Therapeutics I: Essential and Conditionally Essential nutrients

Recommended Dietary Allowance (RDA)

How much of a specific nutrient that is needed to maintain optimal health

Adequate Intake 9AI)

Recommended intake for nutrients for which inadequate scientific data exist to establish an EAR w/ confidence

Tolerable Upper Intake Levels (UL)

Level of chronic intake unlikely to pose a risk of adverse health for most of the population

Fat Soluble Vitamins (A,D,E,K)

• Stored in body tissues, ingestion of excessive quantities may be toxic

• Deficiencies occur when fat intake is limited or fat absorption compromised (celiac, cystic fibrosis, hepatic cirrhosis, short-bowel syndrome)

• Deficiencies may also be precipitated by drugs that affect lipid absorption (cholestyramine, orlistat, mineral oil)

Water Soluble Vitamins (B-Complex and C)

Not stored in body, excessive quantities excreted in urine. Daily intake desirable

Vitamin B12 (Cobalamin) Function

Functions

• Important to the formation of blood and nerve cells

At risk populations

• Vegans

• >50 (inability to absorb food bound B12, reduced intestinal motility, use of gastric acid lowering agents resulting in bacterial overgrowth utilizing more B12)

• Long-term metformin therapy

• Bariatric surgery

Vitamin B12 At-risk populations

At risk populations

• Vegans

• >50 (inability to absorb food bound B12, reduced intestinal motility, use of gastric acid lowering agents resulting in bacterial overgrowth utilizing more B12)

• Long-term metformin therapy

• Bariatric surgery

Vitamin B12 Deficiency

Anemia, malaise, neurologic symptoms (neuropathy, mental confusion, agitation)

Dosing

• Oral/sublingual dose: 500-2,000 micrograms daily

• Intramuscular or deep subcutaneous administration may be necessary due to poor bioavailability of oral administration

Folic Acid (Folate) Function

Function

• Essential for cell division, DNA production and brain and spinal cord development

Folic Acid (Folate) At-Risk populations

Pregnancy, lactation, infancy, infection, hemolytic anemia, blood loss, hypermetabolic states, alcoholism, malabsorption, liver disease, methotrexate, trimethoprim, anticonvulsants, and sulfasalazine

Folic Acid (Folate) Deficiency Presentation

Neural tube defects in newborns, CNS symptoms, megaloblastic anemia

Dosing

• All women of childbearing age should obtain at least 400mcg/day

  • Supplementation most important 1 month before and 3 months into pregnancy

  • Higher doses needed in women who have had a NTD-affected pregnancy

• Folic acid not biologically active, must undergo in vivo enzymatic conversation to methylenetetrahydrofolate reductase (MTHFR).

  • genetic polymorphism of MRHFR that results in inadequate enzyme activity

UL set to minimize risk of masking vitamin B12 deficiency

Folic Acid (Folate) relationship to B12

Vitamin B12 is essential for the metabolism of folates

• Megaloblastic anemia responsive to folic acid administration is a feature of Vitamin B12 deficiency

• Giving folic acid with a B12 deficiency would correct anemia, but wouldn’t stop CNS damage from B12 deficiency

• Folic acid can mask signs, but not progession of vitamin B12 deficiency

Vitamin C (Ascorbic Acid) Function

Antioxidant necessary for connective tissue metabolism, wound healing aids in the absorption of iron. May protect against oxidative stress generated during infection

Vitamin C (Ascorbic Acid) At-risk populations

Anyone not consuming fruits and vegetables, smokers, alcoholics and elderly

Deficiency Presentation

Scurvy, Fatigue, poor wound healing

Vitamin C Dosing

100-125mg/day for smokers

• vitamin C + iron not necessary for patients with normal gastric acidity

• megadose vit C for cold and supplementation for prevention of heart disease and cancer not supported by literature

Vitamin C Safety Considerations

• Supplementation to support wound healing should be supervised by MD

• Chronic megadose supplementation in pregnancy may lead to rebound scurvy in infants after birth

• Chronic high dose supplementation could increase prevalence of kidney stones in patients with renal disease or history of kidney stones

• Possible iron overload in patietns taking iron supplementation

Vitamin C for the Common Cold

Decreased severity and duration of cold when Vitamin C is consumed at doses at or above 200mg daily

• Literature does not support therapeutic vitamin C dosing to treat colds or prophylactic dosing to prevent them

  • Greatest potential for benefit occurs when supplementation is initiated within 24 hours of symptom onset, at high doses when therapy is continued for at least 5 days

• Most resasonable for patients to obtain vitamin C from their diets

  • 5 fruits and vegetables daily provides more than 200mg Vitamin C

Vitamin D Function

Promotes calcium absorption to assist with bone growth and remodeling

• Vitamin D, in conjuction with sufficient calcium, may reduce the risk of bone fractures and falls in postmenopausal women with osteoporosis

Low levels of Vitamin D associated with fracture, cancer, diabetes, CVD, depression, and death

Vitamin D Deficiency & At-risk populations

Deficiency indicated when 25(OH)D <30ng/ml

At-risk populations

• breastfed infants, older adults, individuals with limited sun exposure, patients with dark skin, patients who are obese or have undergone gastric bypass surgery, patients with kidney or hepatic dysfunction

  • Medication induced def: Phenytoin, carbamazepine, primidone

Vitamin D Dosing

DRI: 600-800IU Daily

National Osteoporosis Foundation recommends 800-1000IU Daily for persons 50+ yoa, with higher doses under investigation

• Current upper limit is 4,000IU daily

  • toxicity includes anorexia, hypercalcemia, soft tissue calficiation, kidney stones, renal failure and increased risk of some types of cancer

  • Doses of 50,000 IU may be necessary to replete levels, but dose is toxic for self-care

Vitamin A Considerations

Celiac, Chron’s, Pancreatic disorder, Cancer, excessive excretion

Vitamin B1 (thiamine)

Deficiency common in alcoholism, ≥ 100mg daily in chronic alcholism.

• Deficiency also seen in chronic high-dose furosemide therapy

Vitamin B2

Hair, Skin, and nails-urine turns yellowish-orange

Vitamin B6

Should be given concurrently with isoniazid to avoid neuropathy

Vitamin E

Very low birth weight infants and fat malabsorption may cause defiency. May also increase risk of CHF, hemorrhagic stroke

Vitamin K

Drug-Drug Interaction with warfarin

Niacin

Therapeutic doses used to traet Hyperlipidemia, can cause flushing, Not for self-care, can lead to GI/hepatic side effects

use with caution with diabetes, gout, peptic ulcer disease, gastritis

Calcium Function

Major component of bones and teeth, contributes to normal muscle adn nerve function

BEST source of calcium is from the diet

• evaluate dietary calcium intake before recommending calcium supplement dose

Calcium at-risk populations

Advanced age, malabsorptive sundromes, hypoparathyroidism, vit D deficiency, renal failure, long-term anticonvulsant therapy, during periods of growth, pregnancy and lactation

Calcium Deficiencies

Increases risk for osteoporosis, convulsions, tetany

Calcium Recommended requirements

• Age 19-50, M/F: 1000mg/day

• Age 51-70, M: 1000mg/day

• Age 51-70, F: 1200mg/day

• Age 71+, M/F: 1200mg/day

Calcium Dosing

Based on elemental calcium content, not calcium salt

• Calcium carbonate (40% elemental calcium)

• Calcium citrate (21% elemental calcium)

• Calcium gluconate (9% elemental calcium)

Optimal absorption occurs with individual doses of 500mg or less. Daily doses of >500mg should be divided

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Caltrate 600+D

Calcium Carbonate/Vitamin D

• 600mg/800IU tablet

• Give with Food

Citracal maximum

Calcium citrate/Vitamin D

• 630/1000IU/ 2 tablets

• Absorbed without acidic environment

Tums Regular Strength

Calcium Carbonate

• 400mg/ 2 tablets

• Give with Food

Viactiv Calcium Soft Chews+D

Calcium Carbonate/Vitamin

• 500mg/500IU/ tablet

• Contains Vitamin K, Not good with anticoagulants

Calcium Safety Considerations

• Constipation

• High dose can lead to kidney stones

• Intake greater than 1500mg daily may increase risk of prostate cancer

• Increased deposition of calcium in soft tissue can occur with hypercalcemia

Iron Function

Oxygen and electron transport

Iron At-risk populations

Major blood loss, heavy menstrutation, inadequate intake, lactation, growth, elderly, renal failure, vegan, vegetarian, or other meat restricted diets

Drug-induced through GI irritation or increased bleeding tendency

Iron Deficiency Presentation

Pallor, fatigue, iron-deficiency anemia

Ferrous Sulfate

325mg

• 20% (65mg/tablet elemental iron)

  • Well absorbed, enteri coating improves tolerability but decreases absorption

Ferrous fumarate

60mg

• 33% (20mg/tablet elemental iron)

• Better tolerated than ferrous sulfate

Ferrous gluconate

225 mg

• 12% (27mg/tablet elemental iron)

• Better tolerated than ferrous sulfate

Iron Dosing & Safety Considerations

Upper limit of iron set at 45mg/day to avoid GI irriation

• patients with iron deficiency absorb 20% of elemental iron administered, require 36-48mg of elemental iron daily to treat deficiency

GI Irritation, do not give to patients at high risk for GI bleed

Iron Absorption in Deficiency

Only 20% of administered elemental iron is absorbed in an iron deficient patient

• 36-48mg of elemental iron necessary to treat deficiency

Iron Administration Counseling

Absorption is increased when taken with vitamin C

• GI irritation is decreased when taken with food

• Absorption is decreased when taken with food

• May cause black tarry stools

• May cause constipation

Accidental overdose of iron-containing products is the leading cause of fatal poisoning in children under 6

Calcium, Mg, Fe, and Zn DDI with Tetracyclines/fluoroquinolones

Reduced antibiotic absorption

Solution: separate dosing by at least 2 hours

Calcium, Mg, Fe DDI with levothyroxine

Reduced drug absorption

Solution: separate dosing by at least 4 hours

Calicum DDI with H2RA’s and PPIs

Reduced Ca Carbonate absorption

Solution: Use calcium citrate if on chronic H2RA/PPI

Phosphorus DDI with sucralfate or Mg, Ca or aluminum containing antacids

Decreased iron solubility and absorption

Solution: Separate dosing by at least 2 hours

Phosphorus Deficiency

Rare unless induced

• Prolonged administration of aluminum hydroxide antacids can cause hypophsophatemia (weakness, anorexia, bone loss

Fluoride Deficiency

Deficiency presents as dental decay

Zinc deficiency

Essential for normal immune function

• Insufficient evidence to recommend zinc for treatment or prevention of comon cold

Magnesium Deficiency

Cannot correct hypocalcemia or hypokalemia without first ensuring magnesium levels are adequate