Vitamin D for children – translated from Spanish – July 2012

Vitamin D: pathophysiology and clinical applicability in paediatrics

An Pediatr (Barc). 2012; xxx (xx): xxx.e1-xxx.e10
PEDIATRICS ANALESDí www.elsevier.es / anpediatr
R.M. Masvidal Alibercha, S. Gómezb Ortigosa, M.C. Baraza Mendozaa and O. Garcia-Algarb
to Cútala Institut de la Salut, Dr. Lluís Saye CAP, ABS Raval Nord, Barcelona, ??Spain b Department of Pediatrics, Hospital del Mar, Parc de Salut Mar, Barcelona, ??Spain
Received 2 March 2012, accepted May 15, 2012

Summary Vitamin D has always been associated with mineral metabolism, but Vitamin D receptors have been found vitamin D or its metabolites in different cells
Prophylaxis, body, indicating they may be involved in other physiological mechanisms. The deficit Rickets, vitamin D has been associated with an increased risk of infections, autoimmune diseases Screening; nity, diabetes, metabolic syndrome, obesity, asthma and certain neurological diseases, Sun exposure, such as schizophrenia.

Food, currently there are different techniques for the determination of 25 (OH) cholecalciferol in supplementation blood and there are discrepancies between them as to the results obtained in the same shows. It is important to achieve standardization of techniques to research comparable.

Not yet established the appropriate values ??of vitamin D in the body to ensure all its functions, but are not considered to be less than 20 ng / ml (50 nmol / l), still under discussion how to achieve these minimum standards in all the population. Since the main source of vitamin D is sunlight, look for strategies that are inconsistent with the messages of prevention of skin cancer. In recent years there have been changes in intake recommendations for vitamin D involving prophylactic activities carried out in the field of primary care.

This paper reviews the physiology, action, identification of laboratory desirable levels in the body and intake recommendations for vitamin D, and highlights the many issues raised by new research.
© 2012 Spanish Association of Pediatrics. Published by Elsevier Spain, SL All rights reserved.
- - - - - - - - - - - - - - - -

Comments by VitaminDWiki

This is a very rough translation of the PDF in Spanish attached at the bottom of this page, along with another Spanish paper
Does not include the table, and a section in the middle may be missing.

Google does not translate words which end in numbers, so we tied to separate the reference numbers from the words by inserting a space, but seemed to have missed about a dozen times. This can be seen in the following by Spanish words followed by a number. example: syndrome metabólico3 ==> metabolic syndrome 3

Interestingly, Google did not translate some Spanish words: niñnos ==> children; annos = years; Anno ==> child less than 1 year old?

Their conclusions (copied from the translated text)

  • 1. Infants under one anno breastfed at the breast should receive a supplement of 400 IU / day of vitamin D, beginning his administration in the first days of life. All infants under one anno who eat less than a liter a day of milk fortified with vitamin D should receive a supplement of 400 IU / day - recommendation grade B
  • 2. The ninños or teenagers who have risk factors for vitamin D deficiency and who do not obtain 400 IU / day with drinking a gallon of milk or enriched or fortified foods appropriate sun exposure should receive a vitamin D supplement of 400 IU / day -recommendation grade B
  • 3. In anno ninños over one or adolescents, in general, is recommended for adequate production of vitamin D from exposure to midday sun without protection for 10-15 min per day during the spring, summer and having the face otonño and part of the arms bare. In winter, above 42 degrees north latitude, not produce vitamin D (grade I recommendation)
  • 4. The ninños infants less than a corrected age anno need a vitamin D intake of 200 IU / kg / day to a maximum of 400 IU / day (recommendation grade A).

See also VitaminDWiki

- - - - - - - - - - - - - - - -

Introduction

Vitamin D, or better, vitamins D (ergocalciferol or vitamin D2 and cholecalciferol or vitamin D3) are fat soluble vitamin precursor of the active forms, which require for their formation interorgánicos process. The fact that the active form of vitamin D required of an internal synthesis and has an important role in regulating calcium and phosphorus metabolism has many authors consider more a hormone than a vitamin.

The story of vitamin D may be linked to the raquitismo1. The disease, caused by vitamin D deficiency, was described clinically in the seventeenth century. In 1931, Askaw defined chemical composition of vitamin D2 and subsequent years investigated the mechanisms of production of active forms of vitamin D in the body and their actions on mineral metabolism. Although a general observation that niñnos diagnosed rickets were more prone to disease and vitamin D infecciosas2 was related to the modulation of the immune system, not until this century when performed numerous observational studies on its role in different diseases, ones that involve the immune system and others in which this relationship is not established, such as hypertension, diabetes or syndrome metabólico3, 4. The interest of the scientific community for this vitamin is demonstrated by the fact that in 2 years, more than 5,500 registered PubMed articles on the subject.

The purpose of this paper is to review recent studies on physiology, action, determination, desirable levels in the body and intake recommendations for vitamin D, as well as raise issues related to new lines of research.

Physiology of vitamin D

Vitamin D is a fat soluble vitamin that can be found in the body as endogenous and exogenous 5-7. The endogenous production form, cholecalciferol (D3) is the main source of vitamin D. Is synthesized in mammalian skin by the action of ultraviolet B radiation (UVB), which produces the photolysis of 7-dehydrocholesterol, making vitamin D3 6.8. "10 may also be an external input through cholecalciferol some foods.

The ergocalciferol (D2) is obtained through diet and is absorbed in the duodenum and jejunum, absorption is favored by the presence of fat is between 55 and 99% of oral intake 5 "7.11.
The 2 types of vitamin D must undergo a complex process prior to being metabolically active 5,6,9. 2 suffers prohormone hydroxylations, one in the liver, resulting in 25-hydroxyvitamin D (25 (OH) D) or calcidiol 7,11,12, and other primarily in the renal tubule, by 1-o-hydroxylase , leading to 1,25-dihydroxyvitamin D (1,25 (OH) D) or calcitriol, which is at least 10 times more potent than 25 (OH) D, although it has a circulating concentration inferior7 1,000 times, 12. The 1-hydroxylase or also in other tissues that also express vitamin D receptors, such as placenta, colon, keratinocytes, activated mononuclear cells and osteoblasts, which could produce 1.25 (OH) D with a local function or autocrine paracrine 7,8,11,12.

Values ??of 1.25 (OH) D are regulated by the 1-or hydro-xilasa. The hydroxylation is activated by parathyroid hormone (PTH) and calcitonin, and is inhibited by plasma levels of calcium, phosphorus and self 1.25 (OH) D. The phosphatonins (FGF23), growth hormone, IGF-I or prolactin also act directly or indirectly on the 1-hydroxylase or kidney, although the exact relationship and its clinical significance are still unclear from 6.12 to 14 .

Under normal circumstances, approximately 85% of 1.25 (OH) D is attached to the binding protein or vitamin D transcalciferina (DBP) 6 and 15% albumin, being free circulation in plasma less than 0.5 % to 1.25 (OH) D and less than 0.05% for 25 (OH) D. These forms are the only circulating free available for binding to receptors on target cells 11,12.

Half life varies with the metabolite, 25 (OH) D is about 15 days 7,11,12.
At high doses, vitamin D can be stored in adipose tissue and may have an average life of 7.11 months.

Although both vitamins (D2 and D3) have identical biological functions, some studies suggest that vitamin D3 may be 2 or 3 times more powerful to keep the levels of 25 (OH) D 6,7,12, in addition, 25 (OH) D3 could join DBP with higher affinity than 25 (OH) D2 12.

The main action of vitamin D is to maintain the numbers of calcium and phosphorus within the physiological range allowing metabolism, neuromuscular transmission bone mineralization and 6.7, but described the presence of vitamin D receptors in bone marrow bone, cartilage, hair follicles, adipose tissue, adrenal, brain, stomach, small intestine, distal renal tubule, colon, pancreas (cells (3), liver, lung, muscle, activated B and T lymphocytes, heart, juxtaglomerular cells, vascular smooth muscle, gonads, prostate, breast, parathyroid cells, parotid gland, placenta, retina, thymus and thyroid 7,10,12. For this reason, you assume various functions 10,12,15. has been observed that vitamin D inhibits growth and stimulates keratinocyte differentiation, and vitamin D concentrations above 75 mmol / l (30 ng / ml) keep cell growth under control and prevent the cells are autonomous and malignicen 15.

Determination of vitamin D and normal values

The units used in the determination of the 25 (OH) D in the blood are ng / ml and nmol / l, 1 ng / ml 25 (OH) D is 2.496 nmol / l. The amount is given in vitamin D (cholecalciferol or ergocalciferol) by food or drug is usually expressed in "international units" (IU), equivalent to 1 40 IU of vitamin D2 or D3.

The results of the values ??of 25 (OH) D in blood vary according to the method used to obtain and may even have inter-method differences 16.17 dependent calibration, which can lead to the same sample at higher or lower results laboratory to laboratory. The value of 25 (OH) D can be determined by competitive immunoassay techniques, chemiluminescence or by chromatography nonimmunologic direct detection (HPLC-UVy LC-MS/MS) 18. Chromatographic methods can be measured independently 25 (OH) D2 and 25 (OH) D3, but in most immunoassays ratio of 25 (OH) D2 detected is variable. The UK Food Standards Agency diferentes19 compared 5 methods. The chromatographic results were similar but not those made by immunoassay. Opted for recommending the LC-MS/MS. This method is used by the U.S. CDC. States. since 2007. In Espanña are most commonly used immunoassay-based methods, being more economical.

From a clinical point of view, all methods are valid to detect serious deficiencies of vitamin D 16. For moderate assume a certain risk of error that can be partially alleviated by considering the reference values ??for each laboratory. This does not apply to research studies in which standardized methods must be 16-20.

Periodically, we performed a workshop on vitamin D, which brings together over 400 experts from 35 countries to reach a consensus on the ideal values ??of vitamin D in blood. Most experts meeting in 2009 agreed on the need for a minimum value of 20 ng / ml (50 nmol / l) for good bone health and mineral, although according to this criterion a large proportion of world population is deficient in vitamin D. But there are authors that are based on studies involving bone diseases not considered as normal and anything between 30 and 40 ng / ml 21 -23.

Sources of vitamin D

Humans can get vitamin D from sun exposure (vitamin D3) and intake (vitamin D2, mainly).
In the newborn, the vitamin D depends on maternal status of vitamin D, which passes through the placenta, and after birth depends on domestic production and exogenous 7,13,14. The preterm infant has less time to accumulate vitamin D and, therefore, have higher requirements for vitamin D than the term infant 15.

Solar Power

It is considered that 80-90% of vitamin D in humans comes from cutaneous synthesis from the action of UVB radiation 8.10. Several factors influence the production of vitamin D in skin. The melanin pigment of skin absorbs UVB photons and acts as a natural sunscreen, but it makes dark-skinned people require up to 5 or 10 times more sun exposure than fair-skinned to synthesize similar amounts of vitamin D 7,8,10,12,15,24,25

The incidence of UVB decreases with increasing latitude, because the oblique angle through which the sunlight reaching the atmosphere causes the path through it is greater and will produce a greater scattering and absorption of UV 7,12,15,25.

It is a very small amount of vitamin D during the winter months, due to increased warm clothing, reducing the time spent away from home and the decrease in UV radiation reaching the earth's surface by the greater obliquity of the sun , which means that over the 35-40 ° latitude (the Iberian Peninsula is between 36 ° and 43.5 °) in the winter months, the number of UVB photons that reach the Earth's atmosphere decreases 80-100%, not achieving the minimum threshold required to induce the synthesis of vitamin D and, therefore, their production is negligible during these months 7,8,12,15,24,25

The rays penetrate obliquely into the early hours of the day and late Therefore, at these times only produced pequenñas amounts of vitamin D in the skin, even in the summer months the only time they reach the surface Earth insufficient UVB photons to produce vitamin D is between 10 and 15 hours (solar time) in spring, summer and has been shown otonño a brief statement at noon has a maximum benefit of vitamin D with reduced risk of eritema15, 24 "26.

And the pollution clouds can decrease the amount of solar radiation reaching the earth's surface 7.15.
A factor 2 sunscreen blocks approximately 50% of UVB, SPF 15 to 94% and 97% factor of 30, if applied correctly. These guards seem to block more effective radiation for the synthesis of vitamin D for erythema 7,8,12,15,24,26.

It has been observed that increasing the concentration of vitamin D, at least 20% of body surface must be exposed to UVB 7,8,12,15,24,26. Clothing can decrease the amount of vitamin D synthesized by UVB and the fabric is important, with the black wool 2 times more effective absorbing and preventing the incidence of UVB on the skin than white cotton.

The greater the thickness of the ozone layer 24, less UVB rays reaching the earth's surface, so that high altitudes are associated with increased amount of UV radiation 15. It is considered that for every mile you go up, increasing by 6% incidence of UV radiation 15. Furthermore, the snow can reflect a 20% to 30% of radiation reaching the soil as the water or sand.

The ninños may require less sun exposure to produce adequate amounts of vitamin D by the large surface area relative to the size and the ability to produce more vitamin D than adults 7.15.

Phototherapy applied to infants does not influence the vitamin D 27 values ??for the current phototherapy lamps do not use UVB.

Excessive sun exposure is a rare cause of vitamin D intoxication because the previtamin D can be degraded by UVB radiation as lumisterol inert products and tachysterol and vitamin D to suprasterol fotoisomeriza and other inert 12.15, 28.

Dietary sources of vitamin D

Vitamin D can also be obtained from foods that naturally contain or have been supplemented. Table 1 shows the approximate content of vitamin D of different foods. These values ??can vary according to the "state" of the food. For example, in the eel can vary from 200 IU to 800 IU, and the way they fry, glass eels, can have up to 4,400 IU per 100g, the mushrooms are rich in vitamin D only if they have been subjected to full sunlight for 5 or 10 min or were treated with UV rays. The form also influences cooking: frying fish reduces its vitamin D around 50%, while the cook is not affected 9,15,29.

Breast milk is low in vitamin D, which varies between 4 and 100 IU / l depending on maternal stores, food and sun exposure of the mother 7,9,14,15. In the case of an average consumption of 750ml/día, breast-feeding exclusively without exposure to sunlight provides UI/día15 of 11 to 38 but not known how these values ??relate to the optimal calcium absorption and may bioavailability calcium from milk is different and less dependent transport of vitamin D9, 14.

Supplementation of different foods with vitamin D is based on population to ensure a contribution
R.M. Masvidal Aliberch et al
Table 1

Vitamin D: pathophysiology and clinical applicability
Most provide a minimum of 400 IU of vitamin D per liter of milk reconstituida9, 14, as recommended by the AAP (American Academy of Pediatrics) and ESPGHAN.

Another source of vitamin D dosage forms, available as vitamin D2 or D3.
In situations of intestinal malabsorption, as in celiac disease, gastric or intestinal resection, pancreatic insufficiency (such as cystic fibrosis), Crohn's disease and cholestatic liver disease, can greatly decrease the absorption of vitamin D15.

Values ??of vitamin D in apparently healthy populations

In countries like Iran, vitamin D deficiency is very prevalente30, especially among women and adolescents preteens 31, most likely due to clothing. In EE. States. found values ??<50 nmol / l in more than a quarter of the ninños pequenños of low income families 32 and in 12.1% of ninños and adolescentes33. In Canada, a survey that included a population of 6 to 79 annos, 10% had figures <37.5 nmol/l34, and another study noted that niñnas of low income families had low levels of vitamin D 35 . We found very low levels of vitamin D in ninñas Pakistani adolescents (mean of 10.9 nmol / l) immigrated to Denmark 36. In a study Espanña in Madrid that included 102 children aged 9 to 13 years and found a value <50 nmol / l in 51% of cases 37, and in one study in infants Valencian mean values 25 (OH) D in winter, in the breastfeeding group was 16.8 ng / ml (42 nmol / l) 38.

The low levels of vitamin D in apparently healthy ninños have been linked to sun exposure, race, low intake of foods with vitamin D, obesity, age and social stratum 39-42.

It is also important to know the status for vitamin D in pregnant women, as this may affect the newborn 43.44, especially the premature. In a U.S. study. States., Arab mothers and their premature children had higher vitamin D deficiencies in relation to Caucasian mothers and their children 45. Also have found high rates of deficiency in mothers of Pakistan, Turkey and Somalia immigrants to Noruega46. This is especially relevant given the current high prevalence of immigration in our country.

Classically related diseases with vitamin D deficiency have been bone (rickets, osteomalacia and osteoporosis) 4.43.
These conditions can also be produced by significant deficiencies of calcium and certain metabolic disorders.

Rickets seemed to be a disease eradicated in the vast majority of first world countries due to improved feeding, supplementation with vitamin D and increased outdoor activities in industrial areas, but immigration has led to its resurgence 48-53. Originates with vitamin D values ??of <25 nmol / l (10 ng / ml).
Osteomalacia or adult rickets, presents with an inadequate mineralization of cortical and cancellous bone maturity. Osteomalacia found in patients with values ??<62 nmol / l (25 ng / ml) 4.
Osteoporosis presents with loss of trabecular bone strength and reduced bone cortex and become susceptible to fractures. Supplements of vitamin D and calcium may be useful for prevention if achieved figures of vitamin D of 62 nmol / l, although this is questionable.

Bone mineralization occurs predominantly in the first 2 decades of life and has studied whether administration of vitamin D may increase bone density. Not found in ninños with adequate levels of vitamin D (50 nmol / l) and must do more studies in children with deficiency 54.

Many diseases have been linked to low values ??(<50 nmol / l) or moderate (between 50 and 75 nmol / l between 50 and 100 nmol / l) of 25 (OH) D 4.47. In no bony pathology has been demonstrated that association does not prove a causal effect and in many cases there are confounding etiological factors that cause results have to be observed with caution. There have been case studies of intervention / control, but virtually all conclude that we need more research 22.

The vitamin D can increase the secretion and insulin sensitivity. A meta-analysis of 5 observational studies of vitamin D supplementation in infancy was a reduction of almost 30% risk of type 1 diabetes in ninños that had ever received vitamin D 55, but these studies suffered from methodological problems.
We performed a meta-analysis 56 in relation to vitamin D and cardiovascular risk factors, including type 2 diabetes. Three of 6 analyzes (of 4 different cohorts) found a lower incidence of diabetes in people with a higher value of vitamin D. Moreover, 8 trials found no effect of vitamin D supplementation on blood sugar or diabetes recently established.

Vitamin D deficiency has been associated with obesity 57-61, but it is unknown whether as cause or effect. It seems that excess body fat "kidnap" circulating vitamin D, but has also been postulated that vitamin D deficiency increases the accumulation of fat in the body.

The major deficiency / moderate has been associated with increased mortality general62 and cardiovascular63 various risk factors, 64 and metabólico56 syndrome, 65: hipertensión66, hypertriglyceridemia and diabetes type 256.67. A study in school in Madrid linked vitamin D deficiency with hipertrigliceridemia68: the ninños with a value of vitamin D <17.4 ng / ml had significantly more triglycerides in their blood than those with more than 27.6 ng / ml . Moreover, a study has been associated with vitamin D supplementation with increased LDL cholesterol 69.

Deficiency has been linked to asthma attacks more and more complicated, and a reduced response to corticosteroids 70.71. A study was conducted with 1,024 niñnos with severe or moderate asthma 7 2, determined 25 (OH) D at baseline. Those with values ??<30 ng / ml had a higher probability of any hospitalization or emergency department visit.
There have been many studies linking vitamin D with various neoplasms 73.74. Values ??<33 ng / ml have been associated with increased risk of colorectal cancer. It has also been shown to decrease the risk of breast cancer if women extender supplemented with disabilities, but this was reversed in case of women with high intakes. Moreover, it appears that vitamin D supplementation in people who have an adequate level does not decrease the risk of cancer and, in contrast, high levels can be a risk factor for esophageal cancer and figures> 40 ng / ml are associated with a higher risk of pancreatic neoplasia with a more aggressive prostate cancer 75.

Vitamin D supplements appear to reduce respiratory tract infections in adults significantly 76.77, but not all studies have had the same result. A study of 468 patients found a significant association between chronic infection with hepatitis C and values ??of 25 (OH) D <10 ng / ml 78. There are very few intervention studies ninños. In one, a supplement of 1,200 IU of vitamin D reduced the incidence of influenza during the epidemic among asthmatics niñnos included in the study decreased seizures secondary to infection

Screening recommendations

Conditions that have been associated with vitamin D deficiency have made to increase exponentially the application for determination of 25 (OH) D.

It has to assess whether increased spending means that this justifies its determination in the general population, given that the data only provides about 15 days before (the average life of 25 (OH) D in the blood), not known reference values ??and ideals that the values ??obtained may differ between laboratories, and considering that it is not sufficiently studied the health impact of low levels in healthy individuals. Could be considered more efficient, in healthy subjects, figures ensure adequate vitamin D supplementation with prophylactic and / or proper health education about diet and sun exposure.

Instead, there are other situations that would justify the determination of 25 (OH) D 22.88: clinical suspicion of rickets, genu varus in children or adolescents, pathological fractures, bone pain, hypocalcemia or hypophosphatemia, ninños with chronic liver or kidney diseases

R.M. Masvidal Aliberch et al that present with malabsorption, severe malnutrition, lack of sun exposure, dark-skinned pregnant women or that go great covers, and patients on anticonvulsant therapy, growth hormone, glucocorticoids or drugs against AIDS.

Recommendations for vitamin D

The main source of vitamin D is sun exposure, making it difficult to establish requirements widespread intake of it, especially because of the many variables associated with the deficiency. The IOM (Ins-titute of Medicine) in 1997 recommended intake of 200 IU / day of vitamin D. However, due to an intake of 200 IU / day seems sufficient to maintain concentrations of 25 (OH) D above 50 nmol / L 89.90, the AAP and others 8,13,22,24,29,88 recommend an intake of 400 IU / day in children under Anno and 600 IU / day in older ninños. 14.91 The IOM has also recently revised their recommendations for vitamin D intake: dietary reference intake (Dietary Reference Intakes DRI), expressed as RDA (recommended dietary allowances) or adequate intake (AI) and the maximum permissible level (UL) of vitamin D.

The way to increase the contribution of exogenous vitamin D is varied. In Espanña, various baby foods that are supplemented with vitamin D supplementation and pharmacological regarding the situation in the past has been very irregular annos, coexisting patterns varied in dose and time of administration 14.

The recommendations of systematic contributions of vitamin D in ninños correspond to opinions or expert consensus (level C evidence), based on studies that enable secure minimum values ??of 50 nmol / l in the population with the recommended intake, but not really supported by clinical studies whose results allow diseñno and increase this level of evidence A or B at 92, since there are many factors that influence vitamin D levels in each individual.

No systematic review clarifies whether there is a degree of sun exposure and safe enough to maintain optimal vitamin D figure 22, but it is shown that common exclusion is a risk of deficiency.
– – – – – – – –

Values ??of vitamin D in apparently healthy populations

In countries like Iran, vitamin D deficiency is very prevalente30, especially among women and adolescents preteens 31, most likely due to clothing. In EE. States. found values ??<50 nmol / l in more than a quarter of the ninños pequenños of low income families 32 and in 12.1% of ninños and adolescentes33. In Canada, a survey that included a population of 6 to 79 annos, 10% had figures <37.5 nmol/l34, and another study noted that niñnas of low income families had low levels of vitamin D 35 . We found very low levels of vitamin D in ninñas Pakistani adolescents (mean of 10.9 nmol / l) immigrated to Denmark 36. In a study Espanña in Madrid that included 102 children aged 9 to 13 years and found a value <50 nmol / l in 51% of cases 37, and in one study in infants Valencian mean values 25 (OH) D in winter, in the breastfeeding group was 16.8 ng / ml (42 nmol / l) 38.

The low levels of vitamin D in apparently healthy ninños have been linked to sun exposure, race, low intake of foods with vitamin D, obesity, age and social stratum 39-42.

It is also important to know the status for vitamin D in pregnant women, as this may affect the newborn 43.44, especially the premature. In a U.S. study. States., Arab mothers and their premature children had higher vitamin D deficiencies in relation to Caucasian mothers and their children 45. Also have found high rates of deficiency in mothers of Pakistan, Turkey and Somalia immigrants to Noruega46. This is especially relevant given the current high prevalence of immigration in our country.

Classically related diseases with vitamin D deficiency have been bone (rickets, osteomalacia and osteoporosis) 4.43. These conditions can also be produced by significant deficiencies of calcium and certain metabolic disorders.

Rickets seemed to be a disease eradicated in the vast majority of first world countries due to improved feeding, supplementation with vitamin D and increased outdoor activities in industrial areas, but immigration has led to its resurgence 48-53. Originates with vitamin D values ??of <25 nmol / l (10 ng / ml).

Osteomalacia or adult rickets, presents with an inadequate mineralization of cortical and cancellous bone maturity. Osteomalacia found in patients with values ??<62 nmol / l (25 ng / ml) 4.
Osteoporosis presents with loss of trabecular bone strength and reduced bone cortex and become susceptible to fractures. Supplements of vitamin D and calcium may be useful for prevention if achieved figures of vitamin D of 62 nmol / l, although this is questionable.

Bone mineralization occurs predominantly in the first 2 decades of life and has studied whether administration of vitamin D may increase bone density. Not found in ninños with adequate levels of vitamin D (50 nmol / l) and must do more studies in children with deficiency 54.

Many diseases have been linked to low values ??(<50 nmol / l) or moderate (between 50 and 75 nmol / l between 50 and 100 nmol / l) of 25 (OH) D 4.47. In no bony pathology has been demonstrated that association does not prove a causal effect and in many cases there are confounding etiological factors that cause results have to be observed with caution. There have been case studies of intervention / control, but virtually all conclude that we need more research 22.

The vitamin D can increase the secretion and insulin sensitivity. A meta-analysis of 5 observational studies of vitamin D supplementation in infancy was a reduction of almost 30% risk of type 1 diabetes in ninños that had ever received vitamin D 55, but these studies suffered from methodological problems.

We performed a meta-analysis 56 in relation to vitamin D and cardiovascular risk factors, including type 2 diabetes. Three of 6 analyzes (of 4 different cohorts) found a lower incidence of diabetes in people with a higher value of vitamin D. Moreover, 8 trials found no effect of vitamin D supplementation on blood sugar or diabetes recently established.

Vitamin D deficiency has been associated with obesity 57-61, but it is unknown whether as cause or effect. It seems that excess body fat "kidnap" circulating vitamin D, but has also been postulated that vitamin D deficiency increases the accumulation of fat in the body.

The major deficiency / moderate has been associated with increased mortality general62 and cardiovascular63 various risk factors, 64 and metabólico56 syndrome, 65: hipertensión66, hypertriglyceridemia and diabetes type 256.67. A study in school in Madrid linked vitamin D deficiency with hipertrigliceridemia68: the ninños with a value of vitamin D <17.4 ng / ml had significantly more triglycerides in their blood than those with more than 27.6 ng / ml . Moreover, a study has been associated with vitamin D supplementation with increased LDL cholesterol 69.

Deficiency has been linked to asthma attacks more and more complicated, and a reduced response to corticosteroids 70.71. A study was conducted with 1,024 niñnos with severe or moderate asthma 7 2, determined 25 (OH) D at baseline. Those with values ??<30 ng / ml had a higher probability of any hospitalization or emergency department visit.

There have been many studies linking vitamin D with various neoplasms 73.74. Values ??<33 ng / ml have been associated with increased risk of colorectal cancer. It has also been shown to decrease the risk of breast cancer if women extender supplemented with disabilities, but this was reversed in case of women with high intakes. Moreover, it appears that vitamin D supplementation in people who have an adequate level does not decrease the risk of cancer and, in contrast, high levels can be a risk factor for esophageal cancer and figures > 40 ng / ml are associated with a higher risk of pancreatic neoplasia with a more aggressive prostate cancer 75.

Vitamin D supplements appear to reduce respiratory tract infections in adults significantly 76.77, but not all studies have had the same result. A study of 468 patients found a significant association between chronic infection with hepatitis C and values ??of 25 (OH) D <10 ng / ml 78. There are very few intervention studies ninños. In one, a supplement of 1,200 IU of vitamin D reduced the incidence of influenza during the epidemic among asthmatics niñnos included in the study decreased seizures secondary to infection 79. No relationship was found with vitamin D deficiency and bronchiolitis requiring hospitalization 80 or 81 with recurrent tonsillitis.

Low levels of vitamin D are also associated with autoimmune diseases 82.83, chronic urti-caria/angioedema 84, 85 undifferentiated inflammatory arthritis, multiple sclerosis, schizophrenia 86 and 87.

Screening recommendations

Conditions that have been associated with vitamin D deficiency have made to increase exponentially the application for determination of 25 (OH) D.

It has to assess whether increased spending means that this justifies its determination in the general population, given that the data only provides about 15 days before (the average life of 25 (OH) D in the blood), not known reference values ??and ideals that the values ??obtained may differ between laboratories, and considering that it is not sufficiently studied the health impact of low levels in healthy individuals. Could be considered more efficient, in healthy subjects, figures ensure adequate vitamin D supplementation with prophylactic and / or proper health education about diet and sun exposure.

Instead, there are other situations that would justify the determination of 25 (OH) D 22.88: clinical suspicion of rickets, genu varus in children or adolescents, pathological fractures, bone pain, hypocalcemia or hypophosphatemia, ninños with chronic liver or kidney diseases

R.M. Masvidal Aliberch et al that present with malabsorption, severe malnutrition, lack of sun exposure, dark-skinned pregnant women or that go great covers, and patients on anticonvulsant therapy, growth hormone, glucocorticoids or drugs against AIDS.

Recommendations for vitamin D

The main source of vitamin D is sun exposure, making it difficult to establish requirements widespread intake of it, especially because of the many variables associated with the deficiency. The IOM (Ins-titute of Medicine) in 1997 recommended intake of 200 IU / day of vitamin D. However, due to an intake of 200 IU / day seems sufficient to maintain concentrations of 25 (OH) D above 50 nmol / L 89.90, the AAP and others 8,13,22,24,29,88 recommend an intake of 400 IU / day in children under Anno and 600 IU / day in older ninños. 14.91 The IOM has also recently revised their recommendations for vitamin D intake: dietary reference intake (Dietary Reference Intakes DRI), expressed as RDA (recommended dietary allowances) or adequate intake (AI) and the maximum permissible level (UL) of vitamin D.

The way to increase the contribution of exogenous vitamin D is varied. In Espanña, various baby foods that are supplemented with vitamin D supplementation and pharmacological regarding the situation in the past has been very irregular annos, coexisting patterns varied in dose and time of administration 14.

The recommendations of systematic contributions of vitamin D in ninños correspond to opinions or expert consensus (level C evidence), based on studies that enable secure minimum values ??of 50 nmol / l in the population with the recommended intake, but not really supported by clinical studies whose results allow diseñno and increase this level of evidence A or B at 92, since there are many factors that influence vitamin D levels in each individual.

No systematic review clarifies whether there is a degree of sun exposure and safe enough to maintain optimal vitamin D figure 22, but it is shown that common exclusion is a risk of deficiency.

Adequate sun exposure is not easy to define, but it seems that in adults the beneficial effects obtained with the exposure of the face, hands and arms (approximately 25% of body surface), 2 or 3 times a week , which is the time required for a minimal erythema dose (DME) in summer, spring and otonño, equivalent to an oral dose of 1,000 IU of vitamin D.

This would be adequate to meet the requirements for vitamin D along the Anno. Other organizations such as the UK National Radiological Protection Board, saying that short periods abroad, such as during daily life, would be sufficient to produce adequate vitamin D 28. This contrasts with the high levels of vitamin D deficiency in populations that are supposed to meet this recommendation. According to Specker, 30 min per week in Pannal or 2 h without a hat and dress would keep values ??of 25 (OH) D above 11 ng / ml in 93 infants.

Ho found that exposing the face 24 minutes per day would suficiente94. Other researchers recommend vitamin D short: pathophysiology and clinical applicability periods of sun exposure for vitamin D in older ninños Even a year, as exposure of the arms, face and hands for 5 to 30 min between 10:00 and 15:00 hours, 9,10,15,25,95 2 times per week. However, this conflicts with current clinical guidelines for the prevention of skin cancer so many authors agree on reducing sun exposure and not to recommend the intentional sun exposure without protection 8,24,25,96. Knowledge unclear benefit / risk of sun exposure hinders the development of public health messages are not contradictory 14.

Therefore, until there are no well-balanced recommendations on sun protection to ensure a state of vitamin D sufficiency without significantly increasing the risk of developing cancer, seems adequate vitamin D supplementation 10.

Some studies have shown vitamin D supplementation in pregnant and lactating women, yielding a minimum effect on the levels of 25 (OH) D in newborn s 8.97, seeming that the dose should be supplement greater than those recommended to cause some beneficial effect on the mother or the newborn 98.

Current recommendations made by the AAP since 2008 are as follows 8:

  • 1. Infants should continue prophylaxis with 400 IU / day of vitamin D beginning in a few days of life. The supple-mentation should be continued unless the infant takes a liter a day of formula supplemented with vitamin D.
  • 2. The older ninños taken less than a liter a day of milk or milk formula supplemented with vitamin D should receive 400 IU / day of vitamin D. Other dietary sources of vitamin D, vitamin-fortified foods can be included in the daily intake of each Ninno.
  • 3. Teens who do not obtain 400 IU of vitamin D per day through foods fortified with vitamin D should receive 400 IU / day of vitamin D.
  • 4. Children with increased risk of vitamin D may need higher doses of vitamin D (up to 2 or 3 times) 88 to reach a normal value, and its status should be studied and controlled.


In Espanña, the working group on prevention in childhood and adolescence, Espanñola Association of Pediatric Primary Care and Breastfeeding Committee Espanñola Association of Pediatrics, follow these recommendations although some matices10:

  • 1. Infants under one anno breastfed at the breast should receive a supplement of 400 IU / day of vitamin D, beginning his administration in the first days of life. All infants under one anno who eat less than a liter a day of milk fortified with vitamin D should receive a supplement of 400 IU / day - recommendation grade B
  • 2. The ninños or teenagers who have risk factors for vitamin D deficiency and who do not obtain 400 IU / day with drinking a gallon of milk or enriched or fortified foods appropriate sun exposure should receive a vitamin D supplement of 400 IU / day -recommendation grade B
  • 3. In anno ninños over one or adolescents, in general, is recommended for adequate production of vitamin D from exposure to midday sun without protection for 10-15 min per day during the spring, summer and having the face otonño and part of the arms bare. In winter, above 42 degrees north latitude, not produce vitamin D (grade I recommendation)
  • 4. The ninños infants less than a corrected age anno need a vitamin D intake of 200 IU / kg / day to a maximum of 400 IU / day (recommendation grade A).

{Note by VitaminDWiki: many suggest 100 IU/kg/day}

Recently, several working groups have changed these recommendations, suggesting that vitamin D needs to be more of an anno 600 IU / day to maintain non-skeletal benefits of vitamin D22, 23.88.
Despite these recommendations, yet no studies showing that universal supplementation with vitamin D dosage is essential for improving population health. Ideally, the decision to indicate vitamin D dosage form would have to perform individually, taking into account the diet (food intake or vitamin D-rich or supplemented with), sun exposure, time of Anno, the latitude where they live, breed and level of acceptance, realistically considered, behavior modification. In infants also have to consider all the above variables in your mother and if it was premature or not. But for practical purposes and public health, can help ensure a minimum intake comfortably and easily using the universal supplementations. Vitamin D supplements may be marketed prepared from vitamin D2 or D3. While it was thought that the potential was similar in some studies show that vitamin D3 may be from 1.7 to 3 times more potent than vitamin D2 in their ability to raise levels of 25 (OH) D, so are mainly recommended vitamin D3 supplementation 8,10,15. In Espanña is marketed vitamin D3 drops and each drop corresponds to 66 IU of vitamin D. For prophylaxis in cases of malabsorption is recommended lime-cifediol, soluble in water, drops, each drop provides 240 IU of vitamin D, or blisters, each with 15,960 IU.

Although it has been used for many annos, there are few published studies on the administration of massive doses of vitamin D and those few have been conducted in adolescents and preadolescents, concluding that the administration of high doses of supplementation Vitamin D is effective and safe in adolescents and might facilitate adherence 99.100.
Other products with vitamin D2 or vitamin D3, but are associated with other vitamins or calcium or multivitamin with minerals are. There are also marketed metabolites of vitamin D for patients with diseases associated with vitamin D complex.

It has only been demonstrated toxic effects of vitamin D with very high blood levels (usually above 150 ng / ml) and are usually not seen until they are ingested 10,000 IU daily for 5 months. Although the therapeutic range is high, one must consider the danger of overdose, especially with the use of massive doses 22. Have been published cases of vitamin D intoxication with significant symptoms of hypercalcemia counter supplements administered 101.
Remember that in addition to adequate intake of vitamin D, calcium intake should be optimal to ensure adequate training and bone modeling.

Conclusions

- The multitude of factors that influence vitamin D status affects the extrapolation of data from other countries, it would be advisable to carry out studies on the situation of children and adolescents about vitamin D, in our environment.


Have to standardize the methods of determination of 25 (OH) D in all research on vitamin D.

  • Given the current recommendations regarding vitamin D, the pediatrician must bear in mind the need to address each case individually, ele gir proper preparation and monitoring of treatments ruled.
  • Since the massive doses of vitamin D may improve adherence, it would be interesting to conduct studies on this method of administration, looking especially at-risk populations.
  • The recommendations regarding sun exposure must be adjusted so as to prevent against often contradictory messages for the population (much sunscreen to prevent skin cancer compared to avoid sun exposure for vitamin D deficiency tar), reaching a beneficial balance, all based on evidence. We must promote the inclusion in the diet of foods rich in vitamin D naturally.

Conflict of interest

The authors declare no conflict of interest.

Literature

1. Iglesias A, Restrepo JF. History of vitamin D. Colombian Journal of Rheumatology. 2005, 12:12-32.
2. Chesney RW. Vitamin D and the magic mountain: the anti-infectious role of the vitamin. J Pediatr. 2010, 156:698-703.
3. Adams JS, Hewison M. Update in vitamin D. Acta Derm Vene-Reol. 2011, 91:115-24.
4. Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011, 86:50-60.
5. Cape T, Encouraged N, Dalmau J. New recommended daily intake of calcium and vitamin D: prevention of nutritional rickets. Acta Pediatr Esp 2008; 66:233-6.
6. Marin S, Suarez L, Diaz R. Physiological bases and study of mineral metabolism. Journal of hormones and growth factors. 2011; XIV :3-9.
7. Plotkin H, Lifshitz F. Rickets and osteoporosis. In: Lifshitz F, editor. Pediatric endocrinology, 2. New York: Informa Healthcare SA Inc, 2007. p. 531 -57.
8. Wagner CL, Greer FR, American Academy of Pediatrics Section on Breastfeeding. American Academy of Pediatrics Com-Mittee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008, 122:1142-52.
9. Alonso A, Martinez V, Dalmau J. Prophylactic vitamin D. Acta Pediatr Esp 2011; 69:121-7.
10. Alonso C, Ureta N, Pallas CR. Vitamin D prophylaxis accessed 16 February 2012. Available at: http://www.aepap.org/ PrevInfad / pdfs / previnfad_vitamina_D.pdf
11. Boullata JI. Vitamin D supplementation: a pers-pective pharmacologic. Curr Opin Clin Nutr Metab Care. 2010, 13:677-84.
12. Kelly A, Levine MA. Disorders of Bone and Mineral Metabo-lism. In: Kappy MS, Allen DB, Geffner ME, eds. Pediatric endocrinology practice. Springfield: McGraw-Hill, 2010. p.191 -256.
13. Buñuel Alvarez JC, Gonzalez Rodriguez P, González de Dios J. Vitamin D supplementation in infancy. AEPap. Refresher Course Pediatrics. Madrid: Exlibris Editions, 2010. p. 85 -9.
14. Alonso MA. Prophylactic vitamin D. Bol Pediatr. 2010, 50:95-101.
15. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M. Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. Vitamin D deficiency in children and Its management: review of current recommenda-tions and Knowledge. Pediatrics. 2008, 122:398-417.
16. Lorencio Granado F, Mosteiro JS, Smith-Beard C, Navarro ED, Blanco-Navarro I, Perez-Sacristan B. 25-OH-vitamin D assay variation in clinical and practice management subject. Clin Biochem. 2010, 43:531-3.
17. Lai JK, Lucas RM, Banks E, Ponsonby AL, Inves-tigator Ausimmune Group. Variability in vitamin D impairs clinical assessment Assays of vitamin D status. Intern Med J. 2012, 42:43 -50.
18. Van den Ouweland JM, Beijers PM, Demacker PN, van Daal H. Measurement of 25-OH-vitamin D in human serum using liquid chromatography-tandem mass spectrometry with comparison to radioimmunoassay and automated immunoassay. J Chroma-B Analyt Technol Biomed togr Life Sci 2010; 878:1163-8.
19. The Hunty A, Wallace PM, Gibson S, Viljakainen H, Lamberg-Allardt C, M. Ashwell UK Food Standards Agency Workshop Consensus Report: the choice of method for measuring 25-hydroxyvitamin D to vitamin D status estimate for the UK National Diet and Nutrition Survey. Br J Nutr. 2010, 104:9.
20. RovnerAJ, O'Brien KO. Hypovitaminosis D among healthy chil-drain in the United States: a review of the current evidence. Arch Pediatr AdolescMed. 2008, 162:513-9.
21. Henry HL, Bouillon R, Norman AW, Gallagher JC, Lips P, Heaney RP, et al. Vitamin D 14th Workshop consensus on vitamin D nutritional guidelines. J Steroid Biochem Mol Biol 2010; 121:4-6.
22. Suarez Martinez V, Moreno Villares JM, Dalmau J. Serra Nutrition Committee of the Association of Pediatrics Españnola. Recommended intake of calcium and vitamin D: Position of the Nutrition Committee of the Spanish Association of Pediatrics. An Pediatr (Barc). 2012 Feb 14. Epub ahead of print.
23. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Guidelines for Preventing and Treating vitamin d deficiency and insufficiency revisited. J Clin Endocrinol Metab. 2012, 97:1153-8.
24. Balk SJ. Council on Environmental Health. Sec-tion on Dermatology. Ultraviolet radiation: a hazard Vitamin D: pathophysiology and clinical applicability to children and adolescents. Pediatrics. 2011, 127: e791 -817.
25. Terushkin V, Bender A, Psaty EL, Engelsen O, Wang SQ, Halpern AC. Estimated equivalency of vitamin D production from sun naturally versus oral vitamin D Exposure Supplementa-tion across two seasons at U.S. latitudes. J Am Acad Dermatol. 2010, 62:929.
26. Springbett P, S Buglass, Young RA. Photoprotection and vitamin D status. J Photochem Photobiol B. 2010; 101:160 -8.
27. Gillies DR, Hay A, Sheltawy MJ, Congdon PJ. Effect of photot-herapy on plasma 25 (OH)-vitamin D in neonates. Biol Neonate. 1984, 45:225-7.
28. Diffey BL. Is Exposure to summer sunlight casual Effective at Maintaining Adequate vitamin D status? Pho-toimmunol Photodermatol Photomed. 2010, 26:172-6.
29. Encouraged N, Cape T, Vitoria I, Dalmau J. Multivitamins and minerals in children. Are they necessary? Acta Pediatr Esp 2010; 68:25-33.
30. Neyestani TR, Hajifaraji M, Omidvar N, Eshraghian MR, Shariatzadeh N, Kalayi A, et al. High Prevalence of vitamin D deficiency in school-age children in Tehran, 2008: a red alert. Public Health Nutr. 2011, 15:324-30.
31. Razzaghy-Azar M, Shakiba M. Assessment of vitamin D status in healthy children and adolescents living in Tehran and Its relation to iPTH, gender, weight and height. Ann Hum Biol 2010, 37:692-701.
32. Cole CR, Grant FK Tangpricha V, Swaby-Ellis ED, Smith JL, Jacques A, et al. 25-hydroxyvitamin D status of healthy, low-income, minority children in Atlanta, Georgia. Pediatrics. 2010, 125:633-9.
33. Gordon CM, Feldman HA, Sinclair L, Williams AL, Kleinman PK, Perez-Rossello J, et al. Prevalence of vitamin D deficiency among healthy infants and toddlers. Arch Pediatr Adolesc Med 2008; 162:505-12.
34. Whiting SJ, KA Langlois, Vatanparast H, Greene-Finestone LS. The vitamin D status of Canadians relative to the 2011 Dietary Reference Intakes: an examination in children and adults with and without supplement use. Am J Clin Nutr. 2011, 94:128-35.
35. Mark S. Vitamin D status and vitamin D recommendations to Improve status in Canadian youth. Appl Physiol Nutr Metab. 2010, 35:718.
36. Andersen R, Molgaard C, Skovgaard LT, Brot C, Cashman KD, Jakobsen J, et al. Pakistani immigrant children and adults in Denmark Have Severely low vitamin D status. Eur J Clin Nutr. 2008, 62:625-34.
37. Rodriguez-Rodriguez E, Aparicio A, Lopez-Sobaler AM, Ortega RM. Vitamin D status in a group of Spanish schoolchildren. Minerva Pediatr. 2011; 63:11 -8.
38. Cabezuelo Huerta G, Vidal S Mico, Abeledo Gomez A, Left Border P. 25-Hydroxyvitamin D Levels in infants. Relation with breast-feeding. An Pediatr (Barc). 2007, 66:491 -5.
39. Poopedi MA, Norris SA, Pettifor JM. Factors Influencing the vitamin D status of 10-year-old urban South African children. Public Health Nutr. 2011, 14:334-9.
40. Liang L, Chantry C, Styne DM, Stephensen CB. Prevalence and Risk Factors for vitamin D deficiency among healthy infants and young children in Sacramento, California. Eur J Pediatr. 2010, 169:1337-44.
41. Weng FL, Shults J, Leonard MB, Stallings VA, Zemel BS. Risk factors for low serum 25-hydroxyvitamin D Concentrations in Otherwise Healthy Children and Adolescents. Am J Clin Nutr. 2007, 86:150-8.
42. Tsiaras WG, Weinstock MA. Factors Influencing vitamin D status. Acta Derm Venereol. 2011, 91:115-24.
43. Shibata M, Suzuki A, Sekiya T, Sekiguchi S, Asano S, Udagawa Y, et al. High Prevalence of Hypovitaminosis D Japa-nese in pregnant Women with Threatened premature delivery. J Bone Miner Metab. 2011, 29:615-20.
44. Camargo CA Jr, Ingham T, Wickens K, Thadhani RI, Silvers KM, Epton MJ, et al. Vitamin D status of Newborns in New Zealand. Br J Nutr. 2010, 104:1051-7.
45. Hossain N, Khanani R-Kanani Hussain F, Shah T, Arif S, Pal L. High Prevalence of vitamin D deficiency in Pakistani mothers and Their Newborns. Int J Gynaecol Obstet. 2011, 112:229-33.
46. Madar AA, Stene LC, Meyer HE. Vitamin D status among immi-grant mothers from Pakistan, Turkey and Somalia and Their infants Attending child health clinics in Norway. Br J Nutr. 2009, 101:1052-8.
47. Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab. 2010, 95:471 -8.
48. Alcaina Bonet M, Lopez Segura N, Besora Anglerill R, S Perez Herrero, Esteban Torne E, Seidel V. Padilla Rickets in Asian Immigrants DURING puberty. An Esp Pediatr. 2002, 57:264 -7.
49. Lopez Segura N, Bonet Alcaina M, Garcia Algar O. Rickets in Asian Immigrants. An Esp Pediatr. 2002, 57:227 -30.
50. Morales C, Perkal G. Detecció, prevenció i tractament of raquitisme població deficiency of a risc. Catalan Pediatrics. 2005, 65:182-7.
51. Yeste D, Carrascosa A. Nutritional rickets in childhood: analysis of 62 cases. Med Clin (Barc). 2003 7, 121:23-7.
52. Ojeda L, Ros MA, Thomas C, Alcon JJ, J. Ardit Nutritional rickets in a 5-month-old child. A rare disease in Spain. An Pediatr (Barc). 2010, 72:225-7.
53. Cabezuelo Huerta G, Abeledo Gomez A, Left Border P. Vitamin D deficiency in a lactating mother and her child in severe rickets. An Pediatr (Barc). 2005, 63:561 -2.
54. Winzenberg T, Powell S, Shaw KA, Jones G. Effects of vita-min D supplementation on bone density in healthy children: Systematic review and meta-analysis. BMJ. 2011, 342: c7254.
55. Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and Risk of type 1 diabetes: a Systematic review and meta-analysis. Arch Dis Child. 2008, 93:512-7.
56. Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, et al. Systematic review: Vitamin D and Cardiometabolic out-eat. Ann Intern Med 2010; 152:307-14.
57. Gilbert-Diamond D, Baylin A, Mora-Plazas M, Marin C, Arsenault JE, Hughes MD, et al. Vitamin D deficiency and anth-ropometric Indicators of adiposity in school-age children: a prospective study. Am J Clin Nutr. 2010, 92:1446-51.
58. Gagnon C, Lu ZX, Magliano DJ, Dunstan DW, Shaw JE, Zimmet PZ, et al. Low serum 25-hydroxyvitamin D is Associated with Increased Risk of the Development of the metabolic syndrome at five years: results from a national, population-based prospective study (The Australian Diabetes, Obesity and Lifestyle Study: AusDiab). J Clin Endocrinol Metab. 2012, 97: 1953-61.
59. Soares MJ, LL Murhadi, Kurpad AV, Chan She Ping-Delphi WL, Piers LS. Mechanistic roles for calcium and vitamin d in the regulation of body weight. Obes Rev. 2012 Mar 2. doi: 10.1111/j.1467-789X.2012.00986.x. Epub ahead of print.
60. Awad AB, Alappat L, Valerio M. Vitamin d and metabolic syn-drome Risk Factors: evidence and mechanisms. Crit Rev Food Sci Nutr. 2012, 52:103-12.
61. Soares MJ, Chan She Ping-Delphi W, Ghanbari MH. Calcium and vitamin D for obesity: a review of randomized controlled trials. Eur J Clin Nutr. 2011, 65:994-1004.
62. Ford ES, Zhao G, Tsai J, Li C. Vitamin D and all-cause mor-tality among adults in the USA: Findings from the National Health and Nutrition Examination Survey Linked Mortality Study. Int J Epidemiol. 2011, 40:998-1005.
63. Williams DM, Fraser A, Lawlor DA. Associations of vitamin D, parathyroid hormone and calcium with Cardiovascular Risk fac-tors in U.S. adolescents. Heart. 2011, 97:315-20.
64. NC Grandi, Breitling LP, Brenner H. Vitamin D and cardiovascular disease: Systematic review and meta-analysis of prospective studies. PrevMed. 2010, 51:228-33.
65. Muldowney S, Kiely M. Vitamin D and Cardiometabolic health: a review of the evidence. Nutr Res Rev. 2010; 1:1 -20.
66. Pilz S, Tomaschitz A. Role of vitamin D in arterial hypertension. Expert Rev Ther Cardiovasc. 2010; 8:1599 -608.
67. Mitri J, Muraru MD, Pittas AG. Vitamin D and type 2 diabetes: a Systematic Review. Eur J Clin Nutr. 2011, 65:1005 -15.
68. Rodriguez-Rodriguez E, Ortega RM, Gonzalez-Rodriguez LG, Lopez-Sobaler AM, UCM Research Group VALORNUT (920,030).
Vitamin D deficiency is an independent predictor of ele-vated triglycerides in Spanish school children. Eur J Nutr. 2010, 50:373 -8.
69. Zittermann A, Frisch S, Berthold HK, Götting C, Kuhn J, Kleesiek K, et al. Vitamin D supplementation Enhances beneficial effects of the weight loss on cardiovascular disease markers Risk. Am J Clin Nutr. 2009, 89:1321 -7.
70. Searing DA, Zhang Y, Murphy JR, Hauk PJ, Goleva E, Leung DY. Decreased serum vitamin D Levels in Children with asthma are Associated with Increased corticosteroid use. J Allergy Clin Immunol. 2010, 125:995-1000.
71. Chinellato I, Piazza M, Sandri M, Peroni DG, Cardinale F, Piacentini GL, et al. Serum Vitamin D Levels and Exercise-induced bronchoconstriction in Children with asthma. Eur Respir J. 2011, 37:1366-70.
72. JM Brehm, Schuemann B, Fuhlbrigge AL, Hollis BW, Strunk RC, Zeiger RS, et al. Serum vitamin D and severe asthma exacerbations Levels in the Childhood Asthma Management Program study. J Allergy Clin Immunol. 2010, 126:52-8.
73. National Cancer Institute at the National Cancer Prevention and Institutes.Vitamin D: Strengths and limits accessed 16 February 2012. Available at: http://www.cancer.gov/ cancertopics / factsheet / prevention / vitamin-D.
74. Manson JE, Mayne ST, Clinton SK. Vitamin D and prevention of cancer-ready for prime time? N Engl J Med 2011; 364: 1385-7.
75. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, et al. Serum vitamin D concentration and pros-tate cancer risk: a nested case-control study. J Natl Cancer Inst 2008, 100:796-804.
76. Sabetta JR, DePetrillo P, Cipriani RJ, Smardin J, Burns LA, ML Lan-dry. Serum 25-hydroxyvitamin d and the Incidence of acute viral respiratory tract infections in healthy adults. PLoS One 2010; 5: e11088.
77. Laaksi I, Ruohola JP, Mattila V, Auvinen A, Ylikomi T, H. Pihlaja-maki Vitamin D supplementation for the prevention of acute respiratory tract Infection: a randomized, double-blinded trial among young Finnish men. J Infect Dis. 2010, 202:809-14.
78. Lange CM, Bojunga J, Ramos-Lopez E, von Wagner M, Hassler A, Vermehren J, et al. Vitamin D deficiency and to CYP27B1 promoter polymorphism-1260 are Associated with chronic hepatitis C and poor response to interferon-alpha based therapy. J Hepatol. 2011, 54:887-93.
79. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to Prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010, 91:1255-60.
80. Roth DE, Jones AB, Prosser C, Robinson JL, Vohra S. Vita-min D status is not Associated with the Risk of hospitalization for acute bronchiolitis in early childhood. Eur J Clin Nutr. 2009, 63:297-9.
81. Aydin S, Aslan I, Yildiz I, crouching B, Toptas B, Toprak S, et al. Vitamin D Levels in Children with recurrent tonsillitis. Int J Pediatr Otorhinolaryngol. 2011, 75:364-7.
82. Kriegel MA, Manson JE, Costenbader KH. Does vitamin D Affect Risk of Developing autoimmune disease?: A Systematic Review. Semin Arthritis Rheum. 2011, 40:512-31.
83. Broder RA, Tobin JN, Putterman C. Disease-specific definitions of vitamin D deficiency need to be Established in self-imposed and non-mune chronic autoimmune diseases: a retrospective comparison of three chronic diseases. Arthritis Res Ther. 2010, 12: R191.
84. Goetz DW. Idiopathic itch, rash, and urticaria / angioedema serum vitamin D merit evaluation: a descriptive case series. J. Med V W 2011, 107:14-20.
85. Heidari B, Hajian-Tilaki K, Heidari P. The status of serum vitamin D in Patients with rheumatoid arthritis and inflammatory arthritis undif-ferentiated Compared with controls. Rheumatol Int 2012; 32:991-5.
86. McGrath JJ, Burne TH, Feron F, Mackay-Sim A, Eyles DW. Deve-vitamin D deficiency lopmental and Risk of schizophrenia: a 10-year update. Schizophr Bull. 2010, 36:1073-8.
87. Lucas RM, Ponsonby AL, Dear K, Valery PC, Pender MP, Taylor BV, et al. Sun Exposure and Vitamin D are independent Risk Factors for CNS demyelination. Neurology. 2011, 76:540-8.
88. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011, 96:1911 -30.
89. Viljakainen HT Natri AM, KarkkainenM, HuttunenMM, PalssaA, Jakobsen J, et al. A positive dose-response effect of vitamin D supplementation on site-specific bone mineral Augmen-tation in adolescent girls: a randomized double-blinded placebo-controlled 1-year intervention. J Bone Miner Res 2006, 21:836-44.
90. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum Concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006, 84:18-28.
91. Dietary Reference Intakes for vitamin D. calciun and Institute of Medicine of the National Academies accessed 16 February 2012. Available at: http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx.
92. CF Casey, Slawson DC, Neal LR. D supplementation in infants Vtamin, children, and adolescents. Am Fam Physician. 2010, 81:745-8.
93. Specker BL, Valanis B, Hertzberg V, Edwards N, Tsang RC. Suns-hine Exposure and serum 25-hydroxyvitamin D Concentrations in Exclusively breast-fed infants. J Pediatr. 1985, 107:372-6.
94. Ho ML, Yen HC, Tsang RC, Specker BL, Chen XC, Nichols BL. Randomized study of sunshine Exposure and serum 25-OHD in breast-fed infants in Beijing, China. J Pediatr. 1985, 107:928-31.
95. Kulie T, Groff A, Redmer J, Hounshell J, Schrager S. Vitamin D: an Evidence-based review. J Am Board Fam Med 2009; 22:698-706.
96. Perrine CG, Sharma AJ, Jefferds ME, Serdula MK, Scanlon KS. Adherence to vitamin D recommendations among U.S. infants. Pediatrics. 2010, 125:627-32.
97. Thandrayen K, Pettifor JM. Maternal vitamin D status: implicated-cations for the Development of infantile nutritional rickets. Endocrinol Metab Clin North Am 2010; 39:303-20.
98. Roth DE. Vitamin D supplementation During Pregnancy: Safety Considerations in the design and interpretation of clinical trials. J Perinatol. 2011, 31:449-59.
99. Ghazi AA, Hosseinpanah F, M. Ardakani E, Ghazi S, Hedayati M, Azizi F. Effects of Different doses of oral cholecalciferol on serum 25 (OH) D, PTH, calcium and bone markers fall and winter DURING in schoolchildren. Eur J Clin Nutr. 2010, 64:1415-22.
100. Cipriani C, Romagnoli E, Scillitani A, Chiodini I, Clerico A, Car-Nevale V, et al. Effect of a Single Dose of 600.000 IU oral cholecalciferol on serum of calciotropic hormones in young sub-jects with vitamin D deficiency: a prospective intervention study. J Clin Endocrinol Metab. 2010, 95:4771-7.
101. Channel Alonso L, Ruiz Herrero J, Villalobos J Real, Tristan Piper J, Perez Rodriguez T, Villarroya E. Canedo Vitamin D intoxication in infants born from Latin-American Immigrants. Series of 3 cases. An Pediatr (Barc). 2011, 74:409-12.

11227 visitors, last modified 09 Jul, 2012,
Printer Friendly Follow this page for updates