Physiology

Understanding the normal and abnormal states associated with vitamin and nutrient metabolism is crucial for identifying and managing nutritional disorders

General Principles of Nutritional Status

Nutritional Requirements
- The body requires a balanced intake of macronutrients (carbohydrates, fats, proteins) and micronutrients (vitamins, minerals) for optimal health
- Nutritional requirements vary based on age, sex, activity level, and physiological state (e.g., pregnancy, lactation)
Dietary Intake and Absorption
- Adequate dietary intake is essential for meeting nutritional requirements
- Factors affecting absorption: Digestive function, intestinal health, and interactions with other nutrients and medications
Metabolic Processes
- Nutrients undergo various metabolic processes (digestion, absorption, transport, storage, and utilization)
- Enzymes, hormones, and other factors regulate these processes
Assessment of Nutritional Status
- Dietary Assessment: Evaluation of dietary intake and eating habits
- Anthropometric Measurements: Height, weight, body mass index (BMI), and body composition
- Biochemical Tests: Measurement of nutrient levels and related metabolites in blood, urine, and tissues
- Clinical Assessment: Physical examination to identify signs and symptoms of nutritional deficiencies or excesses

Normal Nutritional States

Adequate Dietary Intake
- Consumption of a balanced diet that meets the body’s nutritional requirements
- Includes a variety of foods from different food groups (fruits, vegetables, grains, protein sources, and dairy)
Normal Absorption and Utilization
- Efficient digestion and absorption of nutrients from the gastrointestinal tract
- Normal metabolic processes for nutrient utilization in cells and tissues
Optimal Nutrient Levels
- Maintenance of nutrient levels within the normal reference ranges
- Adequate storage and mobilization of nutrients as needed

Abnormal Nutritional States

Malnutrition
- A state of nutritional imbalance resulting from inadequate or excessive intake of nutrients, or impaired nutrient utilization
- Includes both undernutrition and overnutrition
Undernutrition
- Definition: Deficiency of one or more essential nutrients
- Causes
  - Inadequate dietary intake: Poverty, food insecurity, eating disorders, fad diets
  - Impaired absorption: Malabsorption syndromes, gastrointestinal disorders
  - Increased nutrient requirements: Pregnancy, lactation, chronic diseases
  - Increased nutrient losses: Diarrhea, vomiting, kidney disease
- Types of Undernutrition
  - Protein-energy malnutrition (PEM): Deficiency of both protein and calories
  - Micronutrient deficiencies: Deficiency of vitamins and minerals
Overnutrition
- Definition: Excessive intake of nutrients, leading to nutrient toxicity and adverse health effects
- Causes
  - Excessive dietary intake: Overeating, consumption of nutrient-dense foods
  - Excessive supplementation: High doses of vitamin and mineral supplements
- Types of Overnutrition
  - Obesity: Excessive accumulation of body fat
  - Vitamin toxicity: Excessive intake of fat-soluble vitamins (A, D, E, K)
Specific Nutritional Disorders
- Vitamin Deficiencies: Scurvy, rickets, beriberi, pellagra
- Mineral Deficiencies: Iron deficiency anemia, iodine deficiency, calcium deficiency
- Eating Disorders: Anorexia nervosa, bulimia nervosa
- Obesity: Excessive accumulation of body fat
- Metabolic Syndrome: A cluster of conditions that increase the risk of heart disease, stroke, and diabetes
Biochemical Markers of Nutritional Status
- Protein Status: Serum albumin, prealbumin, transferrin, retinol-binding protein
- Vitamin Status: Serum vitamin levels, urinary excretion of vitamin metabolites
- Mineral Status: Serum mineral levels, red blood cell mineral levels
- Iron Status: Serum iron, transferrin saturation, ferritin, hemoglobin, hematocrit
- Lipid Status: Cholesterol, triglycerides, HDL cholesterol, LDL cholesterol
- Glucose Status: Fasting glucose, HbA1c, oral glucose tolerance test

Water-Soluble Vitamin Disorders

Thiamin (Vitamin B1)

Normal State: Adequate dietary intake of thiamin
- Sources: Whole grains, meat, and fish
- Requirements: 1.2 mg/day for men, 1.1 mg/day for women
Abnormal State: Thiamin Deficiency
- Causes
  - Inadequate dietary intake: Common in alcoholics and individuals with poor nutrition
  - Impaired absorption: Gastrointestinal disorders
  - Increased requirements: Pregnancy, lactation
- Disorders
  - Beriberi: Neurological and cardiovascular symptoms
  - Wernicke-Korsakoff Syndrome: Neurological disorder associated with chronic alcohol abuse
- Biochemical Findings
  - Decreased erythrocyte transketolase activity
  - Elevated blood pyruvate and lactate levels

Riboflavin (Vitamin B2)

Normal State: Adequate dietary intake of riboflavin
- Sources: Milk, eggs, meat, and green vegetables
- Requirements: 1.3 mg/day for men, 1.1 mg/day for women
Abnormal State: Riboflavin Deficiency
- Causes
  - Inadequate dietary intake: Common in individuals with poor nutrition
  - Impaired absorption: Gastrointestinal disorders
  - Increased requirements: Pregnancy, lactation
- Disorders
  - Ariboflavinosis: Characterized by cheilosis, glossitis, and dermatitis
- Biochemical Findings
  - Decreased erythrocyte glutathione reductase activity
  - Decreased urinary excretion of riboflavin

Niacin (Vitamin B3)

Normal State: Adequate dietary intake of niacin
- Sources: Meat, fish, poultry, and enriched grains
- Requirements: 16 mg/day for men, 14 mg/day for women
Abnormal State: Niacin Deficiency
- Causes
  - Inadequate dietary intake: Common in individuals with poor nutrition
  - Impaired absorption: Gastrointestinal disorders
  - Decreased conversion of tryptophan to niacin
- Disorders
  - Pellagra: Characterized by dermatitis, diarrhea, and dementia
- Biochemical Findings
  - Decreased urinary excretion of niacin metabolites
  - Decreased erythrocyte nicotinamide adenine dinucleotide (NAD) levels
Abnormal State: Niacin Toxicity
- Causes
  - Excessive intake of niacin supplements
- Disorders
  - Niacin Flush: Characterized by skin flushing and itching
  - Liver Damage: Elevated liver enzymes

Pyridoxine (Vitamin B6)

Normal State: Adequate dietary intake of pyridoxine
- Sources: Meat, fish, poultry, and whole grains
- Requirements: 1.3 mg/day for adults
Abnormal State: Pyridoxine Deficiency
- Causes
  - Inadequate dietary intake: Common in alcoholics
  - Drug interactions: Certain medications can interfere with pyridoxine metabolism
- Disorders
  - Neurological Symptoms: Seizures, depression, and peripheral neuropathy
  - Dermatitis: Skin rash
  - Anemia: Microcytic anemia
- Biochemical Findings
  - Decreased plasma pyridoxal phosphate (PLP) levels
  - Elevated urinary xanthurenic acid excretion after tryptophan load
Abnormal State: Pyridoxine Toxicity
- Causes
  - Excessive intake of pyridoxine supplements
- Disorders
  - Peripheral Neuropathy: Nerve damage, causing numbness and tingling in the extremities

Folate (Vitamin B9)

Normal State: Adequate dietary intake of folate
- Sources: Green leafy vegetables, fruits, and fortified grains
- Requirements: 400 mcg/day for adults, 600 mcg/day for pregnant women
Abnormal State: Folate Deficiency
- Causes
  - Inadequate dietary intake: Common in individuals with poor nutrition
  - Impaired absorption: Malabsorption syndromes
  - Drug interactions: Certain medications can interfere with folate metabolism
- Disorders
  - Megaloblastic Anemia: Characterized by large, abnormal red blood cells
  - Neural Tube Defects: Birth defects affecting the brain and spinal cord in developing fetuses
  - Increased risk of cardiovascular disease
- Biochemical Findings
  - Decreased serum and red blood cell folate levels
  - Elevated homocysteine levels
Abnormal State: Folate Toxicity
- Causes
  - Excessive intake of folate supplements
- Disorders
  - Masking Vitamin B12 Deficiency: High folate intake can mask the symptoms of vitamin B12 deficiency, leading to irreversible neurological damage

Cobalamin (Vitamin B12)

Normal State: Adequate dietary intake of cobalamin
- Sources: Meat, fish, poultry, and dairy products
- Requirements: 2.4 mcg/day for adults
Abnormal State: Cobalamin Deficiency
- Causes
  - Inadequate dietary intake: Common in vegans and vegetarians
  - Impaired absorption: Pernicious anemia (lack of intrinsic factor), malabsorption syndromes
- Disorders
  - Megaloblastic Anemia: Characterized by large, abnormal red blood cells
  - Neurological Symptoms: Peripheral neuropathy, cognitive impairment
  - Increased risk of cardiovascular disease
- Biochemical Findings
  - Decreased serum vitamin B12 levels
  - Elevated homocysteine and methylmalonic acid (MMA) levels

Ascorbic Acid (Vitamin C)

Normal State: Adequate dietary intake of ascorbic acid
- Sources: Fruits and vegetables, especially citrus fruits and berries
- Requirements: 90 mg/day for men, 75 mg/day for women
Abnormal State: Ascorbic Acid Deficiency
- Causes
  - Inadequate dietary intake: Common in individuals with limited access to fresh fruits and vegetables
- Disorders
  - Scurvy: Characterized by bleeding gums, poor wound healing, and anemia
- Biochemical Findings
  - Decreased serum ascorbic acid levels

Fat-Soluble Vitamin Disorders

Vitamin A

Normal State: Adequate dietary intake of vitamin A
- Sources: Liver, dairy products, eggs, and orange and yellow fruits and vegetables
- Requirements: 900 mcg/day for men, 700 mcg/day for women
Abnormal State: Vitamin A Deficiency
- Causes
  - Inadequate dietary intake: Common in developing countries
  - Impaired absorption: Fat malabsorption syndromes
- Disorders
  - Night Blindness: Impaired vision in low light conditions
  - Xerophthalmia: Dryness and damage to the cornea
  - Impaired Immune Function: Increased susceptibility to infections
- Biochemical Findings
  - Decreased serum retinol levels
Abnormal State: Vitamin A Toxicity
- Causes
  - Excessive intake of vitamin A supplements
- Disorders
  - Acute Toxicity: Nausea, vomiting, headache, and dizziness
  - Chronic Toxicity: Liver damage, bone pain, and birth defects
- Biochemical Findings
  - Elevated serum retinol levels

Vitamin D

Normal State: Adequate vitamin D status
- Sources: Sunlight exposure, fortified foods, and supplements
- Requirements: 600 IU/day for adults, 800 IU/day for adults over 70
Abnormal State: Vitamin D Deficiency
- Causes
  - Inadequate sunlight exposure: Limited outdoor activities, dark skin pigmentation
  - Inadequate dietary intake: Limited consumption of vitamin D-rich foods
  - Impaired absorption: Fat malabsorption syndromes
  - Kidney and liver disorders: Impaired conversion to active form
- Disorders
  - Rickets: Bone deformities in children
  - Osteomalacia: Softening of the bones in adults
  - Osteoporosis: Decreased bone density, increasing the risk of fractures
- Biochemical Findings
  - Decreased serum 25-hydroxyvitamin D [25(OH)D] levels
  - Elevated parathyroid hormone (PTH) levels in response to hypocalcemia
Abnormal State: Vitamin D Toxicity
- Causes
  - Excessive intake of vitamin D supplements
- Disorders
  - Hypercalcemia: Elevated serum calcium levels
  - Kidney Stones: Calcium deposits in the kidneys
  - Soft Tissue Calcification: Calcium deposits in soft tissues
- Biochemical Findings
  - Elevated serum 25(OH)D and calcium levels

Vitamin E

Normal State: Adequate dietary intake of vitamin E
- Sources: Vegetable oils, nuts, seeds, and green leafy vegetables
- Requirements: 15 mg/day for adults
Abnormal State: Vitamin E Deficiency
- Causes
  - Fat malabsorption syndromes: Cystic fibrosis, celiac disease
  - Genetic disorders: Abetalipoproteinemia
- Disorders
  - Neurological Symptoms: Peripheral neuropathy, ataxia
  - Hemolytic Anemia: Damage to red blood cells
- Biochemical Findings
  - Decreased serum alpha-tocopherol levels
Abnormal State: Vitamin E Toxicity
- Causes
  - Excessive intake of vitamin E supplements
- Disorders
  - Increased Risk of Bleeding: Interferes with blood clotting

Vitamin K

Normal State: Adequate vitamin K status
- Sources: Green leafy vegetables and synthesized by intestinal bacteria
- Requirements: 120 mcg/day for men, 90 mcg/day for women
Abnormal State: Vitamin K Deficiency
- Causes
  - Inadequate dietary intake: Rare
  - Malabsorption Syndromes: Cystic fibrosis, celiac disease
  - Antibiotic Use: Kills intestinal bacteria
  - Newborns: Lack of intestinal bacteria and limited placental transfer
- Disorders
  - Bleeding Disorders: Impaired blood clotting
- Biochemical Findings
  - Prolonged Prothrombin Time (PT) and International Normalized Ratio (INR)
- Poor bone health
Abnormal State: Vitamin K Toxicity
- Causes
  - Excessive intake of synthetic vitamin K (menadione)
- Disorders
  - Rare, but can cause hemolytic anemia and liver damage in infants

Summary Table of Nutritional Disorders

Nutrient	Deficiency Disorder(s)	Toxicity Disorder(s)
Thiamin (B1)	Beriberi, Wernicke-Korsakoff Syndrome	Rare
Riboflavin (B2)	Ariboflavinosis	Rare
Niacin (B3)	Pellagra	Niacin Flush, Liver Damage
Pyridoxine (B6)	Neurological Symptoms, Dermatitis, Anemia	Peripheral Neuropathy
Folate (B9)	Megaloblastic Anemia, Neural Tube Defects	Masks B12 Deficiency
Cobalamin (B12)	Megaloblastic Anemia, Neurological Symptoms	Rare
Ascorbic Acid (C)	Scurvy	GI Distress, Kidney Stones
Vitamin A	Night Blindness, Xerophthalmia, Immune Dysfunction	Liver Damage, Birth Defects
Vitamin D	Rickets, Osteomalacia, Osteoporosis	Hypercalcemia, Kidney Stones, Tissue Calcification
Vitamin E	Neurological Symptoms, Hemolytic Anemia	Increased Bleeding Risk
Vitamin K	Bleeding Disorders	Rare

Clinical Significance

Diagnosis and Management
- Accurate assessment of nutritional status is essential for diagnosing and managing nutritional disorders
Public Health Interventions
- Addressing nutritional deficiencies in populations through food fortification and supplementation programs
Personalized Nutrition
- Tailoring dietary recommendations and supplement use based on an individual’s nutritional status and genetic factors

Key Terms

Malnutrition: Nutritional imbalance resulting from inadequate or excessive intake of nutrients
Undernutrition: Deficiency of one or more essential nutrients
Overnutrition: Excessive intake of nutrients, leading to nutrient toxicity
Scurvy: Vitamin C deficiency
Rickets: Vitamin D deficiency in children
Beriberi: Thiamin deficiency
Pellagra: Niacin deficiency
Megaloblastic Anemia: Anemia characterized by large, abnormal red blood cells, often due to folate or vitamin B12 deficiency
Osteomalacia: Softening of the bones in adults
Osteoporosis: Decreased bone density, increasing the risk of fractures
Biochemical Marker: A measurable substance in blood, urine, or tissues that reflects nutritional status

Metabolic

Properties