Ludzkie koronawirusy - autor: Krzysztof Pyrć z Zakładu Mikrobiologii, Wydział Biochemii, Biofizyki i Biotechnologii, Uniwersytet Jagielloński, Kraków

Chcesz wydać pracę habilitacyjną, doktorską czy monografię? Zrób to w Wydawnictwie Borgis – jednym z najbardziej uznanych w Polsce wydawców książek i czasopism medycznych. W ramach współpracy otrzymasz pełne wsparcie w przygotowaniu książki – przede wszystkim korektę, skład, projekt graficzny okładki oraz profesjonalny druk. Wydawnictwo zapewnia szybkie terminy publikacji oraz doskonałą atmosferę współpracy z wysoko wykwalifikowanymi redaktorami, korektorami i specjalistami od składu. Oferuje także tłumaczenia artykułów naukowych, skanowanie materiałów potrzebnych do wydania książki oraz kompletowanie dorobku naukowego.

Poniżej zamieściliśmy fragment artykułu. Informacja nt. dostępu do pełnej treści artykułu tutaj
© Borgis - Postępy Nauk Medycznych 10/2016, s. 756-759
*Ewa Marcinowska-Suchowierska1, Paweł Płudowski2
Vitamin D toxicity
Zatrucie witaminą D
1Department of Geriatric, Internal Medicine and Metabolic Bone Disease, Centre of Postgraduate Medical Education, Warsaw
Head of Department: Professor Marek Tałałaj, MD, PhD
2Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children’s Memorial Health Institute, Warsaw
Head of Department: Professor Roman Janas, PhD
Streszczenie
Zatrucie witaminą D (VDT), zwane także hiperwitaminozą D, jest rzadkim powikłaniem, będącym najczęściej następstwem podaży dużej ilości witaminy D jako suplementu, a nie skutkiem diety lub ekspozycji na promienie UVB. Następstwem klinicznym VDT może być hiperkalcemia oraz inne niespecyficzne objawy. Dane literaturowe wskazują, że do hipercalcemii w VDT dochodzi, jeśli stężenie 25(OH)D w surowicy jest większe niż 150-200 ng/ml. Wiele różnych mechanizmów może być odpowiedzialnych za powstanie objawów VDT, w tym wzrost: stężenia metabolitów witaminy D, ilości receptorów dla witaminy D (VDR) i białka wiążącego witaminę D (VDBP). Dostępna dokumentacja wskazująca na korzystny wpływ wyższych stężeń witaminy D zarówno na tkankę kostną, jak i wiele innych komórek, zachęca niektóre osoby do przyjmowania (niekontrolowanego) większej ilości witaminy D niż zalecane, co zwiększa ryzyko wystąpienia VDT. Hiperkalcemia wskutek VDT występuje rzadko, ale jest niebezpieczna i wymaga rozważnego leczenia.
Summary
Vitamin D toxicity (VDT), also called hypervitaminosis D, is a rare but potentially serious condition that occurs when an individual has excessive 25(OH)D levels in the bloodstream.
Vitamin D toxicity is usually caused by extremely high doses of vitamin D supplements, not by diet or skin exposure to the sun. The main clinical consequence of VDT is elevated serum calcium level (hypercalcemia) and a variety of nonspecific symptoms. The literature reports that hypercalcemia due to overdosed vitamin D may appear if serum 25(OH)D levels are higher than 150-200 ng/ml. Many different mechanisms have been proposed to account for VDT, including the vitamin D metabolite itself, VDR number, activity of 1 alfa-hydroxylase, inhibition of vitamin D catabolism, and the capacity of VDBP. Mounting evidence that higher levels of vitamin D may have beneficial effects on bone and cellular health may predispose to enhanced administration of vitamin D and increased frequency of VDT. Hypercalcemia from VDT is rare, but a dangerous state for the organism and should receive adequate and sensible treatment.
Introduction
Vitamin D is an important prohormone that plays a vital role in calcium homeostasis and bone mineralisation. Vitamin D also sub subserves in a wide range of fundamental biological functions, such as cell differentiation and the inhibition of cell growth, as well as immunomodulation. Vitamin D deficiency leads to a defect of bone mineralization and to increased risks of several extra skeletal complications such as cardiovascular diseases, hypertension, obesity, metabolic syndrome, chronic obstructive pulmonary disease, autoimmune diseases and cancer. Vitamin D deficiency [25-hydroxyvitamin D – 25(OH)D level < 20 ng/ml] and insufficiency [25(OH)D level 21-29 mg/ml] is a worldwide problem that is widely prevalent (1).
Because of the increased awareness of vitamin D deficiency in recent years, the use of vitamin D supplements by the population has increased, as well as use of high doses of vitamin D prescribed by physicians to treat vitamin D deficiency. This increased use of vitamin D supplements by the general population and the growing number of prescriptions of therapeutic doses without any monitoring may result in a greater risk of hypervitaminosis D, also known as vitamin D toxicity (VDT) (2). This article presents some of the problems associated with VDT.
What is vitamin D toxicity and how often does it occur?
Vitamin D toxicity (VDT), also called hypervitaminosis D, is a rare but potentially serious condition that occurs when an individual is exposed to excessive amounts of vitamin D for prolonged period of time.
Vitamin D toxicity is usually caused by mega doses of vitamin D supplements, not by diet or exposure to the sun. This is because the human body regulates the amount of previtamin D produced by UVB, and even fortified foods do not contain large amounts of vitamin D (3).
VDT may be defined as a state when markedly elevated 25(OH)D levels (> 150 ng/mL) coinciding with hypercalcemia, hypercalciuria and very low or even undetectable PTH activity. However, the major clinical worries related to VDT most often focus on elevated calcium levels (hypercalcemia) and a variety of nonspecific symptoms (see below).
The literature reports that hypercalcemia due to an overdose of vitamin D may appear if serum levels of 25(OH)D reach a range of 150-200 ng/ml (3, 4). For this reason, it is generally accepted that serum 25(OH)D level above 150 ng/ml should be observed before a diagnosis of vitamin D toxicity. The lower 25(OH)D levels (up to 100 ng/mL) are considered perfectly safe for most children and adults, with the exception of individuals who have a hypersensitivity to vitamin D, such as children and adults with idiopathic infantile hypercalcemia, Williams-Beuren syndrome, granulomatous disorders and some lymphomas (5).
The existing knowledge related to VDT is based on case reports, series courses and animal experiments. The experimental analysis of VDT in humans is impossible due to ethical problems. In the 1930s to the 1950s, public health officials in USA and Great Britain recommended the routine fortification of milk and other foods with vitamin D initially as prophylactic for rickets in children and later to improve the general condition of adults. In the 1940s, massive doses of vitamin D (200,000 to 300,000 IU/D) were considered as an effective treatment strategy for many chronic illnesses from tuberculosis to rheumatoid arthritis. In 1950s, the incidence of hypercalcemia significantly increased, mainly in Great Britain as well as in some other countries in Europe. This unexpected and unexplained (at that time) increase of incidence of hypercalcemia resulted in the discontinuation of the fortification of food with vitamin D. Because hypercalcemia was observed at early stages of treatment, the therapy was discontinued and symptoms of vitamin D intoxication disappeared after a few months. This experience alerted physicians to the potential of vitamin D toxicity, and that concern persists to this day (5, 6). During the 1930s to the 1950s, there was no reliable assay for vitamin D and its metabolite, so symptoms of hypercalcemia in some children were based on a survey of dietary intake.
Mechanism of vitamin D toxicity
Vitamin D toxicity involves an increased concentration of vitamin D metabolites reaching the VDR in the nucleus of target cells and causing exaggerated gene expressions. The three mechanisms are suggested to explain vitamin D toxicity (3, 7):
1. Toxicity mediated by the increased levels of plasma 1,25(OH)2D (active hormonal form of vitamin D) leads to its increased intracellular concentration. This hypothesis is not strongly supported, as only Mewar et al. reported elevated 1,25(OH)2D levels at VDT, and many other studies revealed that 1,25(OH)2D levels were only marginally elevated or normal.
2. 1,25(OH)2D has low affinity to the vitamin D binding protein (DBP, transport protein) and high affinity to VDR making it an important ligand with access to the transcriptional signal transduction machinery. At the state of hypervitaminosis D, the levels of various vitamin D metabolites are markedly increased compromising the capacity of the DBP, and in term enable other vitamin D metabolites to enter the cell nucleus. Among these inactive metabolites 25(OH)D has the strongest affinity to the VDR, so at high concentrations 25(OH)D itself may stimulate transcription.
3. Vitamin D intake raises the concentration of many vitamin D metabolites especially vitamin D itself and 25(OH)D. In hypervitaminosis D, vitamin D metabolites such as vitamin D3, 25(OH)D3, 24,25(OH)2D3, 25,26(OH)2D3 and 25(OH)D3-26,23-lactone increase significantly. These concentrations exceed the DBP binding capacity and cause release of free 1-alpha 25(OH)2D3, the latter one enters target cells. The various studies and reports of vitamin D intoxcation indicate that plasma 25(OH)D3 is a good biomarker for toxicity.
Clinical features of vitamin D toxicity
The clinical manifestation of hypervitaminosis D is varied and mostly results from hypercalcemia and reflects the essential role of calcium in many tissues and targets, including bone, cardiovascular system, nerves and cellular enzymes.
Initial signs and symptoms of hypervitaminosis D may be similar to other hypercalcemic states and include generalized weakness and weight loss (6, 8-11).
Central nervous system features may include confusion, difficulty in concentration, drowsiness, apathy and coma. Neuropsychiatric symptoms include depression and psychosis, both of which are resolved following improvement of the hypercalcemia.

Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.

Płatny dostęp do wszystkich zasobów Czytelni Medycznej

Aby uzyskać płatny dostęp do pełnej treści powyższego artykułu oraz WSZYSTKICH około 7000 artykułów Czytelni, należy wprowadzić kod:

Kod (cena 30 zł za 30 dni dostępu) mogą Państwo uzyskać, przechodząc na tę stronę.
Wprowadzając kod, akceptują Państwo treść Regulaminu oraz potwierdzają zapoznanie się z nim.

Piśmiennictwo
1. Bouillon R: Vitamin D and extrasceletal health. UpToDate 2015; www.uptodata.com.
2. Dudenkov DV, Yawn BP, Oberhelman SS et al.: Changing incidence of serum 25-hydroxyvitamin D values above 50 ng/mL: a 10 year population-based study. Mayo Clin Proc 2015; 90: 577-586.
3. Gupta AK, Jamwal V, Sakul, Malhotra P: Hypervitaminosis D and systemic manifestations: a comprehensive review. JIMSA Oct-Dec 2014; 27(4): 236-237.
4. Agraharkar M, Dellinger OD, Gangakhedkar AK et al. (eds.): Hypercalcemia. Medscape References, New York, USA 2012.
5. Holick MF: Vitamin D is not as toxic as was once thought: a historical and up-to-date perspective. Mayo Clin Proc 2015; 90(5): 561-564.
6. Holick MF: Vitamin D update 2015: what we need to know about its health benefits and potential for toxicity? Standardy Medyczne 2015; 12: 759-763.
7. Jones G: Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr 2008; 88: 582S-586S.
8. Khieng V, Stevens C: Vitamin D Toxicity? A Case Study [online]. New Zealand Journal of Medical Laboratory Science 2010; 64(2): 44-50.
9. Bansal R, Tyagi P, Sharma P et al.: Iatrogenic hypervitaminosis D as an unusual cause of persistent vomiting. Journal of Medical Case Reports 2014; 8: 74.
10. Potts JT Jr, Juppner H: Disorders of the parathyroid gland and calcium homeostasis. [In:] Longo DL, Fauci AS, Kasper D et al. (eds.): Harrison’s principles of Internal Medicine. Vol. 2, 18th ed. McGraw Hill, New York 2012.
11. Pandita KK, Razdan S, Kudyar RP et al.: ”Excess gooD can be Dangerous”. A case series of iatrogenic symptomatic hypercalcemia due to hypervitaminosis D. Clin Cases Miner Bone Metab 2012 May; 9(2): 118-120.
12. Selby P, Davies M, Marks JS, Mawer EB: Vitamin D intoxication causes hypercalcemia by increased boneresorption which responds to pamidronate. Clin Endocrinol (Oxf) 1995 Nov; 43(5): 531-536.
otrzymano: 2016-09-01
zaakceptowano do druku: 2016-09-22

Adres do korespondencji:
*Ewa Marcinowska-Suchowierska
Department of Geriatric, Internal Medicine and Metabolic Bone Disease Centre of Postgraduate Medical Education
ul. Czerniakowska 231, 00-416 Warszawa
tel. +48 (22) 584-11-01
emarcinowska@cmkp.edu.pl

Postępy Nauk Medycznych 10/2016
Strona internetowa czasopisma Postępy Nauk Medycznych