Understanding what is the pathophysiology of vitamin C: From collagen defects to scurvy

October 16, 2025 •

4 min read

Scurvy, the disease caused by severe vitamin C deficiency, was a devastating historical affliction for sailors and others with poor diets, providing a stark lesson in what is the pathophysiology of vitamin C and its critical role in human health. While rare today in developed nations, its underlying mechanisms highlight how essential this nutrient is for maintaining healthy connective tissues, immune function, and overall cellular integrity.

Quick Summary

Vitamin C deficiency primarily impairs collagen synthesis, leading to weakened connective tissues, hemorrhages, and impaired wound healing. Secondary effects include increased oxidative stress and compromised immunity, resulting in the full clinical picture of scurvy.

Key Points

Collagen Production: Vitamin C is a critical cofactor for enzymes required to synthesize and stabilize collagen, the body's primary structural protein.
Connective Tissue Fragility: Without sufficient vitamin C, defective collagen leads to weakened blood vessels, bones, skin, and teeth.
Oxidative Damage: As a powerful antioxidant, vitamin C protects against cellular damage from free radicals; deficiency increases oxidative stress.
Compromised Immunity: High concentrations of vitamin C in immune cells support functions like chemotaxis and microbial killing; deficiency impairs immunity and increases infection risk.
Systemic Impact: Beyond connective tissue, deficiency affects iron absorption, neurotransmitter synthesis, and carnitine production, causing anemia, fatigue, and neurological symptoms.
The Disease of Scurvy: The severe, systemic pathology resulting from vitamin C deficiency is the clinical syndrome of scurvy, with symptoms ranging from fatigue to widespread hemorrhage.

The Foundational Role of Vitamin C

Vitamin C, or ascorbic acid, is a crucial water-soluble vitamin that humans cannot synthesize internally due to a genetic mutation. Therefore, adequate dietary intake is essential to prevent a deficiency. The core pathophysiology of vitamin C deficiency stems from its role as a vital cofactor for several key enzymatic reactions within the body. Without it, these reactions fail, leading to widespread systemic problems. Most famously, a severe deficiency leads to the clinical syndrome known as scurvy, but even suboptimal intake can have negative health consequences.

Collagen Synthesis: The Core Pathophysiology

At the heart of vitamin C pathophysiology is its indispensable role in collagen synthesis. Collagen is the most abundant protein in the body, providing structure and tensile strength to connective tissues like skin, bone, cartilage, and blood vessel walls.

Enzymatic Cofactor: Vitamin C is a critical cofactor for the enzymes prolyl hydroxylase and lysyl hydroxylase.
Hydroxylation Process: These enzymes hydroxylate the amino acid residues proline and lysine within the procollagen molecule.
Triple Helix Formation: Hydroxylation is necessary for the stable triple-helix structure of mature, functional collagen.
Structural Failure: Without this process, the resulting collagen is weak, unstable, and less effective, leading to widespread defects throughout the body.

Impaired Connective Tissues and Hemorrhage

This failure in proper collagen formation leads directly to the classic symptoms of scurvy due to fragile connective tissues and weakened capillaries. The resulting defects cause:

Fragile Blood Vessels: The vascular walls, rich in type IV collagen, become weakened, leading to widespread hemorrhaging. This presents as perifollicular hemorrhages (bleeding around hair follicles), easy bruising (ecchymoses), and blood in the joints (hemarthroses).
Gingival Manifestations: Defective collagen in the gums causes them to become swollen, spongy, friable, and prone to bleeding. Eventually, teeth may loosen and fall out.
Skin and Wound Healing: Impaired wound healing is a hallmark of scurvy because new, stable collagen cannot be properly formed at the site of injury. Older scars may even break down and reopen.
Musculoskeletal Issues: Defective osteoid matrix formation leads to weakened bones prone to fracture, pain, and subperiosteal hemorrhages (bleeding under the bone's outer membrane).

Oxidative Stress and Immune Dysfunction

Beyond its role in collagen, vitamin C is a potent antioxidant and critical for immune function.

Antioxidant Function: Vitamin C neutralizes reactive oxygen species (ROS), protecting cells from oxidative damage. Deficiency leads to higher oxidative stress, which can damage macromolecules like DNA, proteins, and lipids.
Immune Cell Support: It accumulates in high concentrations within immune cells like neutrophils and lymphocytes, enhancing functions such as chemotaxis, phagocytosis, and microbial killing.
Increased Infection Susceptibility: A lack of vitamin C impairs these immune functions, rendering individuals more susceptible to infections. Infections, in turn, further deplete vitamin C stores, creating a vicious cycle.

Systemic Effects of Vitamin C Deficiency

The cascading failures caused by vitamin C deficiency manifest in various systemic ways:

Hematological Effects: Anemia is a common feature, stemming from blood loss due to hemorrhage and impaired iron absorption. Vitamin C helps convert dietary iron to a more absorbable form.
Neurological Impacts: Vitamin C is a cofactor in the synthesis of neurotransmitters like norepinephrine. Deficiency can cause irritability, lethargy, depression, and fatigue.
Metabolic Disorders: The vitamin is required for carnitine synthesis, which is essential for transporting fatty acids for energy production. A shortage can result in weakness and lethargy.

Risk Factors for Vitamin C Deficiency

While scurvy is historically associated with poor access to fresh food, modern risk factors exist, especially in developed nations:

Poor Diet: Limited intake of fresh fruits and vegetables.
Alcohol Use: Chronic alcoholism can lead to malnutrition.
Smoking: Smokers have lower plasma vitamin C levels due to increased oxidative stress and metabolic turnover, requiring a higher intake.
Malabsorption: Gastrointestinal conditions like inflammatory bowel disease or bariatric surgery can reduce absorption.
Chronic Illness: Conditions requiring increased metabolism or causing poor intake, like cancer or kidney disease.
Infant Feeding Practices: Historically, boiling milk destroyed vitamin C, but modern formulas are fortified.

The Impact on Different Age Groups

The clinical manifestations of vitamin C deficiency can vary depending on age, with particularly pronounced effects in infants and children due to their rapid growth.


Clinical Feature	Adults (with chronic deficiency)	Infants and Children (during growth)
Hemorrhage	Perifollicular petechiae, ecchymoses, fragile blood vessels.	Subperiosteal hemorrhages leading to joint swelling, severe pain, and pseudoparalysis.
Gums and Teeth	Swollen, purple, spongy gums that bleed easily; loosened teeth.	Painful, swollen gums; poor dentin formation.
Musculoskeletal	Joint and muscle pain (arthralgias, myalgias), bone pain.	Disrupted bone formation, brittle bones, characteristic bone lesions visible on X-rays.
Hair	Corkscrew hairs, rough and scaly skin.	Poor hair growth, corkscrew hairs.
General Symptoms	Lassitude, weakness, fatigue, depression, weight loss.	Irritability, pain during movement, anorexia, slowed growth.

Conclusion

The pathophysiology of vitamin C deficiency is a stark illustration of how a single nutrient deficit can trigger a cascade of systemic failures, from the disruption of foundational collagen synthesis to compromised antioxidant defenses. While severe scurvy is now rare in many parts of the world, recognizing the subtle signs of vitamin C insufficiency is still important for at-risk populations. Adequate intake, whether through diet or supplementation, is a cost-effective and critical measure for maintaining strong connective tissues, a robust immune system, and protecting against oxidative stress. The remarkable and rapid recovery seen with vitamin C replacement underscores the body's dependence on this simple but powerful molecule. For more on the biochemistry of vitamin C, visit the NCBI Bookshelf article on Vitamin C Deficiency.

Frequently Asked Questions

Vitamin C acts as a cofactor for the enzymes prolyl hydroxylase and lysyl hydroxylase, which are essential for adding hydroxyl groups to proline and lysine amino acid residues during collagen formation.

Bleeding gums are a symptom of scurvy because vitamin C is needed for strong collagen, which provides structural integrity to blood vessels and connective tissue in the gums. When collagen is defective, the capillaries become fragile and bleed easily.

As a potent antioxidant, vitamin C neutralizes reactive oxygen species (ROS) that can damage cells. In its absence, these free radicals can accumulate and cause cellular damage, leading to increased oxidative stress.

Yes, vitamin C deficiency compromises the immune system. The vitamin is crucial for various immune cell functions, such as enhancing neutrophil chemotaxis and phagocytosis, and its depletion can increase susceptibility to infections.

Musculoskeletal symptoms include pain, painful joint swelling, hemarthroses (bleeding into joints), and subperiosteal hematomas (bleeding under the membrane covering bones). In children, this can cause bone lesions and impaired growth.

People who smoke often have lower vitamin C levels due to increased oxidative stress from cigarette smoke and a higher metabolic turnover of the vitamin. They require a higher daily intake to compensate.

Vitamin C aids in the absorption of nonheme iron (from plant-based foods) by reducing dietary ferric iron to the more absorbable ferrous form in the small intestine. Deficiency can contribute to anemia.