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Vitamin D, Phosphorus, Magnesium

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Vitamin D

Compound and Structure

  • —Vitamin D is a family of compounds with curative action for rickets

  • —Structurally derived from a steroid with one ring broken

    • —Photolysis of B ring è a seco-steroid

    • —Cholecalciferol (D3) from foods of animal origin

      • —Photolysis of 7-dehydrocholesterol (7-DHC)

      • —UV irradiation of skin

  • —Ergocalciferol (D2) from foods of plant origin

    • Photolysis of plant sterols

  • —All forms must be activated in the body

    • —Multiple organs involved: skin, liver, kidney

  • —Active form - 1,25-(OH) 2 vitamin D3 (calcitriol) which acts as a hormone.

Food Sources

  • —In plants, ergosterol (previtamin D2) is converted to ergocalciferol (vitamin D2)

  • —Ergocalciferol (vitamin D2) is sold commercially

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  • In animals and humans, vitamin D3 can be synthesized from cholesterol in sun-exposed skin

  • ​Vitamin D is unique because our body can synthesize enough vitamin D given proper conditions

study question:

  • name the differences between animal and plant vitamin D

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Absorption, Transportation, Storage

  • —Dietary D3 is absorbed from micelles  and incorporated into chylomicrons.

  • —Epidermal synthesized D3 diffuses into blood and binds to vitamin D binding protein (DBP)

    • —Main destination is the liver

    • —In liver, mitochondrial 25-hydroxylase converts Vitamin D3 to 25-OH D3 by adding a –OH group

  • —When needed, 25-OH D3 is released into blood

  • —25-OH vitamin D3 is the main form of vitamin D

    • —In liver for storage

    • —In blood è index of status in assessment

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Activation of Vitamin D in the Body

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Major Functions of Vitamin D

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Mechanisms of Functions

  • —Similar to vitamin A, vitamin D needs to bind to a receptor to function

  • —Two types of vitamin D receptors (VDR)

  • —Membrane VDR

  • —Nuclear VDRs, members of supergene family nuclear receptors

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study questions:

  • describe the roles of vitamin D in the body. 

  • describe the difference between synthesized vs dietary vitamin D

Calcitriol and Gene Expression

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Vitamin D: Membrane VDR

  • —Located at cell membrane

  • —Ligand: calcitriol

  • —Effects:

    • —Increased calcium absorption by the intestine

    • —Increased calcium uptake into skeletal muscle cells and osteoblasts

  • —Needs secondary messengers to internalize the signal of binding of calcitriol to VDR

    • —Second messengers: MAPK, PKC, cAMP

  • —In this case, calcitriol functions like a hormone. “Hormone D”

Regulation of Calcium Homeostasis

  • —Blood calcium level is tightly regulated and maintained within a narrow range

  • —Involves coordination of

    • —3 organ systems: Bone, Kidney, Intestine

    • —3 hormones

      • —Parathyroid (PTH)

      • —Calcitriol (active form of vitamin D)

      • —Calcitonin (via thyroid)

        • —Kicks in when blood calcium rises above normal level

        • —Counter PTH and calcitriol

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  • Sequence (of small changes)

    • 1. Start:  decrease in serum Ca (can be very small)

      • —Sensed by parathyroid gland --> release of PTH

      • —Bone: PTH stimulates osteoclasts to resorb bone

        • —Stimulates secretion of enzymes and acid  that break down bone mineral

        • —Bone mineral breakdown increases blood levels of both Ca and HPO4-

    • 2. Next: Goal is to keep Ca and excrete HPO4-

      • —Kidney: PTH acts on tubular cells (after filtration) to

        • increased reabsorption of Ca++ (return to blood)

        • decreased reabsorption of phosphorous

          • —Therefore phosphorous in urine ­increased

    • 3. Finally: Intestine

      • —Ultimately stimulates absorption of Ca from diet to “repay” bone loss

Vitamin D and Bone Health

  • —Vitamin D is essential for normal bone growth in childhood and maintaining bone density and strength during adulthood

  • —Vitamin D

    • —Increases calcium absorption in intestine

    • —Decreases PTH with feedback loops --> 

  •   increased bone mineralization

    • —Long loop (indirect): increased blood calcium inhibits PTH

    • —Short loop (direct): decreases transcription of pre-PTH gene

study question:

  • what is the relationship between calcium and vitamin D?

Vitamin D and Cell Differentiation, Proliferation and Growth

  • —Calcitriol induces differentiation of

    • 1.stem cell monocytes in the bone marrow to mature osteoblasts (bone health)

    • 2.stem cells to macrophages and monocytes (immune system)

  • —Calcitriol induces differentiation and decreases the proliferation of epidermal cells (treatment of psoriasis)

  • —Calcitriol diminishes proliferation of abnormal cells in certain tissues (role in cancer development/treatment?)

Other Roles

  • —Vitamin D seems to down-regulate both renin and angiotensin è lower blood pressure

  • —Unclear role in diabetes

    • —Serum calcitriol level is negatively associated with insulin secretion by beta-cells in the pancreas

    • —Serum calcitriol level is positively associated with insulin sensitivity

Deficiency

  • —People at risk

    • —Those on strict vegetarian diets when sunlight exposure is inadequate

    • —Elderly because poor diets, inadequate sunlight exposure, decreased ability to synthesize vitamin D in the skin

    • —Those who live in high latitudes, esp during winter

    • —Those with fat malabsorption

    • —Those with chronic kidney diseases/failure (could not activate vitamin D)

    • —Certain athletes/physically active people who spend most time indoors without adequate dietary intake

  • Rickets in infants and children

    • —Retarded growth

    • —Enlarged wrists, knees, and ankles

    • —Bow legs

    • —Spinal deformities

    • —Delayed tooth eruption

    • —Pain at the end of long bones, esp at knee

    • —Increased risk for infection

  • Deficiency

    • —“Softening” of bones

    • —Inadequate vitamin D leads to increased risk for osteoporosis and fracture

      • —inadequate calcium absorption

      • —Increased PTH level

      • —Increased bone resorption

    • —Hearing loss and ringing in ears

Clinical Assessment

  • —Preferred form

    • —Vitamin D3 is generally preferable to vitamin D2

  • —Bone disorders

    • —Effective in treating children with rickets

    • —Together with calcium can slow or prevent osteoporosis

  • —Psoriasis

    • —Vitamin D regulates epithelial cell growth and development

  • —Immune function

    • —Vitamin D induces differentiation of WBC and enhances resistance to infection

Assessment

  • —25-OH vitamin D3 (calcidiol) is the main form of vitamin D in circulation and often used as an index of vitamin D status

    • —For bone health:   75/80~100 nmol/L (30/32~40 ng/mL)

    • —Insufficiency:      50~72 nmol/L (20~29  ng/mL)

    • —  Deficiency:          < 50 nmol/L (20 ng/mL)

    • —Toxicity:              500 nmol/L (200 ng/mL)

  • —Serum level of total 25-OH vitamin D reflects both cutaneous production and dietary intake (combination of both D3 and D2)

Phosphorus

Food Sources

  • 2nd abundant mineral

  • Wide distribution in foods

    • Organic form

      • Bound to protein, sugar, lipids etc

    • Inorganic form

      • Eg. phytate

  • Animal products are best sources

  • Bioavailability 50%

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Absorption, Transport, Storage

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study question:

  • in what form is phosphorus most absorbed

  • Can be absorbed throughout the small intestine, mainly in duodenum and jejunum

  • In blood, 70% is organic (eg. phospholipids), 30% is inorganic

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Functions

  • —Bone mineralization

    • —Tissue distribution

      • —85% in the skeleton

      • —1% in the blood and body fluid

      • —14% associated with soft tissue

  • —Nucleotide/Nucleoside Phosphates

    • —Structural roles (in DNA and RNA)

    • —Energy storage and transfer, eg ATP/ADP

    • —Intracellular second messenger, cAMP, IP3

  • —Phosphoproteins

    • —Phosphorylation/Dephosphorylation affects enzyme activity

  • —Structural roles

    • —Phospholipid bilayer is the basic structure of cell membrane

  • —Acid-base balance

study question:

  • what is the link between phosphorus and vitamin D?

Deficiency

  • —RDA has been established

  • —Deficiency rare; typically see in people receiving large amounts of antacids containing Ca, Mg, Al

  • —Also seen in refeeding syndrome

    • —increased glycogen, fat, protein synthesis (anabolism) requires high [P]

    • —enteral/parenteral nutrition without adding P

  • —Signs and symptoms

    • —Anorexia

    • —Leukocyte dysfunction

    • —Reduced cardiac output

    • —Arrhythmias

    • —Skeletal muscle and cardiac myopathy

    • —Fluid and electrolyte disorders, along with neurologic, pulmonary, cardiac, neuromuscular, and hematologic problems

Toxicity

  • —UL has been established

  • —Toxicity rare

  • —Hypocalcemia and tetany

    • —Also seen in calcium deficiency

  • —Calcification of soft tissues especially in the kidneys and arteries

    • —Increases osteogenic gene expression

    • —Renal dysfunction elevates PTH, but reduced GFR increases blood phosphorus concentration

    • —Should pay attention to renal patients

Magnesium

Food Sources

  • Wide distribution in foods

  • Hard water is high in Mg

  • Food processing and preparation may reduce Mg content in foods

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Digestions, Absorptions, Transportation

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study question:

  • describe this process

Functions

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  • —Within cells Mg is bound to phospholipids as part of cell membranes

  • —Mg is associated with nucleic acids

  • —Mg serves as structural cofactor or allosteric activator for over 300 enzymes

    • —Glycolysis: hexokinase, phosphofructokinase

    • —TCA cycle: oxidative decarboxylation

    • —Beta-oxidation: initiation by thiokinase

    • —Protein synthesis

    • —cAMP formation (second messenger)

  • Insulin and insulin action

Storage and Excretion

  • —Storage

    • —50~60% in bone

    • —39~49% in soft tissue

    • —1% extracellular fluids

  • —Excretion

    • Renal

    • Fecal

Deficiency

  • —Impaired action of vitamin D

    • —Mg is needed in hepatic hydroxylation of vitamin D

  • —Hypocalcemia and hypokalemia due to increased loss of calcium and potassium, respectively

  • —Muscle cramp and trembling

  • —Anorexia, nausea, and vomiting

  • —Impaired insulin secretion and function esp in diabetic individuals

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Toxicity

  • —UL has been established

  • —Mainly in people with renal diseases

    • —Reduced GFR

    • —Normal kidneys can remove fast enough to prevent serum level from going too high

  • —Signs and symptoms

    • —Nausea, diarrhea

    • —Flushing

    • —Weakness

    • —Double vision

    • Slurred speech

Clinical Application

  • —Preeclampsia/Eclampsia

    • —High intravenous dose of Mg to prevent seizure

    • —No evidence suggests that Mg supplements are helpful

  • —Hypertension

  • —Cardiovascular disease

  • —Diabetes

  • —Migraine headaches

Assessment

  • —Serum level is tightly controlled therefore not a good marker for Mg status

  • —Urine Mg excretion before and after administering a Mg load intravenously

    • —Decreased Mg excretion indicate deficiency

©2023 by Syracuse University Dr.Margaret Voss

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