Vitamin andTrace Mineral Deficiency and Excess¶

Part 10: Disorders of the Gastrointestinal System · Part 10 – Gastrointestinal Disorders · Chapter 344

Key Clinical Points¶

Thiamine must be administered before glucose in patients with alcohol-related deficiency to prevent lactic acidosis.
Pellagra (Niacin deficiency) is characterized by the '4 Ds': Dermatitis, Diarrhea, Dementia, and Death.
Scurvy (Vitamin C deficiency) presents with petechiae, ecchymosis, coiled hairs, and bleeding gums.
Vitamin A serves as a potent regulator of gene transcription via RAR and RXR receptors; toxicity can cause liver disease.
Biotin is often deficient in patients on parenteral nutrition or those consuming large amounts of egg whites (due to avidin).
High-dose biotin interferes with streptavidin-based immunoassays, including TSH and troponin.
Vitamin B6 deficiency causes peripheral neuropathy and sideroblastic anemia; toxicity causes sensory neuropathy.
Vitamin K deficiency leads to elevated prothrombin time; common in fat malabsorption or antibiotic use.
Vitamin D deficiency causes rickets in children and osteomalacia in adults.
Choline is 'conditionally essential'; its deficiency results in fatty liver and elevated aminotransferase levels, while toxicity can cause hypotension and fishy body odor.

DEFINITION & OVERVIEW¶

• Definition: Vitamins are required constituents of the human diet because they are synthesized inadequately or not at all in the human body. • Function: Required in small amounts as coenzymes or prosthetic groups for essential biochemical reactions. • Clinical Relevance: ◦ Deficiency caused by disease (e.g., malabsorption). ◦ Toxicity/Excess can cause disease (e.g., Vitamin A toxicity leading to liver disease). ◦ High doses used therapeutically (e.g., Niacin for hypercholesterolemia). • Prevalence: ◦ Rare in Western countries due to food variety, fortification, and supplements. ◦ Common in 'hidden hunger' (geriatric/socioeconomically deprived populations). ◦ High risk in: chronically ill, alcoholic patients, post-bariatric surgery patients, and refugees/displaced populations. • Storage Dynamics: ◦ Large stores: Vitamins A and B (may take ≥1 year to show deficiency). ◦ Small stores: Folate and Thiamine (can be depleted within weeks).

ETIOLOGY & PATHOPHYYSOLOGY¶

• Thiamine: ◦ Deficiency causes: Poor dietary intake, food processing (heat/duration), and alcohol (interferes with absorption and synthesis of active forms). ◦ Drug interactions: Metformin and verapamil may inhibit ThTR-2 transporters. • Niacin: ◦ Conversion: Tryptophan → Niacin (efficiency 60:1 by weight). ◦ Reduced conversion occurs in: Vitamin B6, riboflavin, or iron deficiency; presence of isoniazid. ◦ Diagnosis: Based on urinary excretion products (2-pyridone and 2-methyl nicotinamide). • Vitamin C: ◦ Absorption: Almost complete if ≥1 g. ◦ Increased requirements: Smoking (including passive), hemodialysis, pregnancy, lactation, and stress (infection/trauma). • Vitamin A: ◦ Forms: Preformed (retinyl esters) and provitamin A carotenoids (e.g., β-carotene). ◦ Conversion: ≥12 μg of all-trans β-carotene ≈ 1 μg retinol activity; ≥24 μg for other carotenoids (e.g., β-cryptoxanthin, α-carotene). ◦ Storage/Transport: 90% stored in liver. Transported as retinol bound to retinol-binding protein, then complexed with transthyretin to prevent renal filtration. ◦ Signaling: Retinoic acid receptors (RAR) and retinoid X receptors (RXR) regulate gene transcription; RXRs are cofactors for PPARs (target of thiazolidinediones). • Biotin: ◦ Function: Coenzyme for carboxylase enzymes; involved in gluconeogenesis, fatty acid synthesis, and histone biotinylation. ◦ Interference: Egg white contains avidin → binds biotin → reduces bioavailability. • Choline: ◦ Role: Precursor for acetylcholine, phospholipids, and betaine; essential for membrane integrity and methyl-group metabolism. ◦ Status: 'Conditionally essential' (deficiency occurs under stress like alcoholic liver disease). • Pantothenic Acid: ◦ Function: Component of coenzyme A and phosphopantetheine; involved in fatty acid metabolism and cholesterol synthesis.

CLINICAL FEATURES¶

• Thiamine Deficiency: ◦ Early stage: Anorexia, irritability, decreased short-term memory. ◦ Beriberi (Wet/Dry): Pain, paresthesia, muscle weakness, cardiomegaly, edema, ophthalmoplegia, confabulation. ◦ Other: Magenta tongue, angular stomatitis, seborrhea, cheilosis. • Niacin Deficiency: ◦ Pellagra: '4 Ds' (Dermatitis of sun-exposed areas, Diarrhea, Dementia/disorientation, Death). ◦ Others: Seborrhea, glossitis, convulsions, neuropathy, depression, microcytic anemia. • Vitamin C Deficiency: ◦ Scurvy: Petechiae, ecchymosis, coiled hairs, inflamed/bleeding gums, joint effusion, poor wound healing. ◦ Xerophthalmia: Night blindness, Bitot's spots, follicular hyperkeratosis. • Biotin Deficiency: ◦ Adults: Mental changes (depression, hallucinations), paresthesia, anorexia, nausea. ◦ Skin/Hair: Scaling, seborrheic, and erythematic rash (eyes, nose, mouth); alopecia. ◦ Infants: Hypotonia, lethargy, apathy; rash including ears. • Vitamin B6 Deficiency: ◦ Symptoms: Peripheral neuropathy, sideroblastic anemia. ◦ Toxicity: Sensory neuropathy. • Choline Deficiency: ◦ Findings: Fatty liver, elevated aminotransferase levels, skeletal muscle damage (high creatine phosphokinase). ◦ Toxicity: Hypotension, increased sweating, diarrhea, salivation, and fishy body odor.

DIAGNOSTIC APPROACH¶

Clinical Presentation Assessment: Identify specific syndromes (e.g., Pellagra for Niacin, Scurvy for Vitamin C).
Laboratory Thresholds (Table 344-1): ◦ Thiamine: <0.3 mg/1000 kcal → Beriberi; <0.4 mg → Magenta tongue. ◦ Niacin: <9.0 niacin equivalents → Pellagra; <0.2 mg → Seborrhea/glossitis. ◦ Folate: <100 μg/d → Megaloblastic anemia; <1.0 μg/d → Neurological symptoms (loss of vibratory sense, etc.). ◦ Vitamin C: <10 mg/d → Scurvy; <300 μg/d → Xerophthalmia. ◦ Vitamin D: <2.0 μg/d → Rickets (children) or Osteomalacia (adults). ◦ Vitamin K: <10 μg/d → Elevated prothrombin time, bleeding.
Metals Assessment (Table 344-2): ◦ Boron: Monitor for developmental defects/sterility; limit to 20 mg/d. ◦ Copper: Assess for anemia or toxicity (liver failure); limit to 10 mg/d. ◦ Fluoride: Monitor for dental caries or fluorosis; limit to 10 mg/d. ◦ Iron: Evaluate for anemia or overload (organ damage); limit to 45 mg/d (to avoid GI effects). ◦ Molybdenum: Check for neurological abnormalities or reproductive issues; limit to 2 mg/d. ◦ Phosphorus: Monitor for rickets/myopathy or hyperphosphatemia; limit to 4000 mg/d.

MANAGEMENT & TREATMENT¶

Acute Thiamine Deficiency: ◦ Action: Replenish thiamine BEFORE glucose in patients with alcohol-related deficiency → prevents lactic acidosis.
Choline Management: ◦ Treatment: Suggested for dementia or high cardiovascular risk (evidence not fully documented). ◦ Toxicity Prevention: Limit intake to ≤3.5 g/d to avoid hypotension and fishy odor; use restricted diets for trimethylaminuria or to reduce TMAO production.
Vitamin C Supplementation: ◦ Note: 40% of U.S. population uses supplements; dosage depends on increased needs (e.g., smoking, hemodialysis).
Toxicity Management: ◦ Vitamin A: Monitor for liver disease and ensure appropriate dosing to avoid toxicity. ◦ Choline Toxicity: Limit intake to ≤3.5 g/d.

KEY PEARLS & CLINICAL TRAPS¶

• Thiamine: Critical in alcoholics; must precede glucose administration. Risk factors include alcohol, bariatric surgery, and thiaminases in food. • Niacin: Pellagra is the classic presentation of deficiency. Tryptophan conversion (60:1) is a key metabolic pathway for Niacin synthesis. • Vitamin A: Complex transport system (Retinol-binding protein + Transthyretin) protects against toxicity while ensuring delivery to tissues. • Biotin: Common in parenteral nutrition; high doses interfere with TSH and troponin assays. Avidin in egg whites reduces bioavailability. • Choline: 'Conditionally essential'; deficiency leads to fatty liver; toxicity causes fishy body odor. Limit: ≤3.5 g/d. • Vitamin K: Primary concern is bleeding due to fat malabsorption or antibiotic use. • Vitamin D: Key for bone health; deficiency leads to rickets (children) and osteomalacia (adults).

Reference Tables¶

TABLE 344-1 Principal Clinical Findings of Vitamin Malnutrition NUTRIENT Thiamine Riboflavin Niacin¶

Harrison's 22e, p.2605

NUTRIENT	CLINICAL FINDING	DIETARY LEVEL PER DAY ASSOCIATED WITH OVERT DEFICIENCY IN ADULTS	CONTRIBUTING FACTORS TO DEFICIENCY
Thiamine	Beriberi: neuropathy, muscle weakness and wasting, cardiomegaly, edema, ophthalmoplegia, confabulation	<0.3 mg/1000 kcal	Alcoholism, chronic diuretic use, bariatric surgery, hyperemesis, thiaminases in food
	Magenta tongue, angular stomatitis, seborrhea, cheilosis, ocular symptoms, corneal vascularization	<0.4 mg
Niacin	Pellagra: pigmented rash of sun-exposed areas, bright red tongue, diarrhea, apathy, memory loss, disorientation	<9.0 niacin equivalents	Alcoholism, vitamin B deficiency, riboflavin 6 deficiency, tryptophan deficiency
	Seborrhea, glossitis, convulsions, neuropathy, depression, confusion, microcytic anemia	<0.2 mg
Folate	Megaloblastic anemia, atrophic glossitis, depression, ↑ homocysteine	<100 μg/d	Alcoholism, sulfasalazine, pyrimethamine, triamterene
	Megaloblastic anemia, loss of vibratory and position sense, abnormal gait, dementia, impotence, loss of bladder and bowel control, ↑ homocysteine, ↑ methylmalonic acid	<1.0 μg/d
Vitamin C	Scurvy: petechiae, ecchymosis, coiled hairs, inflamed and bleeding gums, joint effusion, poor wound healing, fatigue	<10 mg/d	Smoking, alcoholism
	Xerophthalmia, night blindness, Bitot’s spots, follicular hyperkeratosis, impaired embryonic development, immune dysfunction	<300 μg/d
Vitamin D	Rickets: skeletal deformation, rachitic rosary, bowed legs; osteomalacia	<2.0 μg/d	Aging, lack of sunlight exposure, fat malabsorption, deeply pigmented skin
	Peripheral neuropathy, spinocerebellar ataxia, skeletal muscle atrophy, retinopathy	Not described unless underlying contributing factor is present
Vitamin K	Elevated prothrombin time, bleeding	<10 μg/d	Fat malabsorption, liver disease, antibiotic use

TABLE 344-2 Deficiencies and Toxicities of Metals ELEMENT Boron Calcium¶

Harrison's 22e, p.2614

ELEMENT	DEFICIENCY	TOXICITY	TOLERABLE UPPER (DIETARY) INTAKE LEVEL
Boron	No biologic function determined	Developmental defects, male sterility, testicular atrophy	20 mg/d (extrapolated from animal data)
	Reduced bone mass, osteoporosis	Renal insufficiency (milk-alkali syndrome), nephrolithiasis, impaired iron absorption, thiazide diuretics
Copper	Anemia, growth retardation, defective keratinization and pigmentation of hair, hypothermia, degenerative changes in aortic elastin, osteopenia, mental deterioration	Nausea, vomiting, diarrhea, hepatic failure, tremor, mental deterioration, hemolytic anemia, renal dysfunction	10 mg/d (liver toxicity)
	Impaired glucose tolerance	Occupational: Renal failure, dermatitis, pulmonary cancer
Fluoride	↑ Dental caries	Dental and skeletal fluorosis, osteosclerosis	10 mg/d (fluorosis)
	Thyroid enlargement, ↓ T, cretinism 4	Thyroid dysfunction, acne-like eruptions
Iron	Muscle abnormalities, koilonychia, pica, anemia, ↓ work performance, impaired cognitive development, premature labor, ↑ perinatal maternal death	Gastrointestinal effects (nausea, vomiting, diarrhea, constipation), iron overload with organ damage, acute and chronic systemic toxicity, increased susceptibility to malaria, increased risk association with certain chronic diseases (e.g., diabetes)	45 mg/d of elemental iron (gastrointestinal side effects)
	Impaired growth and skeletal development, reproduction, lipid and carbohydrate metabolism; upper body rash	General: Neurotoxicity, Parkinson-like symptoms Occupational: Encephalitis-like syndrome, Parkinson-like syndrome, psychosis, pneumoconiosis
Molybdenum	Severe neurologic abnormalities	Reproductive and fetal abnormalities	2 mg/d (extrapolated from animal data)
	Cardiomyopathy, heart failure, striated muscle degeneration	General: Alopecia, nausea, vomiting, abnormal nails, emotional lability, peripheral neuropathy, lassitude, garlic odor to breath, dermatitis Occupational: Lung and nasal carcinomas, liver necrosis, pulmonary inflammation
Phosphorus	Rickets (osteomalacia), proximal muscle weakness, rhabdomyolysis, paresthesia, ataxia, seizure, confusion, heart failure, hemolysis, acidosis	Hyperphosphatemia	4000 mg/d
	Growth retardation, ↓ taste and smell, alopecia, dermatitis, diarrhea, immune dysfunction, failure to thrive, gonadal atrophy, congenital malformations	General: Reduced copper absorption, gastritis, sweating, fever, nausea, vomiting Occupational: Respiratory distress, pulmonary fibrosis