Vitamin C

Functions of Vitamin C:

• Synthesis of Collagen - important for hyroxylation of lysine and proline in precollagen
• hydroxylation sites are anchors for cross-linking or tropocollagen
  
• Neurotransmitter metabolism - conversion/ hydroxylation of
  
• Dopamine --> norepinephrine
  
• Tryptophan --> serotonin
• Tyrosine --> Homogentisic acid
  
• Aids in fibroblast (connective tissue) and osteoblast (bone) formation and function
  
• Cholesterol metabolism - conversion of cholesterol to steroid hormones and bile acids
• Biosynthesis of Carnitine
• Maintains reduced states of Iron and Copper atoms for use in Cofactors of Metalloenzymes
• Antioxidant (electron donor)
  
• Regenerates Vit E and reduces oxidation of low-density lipoprotein
• Prevents nitrosylation: inhibits amides form combining with nitrites present in food preservatives
• Nitrosamines and nitrosamides are carcinogens implicated in stomach cancer
  
• Redox (oxidation-reduction) reactions
  
• Enhances:
• Non-heme Iron absorption
• Reduces non-heme (+3) iron to ferrous (+2) iron for reabsorption in the duodenum ("2 into the DUOdenum")
  
• Transfer of Iron from transferrin to ferritin
• Formation of tetrahydrofolic acid
  
• Keeps tetrahydrofolate (FH4) in its reduced form
  

Dietary Needs

• Humans cannot make vitamin C, need to get it from dietary sources
• Requirements are increased in infection and diarrheal illness, smoke exposure
  

• Age	Adequate Intake
  0-6mo	40mg
  6-12mo	50mg
  1-3yr	15mg
  4-8yr	25mg
  9-13yr	45mg
  14-18yr	75mg
  Pregnancy	85mg
  Lactation	120mg

Dietary Sources (note: Vitamin C is easily destroyed by prolonged storage, overcooking, and food processing)

• Citrus fruits
• Peppers
• Berries
• Melons
• Guava
• Kiwi
  
• Tomatoes
• Cauliflower
• Green Leafy Vegetables
• Breast milk, Infant formula is supplemented with adequate Vitamin C
• TPN:
• 80mg/day - Term Infants
• 25mg/kg/day - Preterm Infants
  

Physiology

• Absorption of Vitamin C occurs in the upper small intestine - predominantly Ileum
• Saturable, Na-ATP dependent (active process and simple diffusion with large quantities) and is taken up by all tissues with the highest levels found in the pituitary and adrenal glands
  
• Vitamin C is not stored in the body but retains an active pool of 1.2-2g that is used at a rate of 3-5% per day in adults
  

Deficiency

• Scurvy
• Etiology
• Diets deficient in Vitamin C
• Defective formation of Connective Tissues (skin, cartilage, dentine, bone, and blood vessels)
  
• In long bones, osteoid is not deposited by osteoblasts, cortex is thin
• Clinical Features:
• Corkscrew hairs
• Impacted hair follicles
  
• Poor Wound Healing (also seen with Cu deficiency)
  
• Swollen, bleeding gums
  
• Rosary at the costochondral junction and depression at the sternum
• angulation of the scorbutic beads sharper than that of rachitic rosary
• Gum Changes in children with erupted teeth
• bluish purple
• spongy swellings of the mucous membrane esp at upper incisors
• Anemia - due to impaired iron absoprtion, B12, and folate
• Bruising/Bleeding
• Petechiae, purpura, ecchymoses at pressure points (saddle ecchymosis), epistaxis, gum bleeding and characteristic perifollicular hemorrhages
• Hyperkeratosis of hair follicles
• Arthralgia
• Muscle weakness
• Loosened teeth, poor dentition, loss of teeth
  
• Ridges on surface of teeth
  
• Glossitis
• Irritability
• Loss of appetite
• Fever
• MSK pain
• Tenderness in the legs, Gastrocnemius tear
  
• Leg swelling - knees and ankles
• Pseudoparalysis
  

• Dx
  
• Diagnosis is usually clinical - just give them Vit C and see if symptoms resolve
  
• high suspicion in restrictive diet or Autism or other developmental d/o with difficulty walking or with bone pain
  
• Plasma ascorbate concentration of < 0.2 mg/dL indicates deficiency (not typically necessary)
  
• Leukocyte concentration of Vit C <10microgram/10^8 WBCs suggest inadequate body stores
• Urine ascorbic acid saturation test
• Rumpel-Leede Test (tourniquet test for capillary fragility)
  
• in healthy children 80% of a test dose of vitamin C is excreted within 3-5hrs after parenteral administration
• Xray findings:
• Distal ends of long bones particularly at the knees
• ground glass appearance due to trabecular atrophy
• cortex is thin and dense - pencil outlining of diaphysis and epiphysis
• White line of Frankel - thickened white line at metaphysis (well calcified cartilage)
• Trummerfield Zone: a zone of rarefaction under the white line of Frankel is a linear break in the bone that is proximal and parallel to the white line. The zone represents an area of debris of broken down bone trabeculae and connective tissue.
• Pelkan Spur: lateral prolongation of the white line and may be present at cortical ends
• epiphyseal separation can occur along the line of destruction with linear displacement or compression of the epiphysis against the shaft
• Subperiostial homorrhages are not visible on radiography during the active phase of scurvy
• During healing the periosteum becomes calcified and radiopaque
• Bone can appear as a dumbbell or club
• MRI can show acute and healing subperiosteal hematomas, perostitis, metaphyseal changes, and heterogeneous bone marrow signal intensity
  
• DDx
• Arthritis
• Osteomyeltis
• NonAccidental Trauma (NAT)
• Malignancy
• Acrodynia
• Copper Deficiency xrays can look like Vit C deficiency (Scurvy)
• HSP
• TTP
• Leukemia
• Tx
• Vitamin C 100-200mg/day orally (previous text - Tx with 1g daily in adults)
  
• Clinical improvement is seen within 1 week
• Continue treatment for 3 months
• Prevention
• Breastfeeding in infancy
• Ensure Vit C fortified formula, foods in diet
• Antenatal Vit C to smoking mothers may mitigate effects on fetus
• Note: Smoking can also cause Vit C deficiency
• Smoking produces free radical species and Vit C gets used up trying to reduce Vit E which is oxidized when neutralizing these radicals
  
• Alcaptonuria-like syndrome (dark urine and blue/black discoloration of cartilages, whites of eyes, and can develop arthritis when older)
  

Vitamin C - Other Clinic Uses

• Tx for Scurvy
  
• Tx of Methhemoglobinemia
• Treating Wound Healing (Burns, Ulcers)
• Potential Oxytocin action
• High-doses of vitamin C have also been used to treat alkaptonuria because it hinders the accumulation and deposition of homogentisic acid (possibly by funneling homogentisic acid to maleylacetoacetic acid and the TCA cycle)
  

Vitamin C Toxicity

• Daily intake >2g can cause:
• GI upset, abd pain, osmotic diarrhea
• Hemolysis (Rare)
• Avoid excess vitamin C in patients with h/o urolithiasis or conditions related to excessive Iron accumulation (thalassemia or hemochromatosis), patients receiving heparin or warfarin
• Metabolite of Vit C is Oxalic Acid (excess Vit C may cause Calcium oxalate renal stones)
• In animal studies, excess Vit C can damage islet cells of pancreas and lead to Diabetes
  

• Age	Recommended upper limit
  1-3 year	400mg
  4-8 years	650mg
  9-13 years	1200mg
  14-18 years	1800mg

  
  

Structure: