Vitamin D, Calcium, and Iron Metabolism: Deficiency and Toxicity

Posted on Oct 18, 2025 in Medicine & Health

Vitamin D: Synthesis, Absorption, and Health

Synthesis of Vitamin D

Vitamin D3 (cholecalciferol) is synthesized in the skin when 7-dehydrocholesterol reacts with UVB radiation (sunlight).

The liver converts it to 25-hydroxyvitamin D [25(OH)D], the main circulating form.

The kidneys further convert it to the active form: 1,25-dihydroxyvitamin D [1,25(OH)₂D] (calcitriol).

Absorption of Vitamin D

Vitamin D2 and D3 from food or supplements are absorbed in the small intestine, especially with dietary fat.

  • Requires bile salts for proper absorption.
  • Transported via chylomicrons into the lymphatic system, then the blood.

Diseases Related to Vitamin D Status

Deficiency Diseases:

  • Rickets in children – soft, weak bones.
  • Osteomalacia in adults – bone pain, muscle weakness.
  • Osteoporosis – brittle bones due to chronic low calcium and vitamin D.

Excess Vitamin D (Toxicity):

Can lead to hypercalcemia, kidney stones, and organ damage.

Causes of Vitamin D Deficiency

  • Lack of sunlight exposure.
  • Poor dietary intake (especially vegan diets without fortified foods).
  • Malabsorption syndromes (e.g., celiac, Crohn’s disease).
  • Chronic kidney or liver disease.
  • Use of certain drugs (e.g., anticonvulsants, glucocorticoids).

Vitamin D Interactions

  • Enhancers: Fatty meals improve absorption.
  • Inhibitors: Cholestyramine, orlistat, and some anticonvulsants reduce absorption or effect.
  • Calcium & Phosphate Metabolism: Vitamin D enhances the absorption of these minerals in the gut.

Toxicity (Hypervitaminosis D)

Usually due to excessive supplementation, not sun exposure.

Symptoms of Hypervitaminosis D:

  • Nausea, vomiting
  • Weakness, confusion
  • Hypercalcemia
  • Calcification of soft tissues (e.g., kidney, heart)

Calcium: Essential Roles and Regulation

Roles of Calcium in the Body

Bone and Teeth Formation

About 99% of calcium is stored in bones and teeth, providing structure and strength.

  1. Muscle Contraction: Required for muscles (including the heart) to contract properly.
  2. Nerve Transmission: Helps transmit nerve impulses.
  3. Blood Clotting: Essential for activating clotting factors.
  4. Enzyme Function & Hormone Secretion: Acts as a cofactor for many enzymes and is involved in hormone release (e.g., insulin).

Calcium Deficiency Diseases

Hypocalcemia can lead to the following conditions:

  1. Rickets (in children): Softening and weakening of bones. Often linked with vitamin D deficiency as well.
  2. Osteomalacia (in adults): Soft bones due to poor bone mineralization.
  3. Osteoporosis: Decreased bone mass and increased fracture risk.
  4. Muscle Cramps, Tingling, and Numbness: Due to impaired nerve and muscle function.
  5. Tetany: Severe neuromuscular symptoms resulting from low calcium levels.

Calcium Balance and Regulation

  • Regulated by Hormones:
    • Parathyroid hormone (PTH): Increases blood calcium by stimulating bone resorption and increasing intestinal absorption.
    • Calcitonin: Lowers blood calcium by promoting calcium storage in bones.
    • Vitamin D (Calcitriol): Enhances calcium absorption in the intestine.
  • Sources:
    • Dairy (milk, cheese, yogurt)
    • Leafy greens, almonds, fortified foods
  • Absorption Influenced by:
    • Vitamin D levels
    • Age (decreases with age)
    • Oxalates/phytates (found in some plant foods) can inhibit absorption.

Calcium Toxicity (Hypercalcemia)

  • Causes: Excess supplementation, overactive parathyroid gland, some cancers, or excess vitamin D intake.
  • Symptoms:
    • Nausea, vomiting
    • Constipation
    • Confusion, lethargy
    • Kidney stones
    • Abnormal heart rhythms
  • Severe Toxicity: Can cause kidney failure, calcification of tissues, and cardiac arrest.

Iron: Functions, Metabolism, and Absorption

Functions of Iron in the Body

  • Oxygen Transport: Hemoglobin (in red blood cells) carries oxygen from lungs to tissues. Myoglobin (in muscles) stores and releases oxygen.
  • Energy Production: Involved in electron transport and cellular respiration (mitochondria).
  • Immune Function: Supports immune cell growth and activity.
  • DNA Synthesis: Acts as a cofactor for enzymes involved in DNA replication.

Iron Absorption

Absorption occurs mainly in the duodenum (first part of the small intestine).

  • Two Dietary Forms:
    • Heme Iron: Found in animal sources (meat, poultry, fish); absorbed more efficiently.
    • Non-Heme Iron: Found in plant sources (legumes, spinach); less efficiently absorbed.
  • Absorption Enhanced by:
    • Vitamin C (ascorbic acid)
    • Stomach acid
    • Heme sources (can boost non-heme absorption)
  • Absorption Inhibited by:
    • Phytates (grains, legumes)
    • Polyphenols (tea, coffee)
    • Calcium
    • Zinc (competes for absorption)
    • Oxalates (spinach, nuts)

Iron Metabolism and Routes in the Body

  1. Absorption: Enters intestinal cells via DMT1 (divalent metal transporter 1). It is either stored in cells as ferritin or released into the blood by ferroportin.
  2. Transport in Blood: Bound to transferrin (iron transport protein).
  3. Storage: Stored in the liver, spleen, and bone marrow as ferritin or hemosiderin.
  4. Utilization: Delivered to tissues for hemoglobin, myoglobin, and enzyme synthesis.
  5. Recycling: Iron from old red blood cells is recycled by macrophages in the spleen.
  6. Excretion: Very minimal. Lost mainly via:
    • Shedding of intestinal cells
    • Menstruation
    • Sweat and urine (tiny amounts)

Interactions with Other Minerals

  • Calcium: Competes for absorption in the gut (high calcium may reduce iron absorption).
  • Zinc: Competes for absorption (especially when taken in supplements).
  • Copper: Helps mobilize iron from stores (deficiency may lead to iron-deficiency anemia).
  • Magnesium: May slightly interfere with iron absorption if taken in large amounts.
  • Manganese: Shares transport systems with iron; high iron can reduce manganese absorption.