Nutrient Requirements

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General Principles

Energy

  • Total daily energy expenditure (TEE) is composed of resting energy expenditure (normally ∼70% of TEE), the thermic effect of food (normally ∼10% of TEE), and energy expenditure of physical activity (normally ∼20% of TEE).
  • Use of predictive equations can provide a reasonable estimate of daily energy requirements that should be modified based on the factors that affect the patient’s metabolic rate.
  • Malnutrition and hypocaloric feeding may decrease resting energy expenditure to 15%–20% below expected for actual body size, whereas metabolic stressors, such as inflammatory diseases or trauma, often increase energy requirements by ∼30%–50%.
  • The Harris–Benedict equation provides a reasonable estimate of resting energy expenditure (in kilocalories [kcal] per day) in healthy adults. It takes into account the effects of body size and lean tissue mass (which are influenced by gender and age) on energy requirements and can be used to estimate total daily energy needs in hospitalized patients (where W is the weight in kilograms, H the height in centimeters, and A is the age in years).1
    • Men = 66 + (13.7 × W ) + (5 × H ) − (6.8 × A)
    • Women = 665 + (9.6 × W ) + (1.8 × H ) − (4.7 × A)
  • Energy requirements per kilogram of body weight are inversely related to body mass index (BMI) (Table 2-1). The lower range within each category should be considered in insulin-resistant, critically ill patients unless they are depleted in body fat.
  • Ideal body weight can be estimated based on height
    • For men: 106 + 6 lb for each inch over 5 ft
    • For women, 100 + 5 lb for each inch over 5 ft
Table 2-1: Estimated Energy Requirements for Hospitalized Patients Based on Body Mass Index
Body Mass Index (kg/m2)Energy Requirements (kcal/kg/d)
1535–40
15–1930–35
20–2420–25
25–2915–20
≥30<15

Note: These values are recommended for critically ill patients and all obese patients; add 20% of total calories in estimating energy requirements in non–critically ill patients.

Protein

  • Protein intake of 0.8 g/kg/d meets the requirements of 97% of the adult population.
  • Protein requirements are affected by several factors, including the amount of nonprotein calories provided, overall energy requirements, protein quality, baseline nutritional status, and the presence of inflammation and metabolic stressors (Table 2-2).
  • Inadequate amounts of any essential amino acid results in inefficient utilization.
  • Illness increases the efflux of amino acids from skeletal muscle; however, increasing protein intake to >1.2 g/kg/d of prehospitalization body weight in critically ill patients may not reduce the loss of lean body mass.2
Table 2-2: Recommended Daily Protein Intake
Clinical ConditionProtein Requirements (g/kg IBW/d)a
Normal0.8
Metabolic stress (illness/injury)1.0–1.5
Acute renal failure (undialyzed)0.8–1.0
Hemodialysis1.2–1.4
Peritoneal dialysis1.3–1.5

IBW, ideal body weight.

aAdditional protein intake may be needed to compensate for excess protein loss in specific patient populations such as those with burn injury, open wounds, and protein-losing enteropathy or nephropathy. Lower protein intake may be necessary in patients with chronic renal insufficiency who are not treated by dialysis and certain patients with hepatic encephalopathy.

Essential Fatty Acids

  • Humans lack the desaturase enzyme needed to produce the ω-3 and ω-6 fatty acids. Therefore, linoleic acid should constitute at least 2% and linolenic acid at least 0.5% of the daily caloric intake to prevent deficiency.
  • The plasma pattern of increased triene-to-tetraene ratio (>0.4) can be used to detect essential fatty acid deficiency.

Carbohydrate

Certain tissues, such as bone marrow, erythrocytes, leukocytes, renal medulla, eye tissues, and peripheral nerves, cannot metabolize fatty acids and require glucose (∼40 g/d) as a fuel. Endogenous protein and glycerol from lipid stores can undergo gluconeogenesis to supply glucose-requiring organs.

Major Minerals

Major minerals such as sodium, potassium, and chloride are important for ionic equilibrium, water balance, and normal cell function.

Micronutrients (Trace Elements and Vitamins)

Trace elements and vitamins are essential constituents of enzyme complexes. The recommended dietary intake for trace elements, fat-soluble vitamins, and water-soluble vitamins is set at two standard deviations above the estimated mean as to meet the needs of 97% of the healthy population.

See Table 2-3 for specifics regarding the assessment of micronutrient nutritional states as well as signs and symptoms of micronutrient deficiency and toxicity.

Table 2-3: Trace Minerals, Fat-Soluble Vitamins, and Water-Soluble Vitamins: Recommended Daily Intake, Deficiency, At-Risk Populations, Toxicity, and Status Evaluation
NutrientRecommended Daily Enteral Intake3/Parenteral Intake4Signs and Symptoms of Deficiency5,6,7,8,9,10,11,12,13,14,15,16Populations at Risk for DeficiencySigns and Symptoms of ToxicityStatus Evaluation3,17
Chromium (Cr3+)30–35 μg/10–15 μgGlucose intolerance, peripheral neuropathyaNonea,5PO: gastritis
IV: skin irritation
Cr6+: (steel, welding) lung carcinogen if inhaled
Chromiums
Copper (Cu2+)900 μg/300–500 μgHypochromic normocytic or macrocytic anemia (rarely microcytic), neutropenia, thrombocytopenia, diarrhea, osteoporosis/pathologic fracturesa
Intrinsic: Menkes disease18
Chronic diarrhea, high-zinc/low-protein diets17,19PO: gastritis, nausea, vomiting, coma, movement/neurologic abnormalities, hepatic necrosis
Intrinsic: Wilson disease
Coppers,u
Ceruloplasminp
Iodine (I)150 μg/70–140 μg (not routinely added)Thyroid hyperplasia (goiter) + functional hypothyroidism
Intrinsic in utero: cretinism, poor CNS development, hypothyroidism
Those without access to fortified salt, grain, milk, or cooking oil20Deficiency: causes hypothyroidism
Excess: acutely causes hypothyroidism; chronic excess: hyperthyroidism
TSHs, iodineu (24-h intake and iodine: Cr ratio are more representative than a single sample)
Thyroglobulins6,20
Iron (Fe2+,3+)8 mg/1.0–1.5 μg (not routinely added)Fatigue, hypochromic microcytic anemia, glossitis, koilonychiaReproductive-age females, pregnant females, chronic anemias, hemoglobinopathies, post–gastric bypass/duodenectomy, alcoholicsPO or IV: hemosiderosis, followed by deposition in liver, pancreas, heart, and glands
Intrinsic: hereditary hemochromatosis
Ferritins, TIBCs, % transferrin saturationc, irons
Manganese (Mn2+)2.3 mg/60–100 μgHypercholesterolemia, dermatitis, dementia, weight lossbChronic liver disease, iron-deficient populationsPO: noneb
Inhalation: hallucination, Parkinsonian-type symptoms21
No reliable markers
Manganeses does not reflect bodily stores, especially in the CNS
Selenium Descriptive text is not available for this image55 μg/20–60 μgMyalgias, cardiomyopathya
Intrinsic: Keshan disease (Chinese children), Kashin–Beck disease, myxedematous endemic cretinism22
Endemic areas of low soil content include certain parts of China and |New Zealand10PO: nausea, diarrhea, AMS, irritability, fatigue, peripheral neuropathy, hair loss, white splotchy nails, halitosis (garlic-like odor)Seleniums, glutathione peroxidase activityb
Zinc (Zn2+)11 mg/2.5–5.0 mgPoor wound healing, diarrhea (high fistula risk), dysgeusia, teratogenicity, hypogonadism, infertility, acrofacial and oral skin lesions (glossitis, alopecia), behavioral changes
Intrinsic: acrodermatitis enteropathica
Chronic diarrhea, cereal-based diets, alcoholics, chronic liver disease, sickle cell, HIV, pancreatic insufficiency/any intestinal malabsorptive states, fistulas/ostomies, nephrotic syndrome, diabetes, post–gastric bypass/duodenectomy, anorexia, pregnancy19
Intrinsic: acrodermatitis enteropathica
PO: nausea, vomiting, gastritis, diarrhea, low HDL, gastric erosions
Competition with GI absorption can precipitate Cu2+ deficiency
Inhaled: hyperpnea, weakness, diaphoresis
Zincs,p, alkaline phosphatases (good for those on TPN, but in general Zincs,p hair, RBC, WBC levels can be misleading)
Zinc radioisotope studies (most accurate tests at present; limited by cost and availability)7
Vitamin A
Retinol
900 μg/3300 IUConjunctival xerosis, keratomalacia, follicular hyperkeratosis, night blindness, Bitot spots, corneal + retinal dysfunctionAny malabsorptive state involving proximal small bowel, vegetarians, chronic liver diseaseAcute: teratogenic, skin exfoliation, intracranial hypertension, hepatocellular necrosis
Chronic: alopecia, ataxia, cheilitis, dermatitis, conjunctivitis, pseudotumor cerebri, hyperlipidemia, hyperostosis
Retinols, retinol estersp, electroretinogram, liver biopsy (diagnostic for toxicity), retinol binding protein (useful in ESRD; accurately assesses blood levels)23
Vitamin D
Ergocalciferol
5–15 μg/200 IURickets/osteomalaciaAny malabsorptive state involving proximal small bowel, chronic liver disease
Of note: those with higher skin melanin content (i.e., darker skin) have low baseline 25-OH vitamin D levels; it is unclear whether this merits their inclusion as an “at-risk” population23
Hypercalcemia, hyperphosphatemia, which can lead to CaPO4 precipitation, systemic calcification +/− AMS +/− AKI25-OH vitamin Ds
Of note: lively debate between IOM and Endocrine Society regarding definitions of deficiency, goal serum 25-OH levels, and at-risk populations24,25
Vitamin E
(α,γ)-Tocopherol
15 mg/10 IUHemolytic anemia, posterior column degeneration, ophthalmoplegia, peripheral neuropathy
Seen in severe malabsorption, abetalipoproteinemia
Any malabsorptive state involving proximal small bowel, chronic liver diseasePossible increased risk in hemorrhagic CVA, functional inhibition of vitamin K–mediated procoagulantsTocopherol
Must account for cholesterol/triglyceride ratio: otherwise, higher cholesterol/triglyceride ratio overestimates vitamin E, lower cholesterol/triglyceride ratio underestimates vitamin E16,c
Vitamin K
Phylloquinone
120 μg/150 IUHemorrhagic disease of newborn, coagulopathyAny malabsorptive state involving proximal small bowel, chronic liver diseaseIn utero: hemolytic anemia, hyperbilirubinemia, kernicterus
IV: flushing, dyspnea, hypotension (possibly related to dispersal agent)
Prothrombin timep
Vitamin B1
Thiamine
1.2 mg/6 mgIrritability, fatigue, headache
Wernicke encephalopathy, Korsakoff psychosis, “wet” beriberi, “dry” beriberi
Alcoholics, severely malnourishedIV: lethargy and ataxiaRBC transketolase activityb, thiamineb,u
Vitamin B2
Riboflavin
1.3 mg/3.6 mgCheilosis, angular stomatitis, glossitis, seborrheic dermatitis, normocytic normochromic anemiaAlcoholics, severely malnourishedNonebRBC glutathione reductase activityp
Vitamin B3
Niacin
16 mg/40 mgPellagra dysesthesias, glossitis, stomatitis, vaginitis, vertigo
Intrinsic: Hartnup disease
Alcoholics, malignant carcinoid syndrome, severely malnourishedFlushing, hyperglycemia, hyperuricemia, hepatocellular injurybN-methyl-nicotinamideu
Vitamin B5
Pantothenic acid
5 mg/15 mgFatigue, abdominal pain, vomiting, insomnia, paresthesiasbAlcoholics3PO: diarrheaPantothenic acidu
Vitamin B6
Pyridoxine
1.3–1.7 mg/6 mgCheilosis, stomatitis, glossitis, irritability, depression, confusion, normochromic normocytic anemiaAlcoholics, diabetics, celiac sprue, chronic isoniazid or penicillamine use15Peripheral neuropathy, photosensitivityPyridoxal phosphatep
Vitamin B7
Biotin
30 μg/60 μgMental status changes, myalgias, hyperesthesias, anorexiac,26 (excessive egg white consumption results in avidin-mediated biotin inactivation)AlcoholicsNoneb,26Biotinp, methyl-citrateu, 3-methyl-
crotonyglycineu, 3-hydroxyisovalerateu
Vitamin B9
Folic acid
400 μg/600 μgBone marrow suppression, macrocytic megaloblastic anemia, glossitis, diarrhea
Can be precipitated by sulfasalazine + phenytoin
Alcoholics, celiac or tropical sprue, chronic sulfasalazine usePO: may lower seizure threshold in those taking anticonvulsantsFolic acids, RBC folic acidp
Vitamin B12
Cobalamin
2.4 μg/5 μgBone marrow suppression, macrocytic megaloblastic anemia, glossitis, diarrhea, posterolateral column demyelination, AMS, depression, psychosisVegetarians, atrophic gastritis, pernicious anemia, celiac sprue, Crohn disease, patients postgastrectomy or ileal resectionNonebCobalamin (B12)s, methylmalonic acids,p
Vitamin C
Ascorbic acid
90 mg/200 mgScurvy, ossification abnormalities
Tobacco lowers plasma and WBC vitamin C13
Sudden cessation of high-dose vitamin C can precipitate scurvy
Fruit-deficient diet, smokers,13
ESRD27
Nausea, diarrhea, increased oxalate synthesis (theoretical nephrolithiasis risk)Ascorbic acidp, leukocyte ascorbic acid

AKI, acute kidney injury; AMS, altered mental status; CNS, central nervous system; CVA, cerebrovascular accident; ESRD, end-stage renal disease; IOM, Institute of Medicine; GI, gastrointestinal; HDL, high-density lipoprotein (cholesterol); RBC, red blood cell; TIBC, total iron bonding capacity; TPN, total parenteral nutrition; TSH, thyroid-stimulating hormone; WBC, white blood cell.

Subscript: b, blood; c, calculated; p, plasma; s, serum; u, urine.

aOnly reported in patients on long-term TPN.

bNever demonstrated in humans.

cOnly able to induce under experimental conditions and/or only been able to induce in animals.

Special Considerations

  • Both the amount and location of prior gut resection influence nutrient needs. Patients with a reduced length of functional small bowel may require additional vitamins and minerals if they are not receiving parenteral nutrition. Table 2-4 provides guidelines for supplementation in these patients.
  • Ileal inflammation, resection, inflammatory bowel disease (IBD), and bypass (ileojejunal bypass) can cause B12 deficiency and bile salt loss. Diarrhea in this setting may be improved with oral cholestyramine.
  • Proximal gut resection (stomach or duodenum) via partial gastrectomy, Billroth I and II, duodenal switch/biliopancreatic diversion, Roux-en-Y gastric bypass, pancreaticoduodenectomy (Whipple), and sleeve gastrectomy may impair absorption of divalent cations such as iron, calcium, and copper. Copper deficiency is extremely common in post–gastric bypass patients who do not receive routine supplementation.28
  • Patients with excessive gastrointestinal (GI) tract losses require additional fluids and electrolytes. An assessment of fluid losses due to diarrhea, ostomy output, and fistula volume should be made to help determine fluid requirements. Intestinal mineral losses may be calculated by multiplying the volume of fluid loss by the fluid electrolyte concentration (Table 2-5).
  • Hyperammonemic encephalopathy is an uncommon but serious complication of Roux-en-Y gastric bypass with an estimated mortality rate of 50%.29 Laboratory hallmarks include elevated ammonia, elevated plasma glutamate, hypoalbuminemia, nutritional and essential amino acid deficiencies, and low zinc.30 It does not appear to resolve with replacement of trace elements. Some reports suggest improvement with total parental nutrition after several months; however, data remain limited.31
Table 2-4: Guidelines for Vitamin and Mineral Supplementation in Patients with Severe Malabsorption
SupplementDoseRoute
Prenatal multivitamin with mineralsa1 tablet dailyPO
Vitamin Da50,000 units 2–3 times per weekPO
Calciuma500 mg elemental calcium tid–qidPO
Vitamin B12b1 mg dailyPO
100–500 μg q1–2 moSC
Vitamin Ab10,000–50,000 units dailyPO
Vitamin Kb5 mg/dPO
5–10 mg/wkSC
Vitamin Eb30 units/dPO
Magnesium gluconateb108–169 mg elemental magnesium qidPO
Magnesium sulfateb290 mg elemental magnesium 1–3 times per weekIM/IV
Zinc gluconate or zinc sulfateb25 mg elemental zinc daily plus 100 mg elemental zinc per liter intestinal outputPO
Ferrous sulfateb60 mg elemental iron tidPO
Iron dextranbDaily dose based on formula or tableIV

aRecommended routinely for all patients.

bRecommended for patients with documented nutrient deficiency or malabsorption.

Table 2-5: Electrolyte Concentrations in Gastrointestinal Fluids
LocationNa (mEq/L)K (mEq/L)Cl (mEq/L)HCO3 (mEq/L)
Stomach6510100
Bile150410035
Pancreas15078075
Duodenum90159015
Mid–small bowel140610020
Terminal ileum14086070
Rectum40901530

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General Principles

Energy

  • Total daily energy expenditure (TEE) is composed of resting energy expenditure (normally ∼70% of TEE), the thermic effect of food (normally ∼10% of TEE), and energy expenditure of physical activity (normally ∼20% of TEE).
  • Use of predictive equations can provide a reasonable estimate of daily energy requirements that should be modified based on the factors that affect the patient’s metabolic rate.
  • Malnutrition and hypocaloric feeding may decrease resting energy expenditure to 15%–20% below expected for actual body size, whereas metabolic stressors, such as inflammatory diseases or trauma, often increase energy requirements by ∼30%–50%.
  • The Harris–Benedict equation provides a reasonable estimate of resting energy expenditure (in kilocalories [kcal] per day) in healthy adults. It takes into account the effects of body size and lean tissue mass (which are influenced by gender and age) on energy requirements and can be used to estimate total daily energy needs in hospitalized patients (where W is the weight in kilograms, H the height in centimeters, and A is the age in years).1
    • Men = 66 + (13.7 × W ) + (5 × H ) − (6.8 × A)
    • Women = 665 + (9.6 × W ) + (1.8 × H ) − (4.7 × A)
  • Energy requirements per kilogram of body weight are inversely related to body mass index (BMI) (Table 2-1). The lower range within each category should be considered in insulin-resistant, critically ill patients unless they are depleted in body fat.
  • Ideal body weight can be estimated based on height
    • For men: 106 + 6 lb for each inch over 5 ft
    • For women, 100 + 5 lb for each inch over 5 ft
Table 2-1: Estimated Energy Requirements for Hospitalized Patients Based on Body Mass Index
Body Mass Index (kg/m2)Energy Requirements (kcal/kg/d)
1535–40
15–1930–35
20–2420–25
25–2915–20
≥30<15

Note: These values are recommended for critically ill patients and all obese patients; add 20% of total calories in estimating energy requirements in non–critically ill patients.

Protein

  • Protein intake of 0.8 g/kg/d meets the requirements of 97% of the adult population.
  • Protein requirements are affected by several factors, including the amount of nonprotein calories provided, overall energy requirements, protein quality, baseline nutritional status, and the presence of inflammation and metabolic stressors (Table 2-2).
  • Inadequate amounts of any essential amino acid results in inefficient utilization.
  • Illness increases the efflux of amino acids from skeletal muscle; however, increasing protein intake to >1.2 g/kg/d of prehospitalization body weight in critically ill patients may not reduce the loss of lean body mass.2
Table 2-2: Recommended Daily Protein Intake
Clinical ConditionProtein Requirements (g/kg IBW/d)a
Normal0.8
Metabolic stress (illness/injury)1.0–1.5
Acute renal failure (undialyzed)0.8–1.0
Hemodialysis1.2–1.4
Peritoneal dialysis1.3–1.5

IBW, ideal body weight.

aAdditional protein intake may be needed to compensate for excess protein loss in specific patient populations such as those with burn injury, open wounds, and protein-losing enteropathy or nephropathy. Lower protein intake may be necessary in patients with chronic renal insufficiency who are not treated by dialysis and certain patients with hepatic encephalopathy.

Essential Fatty Acids

  • Humans lack the desaturase enzyme needed to produce the ω-3 and ω-6 fatty acids. Therefore, linoleic acid should constitute at least 2% and linolenic acid at least 0.5% of the daily caloric intake to prevent deficiency.
  • The plasma pattern of increased triene-to-tetraene ratio (>0.4) can be used to detect essential fatty acid deficiency.

Carbohydrate

Certain tissues, such as bone marrow, erythrocytes, leukocytes, renal medulla, eye tissues, and peripheral nerves, cannot metabolize fatty acids and require glucose (∼40 g/d) as a fuel. Endogenous protein and glycerol from lipid stores can undergo gluconeogenesis to supply glucose-requiring organs.

Major Minerals

Major minerals such as sodium, potassium, and chloride are important for ionic equilibrium, water balance, and normal cell function.

Micronutrients (Trace Elements and Vitamins)

Trace elements and vitamins are essential constituents of enzyme complexes. The recommended dietary intake for trace elements, fat-soluble vitamins, and water-soluble vitamins is set at two standard deviations above the estimated mean as to meet the needs of 97% of the healthy population.

See Table 2-3 for specifics regarding the assessment of micronutrient nutritional states as well as signs and symptoms of micronutrient deficiency and toxicity.

Table 2-3: Trace Minerals, Fat-Soluble Vitamins, and Water-Soluble Vitamins: Recommended Daily Intake, Deficiency, At-Risk Populations, Toxicity, and Status Evaluation
NutrientRecommended Daily Enteral Intake3/Parenteral Intake4Signs and Symptoms of Deficiency5,6,7,8,9,10,11,12,13,14,15,16Populations at Risk for DeficiencySigns and Symptoms of ToxicityStatus Evaluation3,17
Chromium (Cr3+)30–35 μg/10–15 μgGlucose intolerance, peripheral neuropathyaNonea,5PO: gastritis
IV: skin irritation
Cr6+: (steel, welding) lung carcinogen if inhaled
Chromiums
Copper (Cu2+)900 μg/300–500 μgHypochromic normocytic or macrocytic anemia (rarely microcytic), neutropenia, thrombocytopenia, diarrhea, osteoporosis/pathologic fracturesa
Intrinsic: Menkes disease18
Chronic diarrhea, high-zinc/low-protein diets17,19PO: gastritis, nausea, vomiting, coma, movement/neurologic abnormalities, hepatic necrosis
Intrinsic: Wilson disease
Coppers,u
Ceruloplasminp
Iodine (I)150 μg/70–140 μg (not routinely added)Thyroid hyperplasia (goiter) + functional hypothyroidism
Intrinsic in utero: cretinism, poor CNS development, hypothyroidism
Those without access to fortified salt, grain, milk, or cooking oil20Deficiency: causes hypothyroidism
Excess: acutely causes hypothyroidism; chronic excess: hyperthyroidism
TSHs, iodineu (24-h intake and iodine: Cr ratio are more representative than a single sample)
Thyroglobulins6,20
Iron (Fe2+,3+)8 mg/1.0–1.5 μg (not routinely added)Fatigue, hypochromic microcytic anemia, glossitis, koilonychiaReproductive-age females, pregnant females, chronic anemias, hemoglobinopathies, post–gastric bypass/duodenectomy, alcoholicsPO or IV: hemosiderosis, followed by deposition in liver, pancreas, heart, and glands
Intrinsic: hereditary hemochromatosis
Ferritins, TIBCs, % transferrin saturationc, irons
Manganese (Mn2+)2.3 mg/60–100 μgHypercholesterolemia, dermatitis, dementia, weight lossbChronic liver disease, iron-deficient populationsPO: noneb
Inhalation: hallucination, Parkinsonian-type symptoms21
No reliable markers
Manganeses does not reflect bodily stores, especially in the CNS
Selenium Descriptive text is not available for this image55 μg/20–60 μgMyalgias, cardiomyopathya
Intrinsic: Keshan disease (Chinese children), Kashin–Beck disease, myxedematous endemic cretinism22
Endemic areas of low soil content include certain parts of China and |New Zealand10PO: nausea, diarrhea, AMS, irritability, fatigue, peripheral neuropathy, hair loss, white splotchy nails, halitosis (garlic-like odor)Seleniums, glutathione peroxidase activityb
Zinc (Zn2+)11 mg/2.5–5.0 mgPoor wound healing, diarrhea (high fistula risk), dysgeusia, teratogenicity, hypogonadism, infertility, acrofacial and oral skin lesions (glossitis, alopecia), behavioral changes
Intrinsic: acrodermatitis enteropathica
Chronic diarrhea, cereal-based diets, alcoholics, chronic liver disease, sickle cell, HIV, pancreatic insufficiency/any intestinal malabsorptive states, fistulas/ostomies, nephrotic syndrome, diabetes, post–gastric bypass/duodenectomy, anorexia, pregnancy19
Intrinsic: acrodermatitis enteropathica
PO: nausea, vomiting, gastritis, diarrhea, low HDL, gastric erosions
Competition with GI absorption can precipitate Cu2+ deficiency
Inhaled: hyperpnea, weakness, diaphoresis
Zincs,p, alkaline phosphatases (good for those on TPN, but in general Zincs,p hair, RBC, WBC levels can be misleading)
Zinc radioisotope studies (most accurate tests at present; limited by cost and availability)7
Vitamin A
Retinol
900 μg/3300 IUConjunctival xerosis, keratomalacia, follicular hyperkeratosis, night blindness, Bitot spots, corneal + retinal dysfunctionAny malabsorptive state involving proximal small bowel, vegetarians, chronic liver diseaseAcute: teratogenic, skin exfoliation, intracranial hypertension, hepatocellular necrosis
Chronic: alopecia, ataxia, cheilitis, dermatitis, conjunctivitis, pseudotumor cerebri, hyperlipidemia, hyperostosis
Retinols, retinol estersp, electroretinogram, liver biopsy (diagnostic for toxicity), retinol binding protein (useful in ESRD; accurately assesses blood levels)23
Vitamin D
Ergocalciferol
5–15 μg/200 IURickets/osteomalaciaAny malabsorptive state involving proximal small bowel, chronic liver disease
Of note: those with higher skin melanin content (i.e., darker skin) have low baseline 25-OH vitamin D levels; it is unclear whether this merits their inclusion as an “at-risk” population23
Hypercalcemia, hyperphosphatemia, which can lead to CaPO4 precipitation, systemic calcification +/− AMS +/− AKI25-OH vitamin Ds
Of note: lively debate between IOM and Endocrine Society regarding definitions of deficiency, goal serum 25-OH levels, and at-risk populations24,25
Vitamin E
(α,γ)-Tocopherol
15 mg/10 IUHemolytic anemia, posterior column degeneration, ophthalmoplegia, peripheral neuropathy
Seen in severe malabsorption, abetalipoproteinemia
Any malabsorptive state involving proximal small bowel, chronic liver diseasePossible increased risk in hemorrhagic CVA, functional inhibition of vitamin K–mediated procoagulantsTocopherol
Must account for cholesterol/triglyceride ratio: otherwise, higher cholesterol/triglyceride ratio overestimates vitamin E, lower cholesterol/triglyceride ratio underestimates vitamin E16,c
Vitamin K
Phylloquinone
120 μg/150 IUHemorrhagic disease of newborn, coagulopathyAny malabsorptive state involving proximal small bowel, chronic liver diseaseIn utero: hemolytic anemia, hyperbilirubinemia, kernicterus
IV: flushing, dyspnea, hypotension (possibly related to dispersal agent)
Prothrombin timep
Vitamin B1
Thiamine
1.2 mg/6 mgIrritability, fatigue, headache
Wernicke encephalopathy, Korsakoff psychosis, “wet” beriberi, “dry” beriberi
Alcoholics, severely malnourishedIV: lethargy and ataxiaRBC transketolase activityb, thiamineb,u
Vitamin B2
Riboflavin
1.3 mg/3.6 mgCheilosis, angular stomatitis, glossitis, seborrheic dermatitis, normocytic normochromic anemiaAlcoholics, severely malnourishedNonebRBC glutathione reductase activityp
Vitamin B3
Niacin
16 mg/40 mgPellagra dysesthesias, glossitis, stomatitis, vaginitis, vertigo
Intrinsic: Hartnup disease
Alcoholics, malignant carcinoid syndrome, severely malnourishedFlushing, hyperglycemia, hyperuricemia, hepatocellular injurybN-methyl-nicotinamideu
Vitamin B5
Pantothenic acid
5 mg/15 mgFatigue, abdominal pain, vomiting, insomnia, paresthesiasbAlcoholics3PO: diarrheaPantothenic acidu
Vitamin B6
Pyridoxine
1.3–1.7 mg/6 mgCheilosis, stomatitis, glossitis, irritability, depression, confusion, normochromic normocytic anemiaAlcoholics, diabetics, celiac sprue, chronic isoniazid or penicillamine use15Peripheral neuropathy, photosensitivityPyridoxal phosphatep
Vitamin B7
Biotin
30 μg/60 μgMental status changes, myalgias, hyperesthesias, anorexiac,26 (excessive egg white consumption results in avidin-mediated biotin inactivation)AlcoholicsNoneb,26Biotinp, methyl-citrateu, 3-methyl-
crotonyglycineu, 3-hydroxyisovalerateu
Vitamin B9
Folic acid
400 μg/600 μgBone marrow suppression, macrocytic megaloblastic anemia, glossitis, diarrhea
Can be precipitated by sulfasalazine + phenytoin
Alcoholics, celiac or tropical sprue, chronic sulfasalazine usePO: may lower seizure threshold in those taking anticonvulsantsFolic acids, RBC folic acidp
Vitamin B12
Cobalamin
2.4 μg/5 μgBone marrow suppression, macrocytic megaloblastic anemia, glossitis, diarrhea, posterolateral column demyelination, AMS, depression, psychosisVegetarians, atrophic gastritis, pernicious anemia, celiac sprue, Crohn disease, patients postgastrectomy or ileal resectionNonebCobalamin (B12)s, methylmalonic acids,p
Vitamin C
Ascorbic acid
90 mg/200 mgScurvy, ossification abnormalities
Tobacco lowers plasma and WBC vitamin C13
Sudden cessation of high-dose vitamin C can precipitate scurvy
Fruit-deficient diet, smokers,13
ESRD27
Nausea, diarrhea, increased oxalate synthesis (theoretical nephrolithiasis risk)Ascorbic acidp, leukocyte ascorbic acid

AKI, acute kidney injury; AMS, altered mental status; CNS, central nervous system; CVA, cerebrovascular accident; ESRD, end-stage renal disease; IOM, Institute of Medicine; GI, gastrointestinal; HDL, high-density lipoprotein (cholesterol); RBC, red blood cell; TIBC, total iron bonding capacity; TPN, total parenteral nutrition; TSH, thyroid-stimulating hormone; WBC, white blood cell.

Subscript: b, blood; c, calculated; p, plasma; s, serum; u, urine.

aOnly reported in patients on long-term TPN.

bNever demonstrated in humans.

cOnly able to induce under experimental conditions and/or only been able to induce in animals.

Special Considerations

  • Both the amount and location of prior gut resection influence nutrient needs. Patients with a reduced length of functional small bowel may require additional vitamins and minerals if they are not receiving parenteral nutrition. Table 2-4 provides guidelines for supplementation in these patients.
  • Ileal inflammation, resection, inflammatory bowel disease (IBD), and bypass (ileojejunal bypass) can cause B12 deficiency and bile salt loss. Diarrhea in this setting may be improved with oral cholestyramine.
  • Proximal gut resection (stomach or duodenum) via partial gastrectomy, Billroth I and II, duodenal switch/biliopancreatic diversion, Roux-en-Y gastric bypass, pancreaticoduodenectomy (Whipple), and sleeve gastrectomy may impair absorption of divalent cations such as iron, calcium, and copper. Copper deficiency is extremely common in post–gastric bypass patients who do not receive routine supplementation.28
  • Patients with excessive gastrointestinal (GI) tract losses require additional fluids and electrolytes. An assessment of fluid losses due to diarrhea, ostomy output, and fistula volume should be made to help determine fluid requirements. Intestinal mineral losses may be calculated by multiplying the volume of fluid loss by the fluid electrolyte concentration (Table 2-5).
  • Hyperammonemic encephalopathy is an uncommon but serious complication of Roux-en-Y gastric bypass with an estimated mortality rate of 50%.29 Laboratory hallmarks include elevated ammonia, elevated plasma glutamate, hypoalbuminemia, nutritional and essential amino acid deficiencies, and low zinc.30 It does not appear to resolve with replacement of trace elements. Some reports suggest improvement with total parental nutrition after several months; however, data remain limited.31
Table 2-4: Guidelines for Vitamin and Mineral Supplementation in Patients with Severe Malabsorption
SupplementDoseRoute
Prenatal multivitamin with mineralsa1 tablet dailyPO
Vitamin Da50,000 units 2–3 times per weekPO
Calciuma500 mg elemental calcium tid–qidPO
Vitamin B12b1 mg dailyPO
100–500 μg q1–2 moSC
Vitamin Ab10,000–50,000 units dailyPO
Vitamin Kb5 mg/dPO
5–10 mg/wkSC
Vitamin Eb30 units/dPO
Magnesium gluconateb108–169 mg elemental magnesium qidPO
Magnesium sulfateb290 mg elemental magnesium 1–3 times per weekIM/IV
Zinc gluconate or zinc sulfateb25 mg elemental zinc daily plus 100 mg elemental zinc per liter intestinal outputPO
Ferrous sulfateb60 mg elemental iron tidPO
Iron dextranbDaily dose based on formula or tableIV

aRecommended routinely for all patients.

bRecommended for patients with documented nutrient deficiency or malabsorption.

Table 2-5: Electrolyte Concentrations in Gastrointestinal Fluids
LocationNa (mEq/L)K (mEq/L)Cl (mEq/L)HCO3 (mEq/L)
Stomach6510100
Bile150410035
Pancreas15078075
Duodenum90159015
Mid–small bowel140610020
Terminal ileum14086070
Rectum40901530

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