Vitamins and Minerals | Medical Science Optional Notes for UPSC PDF Download

Minerals

Undertake essential functions within the body and are indispensable for the very survival of the organism.

Chromium

• In the human body, there is approximately 6 mg of chromium per 35 kg, and the chromium content in the blood is around 20 mg/dl.
• Glucose Tolerance Factor (GTF) is naturally synthesized in the body from absorbed dietary chromium. It functions as a physiological enhancer of insulin activity by binding to insulin and augmenting its action approximately threefold. Chromium is a constituent of a protein called chromodulin, which facilitates the binding of insulin to cell surface receptors.
• A comprehensive examination of the numerous physiological actions of insulin suggests various therapeutic applications for GTF. These applications span diverse conditions such as diabetes mellitus, hyperlipidemia, reactive hypoglycemia, obesity, cancer, protein malnutrition or malabsorption, endogenous depression, Parkinsonism, hypertension, and cardiac arrhythmias.
• Chromium's Biochemical Functions
  a. It reduces serum cholesterol levels.
  b. It elevates HDL and reduces LDL.
  c. It facilitates the transport of amino acids into cells, particularly in the heart and liver.
• Chromium Sources - Brewer's yeast, grains, cereals, cheese, and meat.
• Recommended Dietary Allowance (RDA) - Not determined.
• Deficiency Consequences - Impaired glucose tolerance, compromised lipid and protein metabolisms.
• Toxicity Effects - Renal failure, dermatitis, pulmonary cancer.

Selenium

• This micro mineral is indispensable, possessing antioxidant properties akin to vitamin E.
• Abundant dietary sources of selenium encompass seafood, muscle meat, and cereals.
• The Recommended Dietary Allowance (RDA) is 50-200 mg.

Biochemical Functions:

• Averts both muscular dystrophy and muscle dystrophy.
• Selenium, in the form of selenocysteine, is a constituent of the enzyme glutathione peroxidase, safeguarding proteins, cell membranes, lipids, and nucleic acids from oxidative molecules.
• Shields cells from free radicals, thereby preventing lipid peroxidation.
• The selenium-containing enzyme 5-deiodinase converts thyroxine to triiodothyronine.

Deficiency

• Muscular dystrophy
• Parrcreatic fibrosis
• Keshpn disease (endemic cardiomyopathy) 
• Increased risk of cardiovascular disease

Toxicity

• Selenosis-Weight loss, emotional disturbances, diarrhea, hair loss and garlic odor (dimethyl selenide) in breath.

Keshan disease, a prevalent cardiomyopathy, affects children and young women in certain areas of China characterized by low dietary selenium intake (<20 μg/d), attributed to selenium-deficient soil. The absence of selenium leads to the dominance of a virulent strain of the Coxasackie virus, resulting in the manifestation of Keshan disease.

Presentation-Heart failure and pulmonary edema
Selenium supplementation is the prescribed treatment for Keshan disease.

Zinc

•  Intracellular Element
• Recommended Dietary Allowance (RDA): 10-15 mg
• Sources: Meat, fish, eggs, milk, beans, and nuts.

Biochemical Functions:

• Constituent of several enzymes (carbonic anhydrase, alcohol dehydrogenase, alkaline phosphatase, superoxide dismutase).
• Zinc is crucial for the storage and secretion of insulin from the beta cells of the pancreas.
• Aids in wound healing.
• Facilitates cell growth and division.
• Essential for proper reproduction.
• Plays a vital role in taste sensation (GUSTEN - zinc-containing protein).

Deficiency:

• Growth retardation.
• Poor wound healing.
• Anemia.
• Loss of appetite.
• Loss of taste sensation.
• Impaired spermatogenesis.
• Depression, dementia.

Zinc Toxicity:
Nausea, gastric ulcer, pancreatitis, anemia, and excessive salivation.

Acrodermatitis enteropathica

Acrodermatitis enteropathica is a rare autosomal recessive disorder marked by abnormalities in zinc absorption.
Clinical presentations encompass:

• Diarrhea
• Alopecia
• Muscle wasting
• Depression
• Irritability
• A rash affecting the extremities, face, and perineum.

The rash is identified by vesicular and pustular crusting, accompanied by scaling and erythema.

Fluorine

Mostly found in bones and teeth.
Drinking water is the main source. An intake of less than 2 ppm of fluoride will meet the daily requirements.

Biochemical Functions:

• Guards against the development of dental caries.
• Facilitates proper bone development.
• Inhibits Enolase - Sodium fluoride (Glycolysis).
• Inhibits Aconitase - Fluoroacetate (citric acid cycle).

The high-energy compound phosphoenolpyruvate is produced from 2-phosphoglycerate by the enzyme enolase. This enzyme relies on Mg or Mn and is impeded by fluoride. In laboratory blood glucose estimation, fluoride is added to prevent glycolysis by cells, ensuring accurate measurement of blood glucose.

Dental Fluorosis:

• • Excessive intake exceeding 2 ppm.
• • Manifests as enamel mottling and discoloration of teeth.

Skeletal Fluorosis:

• Excessive intake surpassing 20 ppm.
• Results in hypercalcification, elevating the bone density in limbs, pelvis, and spine.
  • Genu valgum.
• Accompanied by neurological disturbances.

Metabolism of Iron

Metabolism of Calcium

Vitamins

Vitamins can be defined as organic compounds necessary in the diet in small quantities to fulfill specific biological functions, contributing to the normal maintenance of optimal growth and overall health in organisms. There are approximately 15 essential vitamins for humans.

Fat-soluble vitamins include A, D, E, and K. Their absorption and transport are linked to fat, and they can be stored in the liver and adipose tissues. These vitamins are not readily excreted in urine, and excessive consumption can lead to their accumulation and toxic effects.

Water-soluble vitamins consist of the B group and vitamin C. They are easily excreted in urine and pose no toxicity risk to the body. Unlike fat-soluble vitamins, water-soluble ones are not stored in the body in large amounts, with the exception of vitamin B12.

Vitamers refer to chemically similar substances possessing qualitatively similar vitamin activity. Examples include retinol, retinal, and retinoic acid, which are vitamers of vitamin A.

Scurvy

Adequate dietary sources of vitamin C can be found in citrus fruits, green vegetables (particularly broccoli), tomatoes, and potatoes. The absence of ascorbic acid (vitamin C) leads to scurvy.

Conditions Associated with Vitamin C Deficiency:

• Inadequate nutrition
• Elderly individuals
• Alcoholics
• Imbalanced diet
• Smoking, hemodialysis, pregnancy, and stress (e.g., infection, trauma) seem to elevate vitamin C requirements.

Clinical Features:
Scurvy is characterized by spongy and tender gums, loose teeth, anemia, swollen joints, fragile blood vessels, decreased immunocompetence, delayed wound healing, periosteal and perifollicular hemorrhages, and osteoporosis.

Role of Vitamin C in Collagen Synthesis:
Proline and hydroxyproline are crucial in maintaining the stability of collagen by facilitating helix twisting. In higher organisms like humans, the hydroxylation of proline is a vital biochemical process for preserving connective tissue integrity.

For a substantial increase in its conformational stability, the synthesis of hydroxyproline, a crucial cofactor in collagen, necessitates the enzyme prolyl hydroxylase. Ascorbic acid plays a vital role in facilitating this biochemical process.

Role of Vitamin C in cholesterol metabolism
Ascorbic acid plays a regulatory role in cholesterol metabolism through various mechanisms. A deficiency in dietary vitamin C indirectly associates with reduced cholesterol absorption, a consequence of diminished availability of bile acids, monoglycerides, and fatty acids. Vitamin C deficiency also leads to a decrease in cholesterol synthesis due to a reduction in the activity of the microsomal enzyme cholesterol 7 alpha-hydroxylase.

Role of Vitamin B3 in cholesterol metabolism
Niacin, or nicotinic acid, administered in higher doses, contributes to the reduction of plasma lipids. This effect is achieved by niacin's inhibition of triglyceride synthesis, leading to a decrease in very-low-density lipoprotein (VLDL) production in the liver. Niacin also hampers intracellular lipolysis in adipose tissue while enhancing the activity of lipoprotein lipase, facilitating triglyceride clearance. It stands out as the most effective drug for elevating high-density lipoprotein cholesterol (HDL-CH) by reducing the rate of HDL destruction. A notable side effect is dose-limiting flushing, accompanied by heat and itching, attributed to its cutaneous vasodilator properties.

Nutritional Anemias

Anemia is characterized by a lower concentration of hemoglobin (typically 14-16 mg/dl) and a diminished ability to transport oxygen.

Nutritional anemias are categorized based on the size of erythrocytes:

• Microcytic anemia is the most common, characterized by reduced RBC size. It occurs due to deficiencies in iron, copper, and pyridoxine.
• Macrocytic anemia involves large and immature RBCs, primarily caused by deficiencies in folic acid and vitamin B12.
• Normocytic anemia features normal-sized RBCs, but their quantity in the blood is low. This type is commonly associated with protein-energy malnutrition.

Vitamin deficiencies in alcoholics

Thiamine Riboflavin Niacin Pyridoxine Folic acid Vitamin C Vitamin A

While insufficient dietary intake remains a primary contributor to vitamin deficiency, various other mechanisms may also play a role. Alcoholism, for instance, can impact the absorption, storage, metabolism, and activation of many vitamins.

Folic acid

• Essential for one-carbon metabolism
• Required for the synthesis of amino acids, purines, and pyrimidines, including thymine
• Active form is THF (transformed by the enzyme dihydrofolate reductase)
• Recommended Dietary Allowance (RDA): 200 micrograms, 300 micrograms (lactation), 400 micrograms (pregnancy)
• Dietary sources: Green leafy vegetables, whole grains, cereals, liver, kidney, yeast, and eggs.
• Biochemical functions:
  a. Production of purines and pyrimidines
  b. Synthesis of glycine, serine, ethanolamine, and choline
  c. Formation of N-formylmethionine, the initiator of protein biosynthesis

Deficiency (Most Common Vitamin Deficiency):

• Commonly observed in pregnant women, lactating women, women on oral contraceptive pills, alcoholics, and individuals using anticonvulsant drugs (Phenobarbitone, dilantin, phenytoin)
•  Results in megaloblastic anemia/macrocytic anemia
•  Associated with neural tube defects

Vitamin B12

• Known as the anti-pernicious anemia vitamin
• Contains a corrin ring with a central cobalt atom
• Two coenzymes: 5-deoxyadenosylcobalamin and methylcobalamin
• RDA: 3 micrograms (4 micrograms in pregnancy and lactation)
• Dietary sources: Liver, kidney, milk, curd, eggs, fish, pork, and chicken (not found in plant foods)
• Biochemical functions:
  • Synthesis of methionine from homocysteine
  • Isomerization of methylmalonyl coA to succinyl coA

Deficiency:

• Causes pernicious anemia, megaloblastic anemia, and macrocytic anemia due to:
  a. Autoimmune destruction of gastric parietal cells
  b. Hereditary malabsorption of vitamin B12
  c. Partial or total gastrectomy
  d. Dietary deficiency (strict vegans)

As a result of the demyelination of the nervous system and neuronal degeneration, symptoms such as paresthesia, confusion, memory loss, and even psychosis may occur.

Walds visual cycle

Wald's visual cycle, also known as visual phototransduction, is the process through which light is converted into electrical signals in the retina of the eye. This mechanism involves G-protein coupled receptors called opsins that contain 11-cis retinal.

Summary

Upon exposure to a photon, 11-cis retinal undergoes photoisomerization, transforming into all-trans retinal. This alteration in the opsin GPCR conformation initiates signal transduction cascades, leading to the closure of cyclic GMP-gated cation channels and hyperpolarization of the photoreceptor cell. After isomerization and detachment from the opsin protein, all-trans retinal is reduced to all-trans retinol and returns to the retinal pigment epithelium for "recharging."

Vitamin D resistant rickets

Also known as X-linked hypophosphatemic rickets, it is inherited in an X-linked dominant manner.

Pathogenesis

• Caused by a mutation in the PHEX gene sequence located on the human X chromosome, X-linked hypophosphatemic rickets is characterized by an inherited X-linked dominant manner.
• The PHEX gene encodes the PHEX protein, responsible for regulating the activity of FGF-23 (fibroblast growth factor-23).
• Fibroblast growth factor 23 typically inhibits the kidneys' reabsorption of phosphate into the bloodstream.
• Mutations in the PHEX gene disrupt its ability to regulate fibroblast growth factor 23 effectively.
• This dysregulation leads to increased FGF-23 activity, resulting in reduced vitamin D la-hydroxylation and decreased phosphate reabsorption by the kidneys, ultimately causing hypophosphatemia and rickets (notably different from other forms of rickets, as vitamin D ingestion is relatively ineffective).

Presentation
Symptoms include bone pain, skeletal abnormalities (such as bow legs and knock knees), and dental abnormalities.

Antioxidant vitamins

Free radicals are atoms or groups of atoms that possess an odd (unpaired) number of electrons, forming when oxygen interacts with specific molecules. Antioxidants are molecules capable of safely interacting with free radicals, thereby interrupting the chain reaction and preventing damage to essential molecules.

The primary micronutrient (vitamin) antioxidants include vitamin E, beta-carotene (a precursor of vitamin A), and vitamin C.

Sulfur containing vitamins

• Thiamine (TPP) 
• Biotin 
• Lipoic acid

Lipoic acid

A vitamin-like compound with sulfur-containing fatty acids, it is soluble in both fat and water. It participates in carboxylation reactions alongside thiamine, niacin, and riboflavin, facilitating the conversion of pyruvate to acetyl co A. With its antioxidant properties, it diminishes free radicals, particularly in the brain where it may play a role in conditions like Alzheimer's disease and multiple sclerosis. Additionally, it promotes the production of glutathione, aids in the recycling of vitamins E and C, and reduces insulin resistance while lowering LDL levels.

Thiamine

Thiamine, also known as the anti-beriberi or antineuritic vitamin, acts as a coenzyme in the form of TPP (thiamine pyrophosphate) and is closely associated with carbohydrate metabolism. The recommended daily allowance (RDA) for thiamine is 1-1.5 mg/day (increased to 2 mg/day during pregnancy and lactation). Dietary sources include cereals, pulses, oilseeds, nuts, and yeasts, although the polishing of rice removes approximately 80% of thiamine.

One of its key biochemical functions is supporting the conversion of pyruvate to acetyl Co-A through the enzyme pyruvate dehydrogenase.

Biochemical functions of thiamine include:

• Facilitating the activity of pyruvate dehydrogenase, involved in the conversion of pyruvate to acetyl Co-A.
• Supporting alpha-ketoglutarate dehydrogenase.
• Aiding in the function of transketolase.
• Playing a role in the transmission of nerve impulses.

Deficiency symptoms of BeriBeri include:

• Wet Beri-Beri: Characterized by edema of legs, face, trunk, and serous cavities, along with shortness of breath, palpitations, and potential death due to cardiac failure (High output cardiac failure).
• Dry Beri-Beri: Manifests with neurological symptoms, such as progressive muscle weakness and difficulty in walking.
• Infantile Beri-Beri: Occurs in infants born to mothers with thiamine deficiency, leading to low thiamine content in breast milk. Symptoms include sleeplessness, restlessness, vomiting, convulsions, and bouts of screaming resembling abdominal colic.
• Wernicke-Korsakoff Syndrome: Typically seen in chronic alcoholics, Wernicke encephalopathy presents with ophthalmoplegia, ataxia, and global confusion. Korsakoff syndrome is characterized by severe amnesia (both retrograde and anterograde) and confabulation.

Biotin

Biotin, formerly known as the anti-egg white injury factor, vitamin B7, or vitamin H, is a sulfur-containing B-complex vitamin.

Dietary Sources: X
RDA: 100-300 mg

Biochemical Functions:

• Serves as a carrier of CO₂ in carboxylation reactions.
• Involved in gluconeogenesis, the citric acid cycle, and fatty acid synthesis.

Causes of Deficiency: 
(a) Destruction of intestinal flora due to prolonged use of drugs such as sulfonamides.
(b) High consumption of raw eggs containing a glycoprotein, avidin. (Avidin tightly binds with biotin and blocks its absorption from the intestine.) Occasional consumption of raw eggs will not result in deficiency. An intake of about 20 raw eggs per day is needed to produce biotin deficiency symptoms in humans.

Manifestations of Deficiency:

• Anemia
• Loss of appetite
• Nausea
• Dermatitis
• Glossitis
• Depression
• Hallucinations
• Muscle pain

Pyridoxine (B6)

•  B6 vitamers include pyridoxine, pyridoxal, and pyridoxamine.
• The active form of vitamin B6 is the coenzyme pyridoxal phosphate (PLP).
• RDA: 2-2.2 mg/day (adult), 2.5 mg/day (pregnancy, lactation, and old age).
• Dietary sources: egg yolk, fish, milk, meat, wheat, corn, cabbage, roots, and tubers.

Biochemical functions:
PLP (pyridoxal phosphate) is involved in the metabolism of amino acids, participating in the following reactions: transamination, decarboxylation, deamination, transsulfuration, and condensation. It plays a crucial role in the synthesis of serotonin, histamine, niacin coenzymes, dopamine, epinephrine, and norepinephrine.

Deficiency symptoms:
Deficiency is rare and is typically observed in women taking oral contraceptives, alcoholics, and infants. Neurological manifestations include depression, irritability, nervousness, mental confusion, convulsions, and peripheral neuropathy. There is also a reduction in heme production, leading to microcytic hypochromic anemia. Additionally, there may be an associated deficiency of vitamin C due to impaired synthesis of niacin coenzymes (NAD+ and NADP+) from tryptophan.

Drug-induced effects:
Certain drugs, such as isoniazid (an anti-TB drug), combine with pyridoxal phosphate to form inactive hydrazone derivatives, inhibiting PLP-dependent enzymes. Another drug with a similar effect is penicillamine, used in the treatment of patients with rheumatoid arthritis, Wilson's disease, and cystinuria.

Vitamins - Repeats

• The utilization of oral contraceptives seems to elevate the demand for a particular vitamin. Which vitamin is implicated? Elaborate on the reasons. How is this clinically identified? (2010)
• What nutritional deficiencies might an 'Alcoholic' individual encounter? Clarify the underlying reasons. (2011)
• Explain the impact of anticonvulsant drugs (Phenobarbital/diphenylhydantoin) on vitamin requirements in the body. Specify the role played by the relevant vitamin/vitamins in the human body. (2011)
• Describe the role of vitamins in preventing Anemia. (2012)
• Avidin, an egg protein, exhibits a strong affinity to a vitamin. Discuss the biochemical role of that vitamin. (2013)
• List the various antioxidant vitamins and elaborate on any one of them. (2014)
• Highlight the role of vitamin C in scurvy and cholesterol metabolism. (2016)
• What are the principal functions of pyridoxine (vitamin B6)? Provide an explanation. (2015)
• Briefly discuss vitamin D resistant rickets. (2015)
• Outline the biochemical functions and deficiency symptoms of sulfur-containing vitamins. (2016)
• What is the folate trap? What methods are used to assess vitamin B12 deficiency? (2018)