1. Hypervitaminosis

2. Introduction
VITAMIN is an essential substance, needed in tiny amounts to facilitate normal metabolism
Not synthesized in the body….must be ingested in the diet
Not provide energy…..BUT….often act as coenzyme in energy producing reactions
OTC
large potential for misuse and toxicity……beliefs that megadoses of vitamins prevent or ameliorate the effects of aging and cancer
Only rarely is an acute vitamins toxicity reaction reported, most cases involved chronic utilization

3. Introduction
Recommended Daily Allowance (RDA)…..vit deficiency / hypervitaminosis
Megadosing: a dose that is 10 or more times the recommended daily allowance (RDA)

4. Vitamins A, D, E, K Vitamin C Thiamine (B1) Riboflavin(B2) Niacin (B3)
Pyridoxine (B6)    
Cyanocobalamin (B12)             
Folic acid (B9)
Biotin (B7)
Pantothenic acid (B5)

5. Vitamin A….Retinoids Sources: RDA: 3000IU First vitamin recognized
An important fat-soluble vitamin, vitamin A’s basic molecule is a retinol, or vitamin A alcohol.
Sources:
Liver, fish and egg (preformed Vit A)
Dark green and deep colored vegetables (pro-vitamin A / beta-carotene)
RDA: 3000IU

6. TOXICOKINETICS OF VITAMIN A
More than 60,000 instances of vitamin toxicity are reported annually to US poison control centers
fat-soluble vitamins have a higher potential for toxicity than do water-soluble vitamins ( Owing to their ability to accumulate in the body).
Vitamin A is absorbed in the small intestine and esterified within epithelial cell…..
Transported in chylomicrons to the liver……unesterified
50-85% stored in the liver, the rest in fatty tissues
After absorption, retinol is transported via chylomicrons to the liver, where it is either stored as retinol ester or reexported into the plasma in combination with retinol-binding protein for delivery to tissue sites.

7. Effects and Deficiency
Vitamin A crucial to cellular differentiation and integrity of the eye
Deficiency causes xerophthalmia (dryness, fragility and clouding of the cornea)
Also important role in phototransduction, and deficiency causes night blindness
Deficiency also associated with
poor bone growth,
nonspecific dermatological problems (eg, hyperkeratosis), and
impaired immune function

8. VITAMIN A TOXICITY
Acute ingestion 12,000 IU/kg. Chronic ingestion 25,000 IU/d for 2–3 weeks. symptoms: GI
Nausea , vomiting, gingivitis, mouth fissures, wt loss
CNS
Drowsiness, Headache, irritability, increased intracranial pressure, vision changes, dizziness
Skin
Dry, peeling skin, cheilosis, pruritis, alopecia
Muscles and joints
Myalgia, arthralgia
Other:
Hepatic enlargement, ascites, hepatocellular injury, elevated hepatic enzymes, hypercalcemia, bony changes
The 2012 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS) documented the total number of exposures for each class of vitamins, the number of patients with major adverse outcomes, and the number of fatalities from that ingestion,[1] in The figures are as follows:
Adult multiple vitamin tablets with iron but without fluoride single exposures, with 159 minor outcomes, 16 moderate outcomes, one major outcome, and no deaths
Adult multiple vitamin tablets without iron or fluoride single exposures, with 155 minor outcomes, 37 moderate outcomes, three major outcomes, and no deaths
Pediatric multiple vitamin tablets with iron but without fluoride single exposures, with 255 minor outcomes, 9 moderate outcomes, and no major outcomes or deaths
Pediatric multiple vitamin tablets without iron or fluoride - 26,484 single exposures, with 410 minor outcomes, 12 moderate outcomes, and no major outcomes or deaths
Vitamin A single exposures, with 16 minor outcomes, two moderate outcomes, one major outcome, and no deaths
Vitamin B single exposures, with 609 minor outcomes, 117 moderate outcomes, six major outcomes, and no deaths
Vitamin B single exposures, with five minor outcomes, one moderate outcome, and no major outcomes or deaths
Other B complex vitamins single exposures, with 89 minor outcomes, 15 moderate outcomes, no major outcomes, and one death
Vitamin C single exposures, with 63 minor outcomes, two moderate outcomes, one major outcome, and no deaths
Vitamin D single exposures, with 137 minor outcomes, 19 moderate outcomes, and no major outcomes or deaths
Vitamin E single exposures, with 18 minor outcomes, one moderate outcome, and no major outcomes or deaths
Overall, 59,028 single exposures to different types of vitamins (tablet and liquid) were reported to poison control centers across the United States in 2012, accounting for 2100 minor outcomes, 263 moderate outcomes, 12 major outcomes, and one death

9. VITAMIN A TOXICITY Teratogenicity:
The risk of infant malformations in the first trimester approaches 25-30%......”retinoic acid dysmorphic syndrome”:……..
CNS defects, optic atrophy, cleft palate small or absent ears, thymic and congenital heart defects
Morbidity and mortality from pure vitamins are rare. As stated above, the American Association of Poison Control Centers reported 59,028 single exposures to vitamins in 2012, but only one death resulted

10. TREATMENT OF VITAMIN A TOXICITY
Immediate discontinuation, most S&S will disappear within several weeks
If very huge dose was taken……GI decontamination (administration of activated charcoal)
High intracranial pressure treated with mannitol, hyperventilation

11. VITAMIN D: THE SUNSHINE VITAMIN
Preparations: Vit D2 (Ergocalciferol) / Vit D3 (Cholecalciferol)
Produced when the skin 7-dihydrocholesterol is exposed to sunlight
Further converted to calcifediol and then calcitriol
They circulate in plasma bound to a carrier
Excess is stored in fatty tissue

13. VITAMIN D: THE SUNSHINE VITAMIN
Functions:
Development of bones and teeth
Assisting in immunity
Vit D supplementation to treat hypoparathyroidsm, rickets, osteoporosis, defective absorption of Vit D
Also patients receiving phenytoin, phenobarbital (accelerate Vit D metabolism)
RDA of vit D ~400mg/day
Normal range of calcifediol 10-50pg/ml

14. VITAMIN D TOXICITY
Vit D acts to maintain serum calcium and phosphate concentration……increase Ca levels by acting on its absorption, excretion and bone resorption
Manifestations of vit D toxicity are related to the effects of hypercalcemia
Hypervitaminosis D & hypercalcemia in pregnant women may suppress PTH function in the newborn…..leading to hypocalcemia, tetany and seizures

15. VITAMIN D TOXICITY
4-5 times the RDA can cause toxicity (conc. >200pg/ml)
Symptoms
Hypercalcemia…..(polydipsia, polyuria, weakness, fatigue, anorexia, headache)
Altered mental status
GI upset
Renal tubular injury
Occasionally arrhythmias
Calcification of soft tissues (heart and lungs)

16. TREATMENT OF VITAMIN D TOXICITY
Immediate discontinuation
Reducing Ca intake by diet
If cardiotoxicity due hypercalcemia…..fluids and diuretics
Administration of glucocorticoids (prednisolone mg), inhibit Ca absorption from the gut
If Ca levels exceed 14mg/dl….Tx with calcitonin (i.m)

17. VITAMIN C-ASCORBIC ACID
Supplements are available in 100 to 500mg doses and found in high concentrations in green tea
RDA for ascorbic acid is 60mg/day

18. VITAMIN C-TOXICITY
WATER SOLUBLE VITAMIN….WHAT IS NOT UTILIZED WILL BE EXCRETED IN THE URINE…..toxicity is rare
Toxicity is related to the osmotic effects in the intestine…. nausea and diarrhea
Chronic excessive use can produce increased levels of the metabolite oxalic acid
Urinary acidification promotes calcium oxalate crystal formation…… nephroliathiasis and nephropathy

19. CLINICAL MANIFESTATIONS
Toxic doses???.....
Acute IV doses 1.5 g OR chronic ingestion 4 g/d have produced nephropathy
Decrease abs of vit B12
MANAGEMENT:
Abrupt withdrawal not recommended….rebound deficiency (scurvy) following prolonged administration of megadose
So…..gradual withdrawal

20. THIAMINE (Vit B1) “Antiberiberi”…….Vit B1..…Thiamine
Source: rice bran extracts, yeast extracts
RDA of thiamine is 1.5mg/day……..Most exceed RDA in diet
Deficiency results from poor dietary intake or more commonly from excess alcohol intake??!!
Alcohol interfere with gastric absorption of vit B1 and its conversion to the active form

21. THIAMINE (B1)….DEFICIENCY
BERIBERI
Wet Beriberi: CVS abnormalities (cardiomegaly, peripheral edema, tachycardia)
Dry Beriberi: CNS, PNS abnormalities (Wernick- Korsakoff encephalopathy, peripheral motor and sensory deficits)

22. THIAMINE (B1) TOXICITY Pain on injection and contact dermatitis
Anaphylactic reaction after i.v administration
Transient vasodilation
Hypotension……vascular collapse
MANAGEMENT:
Administration of epinephrine and antihistamines
Pressor agent may be necessary in extreme cases

23. NIACIN (B3)
Tryptophan is the precursor of niacin so its malabsorption results in niacin deficiency
RDA 20 mg/day
Used for the Tx of hyperlipidemia
Deficiency cause PELLAGRA……The 3 D’s
Diarrhea
Dermatitis
Dementia

24. NIACIN (B3)
Niacin (nicotinic acid) and its amide form (niacinamide) are converted in the liver and erythrocytes to NAD+ & NADP+ respectively
NAD+ & NADP+ are important as oxidants in several reactions
Excess quantities are metabolized in the liver and excreted in the urine
Niacin levels can be measured by the urinary excretion of the metabolites

25. NIACIN (B3) TOXICITY
Niacin promotes PG release……skin flushing, pruritis, hypotension, tachycardia and GI disturbances….”niacin flush”
Niacin and its metabolites appear to cause hepatotoxicity
Elevated transaminase enzymes and prolonged prothrombin time
Myopathies
Dermatologic abnormalities……acanthosis nigrans
May aggravate asthma and peptic ulcer disease
Acanthosis nigricans is a skin condition characterized by areas of dark, velvety discoloration in body folds and creases.

26. MANAGEMENT Discontinuation of the vitamin
Anaphylaxis may required fluids, aspirin, steroids, and careful CV monitoring
Close monitor of liver functions and supportive therapy

27. PYRIDOXINE (vit B6) FUNCTIONS:
Found in many foods….cereals, legumes, vegetables, liver, meat & eggs
RDA of pyridoxine is 2mg/day
FUNCTIONS:
Coenzyme: lipid and cholesterol metabolism, gluconeogenesis
Synthesis and catabolism of amino acids
Modulation of endocrine functions (competes with steroid at the receptor site)
Synthesis of neurotransmitters
Conversion of tryptophan to niacin

28. Toxicity Pyridoxine antagonize the actions of levodopa TOXICITY
Sensory neuropathies….central and peripheral neuronal degeneration
Progressive numbness and tingling in feet, arms, legs
Ataxia
Photosensitivity
Treatment
Complete, & slow discontinuation

29. COBALAMIN (vit B12)
Primary food sources include meat, liver, fish eggs, & milk
RDA of cobalamin is 2mg/day
Functions
Synthesis of thymidine and DNA…..deficiency result in ineffective hematopoiesis……pernicious anemia
Necessary in myelin synthesis….deficiency result in neurologic damage
Methionine synthesis
Fat and CHO metabolism
Maintenance of sulfhydryl groups in the reduced form

30. VITAMIN B12 Pharmacokinetics: Bound to animal protein
Freed from the polypeptide linkages by gastric acid…
Attaches to intrinsic factor produced by parietal cells
The complex intrinsic factor-vit B12 binds to its receptor in the small intestine
Later, the transport protein….transcobalamin II picks up cobalamin and transport it through the portal vein into the tissues

31. VITAMIN B12 TOXICITY
Vitamin B12 is non toxic unless very huge quantities are ingested
Rare instances of allergic reactions…..pruritis, urticaria, anaphylaxis
Contact dermatitis
Management: discontinuation