Professor, Dr.Med. N.N. Petrova¹
Associate Professor, Dr.Med. V.V. Dorofeykov²
Dr.Med. S.A. Varzin¹Saint Petersburg State Polytechnic University, St. Petersburg State University, St. Petersburg
² Lesgaft National State University of Physical Culture, Sport and Health, St. Petersburg

Keywords: vitamin D, calcium, muscles, metabolism, depression.

Introduction. Vitamin D deficiency in human body is a global problem recognized in the last decade due to the new laboratory diagnostics resources that simply did not exist before. In Russia blood vitamin D level testing became available in big cities in the last 2-4 years by means of imported equipment and reagents, and the cost of this testing is unaffordable for the statutory health insurance. Up to now neither public health officials nor health practitioners and trainers are fully aware of the importance of this issue for the preservation of public health and for sport medicine. 

Objective of the study was to attract the readers’ attention to the new facts about the role of vitamin D in metabolism, including that for the musculoskeletal system, health and keeping fit.   

Methods and structure of the study. Vitamin D is fat-soluble. In humans it is synthesized from a provitamin under the influence of the ultra-violet rays when the skin is exposed to the sun. Vitamin D obtained from the food and supplements as well as generated in the skin when exposed to the sun is biologically inactive. For it to be converted into an active metabolite which subsequently binds with specific receptors in tissues, two successive hydroxylation reactions are necessary: the first one occurs in the liver under the influence of 25-hydroxylase, and the vitamin is converted into 25-hydroxyvitamin D [25(OH)D] (calcidiol). The generated metabolite circulates in the blood for a long time (up to 21 days) and is easy to use for laboratory analysis [4, 1]. Then calcidiol is hydroxylated for the second time in tissues (mostly in kidneys) by the 1-alpha-hydroxylase enzyme to form physiologically active 1.25-dihydroxyvitamin D (calcitriol), half-life of which in the blood does not exceed 30 minutes. Calcitriol is also called D-hormone, as it is characterized by the following properties of hormones: it affects target cells through cytoplasmic receptors and intracellular secondary messengers, the effects of calcitriol at the cell level are realized by changing the speed of enzyme catalysis of metabolic reactions or intracellular enzymes synthesis, although the hormone itself is neither an enzyme nor a coenzyme.   

Results and discussion. Classic targets of the active D-hormone are such organs as intestines, kidneys, parathyroid glands and bone tissue. Vitamin D is important for absorption of calcium and phosphorus in the intestines and maintenance of their required blood levels. According to the latest scientific data the functions of vitamin D are not limited to calcium and phosphorus metabolism control. It also influences such physiological processes in the body as cell growth, neuromuscular capacity, immunity and inflammation [1]. Nuclei of many cells contain vitamin D receptors, some cells and tissues have their own 1-alpha-hydroxylase which supports the intracellular concentration of calcitriol for their “own needs”.   

Vitamin D deficiency, as described below, is an extremely common condition and can contribute to muscle weakness in proximal extremities, slowing walking speed, difficulty in standing up from a sitting position as well as when lifting heavy objects. Typical clinical features of calcitriol-dependent myopathy include the so-called waddling gait and loss of muscle mass while preserving sensitivity and tendon reflexes. An electromyographic study of vitamin D deficient patients describes shortening of polyphase motor capacities, a reduction of their amplitude corresponding to the pattern of myopathy. Nerve conduction velocity is also reduced. The symptoms of the disease can be treated by vitamin D medications, confirming its etiological role in the development of myopathy [3]. Observational evidence suggests a connection between vitamin D status and physical capacities of a person. Male and female subjects of the NHANES III study aged over 60, with a high level of 25(OH)D in the blood walked the distance of 8 feet and rose from an armchair faster than those with a lower level of vitamin D, regardless of the level of their daily physical activity [6]. In «Study of Aging Amsterdam», a Dutch prospective study, a low level of 25(OH)D in the blood was a predictor of reduced hand grip strength and muscle mass of the limbs in both men and women over the next three years. An 8 weeks long combined intake of vitamin D and calcium by elderly female outpatients with the levels of 25(OH)D less than 50 nmol/l (the normal value is at least 75 nmol/l, or 30 ng/ml) reduced the body swinging when walking by 9% compared with the patients who took only calcium supplements. Muscle biopsy of adults with severe vitamin D deficiency showed atrophy of muscle fibers of predominantly type II (“rapid response fibers”) which are the first to be activated to prevent falling down. This fact explains the tendency of elderly people with vitamin D deficiency to fall. A histological examination of such patients’ muscles also showed an increase of inter-fiber spaces, fatty infiltration, fibrosis and accumulation of glycogen granules [7]. The impact of vitamin D deficiency replenishment on the composition of muscle fibers was the subject of several studies. In a small research an examination of biopsy material obtained from elderly women after calcidiol and calcium supplementation for 3-6 months showed increased amount and volume of the type IIa muscle fibers. A randomized controlled study of elderly stroke patients found that vitamin D supplementation at 1,000 IU daily for 2 years considerably increased the share and average diameter of muscle fibers of type II; at the same time correlation was observed between the blood level of 25(OH)D and the diameter of muscle fibers [6]. Thus, the research of the past decade confirms the importance of vitamin D for the normal functioning of muscle and bone tissues.  

Latitude of residence is an important determinant of ultraviolet radiation intensity. It is found that the level of 25(ОН)D in the blood of Caucasian people is reduced by 0.7 nmol/l with each latitude degree to the north or to the south of the equator. Thus, the geography of the entire territory of the Russian Federation is a prerequisite for high incidence of vitamin D deficiency. However, no large-scale epidemiological studies with regards to vitamin D levels were carried out in the Russian Federation at present. Systematic reviews and large meta-analyses confirm the association of vitamin D deficiency with an increased risk of osteoporosis, falls, muscle weakness, overall and cardiovascular mortality and low physical activity of elderly people as well as with depression [1, 2, 4]. One of the most important, but insufficiently studied functions of vitamin D is to regulate the development and functioning of the nervous system. Vitamin D is regarded as a neurosteroid, its metabolites can penetrate the blood-brain barrier. Vitamin D receptors are located in the brain areas involved in depression development. It is suggested there is a connection between low levels of vitamin D and depression [9]. Positive therapeutic dynamics is noted when vitamin D is used for treating depression [10]. A positive effect of vitamin D levels normalization on individual symptoms of depression is described – it reduces depression, irritability, fatigue and weakness, i.e. asthenic displays, improves sleep and concentration. 

NHANES results showed that 73% of men and women aged 20 to 50 living in North America had vitamin D levels below normal. In 93% of young people in Canada a decreased blood level of 25-hydroxyvitamin D - lower than 75nmol/l - was found [11]. In general, the results of the studies having been carried out around the world in recent years indicate a high prevalence of vitamin D deficiency in men and women of different age groups in different populations. Seasonality of the deficiency is very clear: in the majority of countries the most severe deficiency period is six months – from October to April. At the same time it should be noted that vitamin D is a fat-soluble compound, is deposited in the liver and in case of overdose (blood level of over 150 ng/ml) can result in development of extremely dangerous complications described in medical literature. Uncontrolled treatment of growing children with vitamin D is especially dangerous.

Another important issue is insufficient intake of calcium with food by the majority of the world’s population. The lowest calcium intake in Europe was in women in Central and Eastern Europe, among women and men – in Estonia, Hungary and Lithuania. Of the 8 countries of Central and Eastern Europe in four of them men and in three of them women had calcium deficiency; for example, in Hungary its average daily intake was 665 mg [12]. To control calcium consumption and metabolism in the body we recommend to assess its concentration in daily urine and control ionized calcium in blood serum. Recommendations on sufficient calcium intake with food have been recently developed by various public and state organizations. Institute of Medicine of the United States (2010) and the US-based National Osteoporosis Foundation (2014) recommended all adults to take 1,000 mg of calcium daily with food to maintain health of the musculoskeletal system; women over 50 years old and men over 70 years old – 1,200 mg/day. At the same time intake of more than 2,500 mg of calcium daily often leads to complications and side effects development. Calcium intake is easily calculated with the help of tables of foods taken by a patient, but absorption and excretion can be estimated only by means of biochemical tests assessing the level of ionized calcium in the blood and daily urine. 

Conclusion. Three laboratory analyses - blood vitamin D (ОН) tests, daily urine and blood calcium tests – will allow to control conditions of the calcium exchange and trace shortage of vitamin D at early stages of deficiency in athletes, the military and other risk groups to make it possible to prevent and cure such conditions and improve the functioning of the musculoskeletal system as well as maintain good athletic fitness throughout the year, particularly in the sunshine-deficient autumn and spring time. Indiscreet administration of vitamin preparations and minerals is very risky and cannot be recommended. 

References

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Corresponding author: petrova_nn@mail.ru

Abstract

Deficiency of vitamin D is a global problem no less acute for the economically developed nations. The latest study reports are indicative of the importance of the relevant metabolites in the human body for due functionality of the musculoskeletal system. The authors recommend three laboratory analyses including blood vitamin D (ОН) tests, daily urine and blood calcium tests; and blood ionized calcium tests, plus calculations of the calcium intake with food – to control conditions of the calcium exchange and trace vitamin D deficiency at early stages to make it possible to prevent and cure such conditions and maintain good athletic fitness, particularly in the sunshine-deficient autumn and spring time. Indiscreet administration of vitamin preparations and minerals is very risky and cannot be recommended.