We can expect vitamin D deficiency in persons with frequent muscle and joint pain, osteomalation, osteoporosis with fracture, and with calcium-phosphate metabolism disturbances [3]. Patients on a wide variety of medications including anticonvulsants and medications to treat HIV/AIDS are at risk because these drugs enhance the catabolism of 25(OH)D and 25(OH)₂D [13]. Patients on long-therm corticosteroid therapy (equivalent of prednisone over 7.0 mg/day) and ketoconazole are at risk for vitamin D deficiency, too [13]. Patients with chronic granuloma-forming primary disorders (tuberculosis, sarcoidosis), some lymphomas, and hyperparathyroidism who have increased metabolism of 25(OH)D to 1,25(OH)₂D are also at high risk for vitamin D deficiency [14, 15].

There are several other causes for vitamin D deficiency [1, 16]. Patients with one of the fat malabsorption syndromes and bariatric patients are often unable to absorb the fat-soluble vitamin D, and in patients with cholestasis, vitamin D emulsification by bile acid is impaired. Severe hepatic parenchymal damage can results in 25(OH)D deficiency [17].

Patients with nephrotic syndrome lose 25(OH)D bound to the vitamin-D-binding protein in the urine. Impaired 1α-hydroxylation is observed in chronic kidney disease once creatinine clearance decreases to approximately 30–40 mL/min [1, 17].

Epidemiological, genetic, and basic studies indicated a potential role of vitamin D in the pathogenesis of certain systemic and organ-specific autoimmune diseases. These studies demonstrate correlation between low vitamin D and prevalence of diseases. There is a body of evidence regarding the plausible roles of vitamin D and VDR’s polymorphism in the pathogenesis of systemic (i.e., systemic lupus erythematosus, rheumatoid arthritis, psoriasis, etc.) and organ-specific (i.e., diabetes mellitus, primary biliary cirrhosis, etc.) autoimmune diseases, in which low level of vitamin D was found compared to healthy subjects [18].

Low level of vitamin D is also found in cardiovascular diseases, i.e., lower serum 25 (OH) D levels are significantly associated with impaired myocardial performance and LVMI [19]. Hypertensive patients who were exposed to a tanning bed raised their blood concentrations of 25(OH)D by >180 % in 3 months and became normotensive [20]. It was observed that in patients with low vitamin D concentrations, such disorders as ischemic heart disease, heart attack, stroke, cardiac arrhythmia, and hypertension were more frequent and mortality was significantly higher [21]. Vitamin D sufficiency may also be an important protective factor for food allergy in the first year of life [22]. There is an inverse association of serum 25(OH)D and body mass index (BMI) greater than 30 kg/m², and thus, obesity is associated with vitamin D deficiency [23]. Low vitamin D level may be found in patients with colon cancer or prostate cancer [24, 25].

Increased use of clothing and sunscreen over sun-exposed areas and decreased consumption of vitamin-D-fortified milk increases the risk for vitamin D deficiency. In addition, age decreases the capacity of the skin to produce vitamin D₃ [1]. Studies have revealed that aging does not alter the absorption of physiological or pharmacological doses of vitamin D [26].

One of the studies on age and vitamin D conducted in Poland – the POLSENIOR study – showed negative correlation between serum vitamin D concentration and biological age in elderly women (r = − 0.2863, p = 0.001) [27].

Vitamin D deficiency is often a silent disease. In adults, vitamin D deficiency results in osteomalacia, which presents as a poorly mineralized skeletal matrix. Adults in these cases can experience chronic muscle aches and bone pains.

Other clinical symptoms suggesting vitamin D deficiency include lack of appetite, diarrhea, insomnia, vision disturbances, bad taste, and burning sensation in the oral cavity and throat [28].

Measurement of serum 25-hydroxyvitamin D (25[OH]D) is the best test to determine vitamin D status [29]. Levels of 25(OH)D are interpreted as follows [30]:

In Central Europe, levels of 25(OH)D are interpreted as follows [31]:

Determination of PTH and calcium concentrations is recommended to establish the cause for calcium-phosphate disorders before starting vitamin D supplementation.

Recommended treatment for vitamin D deficiency (vitamin D level below 20.0 ng/ml = 50.0 nmol/l) comprises [31] the following:

First control of 25OHD concentration is recommended after 3–4 months and then every 6 months. Serum calcium, phosphate, and calcium in 24-h urine calcium measurement should be monitored every 1–3 months [32].

Prevention of hypovitaminosis D (serum 25OHD lower than 30.0 ng/ml) strategies comprises the following doses [30]:

It is very important to apply vitamin D with meal. Recommended vitamin D serum level is between 30.0 and 50.0 ng/ml (75–125 nmol/l) [33].

Polish Recommendation for optimal concentration of vitamin D for pleiotropic actions of vitamin D recommends the following levels [32]:

Treatment dose suggested for first 1–3 months is as follows:

Useful calculations are as follows:

The Drug and Therapeutics Committee of the Pediatric Endocrine Society undertook a systematic review of the safety of currently recommended high vitamin D doses as well as reported cases of intoxications in pediatrics [6].

Vitamin D hydroxylation to 25-hydroxyvitamin D (25OHD) in the liver depends on substrate availability, and therefore, 25OHD concentrations rise in circulation during excess or intoxication. In contrast, the subsequent 1 alpha-hydroxylation to 1,25-dihydrovitamin D₂ in the kidney is tightly regulated by PTH and under negative feedback by calcium, phosphorus, and fibroblast growth factor 23. Consequently, in vitamin D intoxication, serum 1,25-(OH)₂D concentrations are usually normal and do not correlate with serum calcium levels (JCEM 2014) [6]

Both vitamins D₂ and D₃ are lipophilic and rapidly removed from the circulation to various tissues such as adipose and muscle where they may remain stored for almost 2 months. Their metabolite, 25OHD, has high affinity for its transport protein, vitamin D binding protein, which results in a long half-life of 2–3 weeks. 25OHD is also lipophilic and can be stored in adipose tissue, remaining there for months. Hence, vitamin D intoxication may take weeks to resolve and require prolonged course of therapy [6].