JSS092000 Water-Soluble Vitamins Andrew Ukleja, M.D., C.N.S.P. Assistant Professor of Medicine...
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Transcript of JSS092000 Water-Soluble Vitamins Andrew Ukleja, M.D., C.N.S.P. Assistant Professor of Medicine...
JSS092000
Water-Soluble Vitamins
Andrew Ukleja, M.D., C.N.S.P. Assistant Professor of Medicine
Director of Nutrition Support Team Department of Gastroenterology
Cleveland Clinic Weston, FL
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Objectives
• To review • Functions of water-soluble vitamins• Symptoms and signs of vitamin deficiencies• Treatment of the vitamin deficiencies
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The Location of Vitamin The Location of Vitamin AbsorptionAbsorption
Preferentially absorbed in jejunum
Fat-soluble vitamins
Folate (Jejunum only)
Vitamin B12(Ileum only)
Colon
ThiaminRiboflavinNiacinBiotin
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B Vitamins
• Coenzymes in the same energy metabolic pathways
• Overlap in clinical symptoms of deficiency between B vitamins• Cheilosis• Glossitis• Dermatitis
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Vitamin B1 (Thiamine)
• Thiamine was named "the antiberiberi factor“ (1926)
• Absorption: jejunum/ileum
• Biologic half-life: ~10-20 days
• Limited tissue storage • Continuous supplementation is required
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Thiamine
• Functions: Cofactor for enzymes in AA and CHO metabolism
• Dietary sources: yeast, legumes, rice, cereals, pork
• RDI: 1.2-1.5 mg/d; parenteral dose - 3 mg/d
• Thiamine requirement:– based on the total caloric intake– 0.5 mg of vit. B1 daily /1000 Kcal for adults
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Individuals at Risk for Individuals at Risk for Thiamine DeficiencyThiamine Deficiency
• Alcoholics• Calorie-protein poor diet• Severe malnutrition • Malabsorption• Gastric bypass• Chronic renal failure on HD• Prolonged febrile illness
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Thiamine DeficiencyThiamine Deficiency
• Beriberi
• Wernicke-Korsakoff syndrome
• Leigh's syndrome
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Beriberi Beriberi
Adult beriberi:• Dry beriberi: distal symmetrical peripheral neuropathy of
the extremities (sensory and motor impairment)
• Wet beriberi: neuropathy / cardiac involvement – high output CHF (cardiomegaly, cardiomyopathy, tachycardia, pitting peripheral edema)
• Other symptoms: anorexia, weight loss, confusion, muscle wasting, weakness
Infantile beriberi (infants, 2-3 months of age)
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Wernicke-Korsakoff Wernicke-Korsakoff SyndromeSyndrome
• Almost exclusively described in chronic alcoholics
• Wernicke’s encephalopathy: horizontal nystagmus, ophthalmoplegia, gait ataxia, confusion, weakness
• Korsakoff's psychosis
• Impaired short-term memory and confabulation• ? genetic predisposition - impaired synthesis of erythrocyte
transketolase
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Thiamine Deficiency
Detection:• Erythrocyte thiamine transketolase activity (ETKA)• Serum thiamine concentration• Urinary thiamine/transketolase excretion
Treatment:– Vitamin B1: 50-100 mg/d (IV. or IM.) for 7-14 days, then
5-10 mg/d orally until full recovery
Sensitivity to thiamine I.V. has been reported:– Tingling, pruritus, nausea, sweating, anaphylactic
reaction (IgE-mediated)
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Vitamin B2 (Riboflavin)
• Stored in the body as flavoproteins
• Poorly soluble in water
• Functions:– Involved in cellular metabolism, oxidation - reduction
reactions; electron transporter– Essential component of coenzymes
• flavin mononucleotide (FMN)• flavin-adenine dinucleotide (FAD)
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RIBOFLAVIN
• Dietary sources– Milk, green vegetables – Yeast, enriched foods – Liver, meats, fish, eggs
• Daily values: 0.6 mg/1000 kcal
– Adults 1.2-1.7 mg/d– Infants 0.4 mg/d
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Deficiency of Deficiency of Vitamin B2
• Pure deficiency of vit. B2 is rare
• Often accompanied by other water-soluble vitamin deficiencies – Alcoholics– Malabsorption
• Detection of deficiency: – Urinary riboflavin excretion – Erythrocyte glutathione reductase assay
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Patients at Risk for Patients at Risk for Vit. B2 Deficiency Deficiency
• Avoidance of dairy products – lactose intolerance
• Anorexia nervosa
• Malabsorptive syndromes– Celiac sprue – Malignancies – Short bowel syndrome
• Inborn errors of metabolism – defect in riboflavin synthesis
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ManifestationsManifestations of Vit. B2 Deficiency
• Angular stomatitis • Cheilosis • Glossitis• Sore throat • Hyperemia, pharyngeal mucous membranes • Seborrheic dermatitis• Pruritus• Photophobia• Normocytic, normochromic anemia
• Treatment: Vit. B2– 5 mg bid for a few weeks – 3 mg/d - prophylaxis in malabsorption syndrome
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NIACIN (Vitamin B3)
Forms • Nicotinic acid• Nicotinamide
Functions:• Component of NAD/NADP - essential for redox
reactions and hydrogen transport, metabolism of carbohydrates, fatty acids, and proteins
Dietary sources: – Meats (liver), milk, fish, whole-grain, nuts
RDI: 17-20 mg/d
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Niacin Deficiency Pellagra
• Pellagra - meaning "raw skin"• First described in Spain/Italy in the mid 18th century• Epidemic amongst the corn eating population of
southeastern US in the early 1900s
• Seen mainly in alcoholics
• Reported in carcinoid syndrome, Hartnup disease, Isoniazid therapy
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Pellagra
Symptoms (three D’s)• Dermatitis
• Photosensitive symmetric pigmented in sun-exposed areas
• Diarrhea• Dementia
Glossitis/red tongue
Neurologic symptoms – insomnia, anxiety, disorientation,
delusions, encephalopathy, seizures
• Detection: serum niacin level
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Treatment of Treatment of Pellagra
• Niacin: Oral 100 mg tid. until symptoms resolved
• Nicotinamide: • 100mg IM if needed• Only available IV form
• Clinical response:• GI and neurologic symptoms resolve rapidly• Dermatitis subsides over a few months after treatment
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Vitamin B6 (PYRIDOXINE)
• Forms– Pyridoxine (plant foods) active form– Pyridoxal (animal foods) Pyridoxal phosphate– Pyridoxamine (PLP)
• Functions– Transamination and decarboxylation of AA– Gluconeogenesis – Formation of niacin/serotonin from tryptophan– Synthesis of lecithin, RNA, sphingolipids, heme– Immune function (IL-2, lymphocyte proliferation)– Steroid hormone modulation
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PYRIDOXINE
• Dietary sources: – Meats, fish– Whole grains– Vegetables– Nuts
• Recommended daily requirements – Children 0.6 mg – Female 1.6 mg – Pregnancy 1.9 mg– Male 2.0 mg
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Vitamin B6 Deficiency
• Overt deficiencies are rare
• Manifestations – Stomatitis, glossitis, cheilosis– Seborrheic dermatitis– Irritability, confusion, depression – Sideroblastic anemia
serum homocysteine with deficiency– risk factor for atherosclerosis / DVT
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JSS092000
Detection of Vitamin B6 DeficiencyDetection of Vitamin B6 Deficiency
• Plasma pyridoxal-5-phophate (PLP)– Males 27-75 nmol/L– Females 26-93 nmol/L
• Erythrocyte transaminase activity
• Urinary excretion of 4-pyridoxic acid > 3.0 mmol/d– indicates adequate short-term vit. B6 status
• Urinary excretion of xanthurenic acid (< 65 mmol/d)
after a 2 g tryptophan load
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PYRIDOXINE
• Treatment: – Oral 50-150 mg/d– 50 mg/d prophylactic dose with Isoniazide Rx
• Toxicity (long-term megadoses > 250 mg/d)– Peripheral neuropathy/paresthesias– Dermatoses– Photosensitivity– Dizziness– Nausea
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Vitamin B12 (Cobalamin)Vitamin B12 (Cobalamin)
• Functions– A carrier for methyl group and hydrogen– Synthesis of nucleic acids, porphyrins, methionine,
and fatty acids
• Dietary source– Meat– Dairy products
• Daily requirement: 4-5 mcg/d• Total body stores: 2-5 mg (½ stored in the liver)
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Factors Affecting Vitamin B12 Absorption Factors Affecting Vitamin B12 Absorption
– Dietary intake
– Acid-pepsin in the stomach
– Secretion of IF by gastric parietal cells
– Pancreatic proteases
– Presence of ileum
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Causes of Vitamin B12 DeficiencyCauses of Vitamin B12 Deficiency
• Diet– Strict vegetarians– Vegetarian diet in pregnancy
• Gastric abnormalities– Pernicious anemia*– Gastritis, Helicobacter pylori infection – Gastrectomy/gastric bypass – Atrophic gastritis (autoimmune)
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JSS092000
Causes of Vitamin B12 DeficiencyCauses of Vitamin B12 Deficiency
• Small bowel disease– Malabsorption syndromes– Ileal resection/ bypass*
• Crohn’s disease, tuberculous ileitis, lymphoma, radiation enteritis
– Blind loops/bacterial overgrowth– Fish tapeworm (Diphyllobothrium latum)
• Pancreatic exocrine failure – Chronic alcoholism
• Drugs– Antibiotic, Biguanides, PPI, Neomycin
• HIV infection
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Vitamin B12 Deficiency Vitamin B12 Deficiency Pernicious AnemiaPernicious Anemia
• Common in whites (northern European)– Older patients > 50years– Associated with autoimmune diseases under the
age of 30
• Lack of intrinsic factor
• The classic description of patient with PA– Lemon colored skin (anemia/icterus)– Shiny tongue (atrophic glossitis)– Mentally sluggish– Shuffling broad gait
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Hematologic Manifestations ofHematologic Manifestations of
Vitamin B12 DeficiencyVitamin B12 Deficiency
• Macrocytic anemia serum bilirubin / LDH levels– Low-normal WBC/platelet count
• Peripheral blood smear – Megaloblasts– Hypersegmented neutrophils
>5% with 5 +more lobes • Bone marrow aspiration
– hypercellular marrow: megaloblastic erythroid hyperplasia, giant metamyelocytes
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Neurologic Manifestations Neurologic Manifestations of Vitamin B12 Deficiency of Vitamin B12 Deficiency
• Subacute combined degeneration of the posterior/lateral spinal columns – Defect in myelin formation
• Symmetrical neuropathy (legs >> arms)
– Paresthesias (stocking/glove distribution) vibratory and position sense– severe weakness, ataxia, spasticity, clonus,
paraplegia, fecal and urinary incontinence
• Dementia, memory loss, irritability
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ManifestationsManifestations
of Vitamin B12 Deficiencyof Vitamin B12 Deficiency
• Glossitis– Beefy red tongue– Loss of taste
• Diarrhea, dyspepsia, anorexia• Impotence• Vaginal atrophy
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Detection of Vitamin B12 DeficiencyDetection of Vitamin B12 Deficiency
• Serum level of Vitamin B12 – Normal >400 pg/ml– Low <210 pg/ml
serum methylmalonic acid
• Schilling test
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Treatment of Vitamin B12 DeficiencyTreatment of Vitamin B12 Deficiency
• Rx: 100-1000 mcg IM x 5-10 days, then 1000 mcg/monthly• Vegetarians: 3-6 mcg/d orally
• Supplements
1) Sublingual tablet: 350 mcg/day
2) Intramuscular injection: 1000mcg/month
3) Nasal spray (Nascobal): 500mcg weekly
one nostril
4) MVI (1-15mcg)
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Folic AcidFolic Acid
• Functions– A carrier of one-carbon groups– Synthesis of nucleic acids and protein
• Dietary source – Animal products (liver)– Leafy green vegetables
• Small body stores (5-10 mg)
• Daily requirements: 0.2-0.4 mg/d– Pregnancy/lactation 0.5-0.8 mg/d
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Causes of Folate DeficiencyCauses of Folate Deficiency
Nutritional deficiency Poor dietary intake Alcoholism (37% of ETOH users)Elderly (10% in pts >75 years)
MalabsorptionSprueIBDGastric bypassShort bowel
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JSS092000
Causes of Folic Acid DeficiencyCauses of Folic Acid Deficiency
• Increased requirements – Pregnancy– Hemolytic anemia (chronic hemolysis)– Exfoliative skin disease
* Pregnancy – prophylaxis with FA at 0.8-1.0 mg/d to prevent neural tube defects
• Drugs (sulfasalazine)– Interference with folate metabolism
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JSS092000
Symptoms of Folate DeficiencySymptoms of Folate Deficiency
• Macrocytic or megaloblastic anemia • Glossitis, fatigue, diarrhea• Progressive neurologic deterioration
– Neuropathy, ataxia, seizures, mental retardation• Failure to thrive
• Detection – Serum or RBC folate Homocysteine level
• Rx: – Folate 1mg/d orally x 2-3 weeks– Maintenance 0.4 mg (in MVI) with malabsorption
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VITAMIN CVITAMIN C
• Functions: Antioxidant (biologic reductant) – Provides electrons to reduce molecular oxygen– Involved in iron/copper reactions
• RDA: – Adult 75-90 mg/d– Elderly 125 mg/d– Smokers - requirement by ~ 40%
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Vitamin C Vitamin C ASCORBIC ACIDASCORBIC ACID
• Dietary source: – Citrus fruit – Fresh fruit– Vegetables
• Absorption: distal small intestine – Intake up to 100 mg/d - 100% absorbed– Intake >1000 mg/d - <50% absorbed
• Excess of vit. C removed by kidneys
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Functions of Vitamin CFunctions of Vitamin C
• Collagen synthesis– Formation of hydroxyproline/ hydroxylysine synthesis: impaired wound healing, defective tooth
formation, osteoblast and fibroblast dysfunction
• Neurotransmitters– Cofactor in synthesis of norepinephrine, thyroxin
• Prostaglandin metabolism
• Immune functions: chemotaxis and phagocytosis modulation
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Vitamin C DeficiencyVitamin C Deficiency Scurvy Scurvy
• Described in Egyptian, Greek, and Roman literature
• A major cause of morbidity and death in the US during Civil War and the California gold rush
• Ascorbate is an essential nutrient derived from the
diet
• Scurvy develops 2-3 months with diet deficient in ascorbic acid
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Vitamin C Deficiency Vitamin C Deficiency Groups at RiskGroups at Risk
Poor dietary intake– Severely malnourished individuals– Drug and alcohol abusers– Poverty– Elderly, institutionalized pts.
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Symptoms of Vitamin C DeficiencySymptoms of Vitamin C Deficiency
– Swollen and bleeding gums– Loosened teeth– Arthralgias and joint effusions– Lower extremities weakness– Petechiae and periungual hemorrhage – Ecchymoses– Corkscrew hair – Slow wound healing– Anemia – Death
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Vitamin CVitamin C
Rx: Ascorbic acid 250 mg qid. x 1 week, then 100-200 mg/ day + rich Vit. C diet
Toxicity • Seen with large doses of vit. C (grams)
– diarrhea/abdominal bloating– calcium oxalate nephrolithiasis – cardiac arrhythmias if iron overload (oxidative
injury)
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PANTOTHENIC ACID PANTOTHENIC ACID Vitamin B5 Vitamin B5
• Functions: precursor of coenzyme A (CoA)– Essential cofactor in acetylation reactions– Synthesis of vitamins A, D, cholesterol, fatty acids,
proteins, steroids, porphyrins
• Dietary sources: – Egg yolk, liver, kidney, milk, broccoli
• Adequate daily intake 4-7mg/d
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Deficiency of Pantothenic AcidDeficiency of Pantothenic Acid
• It is rare
• Manifestations– Paresthesias and dysesthesias (burning feet syndrome) – Gastrointestinal: nausea, vomiting, cramping
• Growth failure, hemorrhage and necrosis of adrenal cortex, dermatitis, and achromotrichia (gray hair) in rats
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BIOTINBIOTIN
• Growth factor found in yeast, called "bios“
• Called vitamin H, coenzyme R, protective factor X
• Functions:– Cofactor for the carboxylases involved in CHO and lipid
metabolism– Essential in protein and DNA synthesis and cell
replication (CO2 carrier)
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JSS092000
BiotinBiotin
• Dietary sources: – Liver, meats, egg yolk, soybean, yeast
• Adequate dietary intake: 0.03-0.1mg/d
• Biotin deficiency was first noted in patients on long-term parenteral nutrition
• Associated with consumption of large amounts of raw egg whites which contain glycoprotein – avidin (binds to biotin and prevents its absorption)
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JSS092000
Biotin DeficiencyBiotin Deficiency
• Symptoms – Seborrheic dermatitis /maculosquamous/– Alopecia– Anorexia– Lethargy, dysesthesias, seizure – Hypotonia, myoclonus, myalgia – Metabolic acidosis/ organic aciduria
• Detection – Serum biotin level; normal ~1500 pmol/L– Radioligand assays labeled avidin
• Treatment: biotin – oral 0.2-10 mg/d, i.v. 0.15-0.3 mg
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Biotin Deficiency Biotin Deficiency
• Biotin deficiency - defect in metabolism of long-chain fatty acids - seborrheic dermatitis and alopecia
RAT