Vitamin D

Important information about vitamin D

Vitamin D is understood as a group of steroidal organic chemical compounds: vitamin D1 (calciferol), vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). These are fat-soluble vitamins. It means that they are not excreted from the body with urine or sweat, but are stored in the fatty tissue and the liver.1,6

Sources and absorption of vitamin D
From the human nutrition point of view, vitamins D2 and D3 play the most important role. In the human body, these vitamins can be formed under the influence of sunlight (vitamin D3) or can be supplied with food (vitamins D2 and D3).

There are only a few natural sources of vitamin D:1,3,6-8
- ergocalciferol (vitamin D2) occurring naturally in plant tissues – yeasts, cap mushrooms,
- cholecalciferol (vitamin D3) occurring naturally in animal organisms; it is most easily obtained from fatty fish meat (salmon, cod, tuna, herring, mackerel, sardines), fish oils, animal products (beef liver, egg yolks).

The absorption of vitamin D from food sources depends on many factors. Laxatives and corticosteroids reduce its absorption.22

Vitamin D units
1 µg cholecalciferol = 40 IU vitamin D
1 IU vitamin D = 0.025 µg cholecalciferol

Vitamin D synthesis 1-4, 9-11

The synthesis of the most active vitamin D metabolite (1.25 dihydroxycholecalciferol) occurs mainly in three organs: skin, liver and kidneys.

In addition to the possibility of obtaining vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) from food sources, the human body has the ability to independently produce vitamin D3 through skin synthesis. This transformation pathway satisfies 80–100% of the daily requirement; however, it is dependent on many factors (read more - Causes of vitamin D deficiency).

Vitamins D2 and D3 supplied with food are also subject to further metabolism in the liver and kidneys.

Skin synthesis of vitamin D3 (cholecalciferol) 1-4, 9

Sun radiation penetrates into the deeper layers of the epidermis (the basal and spinous layers). These layers contain a cholesterol derivative called
7-dehydrocholesterol (provitamin D3), which under the influence of UVB radiation with a length of 290–315 nm is transformed by photoisomerization into pre-vitamin D3, which in turn is transformed into vitamin D3 (cholecalciferol) in a temperature-dependent reaction.

Vitamin D3 can be both stored in fat cells and released into the intercellular spaces, and then into the blood, where it is transported using the DBP protein carrier (Vitamin D-binding protein) to the liver, where it undergoes further transformation.

Renal synthesis 1,2,4,12

25(OH)D is transmitted, also in combination with the binding protein (DBP), from the liver to the kidneys (as well as to certain other tissues, e.g. the skin, large intestine and immune cells), where, by the action of the enzyme 1α-hydroxylase, a fully active form of vitamin D, 1.25(OH)2D, is formed.

Hepatic synthesis 1,2,4,12

Vitamin D2 and D3 produced in the skin or supplied with food, in combination with the DBP binding protein, is transported to the liver, where the first stage of biosynthesis of the active form of vitamin D takes place. After enzymatic hydroxylation,
25-hydroxy vitamin D – 25(OH)D is formed at the C 25 carbon.

In the human body, both forms [1.25(OH)2D2 and 1.25(OH)2D3] have a similar biological activity.23

It is worth mentioning that due to the fact that 1α-hydroxylase activity is found not only in the kidneys but also in the skin, placenta, bone cells, parathyroid cells, lungs, monocytes and macrophages, the active form of vitamin D can be produced locally, depending on the needs of a given cell.4

Vitamin D deficiency 2,3,13-15

Vitamin D deficiency is a common global problem.

Epidemiological studies have shown that the deficit is still prevalent in all age groups.3

Chronic vitamin D deficiency can cause bone diseases such as rickets or osteoporosis, but also immune system disorders.

In Poland’s latitude, the angle of the sun rays even in the early autumn is too small to allow the production of sufficient amounts of cholecalciferol in the skin. Studies conducted on a group of adults living in northern Poland showed that in early autumn approximately 50% of the respondents have vitamin D deficiency, and in winter this percentage increases to as much as 80%.

Therefore, vitamin D supplementation is recommended from October to March, in accordance with the guidelines for Central Europe, assuming that the optimal vitamin D concentration, measured by determining the concentration of 25-hydroxycholecalciferol, should be 30–50 ng/ml (75–125 nmol/l).2

 

Causes of vitamin D deficiency 3,7,16,17

The most common cause of vitamin D deficit is the lack of exposure to sunlight due to lifestyle (working indoors), as well as fear of exposure to the sun and the use of cosmetics with UV filters. It is estimated that the use of SPF 15 products may reduce the ability to synthesise vitamin D by 99%.18

Skin production of vitamin D is often not sufficient to meet the daily needs, especially in highly industrialised countries, because effective sunlight is dependent on many factors, such as geographical location, season, weather, time of day, air pollution, exposure time, skin complexion, body fat thickness, body surface exposed to sunlight.

People with very dark complexion need several times longer exposure to light than people with light complexion. The high content of melanin pigment in the skin acts as a natural sunscreen.19,20

The main causes of vitamin D deficiency include3: (see table)

causeexample
Insufficient skin synthesis Lifestyle / Cosmetics with UV filters / Dark skin complexion / Skin ageing (age >65) / Latitude of residence / Skin transplant
Reduced absorption Cystic fibrosis / Coeliac disease / Whipple’s disease / Crohn’s disease / Bariatric surgery / Drugs reducing cholesterol absorption
Sequestration in the adipose tissue Obesity
Increased catabolism Certain immunosuppressive drugs
Reduced synthesis of 25(OH)D Hepatic impairment
Increased loss of 25(OH)D in urine Nephrotic syndrome
Reduced synthesis of 1.25(OH)2D Chronic renal failure
Hereditary disorders Genetic mutations causing rickets or resistance to vitamin D
Acquired disorders Primary hypoparathyroidism / Hyperthyroidism / Granulomatous diseases (e.g. sarcoidosis, tuberculosis) / Some lymphomas
Insufficient supplementation Too low supplementation dose / Irregular supplementation

Table 1. Causes of vitamin D deficiency

Effects of vitamin D

Vitamin D performs many important functions in the body:

Witamina D ikona

It contributes to normal absorption/utilisation of calcium and phosphorus

Witamina D ikona

It contributes to normal blood calcium levels

Witamina D ikona

It contributes to the maintenance of normal bones

Witamina D ikona

It contributes to the maintenance of normal muscle function

Witamina D ikona

It contributes to the maintenance of normal teeth

Witamina D ikona

It contributes to the normal function of the immune system

Witamina D ikona

It has a role in the process of cell division

Witamina D

Vitamin D level testing 16,24

The best indicator of vitamin D level in the body is considered to be the concentration of 25(OH)D
(25-hydroxy vitamin D) in blood serum. It informs about the availability of this substrate for the synthesis of the hormonally active form – 1.25(OH)2D.

Serum concentration of 25(OH)D is expressed in nanograms per millilitre (ng/ml) or nanomols per litre (nmol/l).

Information on 25(OH)D2 and 25(OH)D3 concentrations and their total amount, i.e. 25(OH)D, can be obtained at the same time.

Determination of total concentration of 25(OH)D enables the diagnosis and monitoring of vitamin D deficiency, whereas determination of the concentration of 25(OH)D2 and 25(OH)D3 fractions may facilitate the monitoring of treatment.

These tests are performed on doctor’s request. If a patient wishes to perform them independently, the cost is approximately PLN 40 to 100, depending on the site where the tests are performed.

25(OH)D SERUM CONCENTRATIONACTION TO BE CONSIDERED
 nmol/lng/ml 
Deficit 0-50 0-20 Deficit therapy
Sub-optimal concentration >50-75 >20-30 Increase/maintaining vitamin D supplementation
Optimal concentration >75-125 >30-50 Maintaining vitamin D supplementation
High concentration >125-250 >50-100 Maintenance/reduction of vitamin D doses
Potentially toxic concentration >250 >100 Refrain from taking vitamin D until the optimal concentration of 25(OH)D is reached
Toxic level >500 >200 Treatment of potential toxic effects

Source: Płudowski P. et al., Wytyczne suplementacji witaminą D dla Europy Środkowej – rekomendowane dawki witaminy D dla populacji zdrowej oraz dla grup ryzyka deficytu witaminy D, Endokrynologia Polska 2013;64:319-27.

Vitamin D supplementation

There are two basic strategies in the use of vitamin D2:

  • early prevention in a healthy population
  • treatment of deficits identified in patients

 

The detailed recommendations for the use of vitamin D in the population of Central Europe depending on age and health state are presented in the “Vitamin D Supplementation Guidelines of General Population and Groups at Risk of Vitamin D deficiency in Poland- Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies-2018 Update”.5

Recommendations for vitamin D supplementation in Poland:

target groupagevitamin d dosetarget groupagevitamin d dose
Newborns and infants 0-6 months 400 IU/day Preterm neonates < 32 weeks of pregnancy 800 IU/day**
6-12 months 400  - 600 IU/day 33-36 weeks of pregnancy 400 IU/day
Children 1-10 years 600-1000 IU/day* Obese children 1-10 years 1200-2000 IU/day
Adolescents 11-18 years 800-2000 IU/day* Obese adolescents 11-18 years 1600-4000 IU/day
Adults 19-65 years 800-2000 IU/day* Obese adults 19-65 years 1600-4000 IU/day
Seniors 65-75 years 800-2000 IU/day Obese seniors 65-75 years 1600-4000 IU/day
> 75 years 2000  - 4000 IU/day > 75 years 4000-8000 IU/day
People with a dark complexion 800-2000 IU/day Pregnant and breast-feeding women 2000 IU/day**

* especially in the months of September-April or throughout the year if adequate skin synthesis of vitamin D is not ensured in the summer
**  recommended monitoring of 25(OH)D in serum to achieve and maintain  an optimal level  of vitamin D

Developed based on Rusińska A., Płudowski P.,  Walczak M. et al. Vitamin D Supplementation Guidelines of General Population and Groups at Risk of Vitamin D deficiency in Poland- Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies-2018 Update; Front Endocrinol 2018;9;246;DOI:10.3389/fendo.2018.00246.

References

  1. Anuszewska E., Nowe spojrzenie na witaminę D, Gazeta Farmaceutyczna 2011, 32-35. (PDF)
  2. Lisowska K.A., Bryl E., Rola witaminy D w rozwoju chorób autoimmunologicznych, Postępy Hig Med Dosw (online), 2017; 71: 797-810 e-ISSN 1732-2693. (PDF)
  3. Misiorowski W. et al., Stanowisko zespołu ekspertów w sprawie stosowania wysokich dawek witaminy D w zapobieganiu i leczeniu jej niedoboru; Medycyna po Dyplomie 2017; 9: 36-45.(PDF)
  4. Myszka M., Klinger M., Immunomodulacyjne działanie witaminy D, Postępy Hig Med Dosw (online), 2014; 68: 865-878; e-ISSN 1732-2693.
  5. Rusińska A., Płudowski P., Walczak M. et al., Vitamin D Supplementation Guidelines of General Population and Groups at Risk of Vitamin D deficiency in Poland- Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies-2018 Update; Front Endocrinol 2018;9;246;DOI:10.3389/fendo.2018.00246.
  6. Kosińska J. et al., Nowe nieznane funkcje witaminy D, Medycyna Rodzinna 2008 (2), 34-47.
  7. U.S. Department of Health and Human Services, National Institutes of Health, https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
  8. Perzanowska-Brzeszkiewicz K., Marcinowska_Suchowierska E., Witamina D a choroby przewodu pokarmowego, Postępy Nauk Medycznych 2012, t.25, nr 3, 247-251.(PDF)
  9. Reichrath J., Vitamin D and the skin: an ancient friend, revisited, Experimental Dermatology 2007; 16: 618-625.(PDF)
  10. Holick M.F., Sunlight and Vitamin D. Both good for cardioviscular health, Journal of General Internal Medicine 2002; 17: 733-735.
  11. Napiórkowska L., Franek E., Rola oznaczania witaminy D w praktyce klinicznej, Choroby Serca i Naczyń 2009; 6 (4): 203-210.
  12. Bartoszewicz Z. et al., Czy umiemy wiarygodnie mierzyć stężenia klinicznie ważnych metabolitów witaminy D? Problemy i ich konsekwencje, Endokrynologia Polska 2013; 64 (3): 238-245.(PDF)
  13. Kmieć P., Sworczak K., Vitamin D deficiency in early autumn among predominantly non-eldery, urban adults in Northern Poland, Postępy Higieny i Medycyny Doświadczalnej 2015; 69: 918-924.(PDF)
  14. Kmieć P. et al., Widespread vitamin D deficiency among adults from northern Poland (54oN) after months of low and high natural UVB radiation, Endokrynologia Polska 2015; 66 (1): 30-38. (PDF)
  15. Kmieć P. et al., Vitamin D deficiency during winter months among adult, predominantly urban, population in Northern Poland, Endokrynologia Polska 2014; 65 (2): 105-113.
  16. Kennel K.A. et al., Niedobór witaminy D u dorosłych: kiedy badać i jak leczyć?, Mayo Clinic Proceedings 2010; 85 (8): 752-758. (PDF)
  17. Głuszko P., Znaczenie witaminy D dla rokowania sercowo-naczyniowego i sprawności osób starszych, Gerontologia Polska 2010; 18 (2): 66-70.(PDF)
  18. Nowicka G., Promieniowanie słoneczne a witamina D i nowotwory skóry, Studia Ecologiae et Bioethicae 2008, 6: 9-14.(PDF)
  19. Chen T.C. et al., Factors that influence the cutaneous synthesis and dietary sources of vitamin D, Arch Biochem Biophys. 2007; 460 (2): 213-217.(PDF)
  20. Olędzka R., Witamina D w świetle badań ostatnich lat, Bromatologia i Chemia Toksykologiczna 2013; 46 (2): 121-131.(PDF)
  21. Scientific opinion on the tolerable upper intake level of vitamin D, EFSA Journal 2012; 10 (7): 2813 [44pp.] (PDF)
  22. Craig C.R., Stitzel R.E., Modern Pharmacology with Clinical Applications, 6th edition, Philadelpha 2004, Lippincott Williams&Wilkins.
  23. Wicha J., Droga pod słońce. Wczesna historia witaminy D, Wiadomości chemiczne 2012, 66 (7-8): 671-696.
  24. Płudowski P. et al., Wytyczne suplementacji witaminą D dla Europy Środkowej – rekomendowane dawki witaminy D dla populacji zdrowej oraz dla grup ryzyka deficytu witaminy D, Endokrynologia Polska 2013;64:319-27.

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