From NuGOwiki
The NuGOwiki Metabolite Database is a joint initiative of NuGO and HMDB
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All Metabolites | Biochemical | Nutritional | Functional | Metabolic Pathways | Diseases | Phenotypes | Physiological Processes | Protein |
| Vitamin D | ||||||
|---|---|---|---|---|---|---|
 | ||||||
| Chemical Name | (6R)-6-[(1R,3aR,4E,7aS)-4-[(2Z)-2-[(5S)-5-hydroxy-2-methylidene-cyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-2-methyl-heptane-2,3-diol | |||||
| Chemical Formula | C47H84O2 | |||||
| CAS Number | 40013-87-4 | |||||
| Chemical Information | HMDB00430 | |||||
| Biochemical Taxonomy | Sterols Vitamins | |||||
| Functional Taxonomy | Not available | |||||
| Nutritional Taxonomy | Not available | |||||
| Metabolic Pathways | Gamma-Hexachlorocyclohexane Degradation Folate Biosynthesis | |||||
| Biofluid Location | Urine Bile Blood Synovial_Fluid Amniotic_Fluid | |||||
| Tissue Location | Not available | |||||
| Normal Biofluid Concentrations | Blood: 2.1 - 4.9 uM Blood: 0.00290 - 0.0160 uM Amniotic_Fluid: uM Blood: 2.7 - 5.9 uM | |||||
| Normal Tissue Concentrations | Not available | |||||
| Diseases / Conditions Related to Nutrition | Hypophosphatemic Rickets Reduced in Hypoparathyroidism Hypoparathyroidism (hypercalcemic) Malabsorption/post-gastrectomy states Anephric Hyperparathyroidism Hypoparathyroidism (normocalcemic) Rickets Epilepsy Hypoparathyroidism | |||||
| Other (Monogenic Disorders) | Not available | |||||
| Abnormal Biofluid Concentrations | Not available | |||||
| Abnormal Tissue Concentrations | Not available | |||||
| Physiological Processes | Not available | |||||
| Authors: | |
| Affiliations: |
Introduction
guidelines
Vitamin D3 (cholecalciferol) – provided by the diet, or made in the skin from 7-dehydrocholesterol by exposure to sunlight
Vitamin D2 (ergocalciferol) – from diet
D2 and D3 have similar metabolism and potency, can be considered equivalent.
24,25-Dihydroxyvitamin D (24R,25(OH)2D3) circulates in blood at concentrations about 1000 times higher than 1alpha,25(OH)2D3. 24-Hydroxylase is present in the proximal convoluted tubule cells of the kidney and in virtual all target cells of 1alpha,25(OH)2D3. Interestingly, 1alpha,25(OH)2D3 is a very strong inducer of 24-hydroxylase activity and 24R,25(OH)2D3 formation. Also parathyroid hormone (PTH) regulates 24-hydroxylase activity but in a tissue specific manner, i.e. inhibitory in the kidney while a synergistic effect together with 1alpha,25(OH)2D3 is observed in osteoblasts. Generally, 24-hydroxylation has been considered the first step in the degradation pathway of 1alpha,25(OH)2D3 and 25-(OH)D3. However, through the past decades data have accumulated that 24R,25(OH)2D3 is not merely a degradation product but has effects on its own. Classic studies have demonstrated the significance of 24R,25(OH)2D3 for normal chicken egg hatchability and calcium and phosphorus homeostasis. More recently it became apparent that 24R,25(OH)2D3 also has distinct effects on cartilage in particular the resting zone cells. 24R,25(OH)2D3 stimulates osteocalcin synthesis in human osteoblasts. 24R,25(OH)2D3 plays a role in bone metabolism but that it acts in concert with 1alpha,25(OH)2D3 to obtain an optimal effect. (PMID: 11179746 )
Biological Function
guidelines
Vitamin D maintains normal blood levels of calcium and phosphate, which are in turn needed for the normal mineralization of bone, muscle contraction, nerve conduction, and general cellular function in all cells of the body
Active form is 1,25-dihydroxy vitamin D (1,25-(OH)2D) or calcitriol.
- Regulates the transcription of a number of vitain D dependent genes which code for calcium-transporting proteins and bone matrix proteins (1)
- Modulates the transcription of cell cycle proteins, which decrease cell proliferation and increase cell differentiation of a number of specialized cells
- Immunomodulatory properties
Catabolism
Diseases / Conditions Related to Nutrition
- Inadequate mineralization of the skeleton: Rickets
- “premature to categorically suggest that vitamin D deficiency increases cancer risk.” (1)
- Hypophosphatemic Rickets
- Reduced in Hypoparathyroidism
- Hypoparathyroidism (hypercalcemic)
- Malabsorption/post-gastrectomy states
- Anephric
- Hyperparathyroidism
- Hypoparathyroidism (normocalcemic)
- Rickets
- Epilepsy
- Hypoparathyroidism
Other (Monogenic) Disorders
Nutritional Information
Drivers for biological variation
ADME
Absorption in small intestine. Transported in chylomicrons to the liver. In the liver metabolized to 25-hydroxyvitamin D (calcidiol); large circulating pool, in plasma. When ionized calcium in plasma falls, PTH is secreted and stimulates the conversion of calcidiol to calcitriol in the kidney (role of 25-OH-D-1-alpha-hydroxylase). Vitamin D is principally excreted in the bile. More water-soluble metabolites are excreted in the urine (calcitroic acid)
Indicator of adequacy
Plasma 25-OH-D is best indicator for adequacy of intake Levels < 27,5 nmol/l are associated with radiologic evidence of rickets and with biochemical abnormalities associated with metabolic bone disease Skeletal health indicators:
- Neonates and children: bone development and prevention of rickets
- Adults: BMC, BMD, fracture risk, in combination with 25(OH)D and PTH concentration
Status marker(s)
Plasma 25-OH-D or plasma PTH + 25-OH-D
Requirement (EAR) based on
Sunlight exposure is strong confounder Biochemical basis for estimating required intake: mean group dietary intake of vitamin D required to maintain the plasma 25-OH-D levels above 27 nmol/l, which is the level necessary to ensure normal bone health For elderly, bone loss is used as additional indicator of adequacy: vitamin D suppletion reduced bone loss
Underlying studies
- Demay 1995 (3)
- Specker 1992 (4)
- No studies have evaluated how much vitamin D is required to maintain normal blood levels of 25(OH)D and PTH in children or adults who have been deprived of sunlight and dietary vitamin D for a period of more than 6 months.
- Dawson-Hughes et al 1995 (5)
- Dawson-Hughes et al 1991 (6)
- Krall et al, 1989 (7)
Factors affecting requirement (relation intake - status)
Low cutaneous production:
- Aging
- Low exposure to sunlight (pigmentation, latitude, season, time of day)
- Low absorption in intestine (malabsorption disorders)
Factors affecting requirement (relation status - health)
Disturbed metabolism of vitamin D to its active form Alteration in recognition of 1,25-(OH)2-D by its receptor
(potential) indicators of health
Skeletal health:
- Neonates and children: bone development and prevention of rickets
- Adults: BMC, BMD, fracture risk, in combination with 25(OH)D and PTH concentration
Vulnerable groups
Markers of homeostasis and / or health
| Category | Markers | sign yes/no/? | I/D | S/I | ref | score |
| inflammation, immune response | CRP / hsCRP | Info | Info | Info | Info | Info |
| fibrinogen | Info | Info | Info | Info | Info | |
| Albumin | Info | Info | Info | Info | Info | |
| White blood cell count | Info | Info | Info | Info | Info | |
| TNF-alpha | Info | Info | Info | Info | Info | |
| Il-6 | Info | Info | Info | Info | Info | |
| Il1-beta | Info | Info | Info | Info | Info | |
| Il-10 | Info | Info | Info | Info | Info | |
| Prostaglandin F2alpha | Info | Info | Info | Info | Info | |
| Prostaglandin E1 (PGE1) | Info | Info | Info | Info | Info | |
| Prostaglandin E2 (PGE2) | Info | Info | Info | Info | Info | |
| Thromboxane B2 | Info | Info | Info | Info | Info | |
| Nitric Oxide (NO) | Info | Info | Info | Info | Info | |
| Serum Amyloid A (SAA) | Info | Info | Info | Info | Info | |
| NfkB | Info | Info | Info | Info | Info | |
| alpha1-antichymotrypsin | Info | Info | Info | Info | Info | |
| oxidative stress | 8(OH)-DG | Info | Info | Info | Info | Info |
| F2-isoprostanes | Info | Info | Info | Info | Info | |
| 8-iso-prostaglandin F2alpha | Info | Info | Info | Info | Info | |
| oxidized LDL | Info | Info | Info | Info | Info | |
| SOD | Info | Info | Info | Info | Info | |
| TBARS | Info | Info | Info | Info | Info | |
| myeloperoxidase | Info | Info | Info | Info | Info | |
| nitrotyrosine | Info | Info | Info | Info | Info | |
| Metabolic stress | diastolic BP | Info | Info | Info | Info | Info |
| systolic BP | Info | Info | Info | Info | Info | |
| total cholesterol | Info | Info | Info | Info | Info | |
| LDL | Info | Info | Info | Info | Info | |
| HDL | Info | Info | Info | Info | Info | |
| HDL/TC | Info | Info | Info | Info | Info | |
| triglycerides | Info | Info | Info | Info | Info | |
| homocysteine | Info | Info | Info | Info | Info | |
| tPA/PAI-1 | Info | Info | Info | Info | Info | |
| Fibrin fragment D-dimer | Info | Info | Info | Info | Info | |
| Factor VIIa | Info | Info | Info | Info | Info | |
| sICAM | Info | Info | Info | Info | Info | |
| Monocyte chemotactic protein 1 (MCP1) | Info | Info | Info | Info | Info | |
| fasting glucose | Info | Info | Info | Info | Info | |
| fasting insulin | Info | Info | Info | Info | Info | |
| OGTT | Info | Info | Info | Info | Info | |
| insulin tolerance test | Info | Info | Info | Info | Info | |
| HbA1c | Info | Info | Info | Info | Info | |
| fructosamine | Info | Info | Info | Info | Info |
Determinants of requirements
| Category | Determinants of status | sign yes/no/? help | independent of intake yes/no/? |
| general | gender | Info | Info |
| age (adults) | Info | Info | |
| age (children) | Info | Info | |
| ethnicity | Info | Info | |
| physiological status | polymorphisms | Info | Info |
| pregnancy | Info | Info | |
| lactation | Info | Info | |
| menopause | Info | Info | |
| physical fitness | Info | Info | |
| gut flora | Info | Info | |
| anthropometric variables | body weight | Info | Info |
| BMI | Info | Info | |
| waist circumference | Info | Info | |
| fat free mass | Info | Info | |
| Lifestyle variables | smoking | Info | Info |
| physical activity | Info | Info | |
| alcohol use | Info | Info | |
| medication use (incl. contraceptive pill) | Info | Info | |
| stress | Info | Info |
Other resources
- IOM 1997
- FAO/WHO report 2004
- Demay MB. 1995. Hereditary defects in vitamin D metabolism and vitamin D receptor defects. In: DeGroot LJ, Besser M, Burger HG, et al (eds) Endocrinology, Vol 2, third edition. Philadelphia, PA: WB Saunders, pp 1173-1178.
- Specker BL, Ho ML, Oestreich A, et al. 1992. Prospective study of vitamin D supplementation and rickets in China. J Pediatr 120; 733-739.
- Dawson-Hughes B, Harris SS, Krall EA et al. 1995. Rates of bone loss in postmenopausal women randomly assigned to one of two dosages of vitamin D. Am J Clin Nutr 61:1140-1145.
- Dawson-Hughes B, Dallal GE, Krall EA et al, 1991. Effect of vitamin D supplementation in wintertime on overall bone loss in healthy postmenopausal women. Ann Intern Med 115:505-512.
- Krall Ea, Sahyouin N, Tannenbaum S et al. 1989. Effect of vitamin D intake on seasonal variations in parathyroid hormone secretion in postmenopausal women. N Engl J Med 321: 1777-1783.