B Vitamins

Question 1

Essential B Vitamins

Nomenclature

Answer 1

Thiamine = Vit B₁

Riboflavin = Vit B₂

Niacin = Vit B₃

Pantothenic Acid = Vit B₅

Pyridoxine = Vit B₆

Biotin = Vit B₇

Folic acid = Vit B₉

Cobalamin = Vit B₁₂

Question 2

Thiamine

Characteristics

Answer 2

Vitamin B₁

• Sources:
  
  • Lean pork, whole-grain cereals, legumes, and yeast
  • Chronic ethanol ingestion strongly favors thiamine deficiency
  • Absorbed primarily in the jejunum
• Functions:
  
  • Phosphorylated form ⇒ thiamine pyrophosphate (TPP)
    
    • Cofactor for formation or degradation of 𝛼-ketols by transketolase
    • Cofactor in oxidative decarboxylation of 𝛼-keto acids
      
      • conversion of pyruvate to acetyl-CoA by pyruvate dehydrogenase
  • ​Important for
    
    • carbohydrate catabolism
    • proper heart and brain function
    • structural component of nervous system membranes

Question 3

Beri-beri

Answer 3

Caused by a thiamine (Vit B₁) deficiency.

Two forms: “wet” (edematous) and “dry” (non-edematous).

• Causes:
  
  • Most commonly seen with alcoholic patients
    
    • ​due to interference by alcohol on B vitamin absorption
  • Associated with bariatric surgery when Vit B supplementation inadequate
    
    • absorbed primarily in the jejunum
    • restrictive reconstruction results in mild malabsorptive state
    • B₁ level can be depleted after PO or IV carb intake
    • Sx can occur within 6 months of surgery in adolescent cases
• Considered a medical emergency
  
  • can progress to cardiac failure
  • can result in permanent neurological deficits
• Symptoms include:
  
  • muscle weakness
  • ataxia
  • foot drop
  • ophthalmoplegia
  • nystagmus
  • neuropathy
  • cardiac abnormalities
  • GI manifestations

Question 4

Wernicke-Karsakoff Syndrome

Answer 4

Caused by weak TPP binding.

Becomes manifested if thiamine intake is compromised ⇒ alcoholism, poor diet, malabsorption.

Similar symptoms to beri-beri but also memory problems, disorientation, confabulation, and coma.

Question 5

Niacin

Characteristics

Answer 5

Vitamin B₃

• Substituted pyridine derivatives
  
  • Niacin (nicotinic acid)
  • Niacinamide (nicotinamide)
• Sources:
  
  • Dietary:
    
    • Mostly as physiologically active forms: NAD⁺ or NADP⁺
    • Legumes, cereals, lean meat, poultry, and fish
    • Absorption impeded by alcohol
  • Synthesized from tryptophan
    
    • Requires sufficient dietary tryptophan and pyridoxal (Vit B₆) cofactor
      
      • B₆ deficiency or inadequate tryptophan absorption can result in pellagra-like symptoms

Question 6

Niacin

Physiological Functions

Answer 6

• Pyridine nucleotide functions:
  
  • Essential co-substrates/co-enzymes for most dehydrogenase reactions
  • Substrates for ADP-ribosylation reactions
  • Precursors of cyclic ADP-ribose
    
    • Role in intracellular Ca²⁺ handling
  • Important for:
    
    • cellular repair
    • DNA repair

Question 7

Niacin

Pharmacological Uses

Answer 7

Niacin (but not nicotinamide) used at high doses for treatment of hypercholesterolemia.

High doses of niacin only in excess of 1 g/day causes acute flushing.

Chronic intake at these levels can cause biochemical abnormalities.

Abnormal liver function, hyperglycemia, increased plasma uric acid, vasodilation.

Question 8

Pellagra

Answer 8

Caused by a niacin deficiency.

• Clinical signs are the three Ds:
  
  • Diarrhea
  • Dementia
  • Dermatitis
    
    • ​glossitis
    • angular cheilitis
    • characteristic Casal’s necklace
  • Can result in death if untreated
• Serious disease in Africa, Europe, and Southeastern US
  
  • Diet consisting mainly of corn which is low in niacin and tryptophan

Question 9

Secondary Niacin Deficiency

Answer 9

Pellagra due to frank malnutrition rare in the US.

Pellagra-like symptoms can result from:

1. Bariatric surgery
   
   • can result in vitamin malabsorption
   • ↓ plasma pyridoxine and niacin levels can be seen
   • treat with supplements of pyridoxine, nicotinamide, zinc sulfate, and riboflavin
2. Drug-nutrient interaction
   
   • ​​Ex. isoniazid (commonly prescribed anti-Tb drug)
     
     • mimics niacin deficiency
     • competetively inhibits conversion of nicotinamide acid to NAD⁺ and NADP⁺
     • coenzyme deficiency inhibits repair of cell damage
     • affects tissues of high turnover i.e. skin and GI tract
   • Other agents known to cause pellagra-like sx
     
     • 6-mercaptopurine, 5-fluorouracil, and chloramphenicol
3. Abnormalities of tryptophan metabolism
   
   1. Carcinoid syndrome
   2. Hartnup’s disease

Question 10

Folic Acid

Characteristics

Answer 10

Vitamin B₉

• Sources:
  
  • Derived from leafy green vegetables, legumes, and some fruits
  • Grains fortified with folate
  • Most dietary folate with chain of glutamate residues
• ​​Folate masks a B₁₂ deficiency
  
  • TUL is set at 1 mg/day
• Absorption and transport:
  
  • Involves specific enzyme systems:
  • Dietary folate taken up by a saturable transport system
  • Absorbed mostly in jejunum
  • Reduced and some methylated to 5-methyl-THF before entering blood
• Functions:
  
  • One-carbon donor in many biochemical reactions
  • Tetrahydrofolate (THF) ⇒ reduced coenzyme form of folate
    
    • Role in biosynthesis of purines, TMP, and methionine

Question 11

Folate Pool

Answer 11

Reversion of 5-methyl-THF → THF requires Vit B₁₂.

B₁₂ deficiency “traps” folate in the 5-methyl-THF form preventing re-entry into the folate pool.

Question 12

Folate Deficiency

Answer 12

Common, particularly among the poor.

• Forms of folate required for purine and pyrimidine synthesis & DNA synthesis
• Folate deficiency inhibits synthesis of new cells resulting in:
  
  • macrocytic anemia
    
    • ​hypochromic, macrocytic RBCs on blood smear
    • hypersegmented neutrophils possible
  • villous atrophy
  • depapillation of the tongue
  • increased risk for serious diseases
  • weakness and fatigue
  • palpitations
  • shortness of breath
  • increased neural tube defects in fetuses
    
    • 400 mcg/day supplement recommended for pregnant women
• Hyperhomocysteinemia commonly accompanies folate deficiency
  
  • linked to increased risk of CAD
  • folate supplementation lowers homocysteine levels
    
    • not consistently shown to reduce risk of CAD

Question 13

Inadequate Folate

Time Course

Answer 13

1. Serum folate ↓
2. RBC folate ↓
3. Hypersegmented neutrophils appear
4. Mean Corpuscular Volume (MCV) ↑
   
   • months before anemia is apparent
5. Hb levels ↓

Question 14

Cobalamin

Sources and Absorption

Answer 14

Vitamin B₁₂

• Sources:
  
  • Synthesized by microorganisms
  • Found primarily in animal sources
  • Meats, fish, dairy, eggs
• Absorption: requires gastric acid (to release the vitamin from food) and Intrinsic Factor (IF) secreted by the stomach
  
  1. B₁₂ initially bound to “R-proteins” in acidic conditions of stomach
  2. released by proteases in duodenum
  3. binds to intrinsic factor
  4. very efficiently absorbed (or reabsorbed) in ileum by receptor-mediated process
  5. remaining 1% taken up by diffusion
• If absorption mechanisms are intact, B₁₂ stores can last 10-20 years due to recapture
• If absorption mechanisms damaged, anemia can appear within 3-6 months
• Vegetarians, elderly, and bariatric sx patients at risk for deficiency

Question 15

Cobalamin

Functions

Answer 15

Involved in only two metabolic pathways:

1. Conversion of 5-methyl-THF → THF
   
   • B₁₂ deficiency traps folate in methyl form
   • folate can no longer be used in purine and TMP synthesis
2. Conversion of methylmalonic acid → succinyl CoA
   
   • prolonged B₁₂ deficiency results in neuropathy
     
     • due to inability to catabolize odd # FAs

Question 16

Vit B₁₂ Deficiencies

Answer 16

• Common disorder among older adults and vegetarians
  
  • ~ 5-15% in people > 65 y/o
• Folate can mask a B₁₂ deficiency
• Causes:
  
  • food-cobalamin malabsorption
    
    • achlorhydria
    • atrophic gastritis
    • prolonged PPI use
    • bariatric surgery
  • pernicious anemia
    
    • due to IF deficiency
  • inadequate intake of animal sources
• Symptoms:
  
  • megaloblastic anemia
  • neuropathy
  • cognitive impairment
  • psychopathology
  • elevated levels of methylmalonic acid (MMA) and homocysteine (HCYS)
    
    • Only hyperhomocystemia seen with folate deficiency
• Clinical Course:
  
  • monitoring of Vit B₁₂ concentrations in asymptomatic patients taking PPI for > 4 years
  • immediate screening for Vit B₁₂ deficiency if symptoms manifest
    
    • given irreversible nature of neurologic changes
• Treatment:
  
  • Supplementation with non-protein-bound B₁₂
    
    • ↓ in MMA and HCYS levels after replacement suggestive of food-cobalamin malabsorption
    • R/O renal dysfunction as cause of elevated MMA/HCYS
  • B₁₂ injections may be neccessary
    
    • used for treatment of pernicious anemia

Question 17

Pernicious Anemia

Answer 17

B₁₂ deficiency due to inability of parietal cells to synthesize Intrinsic Factor (IF), resulting in malabsorption.

• Results in similar sx as folate deficiency
  
  • megaloblastic anemia and hyperhomocysteinemia
• Neuropathy due to failure to metabolize odd # FAs
• Usually treated with B₁₂ injections

Question 18

Schillings Test

Answer 18

Used for the assessment of B₁₂ absorption.

Question 19

Pyridoxine

Characteristics

Answer 19

Vitamin B₆

• Widely distributed in foods
  
  • Poultry, fish, pork, liver, kidney
  • Whole grains, carrots, cabbage, peas, potatoes and tomatoes
• Deficiency is rare
• Large doses of B₆ > 500 mg/day can cause irreversible peripheral toxic sensory neuropathy
  
  • Abnormal for a soluble vitamin

Question 20

Pyridoxine

Functions and Deficiencies

Answer 20

• Pyridoxine, pyridoxal, and pyridoxamine are precursors to biologically active coenzyme pyridoxal phosphate (PLP)
• PLP functions:
  
  • Associated with amino acid metabolism
  • Conversion of tryptophan → niacin
    
    • ​Deficiency produces pellagra-like sx
  • Involved in glycogen breakdown
  • Factor in conversion of homocysteine → cysteine
    
    • role in reducing elevated homocysteine

Question 21

Riboflavin

Answer 21

Vitamin B₂

• Widely found in a variety of foods
  
  • Dairy products, yogurt, cheese, meat, eggs, broccoli,asparagus, and whole grain foods.
• Component of enzyme prosthetic groups
  
  • Flavin mononucleotide (FMN)
  • Flavin adenine dinucleotide (FAD)
• FAD and FMN are part of oxidation-reduction enzymes
  
  • NADH dehydrogenase
  • Succinate dehydrogenase
  • Riboflavin-containing enzymes critical to life
• Uncomplicated riboflavin deficiency uncommon
• Deficiency usually seen with multiple vitamin deficiencies
  
  • Has surprisingly mild symptoms
    
    • ​dermatitis, cheliosis (fissures at corners of mouth), and glossitis (smooth and dark appearing tongue)
    • corneal vascularization
    • anemia

Question 22

Biotin

Answer 22

Vitamin B₇

• Widely distributed in foods
• Deficiency is ordinarily not seen
  
  • Egg whites contain avidin which has very strong affinity for biotin
  • Consumption of raw egg whites can lead to biotin deficiency
• Functions as coenzyme in carboxylation reactions
  
  • serves as carrier of activated CO₂
  • binds to specific lysine residues in enzymes
    
    • ex. pyruvate carboxylase

Question 23

Pantothenic Acid

Answer 23

Vitamin B₅

• Sources are common
  
  • eggs, liver, and yeast are major sources
• Deficiency is rare
  
  • cooking may destroy some B₅ in foods
  • deficiency only suspected in recorded cases
  • No RDA established
• Toxicity is rare
  
  • No TUL established
• Functions:
  
  • Pantothenic acid itself is a component of the acyl carrier domain of fatty acid synthase
  • Component of CoA
    
    • Functions in the transfer of acyl groups in numerous reactions