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© Borgis - Postępy Nauk Medycznych 1/2012, s. 78-82
*Michał Wąsowski, Ewa Marcinowska-Suchowierska
Efektywność uzupełniania niedoborów witaminy D u osób z otyłością, poprzez stymulację jej syntezy skórnej promieniami UVB
The effectiveness of vitamin D deficiency supplementation in the obese by the stimulation of cutaneous synthesis with UVB**
The Medical Centre of Postgraduate Education, Department of Family Medicine, Internal Medicine and Metabolic Bone Disease
Head of Department: prof. dr hab. med. Ewa Marcinowska-Suchowierska
Streszczenie
Osoby otyłe są grupą predysponowaną do występowania ogólnoustrojowych niedoborów witaminy D. Wśród przyczyn niedoborów witaminy D wymienia się unikanie ekspozycji na promieniowanie słoneczne (zawierające frakcję UVB odpowiedzialną za syntezę witaminy D w skórze), zaburzenia syntezy skórnej witaminy D, czy wreszcie sekwestrację witaminy D w tkance tłuszczowej.
Celem badania była ocena efektywności syntezy skórnej witaminy, po naświetlaniach skóry promieniami UVB, u osób otyłych. Pomiaru stężeń kalcyfediolu w surowicy (jako wskaźnika zaopatrzenia organizmu w witaminę D) dokonywano przed i po (w 4, 7,14, 21 dniu) suplementacji w grupie osób otyłych (n = 40) i 30 osób z prawidłową masą ciała.
Średnie stężenia kalcyfediolu przed rozpoczęciem badania były porównywalne w obu grupach (wynosiły odpowiednio 15,5 ng/ml u otyłych i 15,4 ng/ml w grupie kontrolnej). Przyrosty stężeń 25(OH)D3 uzyskane po naświetlaniach UVB także nie różniły się istotnie w obu porównywalnych grupach. Najwyższe przyrosty stężeń 25(OH)D uzyskano w 14 dniu po naświetlaniach (wynosiły one u otyłych 4,88 ng/ml i 5,42 ng/ml w grupie kontrolnej). Na podstawie badania można wnioskować, że synteza skórna witaminy D u osób otyłych jest efektywna.
Summary
Obese people are predisposed to vitamin D deficiency. The cause of vitamin D deficiency is inadequate solar radiation (containing the UVB faction responsible for the synthesis of the vitamin D in the skin), impaired vitamin D skin synthesis or sequestration of the vitamin D in the fatty tissue.
The objective of this study was to show how effective is cutaneous synthesis of vitamin D measured as calcifediol concentration (as a marker of vitamin D adequacy) before and after (in 4, 7, 14, 21 days) vitamin D supplementation after the stimulation of cutaneous synthesis with UVB irradiation in 40 obese and 30 nonobese individuals.
The mean concentration of vitamin D at the beginning did not differ significantly (15.5 ng/ml in the obese vs 15.4 ng/ml in control group). The increase of 25(OH)D3 after UVB irradiation in the obese and nonobese also did not differ. The largest change was observed 14 days after exposure (in the obese 4,88 ng/ml, in the control group 5.42 ng/ml). In conclusion, the cutaneous synthesis of vitamin D is effective.
Introduction
Obesity, defined as having a body mass index (BMI) greater than 30 kg/m2, is one of major health problems. The prevalence of obesity has been dramatically increasing in the last two decades. Several previous studies show a relation between obesity, poor calcium metabolism and vitamin D deficiency (1-4). Obese individuals have problems with vitamin D deficiency because of the way it is produced and used.
Vitamin D deficiency is one of the most common undiagnosed medical conditions in the world. It is defined as a concentration of 25(OH)D < 30 ng/ml and it is a social problem nowadays (5). It concerns several dozen percent of healthy population irrespective of age, sex and race (1-3). Adequate levels of vitamin D are maintained through its cutaneous synthesis or oral ingestion. Vitamin D deficiency accelerates bone mass loss which decreases the mechanical resistance of bone tissue. It is a cause of muscle weakness and increases falls and bone fractures risk. Recent data have linked low vitamin D levels to a wide range of diseases including cardiovascular diseases, metabolic syndrome, diabetes, cancer (i.e. colorectal cancer, breast and prostate cancer) and autoimmune diseases.
A major source of vitamin D for most humans has always been exposure to sunlight (more than 80% of vitamin D in our body is synthetized in the skin after UV radiation). Sun exposure is not only one of the most effective ways of guaranteeing vitamin D sufficiency, it is also natural and the most long-lived form of vitamin D.
Physiologically vitamin D is produced in the human skin from 7-dehydrocholesterol (7-DHC) following exposure to ultraviolet B (UVB) radiation with wavelength 290 to 320 nm. During exposure to UVB radiation 7-DHC is converted to previtamin-D3, which is considered biologically inactive until it undergoes enzymatic hydroxylation reactions in the liver and kidneys (5). The final product is calcitriol which controls a number of metabolic pathways. Studies have suggested that more than 200 different genes may be directly or indirectly regulated by 1,25(OH)2D3 through its VDR (Vitamin D receptor) (6).
In the actual guidelines the minimal oral dose for adults is 800-1000 IU/day (about 15 IU/kg) during insufficient sun exposure (in Poland from October to April). For all those who avoid sun exposure and in the elderly (after 65 y) this dose should be given (7).
The insufficiency of vitamin D is more common in case of obesity because of decreased bioavailability of vitamin D due to (as Matsuoka et al. show in their study) an inadequate UV exposure (8). In this study we wanted to investigate if the skin synthesis of vitamin D is as effective in the obese as in people with normal weight.
Aim of the study
The purpose of this study was to determine how effective is the cutaneous synthesis of vitamin D in the obese as a way to compensate the vitamin D deficiency compared with the normal weight patients. We sought to explain if vitamin D cutaneous synthesis is effective and could be the method of deficiencies supplementation.
Material and methods
The experimental population was 40 white obese individuals with BMI > 30 kg/m2 (n = 40, 24 women, 16 men, mean age 41,35 y) who were qualified for the study from the initial group of 79 obese patients. They agreed to vitamin D supplementation by the UVB cutaneous synthesis stimulation (OBE-UVB) (n = 20, 12 women, 8 men, mean age 39,35 y). The others who were not qualified to UVB irradiation received oral dose of vitamin D (OBE-DOUSTN) (n = 20, 12 women, 8 men, mean age 43,3 y). The control group (KONTR) was comprised of healthy white people with normal weight (n = 30, 23 women, 7 men, mean age 30,6 y) who also were irradiated with UVB (KONTR-UVB) or were given oral dose of vitamin D (KONTR-DOUSTN). Vitamin D (Devikap drops) was given for four days (in the same time as UVB irradiation) with the dose per kg of body weight (15 IU/kg): OBE 1350-2500 IU, KONTR 800-1000 IU. Patients demographic and laboratory characteristics are outlined in table 1 and table 2.
Table 1. Summary of patients demographic and clinical characteristics.
MeasurementSubject groups
Obese patients (OBE) (n = 40) Nonobese (KONTR) (n = 30)
Range Mean SD Range Mean SD
RaceCaucasian (100%) Caucasian (100%)
Sex
male (?)
female (?)
16 (40%)
24 (60%)
7 (23.3%)
23 (76.6%)
Age (years)18-62 41.35 10.49 24-56 30.63 7.43
BMI (kg/m2)34.2-56.8 43.97 6.02 18.7-26.8 22.19 2.49
Body surface (m2)1.96-3.02 2.45 0.25 1.72-2.11 1.72 0.18
Table 2. Summary of patients laboratory characteristics.
Subject groups
MeasurementObese patients (OBE) (n = 40) Nonobese (KONTR) (n = 30)
Range Mean SD Range Mean SD
25(OH)D3 (ng/ml)6.1-41.1 15.5 7.1 6.2-27.3 15.4 7.1
Cas (mg/dl)8.0-10.1 9.27 0.45 8.6-10.1 9.36 0.35
Ps (mg/dl)2.2-5.1 3.34 0.66 2.6-4.4 3.52 0.54
ALP (U/l)45-129 84.8 18.6 48-115 74.1 16.2
In all patients 25(OH)D concentration were measured before and in 4, 7, 14, 21 days after irradiation (or oral dosing). Then, using Medisun 700 lamp the whole body was irradiated with UVB 311 nm for 4 days. Minimal erythema dose (MED) was established for each patient. The study was performed during winter months (from November to March) to minimalize the influence of sun exposure.
Results
Basal concentrations of vitamin D were not significantly different between the obese and nonobese control groups [mean concentration of 25(OH)D in the obese (OBE, n = 40) was 15,5 ng/ml, and in normal weight (KONTR, n = 30) was 15,4 ng/ml]. Vitamin D cutaneous synthesis stimulated by UVB irradiation led to increase of 25(OH)D concentrations in both groups. It was proportional to the time of UVB radiation. The increase of 25(OH)D in the relation to starting value was observed in both groups, the largest one in 14 day after exposure (in OBE-UVB 4.88 ng/ml, in KONTR-UVB 5.42 ng/ml). The increases after UVB irradiation in the obese (OBE-UVB group) did not differ substantially from these in the nonobese (KONTR-UVB). This suggests that cutaneous synthesis of vitamin D is effective. The exposure time that guaranteed a characteristic increase of 25(OH)D concentration was about 12 min (fig. 1, 2).
Fig. 1. 25(OH)D3 concentrations before (0) and in 4, 7, 14, 21 day after UVB irradiation in OBE-UVB group.
Fig. 2. 25(OH)D3 concentrations before (0) and in 4, 7, 14, 21 day after UVB irradiation in KONTR- UVB group.
Disscussion
The present study of vitamin D synthesis and processing confirmed that obese patients have lower basal kalcyfediol concentrations, what can lead to secondary hyperparathyroidism. But vitamin D insufficiency degree is less than this announced by other authors. Recent studies have shown that obesity itself is associated with vitamin D deficiency and BMI is inversely correlated with vitamin D levels, what is contrary to our results.
The cause of vitamin D deficiency state in obesity is not well-understood. The main role among the possible causes of vitamin D insufficiency in the obese is inadequate sun exposure. It is not well known if it is due to lack of UVB from the sunlight or the vitamin D skin synthesis in the obese is impaired. Flores et al show that the obese exercising outside are 47% less vitamin D insufficient than those exercising inside (9).
It has been also proposed that the low vitamin D status might be due to increased vitamin clearance from serum and enhanced storage of vitamin D by the adipose tissue. This argumentation is suggested Matsuoka et al. These authors show that the increase in blood vitamin concentrations was 57% less in the obese than in the nonobese subjects in 24 hours after UVB irradiation.
Vitamin D is a fat-soluble substance and is stored in adipose tissue. Thus, one of the proposed causes of vitamin D insufficiency in the obese is sequestration in fat tissue. Matsuoka et al. suggest that obesity may have altered the release of vitamin D from the skin into the circulation. Taking this we could have in the obese release of vitamin D after bariatric surgery from adipose tissue. But Lin et al., Aasheim et al. and Czerwinska et al. show, in obese group after Roux-en Y gastric bypass (RYGB), that the increase of vitamin D in blood only a month after surgery was observed (10-12). The results of a 1-year observation show progressive decrease of kalcifediol concentrations in bariatric surgery patients after this preliminary increase.
In our study the increase of 25(OH)D concentrations after UVB radiation was similar in both groups (obese and nonobese). It suggests that UVB-stimulated skin synthesis of vitamin D is effective in the obese as well as in the nonobese and obesity did not affect vitamin D skin synthesis.
Comparing the effectiveness of UVB irradiation influence and oral supplementation of vitamin D in the same time we could say (unpublished data) that the increase of calcifediol concentrations was larger in the irradiated group. It is probably caused by too short time of oral cholecalciferol supplementation. In Goldner et al. study obese (after bariatric surgery) cholecalciferol in 3 doses: 800, 2000 and 5000 IU/day was given. In 12 months after this the 25(OH)D concentration increase was correspondingly 44%, 78% and 70% more than starting value (13). These data show that higher doses and longer period of time is more effective in oral supplementation of vitamin D.
In our study we have shown that UVB irradiation of the skin is an effective method of vitamin D synthesis and could be a possible method of supplementing deficiencies in the obese.
Conclusions
The cutaneous synthesis of vitamin D in the obese is effective.
**This work was supported by a grant from the Medical Center of Postgraduate Education (grant no. 501-2-3-01-25/07).
Piśmiennictwo
1. James WPT: The epidemiology of obesity: the size of the problem. J Intern Med 2008; 263: 336-352.
2. WHO: Obesity and overweight. Fact. Sheet. No.311 September 2006. http://www.who.int/mediacentre/factsheets/JSs311/en/index.html.|Accessed January 13.2009.
3. Fujioka K, Apovian CM, Hill JO et al.: The evolution of obesity therapies: new aplication of obesity therapies; new aplication for existing drugs. Medscape CME Diab & Endocrin http://cme.medscape.com/viewarticle/722366.
4. Caterson I: Obesity and risk. Medicom Intern 1997; 1: 2-7.
5. DeLuca HF: Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004; 80: 1689S-1696S.
6. Vogel A, Strassburg C, Manns M et al.: Genetic Association of vitamin D Receptor Polymorphisms with Primary Biliary Cirhosis and Autoimmune Hepatitis. Hepatology 2002; 35: 126-131.
7. Marcinowska-Suchowierska E, Walicka M, Tałałaj M et al.: Suplementacja witaminy D u ludzi dorosłych – wytyczne. Post Nauk Med 2010; 2: 160-166.
8. Wortsman J, Matsuoka LY, Chen TC et al.: Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000; 72: 690-693.
9. Flores L, Osaba MJ, Andreu A et al.: Calcium and vitamin D supplementation after gastric bypass should be individualized to improve or avoid hyperparathyroidism. Obes Surg 2010; 20: 738-743.
10. Lin R, White JH: The pleiotropic actions of vitamin D. Bio Essays 2008; 26: 21-28.
11. Aasheim E, Hofs D, Hjelmesaeth J et al.: Vitamin status in morbidly obese patients: a cross-sectional study. Am J Clin Nutr 2008; 87: 362-369.
12. Czerwińska E, Marcinowska-Suchowierska E, Walicka M et al.: Wpływ operacji bariatrycznej na homeostazę wapnia i biochemiczne markery obrotu kostnego u osób z otyłością olbrzymią. Endokrynol Pol 2007; 58: 130-138.
13. Goldner WS, Stoner JA, Thompson J et al.: Prevalence of vitamin D insufficiency and deficiency in morbidly obese patients: a comparison with non-obese controls. Obes Surg 2008; 18: 145-150.
otrzymano: 2011-11-28
zaakceptowano do druku: 2011-12-21

Adres do korespondencji:
*Michał Wąsowski
The Medical Centre of Postgraduate Education, Department of Family Medicine, Internal Medicine and Metabolic Bone Disease
Czerniakowska Str. 231, 00-416 Warsaw,Poland
tel.: (22) 628-65-50
e-mail: drneo@wp.pl

Postępy Nauk Medycznych 1/2012
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