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Water-Soluble Vitamins

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... Forms Pyridoxine (plant foods) active form Pyridoxal ... (IL-2, lymphocyte proliferation) Steroid hormone modulation PYRIDOXINE Dietary sources: ... – PowerPoint PPT presentation

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Title: Water-Soluble 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

8
Thiamine Deficiency
  • Beriberi
  • Wernicke-Korsakoff syndrome 
  •                        
  • Leigh's syndrome

9
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)

10
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

11
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)

13
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

14
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

16
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

17
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

18
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

19
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

20
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

22
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

23
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

24
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 gt 3.0
    mmol/d
  • indicates adequate short-term vit. B6 status
  • Urinary excretion of xanthurenic acid (lt 65
    mmol/d) after a 2 g tryptophan load

25
PYRIDOXINE
  • Treatment
  • Oral 50-150 mg/d
  • 50 mg/d prophylactic dose with Isoniazide Rx
  • Toxicity (long-term megadoses gt 250 mg/d)
  • Peripheral neuropathy/paresthesias
  • Dermatoses
  • Photosensitivity
  • Dizziness
  • Nausea

26
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)

27
Factors Affecting Vitamin B12 Absorption
  • Dietary intake
  • Acid-pepsin in the stomach
  • Secretion of IF by gastric
  • parietal cells
  • Pancreatic proteases
  • Presence of ileum

28
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)

29
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

30
Vitamin B12 Deficiency Pernicious Anemia
  • Common in whites (northern European)
  • Older patients gt 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

31
Hematologic Manifestations of Vitamin B12
Deficiency
  • Macrocytic anemia
  • ? serum bilirubin / LDH levels
  • Low-normal WBC/platelet count
  • Peripheral blood smear
  • Megaloblasts
  • Hypersegmented neutrophils
  • gt5 with 5 more lobes
  • Bone marrow aspiration
  • hypercellular marrow megaloblastic erythroid
    hyperplasia, giant metamyelocytes

32
Neurologic Manifestations of Vitamin B12
Deficiency
  • Subacute combined degeneration of the
    posterior/lateral spinal columns
  • Defect in myelin formation
  • Symmetrical neuropathy (legs gtgt arms)
  • Paresthesias (stocking/glove distribution)
  • ? vibratory and position sense
  • severe weakness, ataxia, spasticity, clonus,
    paraplegia, fecal and urinary incontinence
  • Dementia, memory loss, irritability

33
Manifestations of Vitamin B12 Deficiency
  • Glossitis
  • Beefy red tongue
  • Loss of taste
  • Diarrhea, dyspepsia, anorexia
  • Impotence
  • Vaginal atrophy

34
Detection of Vitamin B12 Deficiency
  • Serum level of Vitamin B12
  • Normal gt400 pg/ml
  • Low lt210 pg/ml
  • ? serum methylmalonic acid
  • Schilling test

35
Schilling Test
36
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)

37
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 gt75 years)
  • Malabsorption
  • Sprue
  • IBD
  • Gastric bypass
  • Short bowel

39
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

40
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

41
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

42
Vitamin C ASCORBIC ACID
  • Dietary source
  • Citrus fruit
  • Fresh fruit
  • Vegetables
  • Absorption distal small intestine
  • Intake up to 100 mg/d - 100 absorbed
  • Intake gt1000 mg/d - lt50 absorbed
  • Excess of vit. C removed by kidneys

43
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

44
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

45
Vitamin C Deficiency Groups at Risk
  • Poor dietary intake
  • Severely malnourished individuals
  • Drug and alcohol abusers
  • Poverty
  • Elderly, institutionalized pts.

46
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

47
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)

48
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

49
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

50
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)

51
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)

52
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

53
Biotin Deficiency
  • Biotin deficiency - defect in metabolism of
    long-chain fatty acids - seborrheic dermatitis
    and alopecia

RAT
54
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
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