Vitamin D MediaLab

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Receptors

-The vitamin D receptor is present in most tissues and cells within the body. 1,25(OH)D2 has a wide range of functions within the body. One of these functions includes inhibiting cellular proliferation and inducing terminal differentiation, inhibiting angiogenesis and renin production, stimulating insulin production and macrophage cathelicidin production. -1,25(OH)D2also stimulates its own destruction by enhancing the expression of 25-hydroxyvitamin D -24-OHase to metabolize 25(OH)D and 1,25(OH)D2into water soluble inactive forms.

Vitamin D Forms

-Vitamin D has several different forms. Two of these forms are important to humans: 1) vitamin D2, which is made by plants, and 2) vitamin D3, which is made by human skin when exposed to sunlight. -Foods may be fortified with vitamin D2 or D3 to help people reach their daily consumption requirements. Vitamin D (both D2 and D3) is considered biologically inactive until it goes through two enzyme mediated hydroxylation reactions. The first enzymatic hydroxylation reaction takes place in the liver mediated by the enzyme 25-hydroxylase which forms 25-hydroxyvitamin D3 [25(OH)D3]. The second reaction takes place in the kidney, mediated by 1α-hydroxylase, which converts 25(OH)D3 to the biologically active hormone, calcitriol. Vitamin D2 and D3 are equally effective when they are converted by the liver and the kidney into the active form, 1,25 forms. Vitamin D3 is what is made endogenously (this is usually what is measured in the laboratory).

Recommended Daily Intake of Vitamin D-IOM

1 to 18 years old=600 IU/day 19 to 70 years old=600 IU/day 71+ years old=800 IU/day

Recommended Daily Intake of Vitamin D-Endocrine Society

1 to 18 years old=600-1,000 IU/day 19 to 70 years old=1,500-2,000 IU/day 71+ years old=1,500-2,000 IU/day

The active form of vitamin D is called:

1,25-dihydroxyvitamin D Vitamin D2 is converted to 25-hydroxyvitamin D [25(OH)D] in the liver, and then to the active form, 1,25-dihydroxyvitamin D [1,25(OH)2D], in the kidney (see pg. 4, Vitamin D2 Form). Calcium and phosphorus are different molecules not related in form to vitamin D.

According to the Institute of Medicine (IOM), what is the recommended dietary allowance of vitamin D for a 65 year old person?

600 IU/day The Institute of Medicine (IOM) in the form of recommended dietary allowances (RDA) or adequate intakes (AI) suggests that an individual between the ages of 19 - 70 years of age have a vitamin D daily intake of 600 IU/day (see pg. 11, Recommended Daily Intake of Vitamin D).

Sample Requirements

Although a fasting specimen is recommended, it is not required. There are no special instructions with regard to diet if a fasting sample cannot be obtained. Vitamin D does not follow diurnal variation so timing is not important. Specimens for vitamin D analysis can be fresh or frozen serum or plasma. Specimens may be collected by using regular red-top or serum-separator tubes as well as green top tubes that contain sodium heparin. Specimens can be stored at < -20ºC, because vitamin D is very stable, serum/plasma samples can be frozen for a long period of time if analysis will be greatly delayed. Several freeze-thaw cycles do not seem to adversely affect the assay, although repeated freeze-thaw cycles should be avoided if possible. Specimens may be stored in glass or plastic vials, as long as the vials are tightly sealed to prevent desiccation of the sample. Moderately hemolyzed specimens may be used in certain testing methods because red blood cells do not contain Vitamin D. If using an assay that involves spectrophotometric testing methods, hemolysis may interfere with test results.

Age

As we age, our skin doesn't make as much vitamin D in response to sun exposure. At the same time, the kidneys become less efficient at converting vitamin D into the form calcitriol. Older adults also tend to spend more time indoors, which in turn decreases the amount of sunlight they are exposed to and decreases the amount of vitamin D produced.

Rickets affects which population?

Children Rickets is a condition that affects the development of bones only in children due to a mineralization defect during bone formation. It is most commonly diagnosed in children between the age of three and 18 months of age.

Metabolism

Cholesterol from the diet undergoes conversion to 7 dehydrocholesterol. As it circulates through the bloodstream and is taken up by cells such as skin cells, it is converted to cholecalciferol by UV exposure. Once it is converted and it enters the bloodstream, it is converted to 25-hydroxyvitamin D by the liver. It then goes to the kidneys and is finally converted to 1,25 dihydroxyvitamin D (active form). The specific steps involved in converting vitamin D from the diet and cutaneous synthesis are illustrated in the figure below. Vitamin D, either the D2 or D3 form, is considered biologically inactive until it undergoes two enzymatic hydroxylation reactions. The first reaction takes place in the liver by the enzyme 25-hydroxylase which forms 25(OH)D3. The second reaction takes place in the kidney, mediated by 1α-hydroxylase, which converts 25(OH)D3 to the biologically active hormone, calcitriol. 25(OH)D3, the precursor of calcitriol, is the major circulating form of vitamin D; it circulates bound to a carrier protein (vitamin D binding protein (DBP)). The renal synthesis of calcitriol is tightly regulated by two counter-acting hormones, with up-regulation via parathyroid hormone (PTH) and down-regulation via fibroblast-like growth factor-23 (FGF23). Low serum phosphorus levels stimulate calcitriol synthesis, whereas high serum phosphorus levels inhibit it (a negative feedback system). Following its synthesis in the kidney, calcitriol binds to vitamin D binding protein (DBP) to be transported to target organs. Although the conversion to the active form occurs in the kidneys it can also occur in the skin, prostate, brain, pancreas, adipose tissue, skeletal muscle, heart, colon, monocyte/macrophages and in neoplastic tissues.

Hyperparathyroidism

Chronic vitamin D deficiency causes secondary hyperparathyroidism. Decreases in serum vitamin D levels will result in proportionally higher parathyroid hormone (PTH) levels that serve to maintain normal serum and total body calcium. Vitamin D deficiency reduces intestinal calcium absorption. The decrease in serum calcium levels then triggers PTH release, which quickly corrects the calcium level by taking calcium from bone, increasing renal tubular calcium reabsorption, and increasing renal production of 1,25(OH)2D.

Which of the following factors could result in a decrease in vitamin D?

Crohn's disease Advanced age Kidney disease Vitamin D is a fat-soluble vitamin, which means a gastrointestinal condition such as Crohn's disease may cause lower absorption of fat-soluble substances like vitamin D. As one ages, the skin doesn't make as much vitamin D in response to sun exposure. At the same time, the kidneys become less efficient at converting vitamin D into the form calcitriol. Older adults tend to spend more time indoors, which in turn decreases the amount of sunlight they are exposed to, thus decreasing the amount of vitamin D produced.

Forms of Vitamin D and Function in the body

D2 (Ergocalciferol)=Absorption of calcium and phosphorus D3 (Cholecalciferol)=Helps the body absorb calcium Calcidiol (25-hydroxyvitamin D)=Not an active form of vitamin D until converted to calcitriol (1,25-dihydroxyvitamin D) -Converted in the kidneys Calcitriol (1,25-dihydroxyvitamin D)= -Increases the level of calcium (Ca2+) in the blood by increasing the uptake of calcium from the gastrointestinal tract -Increases reabsorption of calcium by the kidneys -Increases release of calcium from the bone

Decreased Intake

Decreased intake of vitamin D is one of the most common cause of deficiency. This is especially true in those that follow a strict vegan diet. Because most of the natural sources of vitamin D are animal based (egg yolk, beef liver, fish, and fish oils), people who do not consume any animal-based products (e.g. vegans) must be sure to get their daily intake of vitamin D from supplements or risk being deficient

A 40-year-old woman from Alaska presents to her physician with muscle aches and pains and generalized weakness. The following results were obtained (normal ranges in parenthesis): Calcium = 8.2 mg/dL (8.8 - 10.4) Phosphate = 2.2 mg/dL (2.3-4.7) Alkaline phosphatase = 350 U/L (30-120) PTH = 124 pg/mL (10-65) 25-hydroxy vitamin D = < 5 ng/mL (15-40) What is most likely the cause of her symptoms?

Decreased vitamin D The most likely issue is the low vitamin D, often caused by the lack of sunlight where the patient resides plus some form of dietary deficiency. The deficiency reduces the ability of the stomach to absorb calcium and phosphate and leads to hypocalcemia and hypophosphatemia. In response to the deficiency the parathyroid gland secretes more PTH, which then increases calcium reabsorption by the kidneys and increases phosphate excretion in the urine. The increased PTH increases bone turn over which causes the rise in alkaline phosphatase which helps to increase calcium levels.

Vitamin D is NOT responsible for building strong bones and teeth in children. T/F

False Vitamin D plays an important role for proper growth/development during childhood (see pg. 22, Children (Growth and Development)). Not only does vitamin D help build strong teeth and bones, but it strengthens the immune system and improves cardiovascular health.

How much vitamin D is absorbed depends upon the presence of what substance?

Fat Because it is fat soluble, dietary vitamin D (either D2 or D3) is absorbed with other dietary fats in the small intestine. How much vitamin D is absorbed of depends upon the presence of fat in the lumen, which triggers the release of bile acids and pancreatic lipase

John's physician has told him to increase his dietary intake of vitamin D from "naturally occurring sources." What should John put on his grocery shopping list to achieve this?

Fatty fish Fish liver oil Egg yolks Fish liver oil, fatty types of fish, as well as egg yolks are all naturally occurring sources of vitamin D. John should make sure to pick up these items at the store in order to increase his vitamin D intake.

June is a 63-year-old female that takes a multivitamin daily that contains 400 IU of vitamin D and takes in another 50 IU from her diet. June feels she is getting enough vitamin D. Her family is concerned that she is not getting the recommended daily allowance of vitamin D from the supplement and her diet, so they are encouraging June to eat food that is higher in vitamin D to increase her daily intake. Do you agree with June or her family?

Her family is correct. June is not getting the recommended daily allowance of vitamin D from the supplement alone. June's family is correct. According to the Institute of Medicine (IOM) in the form of recommended dietary allowance (RDA) states that 600 IU per day is the RDA for a person age 19 -70. June is not taking in enough from the supplement alone and will need to increase her intake through her diet.

John is a 56-year-old veterinarian who was recently tested for vitamin D levels. His current result came back inconsistent with his results in the past. What could be the explanation for this erroneous results?

Heterophile antibodies are present. For assays that use antibodies, the possibility exists for interference by heterophile antibodies (human anti-sheep antibodies) in the patient sample. Patients who have been regularly exposed to animals or have received immunotherapy or diagnostic procedures utilizing immunoglobulins or immunoglobulin fragments may produce antibodies that interfere with immunoassays. These antibodies may cause erroneous results. Moderate hemolysis will not affect results given that vitamin D is not found inside the red blood cell. Serum is the preferred sample so this would not be a variable in the testing. Cold agglutinins do not affect vitamin D testing.

HPLC

High-performance liquid chromatography (HPLC) is another method which can quantitate 25-hydroxy vitamin D2 and D3. These HPLC methods are available in kit form from several companies in an effort to standardize test quality and to make the assays more cost effective and less labor intensive. One of the methods (Hitachi) uses a reverse phase column and diode array detection, which allows for highly sensitive simultaneous analysis at optimal wavelengths. This method can be used to analyze food as well as biological samples. Newer chromatography methods have been developed to improve sensitivity, to simplify steps, and to measure all forms of vitamin D. An example is a method that was developed to analyze all forms and metabolites of vitamin D (D2, D3, and 25-hydroxy) in serum at the same time. The procedure uses an ionization detector technique known as atmospheric pressure photo ionization (APPI) to provide additional sensitivity for analysis. The method is less difficult compared with other LC methods because it doesn't require pre-concentration steps.

Historical Measurements

Historically, vitamin D was measured by competitive binding methods (RIA) and high-performance liquid chromatography (HPLC). A commonly used RIA kit, developed by DiaSorin S.p.A (Saluggia, Italy), was the method used by many reference laboratories and is considered the historical standard. This method has been used to establish reference ranges during the past decade. The DiaSorin 25-hydroxy vitamin D assay is a 2-step procedure that involves a rapid extraction of 25-hydroxy vitamin D and other hydroxylated metabolites from serum or plasma, followed by a competitive RIA procedure using an antibody with specificity for 25-hydroxy vitamin D.

Dorothy is a 70-year-old female with the following test results: Vitamin D = 9 ng/mL (20 - 50 ng/mL) Calcium = 7.0 mg/dL (8.5 - 10 mg/dL) Based upon these values (normal ranges in parenthesis), predict what the parathyroid hormone (PTH) result would be.

Increased Decreases in serum vitamin D levels will result in proportionally higher PTH levels to maintain serum and total body calcium (see pg. 23, Hyperparathyroidism). Vitamin D deficiency reduces intestinal calcium absorption. The decrease in serum calcium levels then triggers PTH release, which quickly corrects the calcium level by taking calcium from bone, increased renal tubular calcium reabsorption, and increased renal production of 1,25(OH)2D.

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

Liquid chromatography tandem mass spectrometry (LC-MS/MS) combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrophotometry. It has evolved into a widely used technology to perform routine tests in clinical laboratories. Historically, LC-MS/MS had been used primarily by research, pharmaceutical, or commercial laboratories. Advances in the technology, decreasing costs for basic systems, intelligible software, an increased number of published protocols and methods, and the release of Food and Drug Administration (FDA)-approved kits has enabled more clinical laboratories to pursue these instruments as viable clinical analyzers. LC - MS/MS uses two mass filters arranged sequentially with a collision cell between them. The filters can be used in static or scanning mode to select a particular mass-to-charge ratio or range. In the middle collision cell, the precursor ions collide with gas molecules and are fragmented into smaller ions referred to as product ions. The resulting product ions are then separated and detected in a second stage of mass spectrometry. Advantages of this methodology are that it has superior selectivity for many analytes since it recognizes them by at least two physical properties (their precursor and product ion mass). Clinical laboratories have also experienced situations in which manufacturers unexpectedly withdraw immunoassays from the market, leaving labs searching for alternate methods. LC - MS/MS also allows for versatility in enabling laboratories to offer new laboratory-developed tests for biomarkers or for newly approved medications before FDA-approved kits or immunoassays come on the market. In addition, the sensitivity of LC-MS/MS may allow lower limits of detection for some analytes compared to immunoassays and other methods. Cost is also another benefit; the system allows for identifying and quantifying several analytes of interest simultaneously which then lowers the cost per test. One disadvantage of the system is that it requires a high level of technical expertise to develop and validate tests as well as troubleshoot the instruments. In addition, FDA's recently released draft guidance document on regulating laboratory developed tests using this methodology could affect the majority of tests developed and performed on LC-MS/MS. Currently, laboratories develop and validate LC-MS/MS assays according to CLIA. Because these may be FDA-approved tests, they have additional analytical validation requirements including an evaluation of imprecision, accuracy, linearity, recovery, sensitivity, specificity, carry-over, ion-suppression, acceptable sample types/collection tubes/anticoagulants, storage/transport conditions, and the establishment of reference ranges. Determining the appropriate sample preparation, column choice, mobile phase, and selection of suitable internal standards are just a few of the many challenges faced during normal method development of an assay. Other issues are standardization. Variations between LC-MS/MS assays/ users can arise since LC-MS/MS assays are not standardized and commercial calibrators are not available at this time.

Vitamin D is considered biologically inactive until it undergoes two enzymatic hydroxylation reactions. Where do these reactions take place?

Liver and kidney The first enzymatic hydroxylation reaction takes place in the liver mediated by the enzyme 25-hydroxylase which forms 25-hydroxyvitamin D3 [25(OH)D3] (see pg. 3, Vitamin D Forms). The second reaction takes place in the kidney, mediated by enzyme 1α-hydroxylase, which converts 25(OH)D3 to the biologically active hormone, calcitriol. The spleen, lungs and heart do not have a role in the hydroxylation reactions of vitamin D

Which one of these patients is most likely to be deficient in vitamin D?

Mary, a 56-year-old vegan. Mary is the most at risk for being vitamin D deficient because most of the natural sources of vitamin D are animal-based (egg yolk, beef liver, fish, fish oils, etc.). Vegans do not consume any animal products; therefore, they must be sure to get their daily intake of vitamin D from supplements or risk being deficient (see pg. 14, Decreased Intake).

Immunoassays

Most immunoassay methods can separate and quantify vitamin D2 and vitamin D3. But, depending on the specificity of the antibody used in the immunoassay method, some immunoassays measure only one form. Several Food and Drug Administration (FDA)-approved immunoassay tests are available, including quantitative chemiluminescent immunoassay (CIA) methods.

Jane is a two-year-old girl brought to the primary health center for failure to thrive and inability to walk properly. On examination, there are skeletal deformities of both upper and lower limbs with marked bowing. General examination shows pallor, but there are no other signs. The abdomen is distended, otherwise systemic examination is normal. Based upon the above information, what is the most likely diagnosis?

Rickets The most likely diagnosis given the exam findings is Rickets. Rickets is a lack of vitamin D that affects bone development in children. Vitamin A deficiency and Scurvy (vitamin C deficiency) do not cause the physical symptoms Jane is experiencing.

Rickets

Rickets is a condition that affects the development of bones in children. It causes soft weak bones, which can become bowed or curved. It's a condition that only develops in children and is most commonly diagnosed in those between the age of 3 months and 18 months. The main signs and symptoms of rickets include a misshaped or deformed skeleton, pain, fragile bones, and poor growth and development. The most common causes of rickets are an extreme lack of vitamin D, a lack of calcium, or a lack of both.

Which types of samples would be most appropriate for vitamin D testing?

Serum and Plasma Serum or plasma is considered the sample of choice for vitamin D testing

The procedure for most FDA methods (Immunoassays) is as follows:

Step One: 25-hydroxy vitamin D is dissociated from its binding protein and binds to the specific solid phase antibody. Step Two: Vitamin D-isoluminol tracer is added and unbound material is removed with a wash cycle. Step Three: The reagents are added to initiate the chemiluminescent reaction. Step Four: The light signal is detected by a photomultiplier as relative light units; this measurement is inversely proportional to the concentration of 25-hydroxy vitamin D. Aside: Washing steps are necessary to remove unbound material and decrease background, thereby increasing the signal. Insufficient washing will create high background. Since this assay measurement is inversely proportional to the concentration of 25-hydroxy vitamin D, an increased amount of light will result in a inaccurate decrease of results.

All of the following are functions of vitamin D, EXCEPT?

Stimulates maturation of fat cells Vitamin D does function as a hormone to maintain blood calcium levels; however it does NOT stimulate the maturation of fat cells. It is responsible for maintaining calcium levels by increasing absorption in the gut and it is also responsible for building tissue, in particular bone tissue.

Role of Vitamin D

The major role of vitamin D is to maintain normal blood levels of calcium and phosphorus. Vitamin D helps the body absorb calcium, which forms and maintains strong bones. It is used alone or together with calcium to improve bone health and decrease fractures. Vitamin D may also protect against osteoporosis, high blood pressure, cancer, and other diseases.

The Reference Method

The reference method for vitamin D analysis has been liquid chromatography - mass spectrophotometry (LC-MS/MS), which can measure vitamin D2, vitamin D3, and the D3 epimer (one of a pair of stereoisomers) separately and, through a calculation, the total vitamin D is reported. This method was chosen by the Nutritional Laboratory at the Centers for Disease Control and Prevention (CDC) and the National Laboratory in the United Kingdom for analysis of vitamin D for health and nutrition surveys, partly due to its ability to distinguish the various forms of vitamin D in plasma that may be found in people of all ages. The problem with these methods is that they are time and labor intensive and technically difficult to perform.

Immune System Impairment

The vitamin D receptor is expressed on immune cells such as B cells, T cells, and antigen presenting cells, which are all capable of synthesizing the active vitamin D metabolite. Vitamin D binds to intracellular receptors that lead to the activation of cell signaling cascades or gene transcription events which can modulate immune cell function. It can also have a controlling influence on the natural and adaptive immune response of these cells. Deficiency in vitamin D may influence immune function.

Recommended Daily Intake of Vitamin D

There are currently 2 sets of guidelines for daily vitamin D intake. The first is the Institute of Medicine (IOM) in the form of recommended dietary allowances (RDA) or adequate intakes (AI). The RDA is the average daily intake sufficient to meet the nutrient requirements of nearly all (97%-98%) healthy individuals. The second is the Endocrine Society who put together a task force to review the research and come up with a set of guidelines for "people who are at risk for deficiency"

Sources

There are very few foods in nature that contain vitamin D. The best sources are fatty fish such as salmon, tuna, and mackerel, as well as fish liver oil. Small amounts are found in beef liver, cheese, and egg yolks. Vitamin D in these items is primarily in the form of vitamin D3 and its metabolites. Some types of mushrooms can provide vitamin D2 in small amounts. In the 1920's vitamin D was recognized for its role in preventing rickets. It was after this time some foods began to be fortified with the vitamin (milk, cereal, etc.) to help prevent this disease. To this day, fortified foods provide most of the vitamin D in the American diet. For example, almost all of the U.S milk supply is voluntarily fortified with 100 IU/cup of vitamin D. In Canada, milk is fortified by law with 35 - 40 IU / 100 mL, as is margarine at greater than or equal to 530 IU/100 g. Vitamin D3, or cholecalciferol, is the form of vitamin D found in milk.

Sunlight and Skin Pigmentation

There is a direct correlation between vitamin D deficiency and the latitiude at which a person lives. People who live above 37° north or below 37° south of the equator are more at risk for vitamin D deficiency because the skin makes very little vitamin D from the sun in these areas, except during the summer months (Vitamin D is synthesized from ultraviolet radiation). Vitamin D deficiency is also more common in homebound individuals for the same reason. The skin pigment melanin reduces the skin's ability to make vitamin D in response to sunlight exposure. Some studies also show that the skin of older adults (age 65 and over) generates much less vitamin D than the skin of younger people.

Renal Disease

Those that may have kidney disease may not be able to convert 24-hydroxylase or 1-alpha-hydroxylase to 24,25-(OH)2D3 or to calcitriol (see the image below). This will impair vitamin D from becoming biologically active. Phosphorous levels are also elevated due to the renal disease and lack of excretion.

Heterophile antibodies may cause erroneous results in assays that utilize antibodies as their methodology. T/F

True For assays that use antibodies, the possibility exists for interference by heterophile antibodies (human anti -sheep antibodies) in the patient sample (see pg. 38, Antibody and Other Interferences). Patients who have been regularly exposed to animals or have received immunotherapy or diagnostic procedures utilizing immunoglobulins or immunoglobulin fragments may produce antibodies that interfere with immunoassays. These antibodies may cause erroneous results

Absorption Issues

Vitamin D is a fat-soluble vitamin. People with gastrointestinal conditions that affect their ability to absorb fats may have lower absorption of fat-soluble vitamins like vitamin D. Such conditions include like Crohn's disease, celiac disease and non-celiac gluten sensitivity, and other inflammatory bowel diseases.

Osteoporosis and Osteopenia

Vitamin D is essential for the development and maintenance of bone, both for its role in assisting calcium absorption from food in the intestine, and for ensuring the correct renewal and mineralization of bone tissue. People who have decreased vitamin D serum levels run the risk of first acquiring osteopenia. Untreated osteopenia may lead to osteoporosis due to the decrease in calcium absorption, thus increasing their risk of bone fractures (the diagnostic difference between osteopenia and osteoporosis is the measured decrease of bone mineral density).

Children (Growth and Development)

Vitamin D plays an important role for proper growth and development during childhood. Not only does vitamin D build strong teeth and bones, but also it may strengthen the immune system and improve cardiovascular health. Research has found that low vitamin D levles in children corresponds with respiratory infections and dental issues. In order to improve vitamin D status in children, it's important to identify the risk factors associated with vitamin D deficiency. Researchers from the Netherlands2 assessed vitamin D levels in 4,167 children aged six years old to identify determinants of vitamin D deficiency. The researchers found that 29.8% of the children were considered deficient (< 20 ng/mL), while 36.5% were considered sufficient (20-30 ng/mL). About one third of the children had what the researchers considered optimal vitamin D status (above 30 ng/mL). The researchers identified non-modifiable risk factors associated with vitamin D deficiency such as the child's age and race. The older the child was, the more likely they were to be deficient. African, Asian, Turkish, and Moroccan children were more likely to be deficient than those with a Dutch or other Western ethnic background. The researchers also determined modifiable risk factors for low vitamin D levels. They found that children who watch television for two or more hours per day were 32% more likely to be vitamin D deficient than the children who watched less than two hours of television per day. Playing outside for at least one hour per day decreased the child's risk for vitamin D deficiency by 29% compared to the children who played outside for less than one hour. The researchers concluded, "... Important determinants of vitamin D deficiency included a higher child age, more television watching, less playing outside, less biking to school, lower maternal age, lower household income, multiparity, and higher maternal BMI."

Vitamin D does function as a hormone to maintain blood calcium levels; however it does NOT stimulate the maturation of fat cells. It is responsible for maintaining calcium levels by increasing absorption in the gut and it is also responsible for building tissue, in particular bone tissue.

Vitamin D3 Vitamin D3 or cholecalciferol is a steroid hormone produced in the skin when exposed to ultraviolet light or taken in from dietary sources. Sarah now frequents the beach in a sunny climate, so the majority of her vitamin D would be in the form of D3. Vitamin D2 (also known as ergocalciferol) is found in plants.

Vitamin D3 Form

Vitamin D3 is also known as cholecalciferol. It is a steroid hormone produced in the skin when exposed to ultraviolet light (endogenous source) or taken in from dietary sources (exogenous). Its molecular formula is C27H44O. The active form of cholecalciferol or 1,25-dihydroxycholecalciferol has an important role in maintaining blood calcium and phosphorous levels and mineralization of bone. In the activated form, cholecalciferol binds to vitamin D receptors and modulates gene expression. This leads to an increase in serum calcium concentrations by increasing intestinal absorption of phosphorus and calcium, promoting distal renal tubular reabsorption of calcium and increasing osteoclastic resorption.

Vitamin D2 Form

Vitamin D2 is also known as ergocalciferol. The molecular formula is C28H44O. It is a fat soluble vitamin that helps the body absorb and metabolize calcium and phosphorus. It helps the body accomplish this by increasing the efficiency of the small intestine to absorb these minerals from the diet. Vitamin D2 is converted to 25-hydroxyvitamin D [25(OH)D] in the liver, and then to the active form, 1,25-dihydroxyvitamin D [1,25(OH)2D], in the kidney. Once transformed, it binds to the vitamin D receptor, which leads to a variety of regulatory roles, such as calcium and phosphorus balance

Absorption and Excretion

Because it is fat soluble, dietary vitamin D (either D2 or D3) is absorbed with other dietary fats in the small intestine. How much vitamin D is absorbed depends upon the presence of fat in the lumen, which triggers the release of bile acids and pancreatic lipase. Then, bile acids initiate the emulsification of lipids. Pancreatic lipase hydrolyzes the triglycerides into monoglycerides and free fatty acids, and bile acids support the formation of lipid-containing micelles, which diffuse into enterocytes. The products of vitamin D metabolism are excreted through the bile into the feces, and a small amount are eliminated through the urine. This is due to renal reuptake of vitamin D metabolites bound to DBP (vitamin D binding protein).


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