Vitamin D Hilarie Stubbins Colleen Linehan

Chemical Name Calciferol Two main forms are Vitamin D 2 and D 3 – Ergocalciferol (D 2 ) – Cholecalciferol (D 3 ) Source: 1

Structure Derived from a steroid Considered a seco-steroid because one of its four rings is broken Contains three intact rings (A, B, and D) with a break between carbons 9 and 10 in the B ring Vitamin D 2 and D 3 have differing side chain structures Source: 1

Vitamin D 2 Vitamin D 3 Vitamin D 2 is obtained from plant sources Vitamin D 3 is obtained from the sun Source: 1

Chief Functions The primary function of Vitamin D is to work with and help the body absorb and use calcium in order to sustain and build strong bones. Regulate immune system. Protection of the pancreas and stimulation of insulin. Improve blood glucose control in those with a high risk for diabetes. Source: 1

Functions Cont. Diminishes the production of hormones associated with high blood pressure. Decreases LDL. Increases HDL. Protective against autoimmune conditions: – Rheumatoid Arthritis – Type I Diabetes – Multiple Sclerosis Source: 1

Metabolic Pathways Vitamin D3 begins in the skin by exposure to UV rays from sunlight. 7-dehydrocholesterol absorbs the photons from the UV radiation to stimulate previtamin D3. Thermal isomerization occurs to form vitamin D3. This synthesis increases 25-OH D levels. When Vitamin D2 is taken in, it is considered an active substance. Source: 2, 3

Metabolic Pathways Cont. Transported via chylomicrons. Metabolic activation begins with the hydroxylation of carbon 25. Process occurs in the liver. Hydroxylation cannot be regulated. Indication of Vitamin D status is seen through the plasma 25-OH D levels. Source: 2, 3

Metabolic Pathways Cont. After the hydroxylation of Vitamin D, bioactivation occurs. Formed into 1, 25-dihydroxyvitamin D. Occurs in the kidneys. Source: 2, 3

Vitamin D Transportation Transported into circulation by plasma proteins. Most commonly bound to Vitamin D Binding Protein (DBP). DBP levels can be approximately 20x higher than the total amount of vitamin D metabolites in plasma. This leaves limited access to target cells. Source: 2, 3

Cont. The limited access reduces its susceptibility to hepatic metabolism and biliary excretion. This increases its circulating half-life. Predominately excreted through bile in the feces. Less than 30% is excreted through the urine. Source: 1, 2, 3

Recommendations Recommendations assume minimal sun exposure RDAs Infants: 400 IU/day Children and adults, (ages 1-70), male and Female : 600 IU/day Adults 70+ : 800 IU/day Pregnancy/lactating: 600 IU/day Source: 1

Factors affecting synthesis in skin Skin color/tone Age Latitudes Season Time of day Clothing interference Glass in windows Source: 1

Skin Color Persons with darker skin (due to their higher melanin content) require longer exposure to the sun than persons with lighter skin. This is because melanin blocks some of the UVB rays. Source: 1

Age Older people with diminished organ function and 7-dehydrocholesterol content in the skin impair calcitrol production. 7-dehydrocholesterol: a cholesterol precursor Source: 1

Latitude At latitudes above 35degrees, the UVB photon path length is longer, and fewer UVB photons reach the Earth. – This results in less Vitamin D synthesis in the skin. Source: 1

Season/Time of Day During spring, summer, and fall, exposure to sunlight for 5-15 minutes from the times of 10am-3pm is thought to provide sufficient amounts of vitamin D. In U.S.: 1.5 IU/cm 2 /hour in winter 6.0 IU/cm 2 /hour in summer Can be synthesized by skin. Source: 1

Deficiency Widespread throughout the United States and the World. Linked to several health conditions but most directly linked to rickets and osteomalacia Source: 1

Rickets Most common in children Characterized by seizure, growth retardation, and failure of bone to mineralize. In deficient infants, the epiphyseal cartilage grows and enlarges however, without replacement by bone matrix and minerals. Source: 1

Rickets Effects Effects are typically visible at wrists, ankles, and knees, which all enlarge. Long bones of legs bow, and knees knock as child grows and begins weight bearing activity. The spine becomes curved, and pelvic and thoracic deformities occur. – Characterized by costochondral beading at the juncture of the ribs and cartilages. Source: 1

Osteomalacia Occurs in adults and some children Characterized by bone demineralization Results from prolonged elevations in blood parathyroid hormone (PTH). PTH promotes bone resorption and increased urinary phosphorus excretion. As bone turnover occurs, the bone matrix is preserved but mineralization cannot occur. Source: 1

Osteomalacia Indicators of bone resorption include increased urinary excretion of bone collagen by-products such as: -Hydroxyproline -N-telopeptide -Pyridinoline -Deoxypyridinoline With insufficient serum calcium and phosphorous concentrations, the mineralization of bones cannot occur. Source: 1

Osteomalacia Progressive demineralization results in bone pain (throbbing or aching) and soft bones. Muscle weakness and general pain occur as well. Source: 1

Toxicity Tolerable Upper Intake = 4,000 IU for children, adolescents and adults. Vitamin D is one of the most likely vitamins to cause toxicity. Occurs with an intake of 10,000 IU/day for several months. Source: 1

Toxicity Too much sunlight cannot cause toxicity – Only raises serum concentrations to ~ nmol/L, whereas levels greater than 500nmol/l Manifestions of toxicity include: – Hypercalccemia, calcinosis and the calcification of the soft tissues including the heart, kidneys, lungs and blood vessels. Source: 1

Toxicity Additional effects include, hyperphosphatemia, hypertension, anorexia, nausea, weakness, headache, renal dysfunction, and sometime death. Source: 1

Significant Sources Provided by a small number of foods of animal origin. Liver (1 ug/3oz) Eggs (1.1 ug/egg) Fatty Fish- herring (2.4ug/3oz), salmon 11ug/3oz), tuna 1.7ug/3oz) and sardines (4.1ug/3oz) Small amounts in cheese and butter Source: 1

Significant Sources Plant Origin-shitake mushrooms (0.5ug/1/2C) Fortified sources: – Milk – Yogurt – Cheese – Butter, margarine – Orange juice – Breads – Some cereals Supplements Source: 1

References 1.Gropper SS, Smith JL. Advanced Nutrition and Human Metabolism, 6th ed. Belmont, CA: Wadsworth; Battault S, Whiting SJ, Peltier SL, Sadrin S, Gerber G, Maixent JM (2012) 'Vitamin D metabolism, functions and needs: from science to health claims', Eur J Nutr, 52, pp Dusso AS, Brown AJ, Slatopolsky E (2005) 'Vitamin D', Am J Physiol Renal Physiol, 289, pp. 8-22