Water Soluble Vitamins Flashcards
Thiamine B1 Vitamin
THIAMINE (B1)
a. Functions: Thiamine Diphosphate (TDP or thiamin pyrophosphate TPP): coenzyme central to intermediary metabolism in all cells, esp. glycolysis, TCA cycle, amino acid metabolism; decarboxylation; transketolation reactions; TTP thought to bind at Na+ channel in nerve membranes; many function in nerve conduction
b. Food sources: Esp. rich in whole grains (high in germ), enriched grains, lean pork, legumes
c. Requirements/intake recommendations: RDA: 1.1-1.2 mg/d.
d. Biochemical evaluation: Erythrocyte transketolase activity; blood thiamine levels
e. Treatment for deficiency: 50-100 mg intramuscular or intravenous.
Deficiency of B1 (Thiamine)
Classical syndrome: Beriberi:
- Dry (paralytic/nervous) beriberi: peripheral neuropathy w/ impairment of sensory, motor, and reflex functions; affects distal > proximal limbs; muscle tenderness, weakness/ atrophy, foot/wrist drop
- Wet (cardiac) beriberi: edema and high output cardiac failure (tachycardia, cardiomegaly and CHF) + signs/sxs of dry beriberi
- Wernicke-Korsakoff syndrome (cerebral beriberi): “Triad” – ocular signs (nystagmus, ophthalmoplegia), ataxia, and amnesia/mental confusion.
i. Retentive memory impaired out of all proportion to other cognitive function; only partially reversible with pharmacologic doses of thiamin; genetic predisposition for different susceptibility, unmasked by EtOH abuse, dietary deficiency.
ii. Neuro sxs may be only partially reversible (ophthalmoplegia quickly responds)
Populations at risk of B1 deficiency
Populations at risk of deficiency:
a. Alcoholics most at risk in US (low intake, poor intestinal absorption, defective metabolism)
b. elderly may have relatively high incidence of mild deficiency;
c. chronic renal dialysis patients
d. adults on high carbohydrate diet derived mainly from milled rice or unenriched grains; refeeding after starvation may precipitate deficiency as body “stores” insufficient to handle increased demand to metabolize CHO/energy load; bariatric surgery (assoc. w/ bypass, banding, and gastric sleeve).
e. Dietary deficiency still common in many Asian countries with high reliance on refined rice.
Riboflavin (B2)
a. Functions: Part of 2 co-enzymes, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) which function in oxidation/reduction reactions in TCA cycle and oxidative phosphorylation.
i. Amino acid & fatty acid metabolism; metabolism of vit K, folate B6, and niacin.
b. Food sources: Richest sources: liver, wheat germ; Dairy = largest contribution to intake in US diet (UV light destroys the vitamin), meats & poultry; leafy greens
Intake recommendations: RDA: 1.1-1.3 mg/d
c. Deficiency/Toxicity: Deficiency signs: oral-ocular-genital syndrome - cheilosis (cracked lips) and angular stomatitis (sores at corner of mouth), increased vascularization of conjunctiva and photophobia, and seborrheic dermatitis and scrotal dermatitis.
d. Biochemical eval: Erythrocyte glutathione reductase activity co-efficient (EGRAC) ( in def)
Riboflavin B2 Deficiency
Deficiency signs: oral-ocular-genital syndrome
i. cheilosis (cracked lips) and angular stomatitis (sores at corner of mouth),
ii. increased vascularization of conjunctiva and photophobia, and seborrheic dermatitis and scrotal dermatitis.
Things to Look for in B2 deficiency
a. cheilosis (cracked lips) and angular stomatitis (sores at corner of mouth),
b. increased vascularization of conjunctiva and photophobia
Vitamin B1 Deficiency
Classical syndrome: Beriberi:
- Dry (paralytic/nervous) beriberi: peripheral neuropathy w/ impairment of sensory, motor, and reflex functions; affects distal > proximal limbs; muscle tenderness, weakness/ atrophy, foot/wrist drop
- Wet (cardiac) beriberi: edema and high output cardiac failure (tachycardia, cardiomegaly and CHF) + signs/sxs of dry beriberi
- Wernicke-Korsakoff syndrome (cerebral beriberi): “Triad” – ocular signs (nystagmus, ophthalmoplegia), ataxia, and amnesia/mental confusion
Niacin (B3)
NIACIN (B3)
a. Functions: Nicotinamide is substituent of the electron carrying substances NAD & NADP; functions in multiple energy related pathways, including glycolysis, TCA cycle and oxidative phosphorylation and fatty acid synthesis and oxidation.
b. Food sources: Meats, poultry, fish, peanut butter, legumes are major sources of preformed niacin.
i. Tryptophan = precursor; diets w/ liberal amounts of milk and eggs (rich in tryptophan) are likely adequate for niacin, even if low in preformed niacin.
c. Intake recommendations: RDA: 14-16 mg/d; Niacin equivalents (NE): 1 NE = 1 mg niacin or 60 mg tryptophan.
d. Deficiency treatment: 50-100 mg 3x/day for 3-4 days
e. Biochemical evaluation: urinary excretion of N1-methylnicotinamide and 2-pyridone (ratio < 1.0 = def); serum niacin
Niacin (B3) Deficiency
a. Deficiency/Toxicity:
Pellagra: “4 D’s:”
- Dermatitis: characteristic symmetric pattern; aggravated by sun, heat exposure
- Dementia: confusion, dizziness, and hallucinations
- Diarrhea
- Death
b. Toxicity: Relatively nontoxic in doses of 3 ‑ 6 grams/d of nicotinic acid; used to lower serum cholesterol (esp LDL); initially causes peripheral vasodilation & flushing;
i. less common: Increased serum uric acid, glucose intolerance, liver damage.
Niacin (B3) Deficiency- Pellagra
“4 D’s:”
- Dermatitis: characteristic symmetric pattern; aggravated by sun, heat exposure
- Dementia: confusion, dizziness, and hallucinations
- Diarrhea
- Death
Water Soluble Vitamins
a. Generally not “stored” in body
i. (B12 = exception)
b. Chronic intakes do alter tissues levels
c. Toxicity usually low (B6 = exception)
d. Absorption usually high
e. Excretion typically via urine
f. Breast milk reflects maternal intake/status
(folate = exception)
What’s the risk/Dx?
Water soluble vitamin deficiency are rare, happen in unique cases
- 6 mo old breastfed infant, vomiting, ophthalmoplegia, congestive heart failure
- 5 yr old child only eats burgers (w/ bun) & milk, now limping & refusing to walk, ~ rash
- Alcoholic, “found down”, altered mental status, anemic
- Obese adolescent, s/p bariatric surgery, can’t walk; falls down
- Adult, low SES, chronic diarrhea/malabsorption, rash on arms, hands, neck
Thiamin (B1) /Riboflavin (B2) /Niacin (B3)
a. Functions:
i. All involved in glycolysis/TCA cycle
ii. TPP, FAD, NAD; decarboxylation, oxidation-reduction
b. Food sources: whole & enriched grains
i. Thiamin: legumes, rice bran, grains
- (decreased polished rice)
ii. Riboflavin: dairy, eggs, meats
iii. Niacin: meat/poultry; tryptophan = precursor
- (corn = poor source unless alkaline-treated)
Thiamin (B1) Deficiency
Beriberi - nervous & cardiovascular systems
1. “Dry:” peripheral neuropathy; muscle tenderness (esp legs), weakness & atrophy; foot drop;
- “Wet:” edema, circulatory collapse, congestive heart failure
- Wernicke-Korsakoff (cerebral): confusion, ophthalmoplegia, ataxia, memory loss (complete correction 25%; partial 50%); peripheral neuropathy
Thiamin Deficiency – Who’s at Risk
B1 Vitamin
Alcoholics
Vomiting
(e.g. s/p bariatric surgery (esp 1st 6 mo post-op)
TPN (total parenteral nutrition), w/o thiamin
(deficiency occurs w/in 2-3 wk)
Anorexia nervosa
Re-feeding
Endemic in So Asia (maternal & BF infant) – polished rice diet;
Thiamin Deficiency:
Dry beri-beri
a. Peripheral neuropathy
b. Muscle weakness/atrophy
c. Foot drop
d. Eventual inability to walk w/o falling
Thiamin Deficiency:
Cerebral beri-beri
Wernicke-Korsakoff
- Ophthalmoplegia
- Ataxia
- Confusion
- Memory loss
Infantile beriberi
a. Infant formula w/o thiamin
b. 9 infants (2-12 mo) present w/
- Infection
- Vomiting
- Lethargy/restlessness
- Ophthalmoplegia
- Low thiamine pyrophosphate, acidosis
c. Prompt response to high dose (50 mg/d x 2 wk)
Riboflavin (B2) Deficiency:
- Cheilosis–> Inflammation and small cracks in one or both corners of the mouth.
- Angular stomatitis–> is inflammation of one or both corners of the mouth.
i. Often the corners are red with skin breakdown and crusting.
B2 def–>Low dairy, animal products; common in low resource settings
Niacin (B3) Deficiency: Pellagra Predisposing Factors
a. Nutritional/dietary restriction
i. Cornmeal (w/o germ) based diet (esp w/o alkaline/lime treatment)
ii. Food faddism / restriction
b. Malabsorption syndromes
c. Alcoholism
d. Metabolic “shunting” (carcinoid tumor ↑ serotonin tryptophan)
Pellagra: The “4 D’s”
Niacin (B3) Deficiency
- Diarrhea
- Dermatitis
i. symmetric, scaling w/ areas depigmentation & hyperpigmentation
ii. aggravated by sun exposure (“Casal’s necklace”; reflects ↓ DNA repair, UV-light damage) - Dementia
i. confusion, dizziness, hallucination - Death
Folic Acid
a. Functions: single C transfers
i. nucleic acid synthesis
ii. amino acid metabolism
iii. DNA Methylation – regulation of gene expression / epigenetics
b. Food sources:
i. “foliage,” deep green veg
ii. orange juice
iii. whole grains
(Grains enriched in US since 1998)
(Easily destroyed in prolonged cooking)
Situations with Risk of
Folate Deficiency
a. Inadequate intake or increased destruction in food
b. Alcoholics
c. Pregnancy – globally, high rates deficiency; WHO: routine supplementation, women of reproductive age
d. Hematopoietic conditions
e. Drug/nutrient interactions
Signs/symptoms of
Folate Deficiency
- *Macrocytic anemia
- *Hypersegmented neutrophils
- *Glossitis, irritability
- *Homocysteinemia
- Neural tube defects (occurrence/recurrence)
- Reversible with correction of deficiency
- cannot reverse the neural tube deffects
Folate (& Vit B-12) Deficiencies: What is seen with the blood?
Macrocytic Anemia (↑ MCV) + Hypersegmented Neutrophils
Folate and pregnacy
a. Women of child bearing age advised to have intake of 400-800 g/day* to prevent neural tube defects (spina bifida, anencephaly)
i. Recurrence & occurrence
b. Neural tube closes by 4-6 wk gestation - before most women realize they are pregnant
c. (Currently ~30-50% of women in US consume enough from diet or take supplements)
Vitamin B-12 (cobalamin)
Function and Metabolism
a. Functions:
i. Reform tetrahydrafolate from methylfolate (synthesis of methionine)
ii. Catabolism of odd chain length fatty acids
iii. Catalyze isomerization of methylmalonyl Co-A succinyl Co-A (lipid & CHO metabolism)
b. Metabolism intimately related to folate
i. One carbon transfers (methylation)
ii. Interactions essential for homocysteine methionine, protein synthesis, nucleic acid syn
Vit B12 Absorption:
a. Cleave vitamin from dietary protein in stomach
b. Requires Intrinsic Factor from stomach
c. Cobalamin-IF absorbed in distal ileum
d. Transport in circulation: Transcobalamin II
Vitamin B-12:
Absorption, Storage & Excretion
a. Enterohepatic circulation
b. Large liver stores
c. Excretion: primarily via bile
Vitamin B-12:
Dietary Sources & Requirements
a. Food Sources:
i. Synthesized by soil bacteria
ii. Found only in animal products
b. Requirements:
i. Long term storage & supply
ii. Increased Requirements if decreased absorption/reabsorption
iii. Vegans should take a supplement
Vitamin B-12: Deficiency
a. Risk factors/situations:
i. Inadequate IF secretion or antibodies to IF
ii. Gastric atrophy/gastrectomy
iii. Ileal resection
iv. Breastfed infant of B12 deficient vegan mother
b. Effects:
i. Macrocytic anemia & hypersegmented neutrophils
ii. Neurologic disturbances: depression, paresthesias, gait disturbances, burning tongue, dizziness
c. Hematological effects are reversible w/ B12 or folate Rx
i. Neurological effects eventually irreversible
Vitamin B-12: Deficiency
Macrocytic anemia and neurologic effects
a. Hematological effects are reversible w/ B12 or folate Rx
b. Neurological effects eventually irreversible
c. Megaloblastic anemia should not be treated w/ folate unless have ruled out Vitamin B-12 deficiency
Ascorbic Acid (Vitamin C)
Functions & Physiologic Roles
a. Reversible antioxidant, Vitamin E sparing
b. Provides reducing equivalents to enzymes:
i. Reduction of iron–> increased absorption
c. Leukocyte function (Increased [AA] wbc)
d. Co-substrate in hydroxylation:
i. Collagen synthesis: hydroxylation of proline & lysine; cross-links for tropocollagen
ii. Hydroxylation of tryptophan—> serotonin
e. Conversion dopamine–> norepinephrine
Vitamin C – Food Sources
a. Fruits and vegetables
b. Contributions by food group in U.S.:
39% fruits
15% potatoes
38% other vegetables
c. Not in …. ??
Absorption of Ascorbic Acid
vitamin C
a. Active (saturable) process
b. Low intake: ~ 100%
c. Typical intakes (30-180 mg/d): 70-90%
d. Megadoses:
1 - 1.5 g/d: ~ 50%
> 10 g/d: 15%
If taking large doses, better absorption if take in divided doses (< 1 g/dose)
Ascorbic Acid Homeostasis
a. Percent absorption in GI tract high
increased ’g intake—> decreased % absorption
b. Renal excretion/threshold limits plasma levels
c. Little unmetabolized AA in urine at intakes 80 mg/d; >80 mg/d –> increased urine excretion
d. Intakes of 400-500 mg—> no increase plasma [AA]
Vitamin C Deficiency: Scurvy
a. Hemorrhagic signs
i. Bleeding gums, ecchymoses, petechiae
b. Hyperkeratosis of hair follicles + perifollicular hemorrhages
c. Hypochondriasis: depression, weakness
d. Hematologic abnormalities
i. Anemia: iron &/or folate deficiencies, bleeding
e. Progression: weakness, aching joints/bones/muscles, hemorrhagic signs
Scurvy on skin
Ecchymoses, petechiae Hyperkeratosis of hair follicles
43 year old male with scurvy:
i. Symptoms: malaise, dysphagia, cough, nausea, early satiety
ii. PMHx: s/p “Whipple procedure” for pancreatitis
Scurvy in Children
Recent reports in autistic children on restricted diets
i. 9 yo boy, w/ refusal to walk, hip pain, “rash”, gingival hypertrophy (NEJM 2007)
ii. 9 yo boy, sudden onset unable to walk, bruises, very restricted diet (“1 food at a time!”) (Children’s Hospital 2005
Benefits of “megadoses” Vitamin C ?
a. Prevention/treatment of common cold?
i. antihistamine effects
ii. neutrophil chemotaxis; duration symptoms
b. Prevention of CVD, Ca?
i. RCT do not support
ii. (+) Fruits & vegetables
c. Wound healing: inflammation, proliferation, maturation
Toxicity of Vitamin C
a. Relatively low: homeostatic mechanisms protective (saturation of absorption & renal excretion)
b. Potential effects: Diarrhea Renal stones ( oxalate) Iron toxicity “Rebound” scurvy
