Nutritional Pathology Disorders Fat Soluble And Water Soluble Vitamins Advantages Uses Notes

Nutritional Disorders

Common Vitamine Deficiency:

Vitamins are vital organic substances required in limited amounts with key roles in certain metabolic pathways.

Categories of Common Vitamine:

Thirteen vitamins are necessary for health and are categorized as:

Read And Learn More: Pathology for Dental Students Notes

• Fat-soluble vitamins: These include A, D, E, and K. Fat-soluble vitamins are stored in the body, but their absorption may be poor in fat malabsorption disorders or in disturbances of digestive functions.
• Water-soluble vitamins: All other vitamins (vitamins of the B complex group and vitamin

Sources of Common Vitamine:

• Endogenous: Few vitamins can be synthesized endogenously. Examples include vitamin D from precursor steroids, vitamin K and biotin by the intestinal microflora, and niacin from tryptophan (essential amino acid).
• Exogenous: A dietary supply of all vitamins is essential for health.

Deficiency of Common Vitamine:

A deficiency of vitamins may be:

1. Primary: Defiient intake in the diet.
2. Secondary: Due to disturbances in intestinal absorption, transport in the blood, tissue storage, or metabolic conversion.

Fat-Soluble Vitamins

List vitamin A deficiency states Or Write a short note on the clinical features of vitamin A deficiency

1. Vitamin A (retinol):

Vitamin A (retinol) is part of the family of retinoids which is present in food and the body as esters combined with long-chain fatty acids.

• Vitamin A: It is the name given to a group of related compounds and includes:
  • Retinol (vitamin A alcohol): It is the chemical name given to vitamin A. It is the transport form and, as a retinol ester, also the storage form.
  • Retinal (vitamin A aldehyde)
  • Retinoic acid (vitamin A acid)
• Retinoids: It is the generic term that encompasses vitamin A in its various forms and both natural and synthetic chemicals that are structurally related to vitamin A, but may not necessarily have vitamin A–like biologic activity.

Sources of Vitamin A:

• Animal-derived foods: Pre-formed retinol is found only in foods of animal origin. Th richest food source is liver, but it is also found in fih, milk, eggs, butter, and cheese.
• Yellow and green leafy vegetables: Vitamin A can also be derived from carotenoids (most important is β-carotene) which are provitamins that contribute approximately 30% of the vitamin A in human diets. Beta-carotene is the main carotenoid found in green vegetables, carrots, squash, spinach, and other yellow and red fruits. They can be converted to active vitamin A in the body. Other carotenoids, lycopene, and lutein, are of little quantitative importance.

Functions of Vitamin A:

Vitamin A has several metabolic roles. The main functions of vitamin A in humans are as follows:

• Maintenance of normal vision: It is one of the major functions of vitamin A. The visual process involves vitamin A–containing pigments. Retinaldehyde in its cis form is found in the opsin proteins in the rods (rhodopsin) and cones (iodopsin) of the retina. Light causes retinaldehyde to change to its trans isomer, and this leads to changes in membrane potentials that are transmitted via neurons from the retina to the brain.
  • Rhodopsin: 11-cis retinaldehyde is part of the photoreceptor complex in rods of the retina. It is the most light-sensitive pigment and is important in reduced light.
  • Iodopsins: It is responsive to specific colors in bright light.
• Regulation of cell growth and differentiation: It is one of the major functions of vitamin A. Retinol and retinoic acid are involved in the control of proliferation and differentiation of epithelial cells. Vitamin A and retinoids play an important role in the orderly differentiation of mucus-secreting epithelium. In vitamin A deficiency, mucus-secreting cells are replaced by keratin-producing cells and this process is known as squamous metaplasia.
• Regulation of lipid metabolism: It is a key regulator of fatty acid metabolism, including fatty acid oxidation in fat tissue and muscle, adipogenesis, and lipoprotein metabolism. Retinyl phosphate is a cofactor in the synthesis of most glycoproteins containing mannose.
• Host resistance to infections:

Advantages of vitamin A supplementation:

• Reduces morbidity and mortality in diarrhea: Can reduce morbidity and mortality diarrhea. This may be due to the maintenance and restoration of the integrity of the epithelium of the gut.
• Improves clinical outcome in preschool children with measles.
• Immune function: Vitamin A can stimulate the immune system. Retinoids are needed for normal growth, fetal development, fertility, hematopoiesis, and immune function.
• Antioxidant: Retinoids, β-carotene, and some related carotenoids act as photoprotective and antioxidant agents.
• Signal for appropriate morphogenesis in the developing embryo.

Uses of Vitamin A:

• Skin disorders: Retinoids are used for the treatment of skin disorders (e.g. severe acne and certain forms of psoriasis)
• Treatment of acute promyelocytic leukemia and childhood neuroblastoma.

Deficiency of Vitamin A Causes:

• Due to general undernutrition or as a secondary deficiency as a consequence of malabsorption of fats.
• In children: The stores of vitamin A are depleted by infections, and vitamin A absorption is poor in newborn infants.
• In adults: Malabsorption syndromes, such as celiac disease, Crohn’s disease, and colitis, may cause vitamin A deficiency (in conjunction with deficiency of other fat-soluble vitamins). Bariatric surgery and, in the elderly, continuous use of mineral oil as a laxative may produce vitamin A deficiency.

Pathological Effects (Clinical Features) of Vitamin A Deficiency:

•  Effects on the eye:
  • Night blindness: Vitamin A is a component of rhodopsin and other visual pigments. Hence, one of the earliest manifestations of vitamin A deficiency is impaired vision, particularly impaired adaptation to the dark (night blindness).
  • Xerophthalmia: Vitamin A is necessary for maintaining the differentiation of epithelial cells. Persistent deficiency produces epithelial metaplasia and keratinization. In the eyes, it produces keratinization of the cornea—xerophthalmia (dry eye).
  • Initially, there is dryness of the conjunctiva (xerosis conjunctivae) because of the replacement of the normal lacrimal and mucus-secreting epithelium by a keratinized epithelium.
  • Subsequently, there is a buildup of keratin debris in small opaque plaques that gives rise to characteristic Bitot spots that progress to erosion of the corneal surface, softening and destruction of the cornea (keratomalacia), scarring, and irreversible blindness.
• Effects on other epithelia: The epithelium lining the upper respiratory passage and urinary tract also undergoes squamous metaplasia.
  • Upper respiratory tract: Loss of the mucociliary epithelium of the airways predisposes to secondary pulmonary infections.
  • Urinary tract: Desquamation of keratin debris in the urinary tract predisposes to renal and urinary bladder stones.
  • Skin: Hyperplasia and hyperkeratinization of the epidermis with plugging of the ducts of the adnexal glands may cause follicular or papular dermatosis.
  • Immune deficiency: It is responsible for higher mortality rates from common infections such as measles, pneumonia, and infectious diarrhea.
  • Follicular hyperkeratosis.

Vitamin A Toxicity:

Both short- and long-term excesses of vitamin A may produce toxic effects.

• Acute vitamin A toxicity: It produces symptoms such as nausea, headache, dizziness, vomiting, skin desquamation, stupor, increased intracranial pressure, and blurred vision.
• These symptoms may be confused with those of a brain tumor (pseudotumor cerebri).
• Chronic vitamin A toxicity: It produces weight loss, anorexia, nausea, vomiting, and bone and joint pain. Retinoic acid stimulates osteoclast production and activity, leading to increased bone resorption and high-risk osteoclast production and activity, leading to increased bone resorption and high risk of fractures. Repeated moderate or high doses of retinol can cause liver damage.
• Retinol is teratogenic: Synthetic retinoids should be avoided in pregnancy because of their teratogenic effects.

2. Vitamin D:

Write a short note on vitamin D deficiency Or Write short note on rickets
Or
Write a short note on osteomalacia Or Write a short note on causes of vitamin D deficiency

• Vitamin D is a fat-soluble vitamin.
• It is required for the maintenance of adequate plasma levels of calcium and phosphorus to support metabolic functions, bone mineralization, and neuromuscular transmission.

Physiology of Vitamin D:

Vitamin D exists in 2 activated sterol forms.

1. Vitamin D3 (Cholecalciferol)
   • Produced in skin with direct sunlight, cod liver oil
   • The preferred form of supplementation
2. Vitamin D2 (Ergocalciferol)
   1. Less effective as a precursor to 1,25(OH)2-Vit D.

Sources of Vitamin D:

• Endogenous synthesis: About 80% of the body’s vitamin D is endogenously synthesized in the skin from a precursor, 7-dehydrocholesterol, by the action of solar or artificial UV light in the range of 290 to 315 nm (UVB radiation). This reaction synthesizes cholecalciferol (vitamin D3). However, dark-skinned persons generally have a lower level of vitamin D production because of melanin pigmentation.
• Exogenous source: Dietary sources include deep-sea fish, fish oils, plants, and grains, and their absorption depends on adequate intestinal fat absorption. In plants, vitamin D is present in a precursor form (ergosterol).

Metabolism of Vitamin D:

Main steps of vitamin D metabolism:

• Two sources of vitamin D:
  1. Photochemical synthesis of vitamin D from 7-dehydrocholesterol in the skin and
  2. Absorption of vitamin D from the diet in the gut.
• Binding: Vitamin D derived from both of the above-mentioned sources binds to plasma α1-globulin (D-binding protein or DBP) and is transported to the liver.
• Conversion:
  • In the liver: Vitamin D (D3) is converted into 25-hydroxycholecalciferol (25-OH-D) in the liver, by the action of 25-hydroxylases, including CYP27A1 and other CYPs.
  • In the kidney: 25-OH-D is converted into 1,25-dihydroxy vitamin D, [1α,25(OH)2D3] by the enzyme 1α-hydroxylase in the kidney.

Functions of Vitamin D:

1,25-dihydroxy vitamin D mediates its biologic effects by binding to a member of the nuclear receptor superfamily, the vitamin D receptor (VDR). Vitamin D receptors for 1,25-dihydroxy vitamin D are present in most cells of the body.

1. Regulation of plasma levels of calcium and phosphorus: The main functions of 1,25-dihydroxy vitamin D on calcium and phosphorus homeostasis are:
   • Stimulates intestinal absorption of calcium: 1,25-dihydroxy vitamin D stimulates intestinal absorption of calcium in the duodenum through the interaction of 1,25-dihydroxy vitamin D with the nuclear vitamin D receptor.
   • Stimulates calcium reabsorption in the kidney: 1,25-dihydroxy vitamin D increases calcium influx in distal tubules of the kidney.
   • Interaction with PTH in the regulation of blood calcium:
   • Mineralization of bone: Vitamin D plays a role in the mineralization of osteoid matrix and epiphyseal cartilage in both flt and long bones. Vitamin D stimulates osteoblasts to produce the calcium-binding protein osteocalcin, which is involved in the deposition of calcium during the development of bone.
2. Antiproliferative effects: The VDR is expressed in the parathyroid gland, and 1,25(OH)2D has an antiproliferative effect on parathyroid cells and it suppresses the transcription of the parathyroid hormone gene.
3. Immunomodulatory: Vitamin D is involved in the innate and adaptive immune system.

Deficiency of Vitamin D Causes:

• Impaired cutaneous production due to limited exposure to sunlight
• Dietary absence: Diets deficient in calcium and vitamin D
• Malabsorption.

Milder forms of vitamin D deficiency also called vitamin D insufficiency, lead to an increased risk of bone loss and hip fractures in older adults.

Skeletal Effects of Vitamin D Deficiency:

Rickets in Children: In children, before the closure of epiphyses, vitamin D deficiency causes retardation of growth associated with an expansion of the growth plate known as rickets. In the normal growth plate,

There are three layers of chondrocytes namely:

1. The reserve zone,
2. The proliferating zone, and
3. The hypertrophic zone

Rickets due to impaired vitamin D action is characterized by expansion of the hypertrophic chondrocyte layer. In vitamin D deficiency, hypophosphatemia due to secondary hyperparathyroidism is responsible for the development of the rachitic growth plate.

Gross skeletal changes in rickets: It depends on the severity and duration of the vitamin D deficiency and also the stresses to which individual bones are subjected.

During the nonambulatory stage of infancy:

• Head:
  • Craniotabes: The head and chest are subjected to the greatest stresses. The softened occipital bones become flattened, and the parietal bones buckle inward by pressure; with the release of the pressure, elastic recoil snaps the bones back into their original positions (craniotabes). The skull appears square and box-like. Delayed closure of anterior fontanelle.
  • Frontal bossing: Excess of osteoid produces frontal bossing and a squared appearance to the head.
• Chest:
  • Rachitic rosary: Overgrowth of cartilage or osteoid tissue at the costochondral junction causes deformation of the chest producing the “rachitic rosary.”
  • Pigeon breast/chest deformity: The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles and thus bend inward. This creates anterior protrusion of the sternum producing pigeon breast deformity (pectus carinatum).
  • Harrison’s sulcus/groove: It is due to the indrawing of ribs on inspiration.

During the nonambulatory stage:

• Lumbar lordosis: This occurs when an ambulating child develops rickets. It is characterized by deformities affecting the spine, pelvis, and tibia.
• Bowing of the legs: Due to affection of the tibia.

Osteomalacia in Adults:

• Vitamin D deficiency in adults is accompanied by hypocalcemia and hypophosphatemia which result in impaired (hypo/under/inadequately) mineralization of bone matrix proteins, a condition known as osteomalacia.
• Thus hypomineralized bone matrix is biomechanically inferior (weak) to normal bone.
• This bone is prone to bowing of weight-bearing extremities and gross skeletal fractures or micro-fractures which are most likely to affct vertebral bodies and femoral necks.

Proximal Myopathy: It is observed in both children and in adults with severe vitamin D deficiency. It is rapidly resolved by vitamin D treatment.

Hypocalcemic Tetany: Calcium is required for normal neural excitation and the relaxation of muscles. Hypocalcemic tetany is a convulsive state caused by an insufficient extracellular concentration of ionized calcium.

Non-skeletal Effcts of Vitamin D:

Vitamin D receptors is also present in various cells and tissues that are not involved in calcium and phosphorus homeostasis. Many cells such as macrophages, keratinocytes, and tissues such as the breast, prostate, and colon can produce 1,25-dihydroxy vitamin D.

• Low levels of 1,25-dihydroxy vitamin D (<20 ng/mL) may increase in the incidence of cancers of colon, prostate, and breast cancers, but whether vitamin D supplements can reduce cancer risk is not known.

Vitamin D Toxicity:

Prolonged exposure to normal sunlight does not produce an excess of vitamin D, but oral administration of mega doses of vitamin can lead to hypervitaminosis.

• In children: Hypervitaminosis D may cause metastatic calcification of soft tissues (for example, Kidney).
• In adults: It can cause bone pain and hypercalcemia. Insufficiently large doses of vitamin D are a potent rodenticide.

3. Vitamin C (Ascorbic Acid):

Write a short note on clinical features of vitamin C deficiency Or Write a short note on scurvy

It is a water-soluble vitamin.

Functions of Vitamin C:

• Hydroxylation of procollagen: It is necessary for the formation of collagen from procollagen. It is involved in the hydroxylation of proline and lysine in procollagen to hydroxyproline and hydroxylysine in mature collagen.
• Antioxidant properties: Ascorbic acid is the most active powerful reducing agent controlling the redox potential within cells. Vitamin C can scavenge free radicals directly and can act indirectly by regenerating the antioxidant form of vitamin E.
• It is involved in intracellular electron transfer.
• Promotion of nonheme iron absorption.

Sources of Vitamin C:

• Ascorbic acid is not synthesized endogenously in humans; therefore, we depend entirely on the diet for this vitamin.
• Vitamin C is present in milk and some animal products (liver, fish).
• Vitamin C is present in all fresh fruits and vegetables.
• Unfortunately, ascorbic acid is very easily destroyed by heat (e.g. cooking), increased pH, exposure to copper or alkalis and light.
• It is very easily soluble in water; hence traditional cooking methods reduce or eliminate it.

Deficiency of Vitamin C Causes:

• Ascorbic acid is present in abundance in many foods. Hence, it is rare.
• Rarely, it may occur as a secondary deficiency, particularly among older persons who live
  alone, and chronic alcoholics.
• Occasionally, scurvy occurs in patients undergoing peritoneal dialysis and hemodialysis.
• It may develop in infants who are maintained on formulas of evaporated milk without
  supplementation of vitamin C.

Effects of deficiency Vitamin C:

• Scurvy: It is characterized by:
• Bone disease: More common in growing children. It is characterized by deranged formation of an osteoid matrix.
• Hemorrhages: Marked tendency to bleed into the skin (petechiae, ecchymoses, perifollicular hemorrhages), bleeding into muscles, joints and underneath the peritoneum.
• Delayed wound healing
• Anemia
• Gums: Inflanted and bleeding gums.

Vitamin C Excess:

• High/mega doses (1–2 g daily) of vitamin C probably improve immune function (including prevention/resistance to the common cold). However, slight relief of cold is probably due to the mild antihistamine action of vitamin C.
• Vitamin C supplements may prevent atherosclerosis and cancer.

4. Vitamin E:

Vitamin E is a collective name for 8 stereoisomers of tocopherols and tocotrienols. The most important dietary form is α-tocopherol.

Functions of Vitamin E:

• Antioxidant: It prevents oxidation of low-density lipoproteins (LDLs) and polyunsaturated fatty acids in cell membranes by free radicals. Other antioxidants (for example, Vitamin C, glutathione) and enzymes maintain vitamin E in a reduced state. Acts in conjunction with other antioxidants such as selenium.
• It helps maintain cell membrane structure.
• It affects DNA synthesis and cell signaling.
• Anti-inflammatory: Vitamin E also inhibits prostaglandin synthesis and the activities of protein kinase C and phospholipase A2.
• Immune systems

Sources of Vitamin E:

• Vitamin E is high in sunflower oil, safflower oil, and wheat germ oil; γ-tocotrienols are notably present in soybean and corn oils.
• Vitamin E is also present in meats, nuts, and cereal grains, and small amounts are present in fruits and vegetables.

Deficiency of Vitamin E:

• Dietary deficiency of vitamin E is very rare.
• Vitamin E deficiency is seen in only in premature infants and in severe and prolonged malabsorption diseases, such as celiac disease, or after small-intestinal resection.
• It can cause mild hemolytic anemias, ataxia, and visual scotomas.

5. Vitamin K:

Forms of vitamin K:

There are two natural forms: vitamin K1 (phylloquinone) derived from vegetables (green leafy vegetables such as kale and spinach) and animal sources (liver), and vitamin K2 (menaquinone) which is synthesized by bacterial flora in the colon and in hepatic tissue. Phylloquinone can be converted to menaquinone in some organs.

Functions of Vitamin K:

• Coagulation: Vitamin K is a co-factor for carboxylation of glutamic acid which is necessary for the production of carboxyglutamate (gla). Gla residues are found in four of the coagulation factor proteins (II, VII, IX, and X). This it is involved in the coagulation process.
• Others: Other important gla proteins include osteocalcin (in bone) and matrix gla protein (vascular smooth muscle) which are important in the mineralization of bone. However, the importance of vitamin K for the mineralization of bone and the prevention of vascular calcification is unknown.

Deficiency Vitamin K Causes:

In adults:

• Chronic small-intestinal disease: For example, Celiac disease, Crohn’s disease
• Obstruction of biliary tracts: In obstructive jaundice, dietary vitamin K is not absorbed and it is necessary to administer the vitamin in parenteral form before surgery.
• After small-bowel resection.
• Broad-spectrum antibiotics: They can precipitate vitamin K deficiency by reducing gut bacteria, which synthesize menaquinones, and by inhibiting the metabolism of vitamin K.
• Warfarin and related anticoagulants: Warfarin-type drugs prevent the conversion of vitamin K to its active hydroquinone form.

Deficiency in newborns: It is because of

• Low-fat stores
• Low breast milk levels of vitamin K
• Sterility of the infantile intestinal tract
• Liver immaturity, and Poor placental transport.

Effects of Deficiency Vitamin K:

• Vitamin K deficiency leads to delayed coagulation and bleeding. Hence, the symptoms of vitamin K deficiency are due to hemorrhage.
• Newborn: In breast-fed newborns it may cause hemorrhagic disease of the newborn. Intracranial, gastrointestinal, and skin bleeding, can occur in vitamin K–deficient infants 1–7 days after birth. Thus, vitamin K (1 mg IM) is given routinely to newborn babies to prevent hemorrhagic disease.

Water-soluble Vitamins-Vitamin B Complex

Thiamine (Vitamin B₁ ):

Thamine was the first B complex vitamin identified and is referred to as vitamin B1.

Functions of Vitamin B₁ :

• Thiamine functions as a coenzyme in manyα-ketoacid decarboxylation and transmetalation reactions.
• Inadequate thiamin results in inadequate adenosine triphosphate synthesis and abnormal carbohydrate metabolism, respectively.
• May have an additional role in neuronal conduction.

Sources of Vitamin B₁ :

• Yeast, organ meat, pork, legumes, beef, whole grains, and nuts.
• Milled rice and grains contain little or no thiamine. Thus, thiamine deficiency is more common in individuals who rely heavily on a rice-based diet.
• Tea, coffee (regular and decaffeinated), raw fish, and shellfish contain the enzyme thiaminases, which can destroy thiamine.
• Thus, drinking large amounts of tea or coffee lowers thiamine body stores.

Deficiency of Vitamin B₁ Causes:

• Most dietary deficiency of thiamine is due to poor dietary intake.
• Alcoholism, chronic renal dialysis, and chronic illnesses such as cancer are common precipitant factors.
• High carbohydrate intake increases the need for B1. Alcohol interferes with the absorption of thiamine and with the synthesis of thiamine pyrophosphate.
• Women with prolonged hyperemesis gravidarum. Maternal thiamine deficiency can lead to infantile beriberi in breast-fed children
• Anorexia
• Patients:
  • With overall poor nutritional status on parenteral glucose
  • After bariatric bypass surgery
  • On chronic diuretic therapy due to increased urinary thiamine losses.

Effects of Deficiency Vitamin B₁ :

• Mild deficiency: Thiamine deficiency in its early stage is characterized by irritability, decrease in short-term memory, anorexia, fatigue, and headaches.
• More severe deficiency-beriberi: Prolonged thiamine deficiency causes beriberi. It is classically categorized as wet or dry or a combination of two. It is the classic deficiency syndrome observed in individuals consuming a polished rice diet. It shows combinations of peripheral neuropathy, cardiovascular dysfunction, and cerebral dysfunction.
  • Peripheral neuropathy:
    • Complaint of pain and paresthesia associated with diminished reflexes.
    • The neuropathy affects the legs most markedly, and these patients have difficulty rising from a squatting position.
  • Cardiovascular dysfunction (“wet beriberi”): Congestive heart failure and low peripheral vascular resistance.
• Cerebrovascular dysfunction:
  • Wernicke’s encephalopathy: Acute appearance of nystagmus, ophthalmoplegia, ataxia, and psychotic symptoms.
  • The acute symptoms are reversible when treated with thiamine. However, if untreated, they may be followed by a prolonged and largely irreversible condition, called Korsakof syndrome.
  • Korsakof syndrome: Characterized clinically by hallucinations, disturbances of short-term memory, and confabulation. The syndrome is common in chronic alcoholics but may also be seen with thiamine deficiency resulting from gastric disorders, including carcinoma, chronic gastritis, or persistent vomiting.
• Wet beriberi presents primarily with cardiovascular symptoms.
• Dry beriberi presents with a symmetric peripheral neuropathy of the motor and sensory systems with diminished reflexes.

2. Riboflavin Vitamin B₂:

• It is important for the metabolism of fat, carbohydrate, and protein. It also plays a role in drug and steroid metabolism, including detoxification reactions.
• Serves as a coenzyme for a diverse array of biochemical reactions and as an electron donor.
• The primary enzymatic forms of riboflavin are flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) and are known as flavoenzymes (for example, succinic acid dehydrogenase, monoamine oxidase, glutathione reductase).

Sources  of Vitamin B₂:

• Important dietary sources of riboflavin include milk, other dairy products, and enriched breads and cereals.
• Other sources: Lean meat, fish, eggs, broccoli, and legumes.
• Riboflavin is extremely sensitive to light.

Deficiency of Vitamin B₂ Causes:

Almost always is due to dietary deficiency and is usually seen in conjunction with deficiencies of other B vitamins.

Effects of Deficiency Vitamin B₂:

• Nonspecific and mainly manifests as lesions of the mucocutaneous surfaces of the mouth and skin.
• These include hyperemia and edema of nasopharyngeal mucosa, cheilosis, angular stomatitis, glossitis, and seborrheic dermatitis.
• Other lesions include corneal vascularization, normochromic-normocytic anemia, and personality changes.

3. Niacin (Vitamin B₃):

• The term niacin refers to nicotinic acid and the corresponding amide, nicotinamide, and their biologically active derivatives.
• Nicotinic acid and nicotinamide serve as precursors of two coenzymes, nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), which are important in numerous oxidation and reduction reactions.
• NAD and NADP are active in adenine diphosphate–ribose transfer reactions involved in DNA repair and calcium mobilization.

Sources of  Vitamin B₃:

Nicotinic acid and nicotinamide are absorbed from the stomach and small intestine. Sources of niacin include beans, milk, meat, and eggs. The essential amino acid tryptophan is a precursor of niacin.

Defiiency of  Vitamin B₃: Pellagra:

• Niacin deficiency causes pellagra: It is found mostly in populations in which corn is the major source of energy in parts of China, Africa, and India.
• Early symptoms: Loss of appetite, generalized weakness, irritability, abdominal pain,
  and vomiting.
• Early signs: Bright red glossitis, stomatitis, vaginitis, esophagitis, vertigo, and burning dysesthesias
• Advanced stages: Characteristic skin rash develops that is pigmented and scaling that develops in skin areas exposed to sunlight. This rash is known as Casal’s necklace because it forms a ring around the neck.
• Four Ds: Diarrhea (in part due to proctitis and in part due to malabsorption), depression, seizures, and dementia (or associated symptoms of anxiety or insomnia) leading to death and dermatitis, are part of the pellagra syndrome.

4. Pyridoxine (Vitamin B₆):

• Vitamin B₆ refers to several derivatives of pyridine that including pyridoxine (PN), pyridoxal (PL), and pyridoxamine (PM), which are interconvertible in the body. Th enzymatic forms are pyridoxal-5-phosphate (PLP) and pyridoxamine-5-phosphate (PMP). 5’-Pyridoxal phosphate (PLP) is a cofactor for more than 100 enzymes involved in amino acid metabolism.
• Vitamin B 6 is also involved in the synthesis of heme and many neurotransmitters and in the metabolism of glycogen, lipids, steroids, sphingoid bases, and several vitamins, including the synthesis of niacin from tryptophan.

Sources of Vitamin B₆:

• Plants contain vitamin B₆ in the form of pyridoxine.
• Animal tissues contain PLP and pyridoxamine phosphate.
• Rich food sources: Legumes, nuts, wheat bran, and meat.

Deficiency of Vitamin B₆:

• Deficiency is usually seen in conjunction with other water-soluble vitamin deficiencies.
• Certain medications, such as isoniazid, cycloserine, penicillamine, l-dopa, ethanol, and theophylline can inhibit B₆ metabolism. Pyridoxine should be given concurrently with isoniazid to avoid neuropathy. Because vitamin B6 interferes with the action of l-dopa, it should not be given with this drug.

Effects of Deficiency Vitamin B₆:

• Stomatitis, angular cheilosis, glossitis, irritability, depression, and confusion occur in moderate to severe depletion
• Microcytic hypochromic anemia is due to diminished hemoglobin synthesis, since the first enzyme involved in heme biosynthesis. It may also produce normochromic-normocytic anemia.
• In infants: Diarrhea, seizures/convulsions, and anemia.
• Severe vitamin B 6 Deficiency: Peripheral neuropathy and abnormal electroencephalograms.

5. Vitamin B₁₂:

A group of closely related cobalamine compounds.

Sources of VitaminB₁₂:

• Microorganisms are the ultimate source of all naturally occurring vitamin B₁₂.
• Human beings are dependent on animal products in the diet for vitamin B₁₂ requirements. Vitamin B₁₂ is not present in food from vegetable sources.
• Therefore, strict vegetarians do not get an adequate quantity of vitamin B₁₂.
• A balanced diet (not rigid vegetarian!) contains significantly large amounts of vitamin B₁₂ which accumulates in the body (liver) and is enough for several years.
• Due to this adequate storage, if there is any dietary deficiency or malabsorption of vitamin B₁₂, its clinical manifestations appear only after about 2 to 4 years.
• Vitamin B₁₂ is a complex compound known as cobalamin.

Functions of VitaminB₁₂:

• Vitamin B₁₂ is indirectly required for DNA synthesis in various metabolic steps and its deficiency impairs DNA synthesis. The two active coenzyme forms are deoxy adenosylcobalamin and methylcobalamin.
• Methylcobalamin is the main form of vitamin B₁₂ in plasma and is an essential coenzyme for the conversion of homocysteine to methionine and the formation of tetrahydrofolate (THF) from methyl THF.

Vitamin B₁₂: is also required for the conversion of methyl malonyl CoA to succinyl malonyl CoA.

Deficiency of  Vitamin B₁₂ Causes:

• Dietary inadequacy is a rare cause of deficiency except in strict vegetarians.
• Mostly due to loss of intestinal absorption. These include pernicious anemia, pancreatic insufficiency, atrophic gastritis, small bowel bacterial overgrowth, or ileal disease.

Effects of Deficiency Vitamin B₁₂:

• Hematological changes: Megaloblastic anemia and megaloblastic changes in other epithelia.
• Neurologic complications: Demyelination of peripheral nerves, posterior and lateral columns of the spinal cord, and nerves within the brain. Altered mentation, depression, and psychoses occur.

6. Folic Acid:

• Folates are a group of related pterin compounds.
• The fully oxidized form is called folic acid, which is not found in nature but is the pharmacologic form of the vitamin.

Source Folic Acid:

• Entirely dependent on dietary sources. Green vegetables, yeast, legumes, fruits, and animal proteins are the richest sources and most normal diets contain sufficient amounts of folic acid.
• The folic acid in these foods is largely in the form of polyglutamate. Polyglutamates are sensitive to heat (thermolabile); boiling, steaming or frying, and cooking destroy most of the folic acid.

Functions of  Folic Acid:

• All folate functions relate to its ability to transfer one-carbon groups.
• The active form of folic acid is tetrahydrofolate [THF] which is the biological “middleman” involved in metabolic processes which synthesize DNA.

Deficiency of  Folic Acid Causes: Given in the table

Effects of Deficiency  Folic Acid

• Megaloblastic anemia, diarrhea.
• Vitamins and their principal clinical manifestations are summarized in Table.

Vitamins and their principal clinical manifestations: