Ch 8: Vitamins & Trace Elements Flashcards
What amount of retinol is equivalent to 24 mcg of beta-carotene from food?
A. 2 mcg
B. 4 mcg
C. 2mcg
D. 1mg
A. 2 mcg
1 mcg of retinol has the Vitamin A activity of 12 mcg beta-carotene. The
Which of the following nutrients does NOT engage in conversion of homocysteine to methionine?
A. Choline
B. Vitamin D
C. Vitamin B12
D. Folate
B. Vitamin D
B12/folate are main factors in conversion of homocysteine to methionine
Alternatively, choline may be used for this conversion.
The first B vitamin deficiency to manifest in people with alcoholism is usually:
A. Niacin
B. Pantothenic Acid
C. Vitamin B6
D. Thiamin
D. Thiamin
Small amounts of thiamin stored in liver = first to become deficient
in malabsorptive or inadequate intake situations
Which of the following trace elements is regulated at the level of absorption but not excretion?
A. Zinc
B. Copper
C. Manganese
D. Iron
D. Iron
The control mechanisms that keep iron levels stable in the body occur at the absorption phase.
It is very difficult to eliminate iron except in conditions of blood loss (e.g., blood donation or menstruation)
Estimated Average Requirement (EAR)
Intake that meets estimated nutrient needs of 50% of the individuals in a group
Must be derived from scientific studies
Serves as basis for RDA
Recommended Dietary Allowance (RDA)
Intake that meets ENN of almost all (97-98%) individuals in that group
Adequate Intake (AI)
Established when evidence is insufficient to develop an RDA
Set at a level assumed to ensure nutritional adequacy
Tolerable Upper Intake Level (UL)
The max intake = unlikely to pose risk of adverse health effects in almost all individuals
What are the 13 vitamins & 1 dietary component that are considered essential?
B-vitamins (8 total): thiamin, niacin, riboflavin, folate, Vitamin B6, Vitamin B12, biotin, and pantothenic acid)
Vitamin C (ascorbic acid)
Fat soluble: A, D, E, K
Dietary component: choline
Fat soluble vitamin absorption
In duodenum: fat soluble vitamins → micelles → absorbed into enterocyte
In enterocyte: repackaged into chylomicrons (distribution to extrahepatic tissues)
What are Provitamins?
A substance that may be converted within the body to a vitamin
The term previtamin is a synonym
Retinol-binding protein (RBP)
Is synthesized in the liver
Required to transport retinol from liver to target tissues
Highly sensitive to nutrition status
What is RBP bound to in plasma?
RBP bound to prealbumin
(aka protein transthyretin, TTR)
4 functions of Vitamin A
Vision
Epithelial cell regulation
Wound healing
Bone and cellular health
How does Vitamin A impact corticosteroids in wound healing?
Reverses inhibitory effect of corticosteroids on wound healing
Vitamin A storage
Main: hepatocyte (liver)
Additional: adipose, kidneys, bone marrow, lung, eyes
Vitamin A excretion
Feces & Urine
increased amounts excreted in urine during sepsis
Vitamin A deficiency - disease states
Malabsorptive disorders (IBD, bariatric surgery, liver disease)
Pregnancy with low PO intakes
Alcoholism - impacts absorption, liver stores Vit A and processes ETOH
Vitamin A deficiency - signs and symptoms:
SKIN
- Follicular hyperkeratosis (keratin buildup around the hair follicles → bumps on the skin)
- Dry skin, itching, irritation
Vitamin A deficiency - signs and symptoms:
EYES
Roughened conjunctiva
Bitot’s spots (rough corneal keratin deposition)
Xerophthalmia (dry eyes)
Night blindness
Keratomalacia (cornea soft/cloudy, preceded by xerophthalmia)
Vitamin A deficiency - signs and symptoms:
BONES
Excessive bone deposition (new bone is formed)
Vitamin A deficiency - signs and symptoms:
OTHER
Impaired wound healing
Vitamin A toxicity - disease states
Renal failure (chronic and acute)
Binding capacity of RBP is exceeded → more Vit A circulating unbound → potential to damage cell membranes
Vitamin A toxicity - signs and symptoms:
SKIN
Pruritus (itchy skin)
Vitamin A toxicity - signs and symptoms:
HAIR
Alopecia (patchy hair loss)
Vitamin A toxicity - signs and symptoms:
EYES
Vision disorders (e.g., blurry vision)
Conjunctivitis
Vitamin A toxicity - signs and symptoms:
MOUTH
Cheilitis (inflammation of lips; chapped lips)
Vitamin A toxicity - signs and symptoms:
NERVOUS SYSTEM
Ataxia (impaired balance or coordination)
Vitamin A toxicity - signs and symptoms:
BONES
Bone loss
Bone pain
Hip fractures
Vitamin A toxicity - signs and symptoms:
OTHER
Hyperlipidemia
Renal osteodystrophy
= Metabolic bone disease characterized by bone mineralization deficiency due to electrolyte and endocrine abnormalities
Membrane dryness
Muscle pain
Hepatotoxicity
Birth defects
Nutrient deficiency that impacts vitamin a
Protein-energy malnutrition and/or zinc deficiency
- Due to RBP-TTR complex
- May compromise circulating serum Vitamin A levels
- Zinc is a component of retinol-binding protein, a protein necessary for transporting vitamin A in the blood.
Decreased circulating serum retinol levels may reflect impaired RBP synthesis and mobilization 2/2 inflammatory process/disease → does not require correction w/ supplementation
Vitamin A -
Medication to nutrient interactions
Through fat malabsorption:
Cholestyramine (bile acid sequestrant)
Lomitapide (lipid-lowering agent)
Octreotide (antidiarrheal)
Orlistat (weight control medication)
Mineral oil (laxative)
Corticosteroids (anti-inflammatories) - can cause decreased serum vitamin A
How long should Vitamin A be supplemented in setting of wound healing & corticosteroid use?
7 days
Dose of PO Vitamin A administration to enhance wound healing w/ concurrent steroid use?
3000-4500 RAE/day
Calcidiol
25-hydroxy-D
- Major circulating form that has no biological activity
Calcitriol
1,25-dihydroxyvitamin D
- Active form of Vitamin D
Principal function of Vitamin D
To maintain serum calcium and phosphorous levels to support:
- Neuromuscular function
- Bone calcification
- Other cellular processes
Vitamin D functions (3)
Calcium homeostasis
Pleiotropic effects of Vitamin D
Nosocomial infection (ex: Cdiff)
Vitamin D - absorption
80% dietary Vitamin D intake incorporated into micelle
- Primarily in distal small intestine
- Duodenum uptake = more rapid
Vitamin D - storage
Adipose tissue
Liver s/p conversion to calcidiol
Vitamin D - excretion
Bile
- Minimal amounts lost in urine
Vitamin D - populations at risk for deficiency
Inadequate sun exposure
- People wearing clothing/veils with minimal skin exposure
- People indoors much of the time
- Daily use of sunscreen
- Older adults and NH residents
- Dark-skinned individuals
Exclusively breastfed infants
Extensive skin damage (burns)
Fat-malabsorptive disorders
Renal disease (insufficient renal calcitriol production)
Long-term PN
Long term PN and Vitamin D status
One study suggests patients on home PN with high prevalence of Vitamin D deficiency despite PO supplementation
Best lab to evaluate Vitamin D status?
Circulating 25-hydroxyvitamin D [25(OH)D]
Which is NOT a good lab marker to evaluate Vitamin D status and why?
Calcitriol
Decreased calcidiol → serum calcium/phosphorous levels drop → PTH → renal production of calcitriol
= leaves levels elevated/normal in deficiency state
Which lab does ASPEN core curriculum (2016) say is a reasonable assay to evaluate Vitamin D status?
Calcidiol
- More clearly defined status with surrogate markers (PTH, calcium)
Nutrient to nutrient interactions:
Excess vitamin D
Excess Vitamin D stimulates hepatic oxidation and excretion of Vitamin K
Certain medications can impact Vitamin D. What are some generalized effects?
- Fat malabsorption
- Increased vitamin D metabolism, decreased serum levels
- Cause decreased serum levels
- Increase drug effects
Meds that decrease the absorption of Vitamin D through fat malabsorption
Cholestyramine (bile acid sequestrant)
Lomitapide (lipid-lowering agent)
Octreotide (antidiarrheal)
Orlistat (weight control medication)
Mineral oil (laxative)
Meds that increase vitamin D metabolism and decrease its serum levels
Phenobarbital (anticonvulsant)
Phenytoin (antiepileptic)
Valproic acid (antiepileptic)
Rifampin (antibiotic)
Meds that may cause decreased serum levels of Vitamin D
Corticosteroids (anti-inflammatories)
Carbamazepine (anti-epileptic)
Isoniazid (antitubercular)
Vitamin D may increase the drug effects of this medication:
Digoxin (antiarrhythmatic)
Vitamin D deficiency - signs and symptoms:
BONES
Osteomalacia (softening of the bones; ratio of bone mineral to bone matrix is low)
Vitamin D deficiency - signs and symptoms:
NERVOUS SYSTEM
Tetany (involuntary muscle contractions and overly stimulated peripheral nerves)
Caused by electrolyte imbalances — most often low blood calcium levels
Vitamin D deficiency - signs and symptoms:
OTHER
Hypocalcemia
Vitamin D toxicity - signs and symptoms:
BONES
Calcification of soft tissues (cardiovasculature, lungs)
Bone pain
Vitamin D toxicity - signs and symptoms:
NERVOUS SYSTEM
Confusion
Psychosis
Tremor
Vitamin D toxicity - signs and symptoms:
OTHER
Hypercalcemia
Can cause N/V, weakness, and frequent urination
Hypercalciuria
→ kidney problems (formation of calcium stones)
Causes of Vitamin D toxicity
Large doses of vitamin D supplements
Supplementation Rx for Vitamin D deficiency
50,000 IU 1x/week x8 weeks →
1000 IU/d for several months
Vitamin E - What is ɑ-tocopherol?
Most active and naturally occurring form of Vitamin E
Antioxidant activity, inhibits cell proliferation, platelet aggregation, monocyte adhesion
Vitamin E - What is 𝝲-tocopherol?
Predominant form of Vitamin E in American diet
Anti-inflammatory, anti-neoplastic, and natriuretic properties
What is Vitamin E’s primary function?
Antioxidant activity
Principal function is maintenance of membrane integrity in body cells via antioxidant activity
Inhibits lipid peroxidation → protects integrity of all biological membranes
Antioxidant activity: trapping peroxyl free radicals in cell membranes to protect against oxidation
Sufficient Vitamin E is critical in oxidative stress states (chronic inflammation, sepsis, SIRS, organ failure)
Where is Vitamin E absorbed?
Jejunum
Non-saturable passive diffusion with percentage absorbed decreasing with increases of PO intake
Where is Vitamin E stored?
Adipose tissue, muscle, liver
How is Vitamin E excreted?
Primarily: urine and bile
Significant amounts found in feces d/t body’s limited absorption of Vitamin E
Populations at risk for Vitamin E deficiency?
Fat malabsorptive disorders
- Prolonged steatorrhea
- Crohn’s disease
- Cystic fibrosis
Compromised biliary function
Resection of ileum or small intestine
Long-term PN without Vitamin E supplementation
Vitamin E Deficiency - SKIN
Ceroid pigmentation (age spots)
Vitamin E Deficiency - EYES
Vision changes
Deficiency weakens light receptors in the retina and other cells in the eye. This can lead to loss of vision over time
Vitamin E Deficiency - Nervous System
Ophthalmoplegia (paralysis of muscle that controls eye movement)
Ptosis (drooping upper eyelid)
Vision loss
Dysarthria (weakness in muscles used for speech → slurred speech)
* Can’t control tongue or voicebox
Ataxia (impaired balance or coordination)
Neuronal degeneration
What nutrient deficiency is associated with the following:
- Hemolytic anemia (RBC are destroyed faster than they can be made)
- Increased platelet aggregation
- Urinary creatinine wasting
Vitamin E deficiency
Vitamin E Toxicity - SKIN
Bruising from decreased Vitamin K absorption
Vitamin E Toxicity - BONE
Inclusion bodies in bone marrow
Vitamin E Toxicity - OTHER
Thrombocytopenia (low platelet level)
→ bleeding into the tissues, bruising, and slow blood clotting after injury
Cerebral hemorrhage
Impaired neutrophil function
Abrogated granulocytopenic response to antigen
Impaired coagulation
Skeletal muscle lesions with ceroid deposits in smooth muscle is a result of what micronutrient deficiency?
Prolonged depletion of Vitamin E
Vitamin E - Biomarkers
Plasma or serum Vitamin E (ɑ-tocopherol)
What does a ratio of ɑ-tocopherol (mcmol/L) to plasma cholesterol (mmol/L) below 2.2 indicate?
A risk for Vitamin E deficiency
Vitamin E - nutrient to nutrient interactions
Intakes >1200 mg/d Vit E interferes with Vitamin K absorption and metabolism
- May be problematic for patients on Warfarin
800-1200 mg/d Vitamin E may decrease platelet adhesion
Vitamin E - drug nutrient interactions
Through fat malabsorption:
Cholestyramine (bile acid sequestrant)
Lomitapide (lipid-lowering agent)
Octreotide (antidiarrheal)
Orlistat (weight control medication)
Mineral oil (laxative)
Which medication does water soluble Vitamin E increase the absorption of?
Cyclosporine (immunosuppressant)
Consistent intake of excessive amounts of Vitamin E is contraindicated in which patient population?
Patients with a coagulation defect
Functions of Vitamin K
Clotting
Bone Health
PT & INR
Clotting is measured in terms of Prothrombin Time (PT)
Variance in measurement → use of international normalized ratio (INR)
INR - high and low meanings
High INR: blood clots slower than desired
Low INR: blood clots faster than desired
Does Warfarin increase or decrease INR?
Warfarin increases INR
Does Vitamin K increase or decrease INR?
Vitamin K decreases INR
Vitamin K deficiency - populations at risk (5 different groups)
Fat malabsorption
IBD
Antibiotic therapy
Long-term PN without ILE
NPO status
Vitamin K deficiency
signs and symptoms - SKIN
Bruising
Prolonged bleeding
Vitamin K deficiency
signs and symptoms - BONE
Decreased bone density
Vitamin K deficiency
signs and symptoms - OTHER
Increased prothrombin time
What are the signs/symptoms of Vitamin K deficiency?
None
Which patient population was shown to have adverse effects with large doses of vitamin K?
Severely compromised liver function
What has Menadione (water soluble synthetic Vitamin K analog) caused?
fatal anemia
hyperbilirubinemia
severe jaundice
anaphylactoid reaction
Vitamin K - biomarkers
Plasma phylloquinone - major circulating form
More sensitive indicator of Vit K status
Vitamin K nutrient to nutrient interactions
Excess Vitamin A or Vitamin E → decrease absorption of Vitamin K
Excess serum/plasma Vitamin D stimulate hepatic oxidation → excretion of Vitamin K
Drugs that decrease Vitamin K absorption through fat malabsorption
Cholestyramine (bile acid sequestrant)
Lomitapide (lipid-lowering agent)
Octreotide (antidiarrheal)
Orlistat (weight control medication)
Mineral oil (laxative)
Drugs that increase Vitamin K metabolism
Phenobarbital (sedative)
Phenytoin (antiepileptic)
What does Vitamin K do to Warfarin?
Negates its effects
Treatment for Vitamin K deficiency
Guidelines for Vitamin K deficiency do not exist
PO or IVPB: 2.5 to 10mg 2x/week to daily is common
Warfarin, Vitamin K, and TFs
Warfarin + continuous TFs → decreased Warfarin absorption
Evidence supports that Warfarin irreversibly binds with plastic tubing
Non-PO sources of Vitamin K
Parenteral MVI infusions
Lipid emulsions (ILEs) - amount varies between manufacturers
Propofol administration (1.7 mcg Vitamin K per mL)
Vitamin C functions
Antioxidant
* Reacts directly with superoxide, hydroxyl radicals, and singlet oxygen
Reducing equivalents and cofactor for reactions requiring reduced metals
Many complex, functional roles
- Collagen synthesis
- Carnitine
- Neurotransmitters
- Enhancement of intestinal absorption of nonheme iron
- Cholesterol hydroxylation → bile acids
- Reduction of toxic transition metals
- Reductive protection of folic acid and Vitamin E
- Immune-mediated and antibacterial functions of WBC
Vitamin C absorption:
location and features
(ex: active vs passive)
Ileum - primary
Some absorption in jejunum via sodium/energy-dependent active transport
SATURABLE AND DOSE DEPENDENT
Vitamin C transport - active or passive?
Sodium/energy-dependent active transport
Vitamin C storage
Vitamin C is not stored in the body
Vitamin C excretion
Urine
When serum ascorbic acid levels reach 90 mcmol/L, renal clearance sharply increases
Studies show intake < __ mg/d of vitamin c causes frank signs of __ within __ days
Studies show intake <10mg/d causes frank signs of scurvy within 30 days
Vitamin C - nutrient/nutrient interactions
Increases absorption of iron (reduced Fe3+ to Fe2+)
- Absorptive benefit plateaus at 75mg Vit C
Same mechanism is believed to increase oxidative stress if Vit C taken in excess because Fe2+ can react with hydrogen peroxide → deleterious hydroxyl radical
What did one study find about large doses of vitamin C and acetaminophen?
> 3g/d Vit C decreased acetaminophen excretion by 75% (per one study)
What medications increase urinary wasting of Vitamin C?
- Tetracycline (antibiotic)
- Aspirin
- Corticosteroids
What drug, when taken with large amounts of Vitamin C, increase the risk of renal calculi?
Allopurinol (xanthine oxidase inhibitor AKA uric acid reducer)
Vitamin C - populations at risk for deficiency (5)
Older adults
Malabsorptive disorders
Poor diets combined with ETOH
DM2 and certain cancers can increase Vitamin C turnover
Tobacco increased need → tobacco use increases free radical production
NFPE: Vitamin C deficiency
SKIN
Capillary rupture
Delayed wound healing
Petechiae
- Tiny round brown-purple spots due to bleeding under the skin
Perifollicular hemorrhage
Hyperkeratotic papules
- Pruritic, dry, scaling, hyperpigmented, and thickening plaques and papules that are skin-colored or erythematous
NFPE: Vitamin C deficiency
HAIR
Corkscrew hairs
NFPE: Vitamin C deficiency
MOUTH
Bleeding gums (from weakened collagen)
NFPE: Vitamin C deficiency
JOINTS
Joint effusions
NFPE: Vitamin C deficiency
OTHER
Hypochondriasis
* Obsession with the idea of having a serious but undiagnosed medical condition
Increased susceptibility to infection
NFPE: Vitamin C toxicity
OTHER
N/V/D
Kidney stones
Populations to avoid large Vitamin C doses:
Renal failure
Kidney stones
Iron overload disease
Heparin/warfarin therapy
Vitamin C deficiency treatment
100 mg TID (PO)
or can give an initial dose of 60-100 mg IV
Vitamin C dosing for wounds (stage 1-2 pressure ulcers)
100-200 mg/day
Vitamin C status in surgical & burns patients:
frequent reports of ascorbate deficiency
Reports indicate Vitamin C status deteriorates during hospitalization and from medical/surgical stress → poor wound healing
1) Blood glucose and Vitamin C:
2) Hyperglycemia effect on Vitamin C
Hyperglycemia: prevents Vitamin C transport
Needed for normal leukocyte function
Can alter glucometer blood glucose measurements
Vitamin C and kidney function
Competes with uric acid reabsorption in the kidneys (gout)
Increases oxalate formation and absorption → more pronounced in renal failure
Thiamin - function
Energy transformation (CHO, BCAA)
Synthesis of pentoses and reduced NADPH (nicotinamide adenine dinucleotide phosphate)
Membrane nerve conduction, muscle contraction
The synthesis of TPP from free thiamin requires:
Magnesium
Adenosine triphosphate (ATP)
The enzyme, thiamin pyrophosphokinase
Thiamin - function
Energy transformation
Synthesis of pentoses and reduced NADPH (nicotinamide adenine dinucleotide phosphate)
Membrane nerve conduction / muscle contraction
* TTP - structural component of nerve membranes, can also function in nerve conduction
Thiamin - what enzymatic functions is TPP involved in?
Metabolism of carbohydrates, branched-chain amino acids, and fatty acids
Thiamin is absorbed in what part of the bowel?
Proximal small intestine – especially the jejunum
Is thiamin absorption an active or passive process?
Both an active or passive diffusion
- Dependent on intestinal thiamin concentration
- Saturable, energy-dependent active transport at low physiological levels
- Passive during high intake
What is thiamin bound to in the blood?
Albumin
Thiamin storage
30mg stored in the body as TPP or TMP
Most found in skeletal muscle (50%)
Thiamin excretion
Urine
Disease states at risk for thiamin deficiency
ETOH use → impaired thiamin absorption
Long term PN or dialysis
Refeeding syndrome or malabsorption
Hyperemesis gravidarum and patients with protracted vomiting
Gastric surgery
Increased demand with marginal nutrition status
Signs and symptoms of a thiamin deficiency -
EYES
Nystagmus
- Involuntary rhythmic side-to-side, up and down or circular motion of the eyes
Signs and symptoms of a thiamin deficiency -
NERVOUS SYSTEM
Dry beriberi
* Paresthesia (pins and needles)
* Weakness in lower extremities
Wernicke-korsakoff syndrome & Wernicke encephalopathy
* Mental status changes
* Global confusion
* Nystagmus
– Involuntary rhythmic side-to-side, up and down or circular motion of the eyes
* Polyneuritis
–Inflammation of several peripheral nerves at the same time
* Gait ataxia (abnormal, uncoordinated movements)
* Stupor
Signs and symptoms of a thiamin deficiency -
OTHER
Wet beriberi:
High-output cardiac failure
Dyspnea
Hepatomegaly
Tachycardia
Oliguria
Sodium and water retention
Elevated lactic acid
Bariatric beriberi: acute post-gastric reduction surgery
* More prevalent since increase in bariatric surgery
What organ system does thiamin deficiency affect?
Central nervous system
Does thiamin deficiency cause anemia?
It can cause neuropathy but NOT anemia
What is beriberi characterized by in thiamin deficiency?
Beriberi is characterized by muscle weakness in BLE with impaired nerve conduction 2/2 inadequate thiamin intake with adequate CHO intake
How does the absence of thiamin impact CHO metabolism?
Absence of thiamin →
inhibition of pyruvate dehydrogenase →
CHO metabolism driven toward lactic acid fermentation →
build up of lactic acid
When left untreated → fatal lactic acidosis
What are the signs/symptoms of thiamin toxicity?
N/A
What nutrient is required for thiamin to be useable by the body?
Magnesium
Necessary for conversion of thiamin → active form (TPP)
* Deficiency renders thiamin unusable
What does Lasix/furosemide do to thiamin?
Causes deficiency 2/2 diuretic effect → increased urinary thiamin excretion
Which bronchodilator decreases serum thiamin?
Theophylline
In what organ is TPP synthesized, and what disease state can impact/contribute to thiamin deficiency?
Synthesized in the liver → cirrhosis can contribute to deficiency
Riboflavin is the precursor to:
Precursor to 2 major enzyme derivatives involved in enzymatic reactions and intermediary metabolism
FMN (flavin mononucleotide)
FAD (flavin adenine dinucleotide)
What is riboflavin’s major function?
Serves as a component of FMN and FAD as an electron transport intermediary for oxidation-reduction reactions
Other functions of Riboflavin?
Antioxidant activity
- Coenzyme FAD is required for glutathione reductase which protects against lipid peroxidases
- FAD is involved in micronutrient metabolism
- Receives electrons from fatty acid oxidation and Krebs cycle intermediates → donates to ETC for production of ATP
Which micronutrient pathways is riboflavin involved in?
- Conversion of Vitamin B6 to its active form
- Synthesis of active form of folate
- Catabolism of choline
How is riboflavin digested?
Dissociates from the coenzyme derivatives in the stomach via HCl (hydrochloric acid)
Where is riboflavin absorbed?
Proximal portion of the small bowel
via a saturable, sodium-dependent carrier mechanism
What increases/enhances the absorption of riboflavin?
Presence of food (likely from delaying intestinal transit)
Bile salts
What impedes the absorption of riboflavin?
Copper, zinc, iron, manganese → form chelates with riboflavin → prevent abs
ETOH can impair digestion and absorption
Where is riboflavin stored?
Most riboflavin is used immediately and not stored in the body
How is riboflavin excreted?
Urine
Disease states at risk for riboflavin deficiency:
Alcoholism 2/2 decreased intake and absorption
Thyroid disorders 2/2 altered riboflavin metabolism
DM2, trauma, extreme stress → excrete more riboflavin than normal
Chronic malabsorptive disorders
Critically ill patients
Signs/symptoms of riboflavin deficiency
SKIN
Seborrheic dermatitis of face or scrotum
Signs/symptoms of riboflavin deficiency
EYES
Visual impairment
Corneal vascularization
Photophobia
Signs/symptoms of riboflavin deficiency
MOUTH
Cheilosis/Angular stomatitis
* Cracking, crusting, and scaling of the corners of the mouth
Glossitis
* Swollen and inflamed; makes the surface of the tongue appear smooth
Edema
Hyperemia of oral/pharyngeal mucosa
Sore throat
Signs/symptoms of riboflavin deficiency
NERVOUS SYSTEM
Peripheral nerve dysfunction
Signs/symptoms of riboflavin deficiency
OTHER (blood related)
Normochromic normocytic anemia
- riboflavin deficiency can lead to anemia because it alters iron absorption
Riboflavin toxicity
Toxicity from food and supplements is rare
What 2 medications inhibit riboflavin absorption?
Tricyclic antidepressants
Tetracycline (antibiotic)
Niacin
NAD can be synthesized from which amino acid?
NAD can be synthesized from tryptophan
Requires riboflavin (as FAD or FMN)
__ mg tryptophan = 1 mg niacin
60 mg tryptophan
Niacin - functions
NAD/NADP: hydrogen donors or electron acceptors
* Participates in metabolism of amino acids, fatty acids, CHO
* Donates to electron transport chain to produce ATP
Repair DNA
Calcium mobilization
NADPH: helps regenerate body’s antioxidant systems
* Reduces dehydroascorbate (oxidized vitamin C) and glutathione
Treatment for hyperlipidemia
Niacin - absorption
Rapid absorption from stomach and intestine by active transport (low concentrations) and passive diffusion (high concentrations)
NAD & NADP → enzymatically hydrolyzed in intestinal mucosa → release nicotinamide (major form in the blood)
Niacin - storage
None
Niacin - route of excretion
Urine
Amount excreted r/t form of niacin ingested and niacin status of individual
- Little nicotinamide and nicotinic acid is excreted → actively reabsorbed by glomerular filtrate
- Methylnicotinamide (methylated in the liver) is primary urinary metabolite
What is the most commonly known disease state in a niacin deficiency, and what are its symptoms?
Pellagra: can affect the GI tract, skin and nervous system
Four D’s -
dermatitis, diarrhea, dementia, death
Niacin - populations at risk of deficiency
Malabsorptive disorders
Alcoholism
Older adults
Patients on antitubercular medication (isoniazid or mercaptopurine)
Clinical presentation of niacin deficiency:
SKIN
Dermatitis
Sun sensitivity causing symmetrical pigmented rash
Clinical presentation of niacin deficiency:
MOUTH
Glossitis
* Swollen and inflamed; makes the surface of the tongue appear smooth
Clinical presentation of niacin deficiency:
NERVOUS SYSTEM
Dementia
Apathy
Fatigue
Memory loss
Peripheral neuritis
Extremity paralysis
Clinical presentation of niacin deficiency:
OTHER
Diarrhea
Vomiting
Risk of niacin toxicity
Longterm use of high dose supplementation
Clinical presentation of niacin toxicity:
SKIN
Flushing
Heat
Vasodilation
Itching
Clinical presentation of niacin toxicity:
OTHER
GI irritation
Severe hepatitis
Glucose intolerance (DM)
Myopathy
Niacin - nutrient/nutrient interactions
No interactions identified
Niacin - drug/nutrient interactions with isonazide and mercaptopurine
Isoniazid (tuberculosis treatment) → decrease niacin levels by inhibiting production from tryptophan
Mercaptopurine (cancer/autoimmune treatment) → interferes with conversion of niacin to NAD
How does Isoniazid (tuberculosis treatment) impact niacin levels?
Isoniazid (tuberculosis treatment) → decrease niacin levels by inhibiting production from tryptophan
How does Mercaptopurine (cancer/autoimmune treatment) impact niacin levels?
Mercaptopurine (cancer/autoimmune treatment) → interferes with conversion of niacin to NAD
Vitamin B6 functions
Coenzyme forms participate in 100+ enzymatic reactions:
* Protein, AA, lipid metabolism
* Gluconeogenesis
* CNS development
* Neurotransmitter synthesis
* Heme biosynthesis
* Normal immune function
PLP and PMP – interconversion of AA, facilitating transamination and deamination reactions
Pathway for decreasing homocysteine levels → conversion to cysteine
Vitamin B6 Absorption
Jejunum
Ingested phosphorylated forms → hydrolysis to remove phosphate group
Uptake by intestinal epithelial cells → via carrier-mediated, pH-dependent mechanism prior to entry into the portal vein
Absorption: 71-82%
Liver hepatocyte converts → PLP (metabolically active form)
B6 + Plasma transport
60-90% of Vitamin B6 in the plasma = PLP → most bound to albumin for transport
What is most B6 bound to in plasma?
Albumin for transport
Where is B6 stored?
Muscle contains the most PLP (75-80%)
How is B6 excreted?
Urine
Populations at risk for B6 deficiency
Alcoholism
Renal patients maintained on dialysis
Older adults
Medication therapies that inhibit vitamin activity (see drug-nutrient interaction)
Clinical manifestations of B6 deficiency
SKIN
Seborrheic dermatitis
Clinical manifestations of B6 deficiency
MOUTH
Angular stomatitis
Cheilosis
Glossitis
Symptoms of which nutrient deficiency?
- Epileptiform convulsions
- Confusion
- Depression
Vitamin B6
Clinical manifestations of B6 deficiency
OTHER
Microcytic anemia
Populations at risk for B6 toxicity
High food intake of B6 and large oral supplementation (>500mg/d)
100mg/d have been associated with Lhermitte’s sign
* An electric shock-like sensation that occurs on flexion of the neck
* Suggestive of an effect on the spinal cord
50mg more than the UL (100mg) in patients undergoing intestinal transplant → accumulation of PLP in RBC 30x the upper limit of normal
> 2000mg have impaired motor control and paresthesia (pins & needles)
Clinical manifestations of B6 toxicity
SKIN
Dermatologic lesions
Clinical manifestations of B6 toxicity
OTHER
Sensory neuropathy
Ataxia
Areflexia (the absence of deep tendon reflexes)
Impaired cutaneous and deep sensations
What process is B6 required for?
What will a B6 deficiency cause related to this?
B6 is needed for interconversion of one amino acid to another
Deficiency can lead to alterations in amino acid pool
Medications with the potential to diminish B6 levels or activity:
Isoniazid (tuberculosis medication)
Oral contraceptives
Corticosteroids (anti-inflammatories)
Penicillamine (chelating agent)
What are primary sources of B12?
Naturally occurring in foods of animal origin → provide B12 in the following coenzyme forms:
Methylcobalamin - biologically active form
Hydroxylcobalamin
Deoxyadenosylcobalamin - biologically active form
Which form of B12 is primarily used in supplements/fortified foods?
Cyanocobalamin
What are B12’s two major functions?
1) Needed for conversion of homocysteine to methionine (benign amino acid)
2) Conversion of methylmalonyl coenzyme A (CoA) → succinyl-CoA
* For degradation of certain amino acids and odd chain fatty acids
What is elevated homocysteine associated with?
Increased risk of CVD, stroke, dementia, Alzheimer’s disease, and osteoporosis
Methyl-Folate Trap
When deficient in B12, folate becomes “trapped” in its methyl (inactive) form
1) Homocysteine (+MS) → methionine
2) Simultaneous: demethylation of 5-methyltetrahydrofolate → THF
Methylcobalamin is a cofactor for methionine synthetase (MS, enzyme that converts homocysteine to methionine)
Why does a B12 deficiency frequently appears as folate deficiency?
Methyl-folate trap where folate is “trapped” in its inactive form
B12 deficiency + methyl-folate trap:
What alternate nutrient can aid in the conversion of homocysteine to methionine?
Choline
Digestion of B12 - in the stomach
HCl and pepsin (from gastric secretions) release B12 from proteins
→ haptocorrin + free B12 → small intestine
Haptocorrin: glycoprotein secreted by salivary glands, swallowed with food
Digestion of B12 - in the small intestine
Pancreatic proteases hydrolyze haptocorrin and free B12 is released
Digestion of B12 - in the duodenum
free B12 + IF = IF-B12 complex → ileum
Intrinsic factor: glycoprotein produced by gastric parietal cells
Digestion of B12 - in the ileum
IF-B12 complex binds to cubilin for absorption → enterocyte
Cubilin: specific IF receptor on GI epithelial cells
B12 - absorption
3-4 hours after intestinal absorption: transferred to transcobalamin II (transport protein) → portal circulation
Taken up by liver first, then bone marrow and erythrocytes
Normal gastric function: 50% dietary B12 absorbed
B12 is secreted into bile and most is reabsorbed via enterohepatic circulation
B12 - Storage
Liver
- Unlike other water soluble vitamins
B12 - excretion
Urine
Populations at risk for B12 deficiency
Pancreatic insufficiency
* Interfere with release of free B12 from haptocorrin → prevent attachment to IF
Impaired HCl production/low secretion
* Older adults
* Patients with H.pylori infections
* Histamine-2 (H2) antagonists and proton pump inhibitors (PPI)
All or part of ileum or stomach removed
Chronic malabsorption
Vegetarian and vegan populations
Metformin use
* Lowers absorption, mechanism unknown
First manifestations of marginal or inadequate B12 status
Neurologic → hematologic and GI abnormalities
Clinical B12 deficiency is associated with what diseases/surgical procedures?
Malabsorption syndromes
- Gastrectomy
- Gastric bypass
- Ileal resection
- Crohn’s dz
Clinical signs/symptoms of B12 deficiency -
BONE
Bone marrow changes
Bone fractures
Clinical signs/symptoms of B12 deficiency -
MOUTH
Glossitis
Clinical signs/symptoms of B12 deficiency -
NERVOUS SYSTEM
Diminution of vibration and/or position sense
Paresthesia (pins & needles) of hand/feet
Unsteadiness
Cognitive decline
Confusion
Depression
Mental slowness
Poor memory
Delusions
Overt psychosis
Clinical signs/symptoms of B12 deficiency - related to blood
Megaloblastic anemia
- Type of anemia characterized by very large red blood cells
Leukopenia
- Low white blood cell count
Thrombocytopenia
- Decreased platelets
CVD
Neutrophil nuclei hypersegmentation
Pancytopenia
- A rare manifestation of vitamin B12 deficiency
- Combination of: anemia, leukopenia, thrombocytopenia
B12 toxicity
No Tolerable Upper Intake Level (UL) has been established for B12, due to its low level of toxicity
B12 & vitamin c
Excess Vitamin C intake (500mg) in single dose may temporarily impair B12 bioavailability from foods and destroy the vitamin
Folate - what is MTHF bound to in plasma?
Loosely bound to albumin and folate-binding proteins (AKA folate carriers or folate receptors)
Folate’s primary biochemical function:
AA metabolism and nucleic acid synthesis
- Coenzyme in transfer of single carbon fragments from one compound to another
Additional functions of folate:
Homocysteine
- THF donates a methyl group to cobalamin for regeneration of methionine from homocysteine
Pregnancy - DNA synthesis for embryonic development
- Neural tube defects (NTDs) = DNA fragility and strand breakage
Folate - digestion
Polyglutamates → monoglutamate in order to be absorbed
Zinc dependent enzymes (conjugases) in jejunal brush border
How does folate circulate?
Secreted into bile → recirculate via enterohepatic circulation
Folate excretion
Minimal due to reabsorption via enterohepatic bile circulation
Populations at risk for folate deficiency
Alcoholism (decreased intake and absorption
Pregnancy - increased demand for DNA synthesis in embryonic development
Periconceptual and premenopausal women
Conditions/diseases that impair bile secretion → limit folate recirculation
Clinical signs and symptoms of folate deficiency:
MOUTH
Cheilosis
Clinical signs and symptoms of folate deficiency:
NERVOUS SYSTEM
Nervous instability
Dementia
Clinical signs and symptoms of folate deficiency:
OTHER
Megaloblastic or macrocytic anemia
Neutrophil hypersegmentation (early indicator of deficiency)
Diarrhea
Weight loss
Depression of cell-mediated immunity
CVD
Folate toxicity:
It is extremely rare to reach a toxic level when eating folate from food sources
UL for folic acid is set at 1,000 mcg daily because studies have shown that taking higher amounts can mask a vitamin B12 deficiency
Folate: nutrient-nutrient interactions
Zinc can impair the absorption rate of folate
Drugs that decrease serum folate
Carbamazepine (antiepileptic)
Estrogen therapy
Oral contraceptives
Phenobarbital (sedative)
Phenytoin (antiepileptic)
Triamterene (diuretic)
Drugs that decrease folate absorption
Cholestyramine (bile acid sequestrant)
Metformin (insulin sensitizer)
Sulfasalazine (anti-inflammatory)
Pancrelipase (pancreatic enzyme)
Pancrelipase may reduce the effectiveness of folic acid and iron by interfering with their absorption.
Drug that interferes with folate metabolism
Trimethoprim (antibiotic)
Drug that confounds folate assay measurements
Rifampin (antitubercular agent)
What can excessive amounts (100x RDA) of folate cause?
Seizures in phenytoin therapy
What are the forms of Biotin in the diet?
Free biotin
Biocytin (protein-bound coenzyme; biotin bound to lysine)
Why is biotin deficiency rare?
Bacteria in the intestine can synthesize biotin
What dietary component in raw eggs prevents biotin absorption?
Avidin
Glycoprotein in raw egg whites
Binds tightly to dietary biotin and prevents biotin’s absorption in the GI tract
Biotin’s functions
Necessary for the genetic expression of >2000 enzymes
Cofactor for 4 carboxylase enzymes
Which metabolic pathways does biotin aid in catalyzing?
Acetyl-CoA carboxylase for FA synthesis
* Leucine catabolism yields acetyl CoA and acetoacetate
Pyruvate carboxylase for gluconeogenesis
Propionyl-CoA carboxylase for propionate metabolism
3-methylcrotonyl-CoA carboxylase for BCAA catabolism
What amino acid is biotin bound to in the dietary form of biocytin?
Leucine
Where is biotin absorbed?
Jejunum
- Facilitated diffusion
Where is biotin stored in the body?
Water soluble vitamin; it’s not stored
How is biotin excreted?
Urine
Populations at risk for a biotin deficiency?
Long term PN
Alcoholism - chronic exposure to alcohol inhibits the absorption of biotin
Partial gastrectomy
Biotinidase deficiency (inherited autosomal recessive trait)
Why do we give AF about Biotinidase deficiency ?
Biocytin requires biotinidase (enzyme in small intestine) to cleave lysine from biocytin
Clinical signs/symptoms of Biotin deficiency:
SKIN
Pallor
Erythematous seborrheic dermatitis
Clinical signs/symptoms of Biotin deficiency:
HAIR
Alopecia
Clinical signs/symptoms of Biotin deficiency:
EYES
Vision problems
Clinical signs/symptoms of Biotin deficiency:
MOUTH
Glossitis
Cheilosis
Clinical signs/symptoms of Biotin deficiency:
NERVOUS SYSTEM
Nervous instability
Dementia
Hallucinations
Paresthesia (pins and needles) in extremities
Depression
Clinical signs/symptoms of Biotin deficiency:
OTHER
Hypotonia – decreased muscle tone
Anorexia
N/V
Lethargy
Muscle pain
Ketolactic acidosis
Elevated cholesterol
Biotin toxicity:
No UL has been established because there are no reports of toxicity
Biotin Nutrient-Nutrient Interactions
No nutrient interactions identified
What drug decreases serum biotin?
Carbamazepine (antiepileptic)
What is pantothenic acid?
Component of CoA
What is pantothenic acid’s functions?
As CoA - involved in energy released from fat, CHO, and ketogenic amino acids
Gluconeogenesis
Heme and sterol synthesis
Most acetylation reactions
Synthesis of bile salts, cholesterol, steroid hormones, and fatty acids
Transport of long chain fatty acids → mitochondria for catabolism through beta-oxidation
Pantothenic acid - absorption
Dietary CoA → pantothenic acid in intestinal lumen
Passive diffusion or saturable, sodium-dependent active transport
Transported by erythrocytes throughout the body
Pantothenic acid - storage
CoA, in body tissues
Pantothenic acid - excretion
Urine
Populations at risk for deficiency of pantothenic acid
Occurs in conjunction with other MN deficiencies or conditions such as:
Diabetes
IBD and alcoholism 2/2 impaired absorption
Ingestion of large amounts of ethanol → may have an increased requirement
Clinical signs/symptoms of pantothenic acid deficiency:
SKIN
Poor wound healing
Clinical signs/symptoms of pantothenic acid deficiency:
NERVOUS SYSTEM
Neuromuscular disturbances
Numbness
Parethesias - pins and needles
Staggering gait
Mental depression
Listlessness
Irritability
Restlessness
Malaise
Sleep disturbances
Clinical signs/symptoms of pantothenic acid deficiency:
OTHER
Muscle cramps
Fatigue
N/V/D
Abdominal cramps
Hypoglycemia
Increased insulin sensitivity
Compromised immune function
Diminished engraftment
Pantothenic acid toxicity
Rare. Diarrhea noted to occur in doses >10g/day
Pantothenic acid: Nutrient-Nutrient Interactions
None identified
Pantothenic acid: drug-nutrient interactions
Tetracycline (antibiotic) – may cause decreased serum pantothenic acid
Choline - dietary forms
Nearly all dietary choline found in the form of choline phosphatides (lecithin and sphingomyelin)
Betaine (oxidized form) also present in diet, but can’t be directly converted to choline
What is the demand for choline influenced by?
Methionine, folic acid, B12, and betaine
Choline functions
Needed for neurotransmitter synthesis (acetylcholine), cell membrane signaling (phospholipids), and lipid transport (lipoproteins)
By-product betaine can act as a B12 substitute for regeneration of methionine from homocysteine
Choline is essential for:
Cell membrane integrity
Methyl metabolism
Cholinergic neurotransmission
Transmembrane signaling
Transport and metabolism of lipid cholesterol
Choline absorption
Small intestine
Uptake via choline transporter proteins → liver via portal vein
Choline storage
Liver
When supply is low, choline is recycled in liver and redistributed by kidneys, lungs, and intestines → liver and brain
What happens with excess choline?
Excess choline → betaine (provides methyl groups for compounds like homocysteine)
Choline excretion
Very small amounts excreted in urine
Populations at risk for choline deficiency:
When demand for choline is high–
* Pregnancy
* Lactation
* Hypermetabolic states
Postmenopausal
De novo synthesis diminishes with diminished estrogen
Long-term PN without choline
Clinical signs and symptoms of a choline deficiency
Impairment of verbal and visual memory
Hepatic steatosis
What does evidence a choline deficiency may contribute to in PN patients?
Evidence indicates choline deficiency may contribute to PN-induced liver dysfunction → hepatic steatosis and eventual hepatic failure
What particular population is at risk for PN complications r/t choline deficiency?
PN 2/2 SBS who develop a choline deficiency are more susceptible to hepatic issues
Impairment in verbal/visual memory may be r/t insufficient acetylcholine synthesis
Significant evidence demonstrates relationship between choline deficiency and development of diseases like:
liver disease
atherosclerosis
cancer
possibly neurologic disorders (NTDs, Alzheimer’s disease, memory problems)
Choline toxicity occurs in
Very high PO intakes
Clinical signs and symptoms of choline toxicity;
SKIN
Sweating
Clinical signs and symptoms of choline toxicity;
MOUTH
Excessive salivation
Clinical signs and symptoms of choline toxicity;
OTHER
Hypotension
Anorexia
Fishy body odor
Hepatotoxicity
Choline - nutrient-nutrient interactions
Betaine can replace B12 to replenish methionine from homocysteine through methyl group donation
Choline - drug/nutrient interactions
Interactions between choline and meds have not been identified
Choline - repletion/treatment of deficiency:
No parenteral supplements at this time
Dextrose and protein components of PN do not contain choline
Part of lipid emulsions in form of phosphatidylcholine
- 20% lipid emulsion contains 13.22 mcmol of choline per mL
Forms of iron?
Which are they derived from?
Which is better absorbed?
Heme & Nonheme
Iron - what are heme and nonheme derived from?
Heme - derived from hemoglobin and myoglobin molecules found in animal flesh
Nonheme - plant derived
Which form of iron (heme or nonheme) is more efficiently absorbed?
Heme is more efficiently absorbed
How to enhance nonheme iron absorption?
Presence of organic compounds that increase acidity:
Vitamin C
HCl
Lactic acid
Acidic amino acids aspartic and glutamic acids
What is the difference between ferrous and ferric forms of iron?
Ferrous (Fe2+) = better absorbed
* Acidic compounds help maintain nonheme iron in this form
* Animal heme is in this form
Ferric (Fe3+)
Primary sites of iron absorption:
Duodenum and jejunum
How is heme iron absorbed?
Heme iron → globin fraction removed → absorbed intact into enterocyte
In intestinal cell: hydrolyzed to ferrous iron
How is nonheme iron absorbed?
Nonheme iron → released from food in the stomach in ferric form (Fe3+) → converted to ferrous iron via gastric acid
Binds to receptors in intestinal cell (glycocalyx and brush border)
What are the 2 transport proteins of iron and what are their functions?
Transferrin
* Regulates the absorption of iron into the blood
Ferroportin
* Controls export of iron from cells to blood
* Regulated by the hormone hepcidin
What are the 2 forms of iron storage?
Ferritin
* Short term iron storage – found in cells and plasma
* Soluble iron; readily available to body when needed
Hemosiderin
* Long-term iron storage site – found only in cells
* Insoluble form; not readily available to body
Functions of iron:
Hemoglobin - oxygen transport
Myoglobin - muscle iron storage
DNA synthesis
Electron transport – oxidative production of cellular energy (ATP)
What happens to iron during the Acute-Phase response to injury and infection?
Suppresses iron transport (upregulation of hepcidin production)
Serum iron depressed
Serum ferritin increased
Why is the sequestration of iron into storage form thought to be physiologically protective?
Reduces availability of iron for iron-dependent microorganism proliferation
May also reduce free radical production and oxidative damage to membranes and DNA
How is iron excreted?
Tightly regulated, most iron is conserved and recycled
Primarily excreted via Feces
Populations at risk for iron deficiency:
Women of childbearing age
Patients hospitalized with excess blood sampling or loss
Decreased gastric acid production
* Older adults (gastric acid production decreases with age)
Concomitant use of meds that reduce stomach acidity → impair iron absorption
* Antacids
* H2 antagonists
* PPIs
Malabsorptive states → ineffective absorption
* Celiac disease
* Crohn’s disease
* Pernicious anemia
* Achlorhydria (stomach does not produce HCl, part of gastric acid)
Reduced absorption
* Roux-en-Y GBP or other GI surgery
* Injury
* Inflammation
Iron deficiency - clinical s/s
- Skin
- Nails
- Eyes
- Mouth
- Nervous system
SKIN - Pallor
NAILS - Koilonychia (spoon nails; soft nails that look scooped out)
EYES - Conjunctival pallor
MOUTH - Glossitis
NERVOUS SYSTEM
Impaired behavioral and intellectual performance
Iron deficiency - clinical s/s
OTHER
Microcytic, hypochromic anemia
Tachycardia
Poor capillary refilling
Fatigue
Sleepiness
Headache
Anorexia
Nausea
Reduced work performance
Impaired ability to maintain body temperature in cold environments
Decreased resistance to infections
Increased lead absorption
Adverse outcomes during pregnancy
Populations at risk for iron toxicity
Exposure to iron that exceeds body’s physiological protection mechanisms
Hemochromatosis (genetic disorder) → increases amount of iron absorbed from diet
Iron toxicity - clinical s/s:
SKIN
Skin pigmentation
OTHER
Organ damage (e.g., liver cirrhosis, heart enlargement, pancreatic damage)
Iron - nutrient/nutrient interactions
Impact on nonheme absorption → insoluble iron complexes
Phytic acid - grain fibers
Oxalic acid - spinach, chard, tea, chocolate
Polyphenols - coffee, tea, cocoa
Other nutrients - calcium, zinc, manganese
Iron - nutrient/nutrient interactions
Chromium
In chromium toxicity - chromium receptor site competes with iron
Medications that decrease iron absorption:
PO bisphosphonates (osteoporosis treatment)
Caffeine
Phosphate binders
Calcium polycarbophil (bulk-forming fiber therapy - Fibercon)
Cholestyramine (bile acid sequestrant)
Magnesium hydroxide
Miglitol (DM medication)
Oral contraceptives
PPIs
Sodium bicarbonate (antacid)
Tetracyclines (antibiotic)
Levothyroxine (thyroid hormone)
Medications that decrease serum iron levels:
Eltrombopag (thrombocytopenia medication)
Vorapaxar (antithrombotic)
Carbamazepine (antiepileptic) → can decrease levels with long term use
What medication uses iron and may require supplementation in long term use?
Epoetin alfa (erythropoietin)
Iron decreases the absorption of these meds:
Cefdinir (antibiotic)
Ciprofloxacin (antibiotic)
Dolutegravir sodium (HIV antiviral)
Iron increases the absorption of:
methyldopa (antihypertensive)
Why is parenteral and enteral use of iron not recommended during acute illness/sepsis?
May contribute to oxidative reactions that exacerbate tissue damage
May stimulate bacterial proliferation
What form of iron is preferred to add to PN?
Dextran formulation is preferred to add to PN (dextrose/AA)
Do not add to TNAs as this can destabilize these emulsions
Plasma levels of zinc may decrease from:
Fasting: plasma zinc increases
Infection: zinc is redistributed → hypozincemia
* Secretion of cytokines IL-1 and IL-6 → increase hepatic zinc uptake
Injury: within hours, plasma levels decrease by 10-69%
Functions of zinc:
Overall biochemical functions: catalytic, structural, and regulatory
May also have mild antimicrobial and antiinflammatory properties
Zinc is necessary for other physiological processes:
Lipid peroxidation
Apoptosis
Neuromodulation
Cellular proliferation and differentiation
Wound healing
Insulin synthesis and glucose control
Immune function
Zinc - digestion
Hydrolyzed from amino acids and nucleic acids via gastric HCl and other enzymes in the small intestine before absorption
___ gastric acidity can ___ zinc availability for absorption
Reduced gastric acidity can decrease zinc availability for absorption
Zinc - absorption
Primarily duodenum and jejunum
Lesser extent in ileum
How is metallothionein related to zinc?
Protein responsible for regulation of zinc absorption
Excretion of zinc:
GI tract, kidneys, and skin
Populations at risk for zinc deficiency:
- Zinc deprivation
- Older adults
- Alcoholism
- Postoperative patients
- Burn patients
- Malabsorptive diseases or conditions
Intestinal bypass or resection - Renal disease
- Liver disease
- Wound drainage
- Excessive GI losses (diarrhea, high output fistula)
- Sickle cell anemia
- Acrodermatitis enteropathica (a disorder of zinc metabolism)
- Malignancy
- Phytic acid and calcium supplements
- Decrease absorption up to 50%
- Certain milk proteins may have a negative effect on absorption
Zinc deficiency - signs/symptoms:
SKIN
HAIR
EYES
NERVOUS SYSTEM
SKIN
- Rash (periorificial [skin around mouth], perianal, buttocks)
- Impaired wound healing and epithelization
HAIR
Alopecia
EYES
Impaired night vision (2/2 vitamin A deficiency)
NERVOUS SYSTEM
Altered taste and smell
Zinc deficiency - signs/symptoms:
OTHER
Impaired immune function
Hypogonadism
Anorexia
Diarrhea
Populations at risk for zinc toxicity
Dietary supplements or accidental ingestion of too much zinc
Skin contact
Breathing in fumes
Zinc toxicity - signs/symptoms:
Gastric distress
Nausea
Dizziness
Decreased immune function
Decreased levels of HDL
Zinc - nutrient/nutrient interactions
Zinc deficiency → secondary Vitamin A deficiency
High levels of calcium or iron
* Compete with zinc for binding to ligands/chelators necessary for zinc absorption
High levels of zinc (>40 mg/d) → copper deficiency
* Due to increased metallothionein production
* Copper binds strongly to metallothionein; trapped in enterocyte
* Copper deficiency anemia → interferes with iron absorption/metabolism and transport of iron out of cells
Meds that decrease zinc absorption
Tetracycline (antibiotic)
Ciprofloxacin (antibiotic)
Levofloxacin (antibiotic)
Phosphate binders
Calcium polycarbophil (bulk-forming fiber therapy - Fibercon)
Eltrombopag (thrombocytopenia medication)
Ferrous salts
Meds that increase urinary zinc wasting
Corticosteroids (anti-inflammatory)
Hydrochlorothiazide (antihypertensive)
Propofol (sedative)
What do oral contraceptives do to zinc status?
Oral contraceptive → decrease serum zinc levels
What medication does zinc decrease the absorption of?
Zinc decreases absorption of Dolutegravir sodium (HIV antiviral)
Copper- primary function:
Oxidation-reduction and electron-transfer reactions involving oxygen
** Cytochrome C oxidase (Enzyme in the ETC → ATP)
Copper - additional functions:
Cholesterol metabolism
Glucose metabolism
Formation of melatonin pigment
What is ceruloplasmin and what is its significance to copper?
Stores and carries copper from the liver into the bloodstream → tissues
Positive acute phase reactant
Rise in serum level is to increase copper transport to stimulate cuproenzyme synthesis and inactivate inflammation-induced free radicals
Responsible for manganese oxidation and oxidation of ferrous iron (Fe2+) → ferric iron (Fe3+)
Scavenger of free radicals
Copper digestion:
Gastric secretions, HCl, and pepsin → release bound copper in the stomach
Copper absorption:
Duodenum is primary site
- Absorption throughout small intestine
- Stomach has some degree of copper absorption capacity
Copper transport:
Protein carriers, albumin, and specific copper transporters from intestinal cell → hepatocytes and Kupffer cells in the liver →
1) Liver enzymes (cytochrome C oxidase, superoxide dismutase)
2) Ceruloplasmin → blood → extrahepatic tissues OR → bile for excretion
Copper excretion:
Feces → aids in regulating copper status
Ex: as copper stores increase, biliary copper excretion increases
Populations at increased risk of copper deficiency:
Malabsorptive disorders (e.g., celiac disease)
Pts recovering from undernutrition associated with chronic diarrhea
Pts recovering from intestinal surgery
Hemodialysis (copper losses can be excessive)
Bariatric surgery (increased risk)
Clinical manifestations of copper deficiency:
Skin
Hair
Eyes
SKIN - hypopigmentation
HAIR - hypopigmentation
EYES- Kayser-Fleischer rings (copper colored ring around the iris)
Clinical manifestations of copper deficiency:
NERVOUS SYSTEM
Sensory ataxia
Lower extremity spasticity
Paresthesia in extremities (peripheral neuropathy)
Myeloneuropathy
Clinical manifestations of copper deficiency:
OTHER
Hypochromic, microcytic anemia
Leukopenia
Neutropenia
Hypercholesterolemia
Increased erythrocyte turnover
Abnormal electrocardiographic patterns
Populations at increased risk of copper toxicity
Wilson’s disease: inherited disorder → too much copper → accumulates in organs
* Can cause cirrhosis
Impaired biliary excretion or cholestasis can cause copper retention in the hepatocyte → oxidative damage
Clinical manifestations of copper toxicity:
MOUTH - metallic taste
OTHER - blood in urine, liver damage
Copper - nutrient/nutrient interactions
High zinc supplementation → hamper copper absorption
Copper deficiency → iron deficiency 2/2 decreased release of iron from the enterocyte
Excess molybdenum → increases urinary copper wasting
Additional dietary factors that negatively impact copper absorption:
phytates
dietary fiber
iron
large doses of calcium gluconate
large doses of Vitamin C
What medications decrease copper absorption?
H2 antagonist or PPIs
What medications increase serum copper?
oral contraceptives
Copper treatment considerations:
Celiac disease: prophylactic supplementation when anemia or neutropenia is present
Caution in administration in patients with hepatic dysfunction (excreted via liver/bile)
PN: risk of iatrogenic hepatic copper overload → potential to do irreparable harm to liver
Manganese functions:
Component of metalloenzymes
Activator of certain enzymes
Which metalloenzymes is manganese important for?
- Arginase (urea formation)
- Pyruvate carboxylase (CHO synthesis from pyruvate)
- Manganese superoxide dismutase (essential prep step in neutralizing free radicals produced from ETC → water)
Where does manganese absorption occur?
Throughout the small intestine
How does manganese circulate?
Enters liver via portal circulation → oxidized by ceruloplasmin to Mn3+ → extrahepatic tissues
How is manganese excreted?
Bile –> feces
Populations at risk for manganese deficiency:
Rare unless completely absent from diet
Clinical s/s of manganese deficiency:
Bones/joints
Nervous system
BONES/JOINTS - abnormal bone and cartilage formation
NERVOUS SYSTEM - ataxia
Clinical s/s of manganese deficiency:
Other
Poor reproductive performance
Congenital abnormalities in offspring
Growth retardation
Defects in lipid/CHO metabolism
Populations at risk for manganese toxicity
Hepatobiliary disease (ex: cholestatic liver disease) d/t being almost exclusively excreted via hepatobiliary system
Long-term PN (>30 days) who develop obstruction of biliary duct and unable to excrete
Clinical s/s of manganese toxicity:
Nervous System
Hyperirritability
Violent tendencies
Hallucinations
Disturbances of libido
Ataxia
Mn deposition in the basal ganglia 2/2 perioperative PN following GI surgery
Parkinson-like motor dysfunction (e.g., tremors, difficulty walking, facial muscle spasms)
Clinical s/s of manganese toxicity:
Other
Immune system and reproductive dysfunction
Nephritis
Pancreatitis
Hepatic damage
Testicular damage
What nutrient does manganese interact with?
Iron – competes for similar binding sites, can impair Mn absorption
What medication can decrease manganese absorption and how?
Tetracycline (antibiotic) chelates with Mn → decreased absorption
What amino acids is selenium bound to in food?
Methionine and cysteine
Selenomethionine: primary dietary form – plant sources
Selenocysteine: animal sources
Selenium functions:
Cofactor in glutathione, iodine, and thyroid metabolism
Some selenium dependent enzymes:
Glutathione peroxidase: eliminates hydrogen peroxide
Iodothyronine deiodinase: key role in regulation of metabolism
How is selenium excreted?
Urine and feces
Populations at risk for selenium deficiency
Cardiomyopathy and skeletal muscle weakness reported in:
- Long-term PN without selenium
- Thermal injury
Statins
* Inhibit 3-hydroxy-3-methylglutaryl CoA reductase → induce myopathy by interfering with synthesis of selenoproteins
Trauma patients
* Depressed serum selenium levels post-injury → decreased thyroxine deiodination which may explain impact on thyroid metabolism
Selenium deficiency - s/s
Increased susceptibility to mercury exposure
Altered thyroid hormone metabolism
Congestive cardiomyopathy 2/2 Keshan disease
N/V
Populations at risk for selenium toxicity:
Acute/chronic intake of excess selenium
Selenium toxicity - s/s
Skin lesions
Hair loss
Nail loss
Tooth decay
Peripheral neuropathy
Fatigue
Irritability
Selenium - nutrient/nutrient interaction
Selenium deficiency → decreased production of iodine-dependent selenoprotein deiodinases → limiting role of iodine
What medication decreases selenium absorption?
Eltrombopag (thrombocytopenia medication)
Iodine - function
Integral component to thyroid hormones thyroxine (T4) and triiodothyronine (T3)
T3 metabolically active form which regulates the rate of cell metabolism and activity and growth in multiple tissues
Iodine - absorption
Rapidly absorbed in stomach and upper small intestine
Iodine - storage
Appears in portal blood, rapidly taken up by thyroid (70-80%) for thyroid hormone synthesis
Lesser amounts found in kidneys, salivary glands, other tissues
Iodine - excretion
Kidneys main route of excretion
What happens in an iodine deficiency?
Deficiency in iodine →
insufficient T4 →
constant release of TSH →
hyperplasia of thyroid gland (goiter) to more effectively capture iodide from the blood
Populations at risk for iodine deficiency
Low salt diets
Consumption of salt from unfortified sources (e.g., sea salt)
Low iodine levels in soil
Signs/symptoms of iodine deficiency
Elevated TSH
Jod-Basedow phenomenon:
Nodular goiter
Weight loss
Tachycardia
Muscle weakness
Skin warmth
Populations at risk for iodine toxicity:
Deficiency with aggressive/rapid intake of iodine → thyrotoxicosis can occur
Common in older adults
signs/symptoms of iodine toxicity
Elevated TSH
Depressed thyroid activity
Iodine - nutrient/nutrient interactions
Selenium deficiency: T3 and T4 dependent on selenoprotein deiodinases to interconvert between inactive and active forms of thyroid hormone
Cruciferous vegetables: contain goitrogens which compete with iodide for entry into thyroid gland
What drug inhibits thyroid hormone release from the thyroid?
Lithium (antimanic agent)
Chromium - function
Essential for glucose, protein, and lipid metabolism
–> Required for growth
Potentiates role of insulin
What happens to chromium with increases in serum glucose?
Increases in serum glucose → increases in chromium excretion
Suggested that Cr stored in blood is mobilized in response to insulin concentrations → excretion in urine
Chromium - absorption
Primarily jejunum (for passive diffusion)
Chromium - transport
Trivalent form of Cr binds competitively with transferrin → blood with iron
Then moves into cells where Cr is transferred from transferrin to chromodulin
Chromium - excretion
Urine
DM2 and pregnancy can increase urinary excretion
Chromium deficiency can cause what?
Can result in impaired glucose and amino acid use, increased plasma LDL, peripheral neuropathy
Populations at risk for Chromium deficiency
PN without chromium supplementation
Chromium deficiency s/s
Peripheral neuropathy
Weight loss
Hyperglycemia refractory to insulin
Glycosuria (excess sugar in urine)
Elevated plasma FFA
Chromium - populations at risk for toxicity
Repeated exposure either through oral ingestion (acute) or skin contact and inhalation
Chromium toxicity s/s
Muscle rhabdomyolysis
Liver dysfunction
Renal failure
Chromium - nutrient/nutrient interactions
Iron status can be compromised w/ Cr supplementation 2/2 competition for binding sites on transferrin
Serum ferritin levels decrease with Cr intakes at 200 mcg/d
What medication causes increased urinary chromium wasting?
Corticosteroids (anti-inflammatories)
Role of fluoride:
Role in bone mineralization and hardening of tooth enamel
Helps inhibit and reverse the initiation and progression of dental caries
Stimulates new bone formation → stimulating osteoblasts
May reduce risk for osteoporosis
Some studies suggest it may inhibit calcification of aorta and soft tissue
Where is fluoride absorbed?
Stomach
How is fluoride excreted?
Kidneys (50%)
Deposition in the calcified tissue (bone and developing teeth)
Fluoride:
1) Populations at risk for deficiency
2) Clinical s/s
1) Non-fluoridated water as primary water source
2) Increased risk of dental caries
Fluoride - populations at risk for toxicity
Chronic excessive fluoride intake
Swallowing fluoridated toothpaste
** Children **
Fluoride - toxicity s/s
EYES - lacrimation (tears)
MOUTH - excessive salivation
BONE - enamel and skeletal bone fluorosis (mottled teeth)
Fluoride - toxicity s/s
Nervous system
Convulsions
Sensory disturbances
Paralysis
Coma
Fluoride - toxicity s/s
other
N/V/D
Abdominal pain
Pulmonary disturbances
Cardiac insufficiency
Arrhythmias
Weakness
What nutrients form insoluble complexes when combined with fluoride?
Calcium/Magnesium
What drugs interfere with fluoride absorption?
Phosphate binders
Calcium polycarbophil (bulk-forming fiber therapy - Fibercon)
Molybdenum - function
Cofactor for metalloenzymes:
1) Aldehyde oxidase
Metabolism of drugs and toxins
2) Xanthine oxidase
Catalyzes the breakdown of nucleotides (precursors to DNA and RNA) to form uric acid, which contributes to the plasma antioxidant capacity of the blood
3) Sulfite oxidase
Transformation of sulfite to sulfate, a reaction that is necessary for the metabolism of sulfur-containing amino acids (methionine and cysteine)
Molybdenum absorption
Proximal small intestine
Molybdenum transport
Mo is transported as Molybdate – loosely attached to erythrocytes
Tends to bind to albumin and a-macroglobulin
Molybdenum excretion
Excreted by kidneys as molybdate
Molybdenum - populations at risk for deficiency
can occur in long-term PN
Molybdenum - s/s of deficiency
Dislocation of ocular lens
Altered vision
AMS
Attenuated (reduced) brain growth
Neurologic damage
Tachycardia
Tachypnea (rapid breathing)
Elevated methionine
HA
Lethargy
N/V
Molybdenum - populations at risk for toxicity
Excessive dietary intake (10-15 mg/d)
Exposure to environmental contamination
Molybdenum - s/s of toxicity
Rare: hyperuricemia and gout-like symptoms
Molybdenum - nutrient/nutrient interactions
Moderate doses of Mo (0.54 mg/d): associated with copper wasting in urine
Tetrathiomolybdate is compound responsible and is used to treat Cu toxicity (Wilson dz)
