Ignored Epidemic. Int J Health Sci (Qassim). 2010 Jan; 4(1): V–VI.

4.  Baidal DA, Ricordi C, Garcia-Contreras M, Sonnino A, Fabbri A. Combination high-dose omega-3 fatty acids and high-dose cholecalciferol in new onset type 1 diabetes: a potential role in preservation of beta-cell mass.Eur Rev Med Pharmacol Sci. 2016 Jul;20(15):3313-8.
5. Mazokopakis EE, et al. Is vitamin D related to pathogenesis and treatment of Hashimoto’s thyroiditis? Hell J

Nucl Med. 2015 Sep-Dec;18(3):222-7.

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