Evolving Concepts And Importance In Overall Health Status

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VITAMIN D DEFICIENCY

• Evolving Concepts And Importance In Overall
  Health Status

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• Silent epidemic.
• Vitamin D deficiency is a highly prevalent
  condition, present in approximately 30 to 50 of
  the general population.
• More prevalent in elderly, women of child bearing
  age and infants.
• Often unrecognized by clinicians.

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Case 1

• An elderly AA obese woman was readmitted to the
  hospital from a nursing home because of
  progressive weakness. She had been discharged two
  weeks earlier following a four-month
  hospitalization for severe chronic obstructive
  pulmonary disease. During her previous hospital
  stay, she required prolonged mechanical
  ventilation through a tracheostomy tube and
  total, or central, parenteral nutrition (CPN).
  She was discharged to the nursing home on
  low-flow oxygen therapy. On readmission, she had
  a weak cough and required vigorous tracheal
  suctioning through her tracheostomy tube. PMH is
  significant for seizure disorder, HTN, CRF.
  Depressed levels of serum calcium and phosphate
  resistant to vigorous oral and intravenous
  replacement were noted on both hospital
  admissions.

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Question

• Can you identify risk factors for Vitamin D
  deficiency in this patient?

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• Elderly
• Dark skin
• No sun exposure
• Diet
• Obesity
• CPN-provides 200 IU/d.
• Dilantin
• CRF

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• For our patient, before she was to return to the
  nursing home, her 25-hydroxyvitamin D level was 7
  ng per mL (17 nmol per L normal 8 to 38 ng per
  mL 20 to 95 nmol per L), and her PTH level was
  161 pg per mL (17 pmol per L normal 9.5 to 49.4
  pg per mL 1.0 to 5.2 pmol per L). Vitamin D and
  calcium supplementation was to begin in the
  nursing home.

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Risk Factors

• Individuals older than 65 years
• Nursing home residents
• Individuals with nonvertebral
• or hip fractures
• Individuals with kidney disease
• Individuals with low bone mass
• or osteoporosis
• Individuals with a history of falls

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Causes

• Inadequate sun exposure
• Sunscreen use SPFgt8
• Pigmented skin
• Aging (older than 65 years)
• Winter season
• Northern latitudes above 40
• Decreased absorption
• Bowel bypass surgery
• Crohns disease
• Celiac disease
• Fat and cholesterol absorption inhibitors

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Other Causes

• Breastfeeding
• Liver failure
• Chronic renal disease
• Medications Steroids decrease half life of
  vitamin D. Dilantin, Phenobarbital, and Rifampin
  can induce hepatic p450 enzymes to accelerate the
  catabolism of vitamin D.

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Metabolism Of Vitamin D
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Metabolism

• Source Skin and diet
• Stores 25 OH Vitamin D3 (calcidiol)
• Active form 1,25(OH)2 Vitamin D (calcitriol)
• MOA Steroid hormone. Binds to VDR in nucleus to
  upregulate gene expression in target cells.
• Functions
• Calcium absorption in the intestines and is
  required for the efficient utilization of dietary
  calcium.

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Metabolism

• Involved in cellular growth, differentiation and
  apoptosis
• Simulates insulin secretion
• Modulates the immune system.
• Reduces inflammation
• Muscle development
• Telomere protective

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Associated Clinical Conditions

• Muscle Weakness and Falls
• Proximal muscle weakness
• Chronic muscle aches
• Myopathy
• Increase in falls
• Recent studies suggest that vitamin D
  supplementation at doses between 700 and 800 IU/d
  in a vitamin D-deficient elderly population can
  significantly reduce the incidence of falls.

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• Bone Density and Fractures
• Risk of osteoporosis may be reduced with adequate
  intake of vitamin D and calcium.
• Studies support the concept that vitamin D at
  doses between 700 and 800 IU/d with calcium
  supplementation effectively increase hip bone
  density and reduced fracture risk, whereas lower
  vitamin D doses may have less effect.

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• Role in Cancer Prevention
• Low intake of vitamin D and calcium has been
  associated with an increased risk of non-Hodgkin
  lymphomas, colon, ovarian, breast, prostate, and
  other cancers.
• The anti-cancer activity of vitamin D is thought
  to result from its role as a nuclear
  transcription factor that regulates cell growth,
  differentiation, apoptosis and a wide range of
  cellular mechanisms central to the development of
  cancer. These effects may be mediated through
  vitamin D receptors expressed in cancer cells.
• Vitamin D is not currently recommended for
  reducing cancer risk

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• Autoimmune Disease
• Vitamin D supplementation is associated with a
  lower risk of autoimmune diseases.
• In a Finnish birth cohort study of 10,821
  children, supplementation with vitamin D at 2000
  IU/d reduced the risk of type 1 diabetes by
  approximately 78, whereas children who were at
  risk for rickets had a 3-fold higher risk for
  type 1 diabetes.
• In a case-control study of 7 million US military
  personnel, high circulating levels of vitamin D
  were associated with a lower risk of multiple
  sclerosis.
• Similar associations have also been described for
  vitamin D levels and rheumatoid arthritis.

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• Role in Cardiovascular Diseases
• Vitamin D deficiency activates the
  renin-angiotensin-aldosterone system and can
  predispose to hypertension and left ventricular
  hypertrophy.
• Additionally, vitamin D deficiency causes an
  increase in parathyroid hormone, which increases
  insulin resistance secondary to down regulation
  of insulin receptors and is associated with
  diabetes, hypertension, inflammation, and
  increased cardiovascular risk.

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• Role in Reproductive Health
• Vitamin D deficiency early in pregnancy is
  associated with a five-fold increased risk of
  preeclampsia.
• Role in All Cause Mortality
• Researchers concluded that having low levels of
  vitamin D (lt17.8 ng/mL) was independently
  associated with an increase in all-cause
  mortality in the general population.

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Diagnostic Tests

• Measurement of 25(OH) vitamin D serum levels best
  reflects the vitamin D status of an individual.
• Normal levels 25 (OH) vitamin D are in the range
  of 30 to 80 ng/mL (75 to 200 nmol/L).
• Concentrations lt 12 to 20 ng/mL (30 to 50 nmol/L)
  are considered deficient.
• Levels gt 150 ng/mL (374 nmol/L) are considered
  toxic.

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Dietary Reference Intakes Vitamin DEstablished
in 1997
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Dietary Sources

• Natural sources of vitamin D include
• Fish liver oils, such as cod liver oil, 1 Tbs
  (15 mL) provides 1,360 IU
• Fatty fish species, such as
• Herring, 85 g (3 ounces) provides 1383 IU
• Catfish, 85 g (3 oz) provides 425 IU
• Salmon, cooked, 100 g (3.5 oz) provides 360 IU
• Mackerel, cooked, 100 g (3.5 oz), 345 IU
• Sardines, canned in oil, drained, 50 g (1.75 oz),
  250 IU
• Tuna, canned in oil, 85 g (3 oz), 200 IU
• Eel, cooked, 100 g (3.5 oz), 200 IU
• A whole egg, provides 20 IU
• Beef liver, cooked, 100 g (3.5 oz), provides
  15 IU

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Fortified Sources

• Some of the dietary sources
• Fortified milk (100 IU/8 oz)
• Cheeses and yogurt
• Fortified cereals

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Updated Recommendations In Process

• Studies suggest that the daily vitamin D intakes
  should be much higher than 400 IU/d.
• Daily intakes in the range of 800 to 1000 IU/d
  should be strongly considered.
• Although there are concerns regarding vitamin D
  toxicity, side effects at intakes exceeding the
  current upper limit of 2000 IU/d have not been
  reported to date.
• Assessment of vitamin D status with serum
  measurements of 25(OH) vitamin D levels for a
  broader range of patients should be encouraged.

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Causes and Management of Vitamin D Deficiency

• Lack of adequate sunlight or chronic sunscreen
  use Ultraviolet lamp or increased sun exposure.
  In a Boston study, exposure of hands, face, and
  arms to sunlight for five to 15 minutes daily
  between 11 a.m. to 2 p.m. provided adequate
  vitamin D.
• Total (central) parenteral nutrition 400 to 800
  IU of vitamin D orally per day, or 20 to 25 IU of
  vitamin D per kg intravenously per day.

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Causes and Management of Vitamin D Deficiency

• Vitamin D-deficient diet Usually 1,500 to 5,000
  IU of vitamin D2 orally per day, or 50,000 IU of
  vitamin D2 orally per week or 10,000 to 50,000 IU
  of vitamin D2 intramuscularly per month
• Fat malabsorption 25-hydroxyvitamin D, 20 to 30
  mcg per day
• Cirrhosis, nephrotic syndrome, renal failure,
  gastric or small bowel resection, rifampin,
  chronic corticosteroids, anticonvulsants
  1,25-dihydroxyvitamin D, 0.15 to 0.5 mcg daily.

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Key clinical recommendation

• Daily vitamin D supplementation of 800 to 1,000
  IU is a reasonable dose for adults. Levels of
  25-OH vitamin D should be maintained gt 32 ng per
  mL (80 nmol per L) to maximize bone health.
• The (AAP) has doubled the recommended intake of
  vitamin D to 400 IU per day for infants,
  children, and adolescents.
• In patients with severe vitamin D deficiency,
  50,000 IU of vitamin D should be given daily for
  one to three weeks, followed by weekly doses of
  50,000 IU.

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• After repletion of body stores, 800 IU of vitamin
  D daily or 50,000 IU of vitamin D once or twice
  monthly is adequate maintenance therapy.
• Patients with no sun exposure, malabsorption, or
  those taking antiepileptic drugs may require
  larger maintenance doses of vitamin D (i.e., up
  to 50,000 IU one to three times week.
• In critically ill patients, albumin-adjusted
  calcium levels underestimate true or ionized
  hypocalcemia. Therefore, measured ionized calcium
  levels are recommended, particularly in patients
  who are being treated in an intensive care unit.
• If calcium supplementation alone fails to
  maintain normal serum levels, the patient is
  vitamin D deficient or resistant and may benefit
  from a trial of calcitriol (Rocatrol).
• Vitamin D toxicity is very uncommon, and there is
  a wide safety margin at these higher supplement
  doses.

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References

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