WaterSoluble Vitamins

1
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

2
Objectives

• To review
• Functions of water-soluble vitamins
• Symptoms and signs of vitamin deficiencies
• Treatment of the vitamin deficiencies

3
The Location of Vitamin Absorption
Thiamin Riboflavin Niacin Biotin
Preferentially absorbed in jejunum
Fat-soluble vitamins
Folate (Jejunum only)
Colon
Vitamin B12 (Ileum only)
4
B Vitamins

• Coenzymes in the same energy metabolic pathways
• Overlap in clinical symptoms of deficiency
  between B vitamins
• Cheilosis
• Glossitis
• Dermatitis

5
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

6
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

7
Individuals at Risk for Thiamine Deficiency

• Alcoholics
• Calorie-protein poor diet
• Severe malnutrition
• Malabsorption
• Gastric bypass
• Chronic renal failure on HD
• Prolonged febrile illness

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Thiamine Deficiency

• Beriberi
• Wernicke-Korsakoff syndrome 
•                        
• Leigh's syndrome

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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 Syndrome

• Almost exclusively described in chronic
  alcoholics
• Wernickes 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)

12
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 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

15
Patients at Risk for Vit. B2 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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Manifestations 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 Ds)
• 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 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

21
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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Detection 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 (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)

• 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

• 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 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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Causes of Vitamin B12 Deficiency

• Small bowel disease
• Malabsorption syndromes
• Ileal resection/ bypass
• Crohns 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 Pernicious 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 ofVitamin 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 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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Manifestationsof Vitamin B12 Deficiency

• Glossitis
• Beefy red tongue
• Loss of taste
• Diarrhea, dyspepsia, anorexia
• Impotence
• Vaginal atrophy

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Detection of Vitamin B12 Deficiency

• Serum level of Vitamin B12
• Normal 400 pg/ml
• Low
• ? serum methylmalonic acid
• Schilling test

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Schilling Test
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Treatment 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 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

38
Causes of Folate Deficiency

• Nutritional deficiency
• Poor dietary intake
• Alcoholism (37 of ETOH users)
• Elderly (10 in pts 75 years)
• Malabsorption
• Sprue
• IBD
• Gastric bypass
• Short bowel

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Causes 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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Symptoms 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 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 ASCORBIC ACID

• Dietary source
• Citrus fruit
• Fresh fruit
• Vegetables
• Absorption distal small intestine
• Intake up to 100 mg/d - 100 absorbed
• Intake 1000 mg/d -
• Excess of vit. C removed by kidneys

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Functions 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 Deficiency 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 Groups at Risk

• Poor dietary intake
• Severely malnourished individuals
• Drug and alcohol abusers
• Poverty
• Elderly, institutionalized pts.

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Symptoms 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 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 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 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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BIOTIN

• 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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Biotin

• 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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Biotin 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 - defect in metabolism of
  long-chain fatty acids - seborrheic dermatitis
  and alopecia

RAT
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Conclusions

• Diagnosis of deficiency can be difficult
• History is a key to diagnosis of vitamin
  deficiency
• Blood tests are important in diagnosis
• The majority of patients with unclear diagnosis
  should receive vitamin supplementation