Understanding the Pathophysiology of Vitamin C Deficiency (Scurvy)

December 24, 2025 •

4 min read

Vitamin C deficiency, also known as scurvy, occurs when the body's total vitamin C pool drops below 350 mg after being eliminated from the diet for at least three months. The pathophysiology of vitamin C deficiency is primarily rooted in the disruption of vital biochemical pathways, most notably defective collagen formation.

Quick Summary

Severe lack of dietary vitamin C disrupts crucial biochemical processes, particularly the synthesis of stable collagen. This compromised connective tissue integrity leads to hemorrhages, impaired wound healing, bone abnormalities, and widespread systemic issues characteristic of scurvy.

Key Points

Defective Collagen Synthesis: The most critical pathway affected is the hydroxylation of collagen precursors, leading to the formation of unstable collagen and widespread connective tissue weakness.
Vascular Fragility: Weakened blood vessel walls, caused by unstable collagen, result in easy bruising, petechiae, and mucosal bleeding, such as bleeding gums.
Impaired Wound Healing: Without sufficient collagen, the body's ability to repair and heal wounds is compromised, leading to delayed recovery and the reopening of old scars.
Musculoskeletal Abnormalities: Disrupted bone and cartilage formation, due to the lack of a stable collagen matrix, leads to brittle bones, joint pain, and hemorrhages into joints and surrounding tissue.
Antioxidant Compromise: As a vital antioxidant, vitamin C protects cells from oxidative stress; its deficiency leaves the body vulnerable to free radical damage, contributing to fatigue and weakened immunity.
Anemia and Fatigue: The role of vitamin C in aiding iron absorption is diminished, which, combined with blood loss from fragile capillaries, can contribute to anemia and pronounced fatigue.
Neurotransmitter and Carnitine Disruption: Vitamin C is a cofactor for the synthesis of carnitine and certain neurotransmitters, so deficiency can cause muscle weakness and mood changes like depression.

The Core Mechanism: Impaired Collagen Synthesis

At the heart of the pathophysiology of vitamin C deficiency is its indispensable role as a cofactor in collagen synthesis. Collagen is the most abundant protein in the body, acting as a structural 'glue' for connective tissues, including skin, blood vessels, bones, cartilage, and teeth.

The Hydroxylation Process

Vitamin C, or ascorbic acid, is essential for the function of two key enzymes: prolyl hydroxylase and lysyl hydroxylase. These enzymes catalyze the hydroxylation of the amino acids proline and lysine within the nascent collagen molecule. This hydroxylation is a critical step that allows collagen to form its stable, triple-helix structure. Without sufficient vitamin C, this process fails, resulting in the production of weak, unstable collagen molecules.

Effects on Connective Tissues

The production of defective collagen has systemic consequences that define the symptoms of scurvy:

Vascular Fragility: Blood vessel walls, which rely heavily on collagen, become weak and fragile. This leads to easy bruising, petechiae (small red spots from bleeding under the skin), and perifollicular hemorrhages (bleeding around hair follicles). Capillary fragility in the lower extremities can even lead to gravity-dependent hemorrhages and swelling.
Impaired Wound Healing: The body's inability to synthesize new, strong collagen for tissue repair means that wounds heal slowly and poorly, with existing scar tissue sometimes breaking down. This is a direct consequence of the lack of a stable collagen framework necessary for effective tissue regeneration.
Musculoskeletal Issues: Defective collagen synthesis affects cartilage and bone formation. Children may experience impaired bone growth, while both children and adults can suffer from painful joint swelling, hemorrhages into joints (hemarthroses), and subperiosteal hemorrhages. In bones, normal resorption continues while new bone formation is impaired, leading to brittle bones and fractures.
Oral Manifestations: The gums can become swollen, spongy, purple, and bleed easily (gingivitis) due to the breakdown of collagen that supports dental tissue. Teeth may eventually become loose or fall out.

Broader Biochemical Impacts of Deficiency

Beyond collagen synthesis, vitamin C is involved in several other important biochemical pathways. Its absence or insufficient levels contributes to the multisystemic nature of scurvy.

Antioxidant Failure

Vitamin C is a potent antioxidant that protects cells from oxidative stress caused by free radicals. When vitamin C is deficient, this protective mechanism is compromised, leading to increased cellular damage. This can affect various bodily functions and may contribute to fatigue and a weakened immune system, making individuals more susceptible to infections.

Iron Absorption Impairment

Vitamin C enhances the absorption of nonheme iron (plant-based iron) by reducing it from the ferric ($ ext{Fe}^{3+}$) to the more absorbable ferrous ($ ext{Fe}^{2+}$) state. A deficiency can impair this process, contributing to the anemia often observed in scurvy, especially when combined with blood loss from bleeding capillaries.

Neurotransmitter and Carnitine Synthesis

Ascorbic acid acts as a cofactor for the enzyme dopamine-beta-monooxygenase, which converts dopamine to the neurotransmitter norepinephrine. Low vitamin C levels can therefore disrupt this process, potentially contributing to the fatigue, lethargy, and depression associated with the early stages of scurvy. Furthermore, vitamin C is needed for the synthesis of carnitine, which is vital for transporting fatty acids into the mitochondria for energy production. A carnitine deficiency may also contribute to the muscle weakness and fatigue observed.

Comparison of Healthy vs. Deficient States


Aspect	Healthy State (Sufficient Vitamin C)	Deficient State (Low Vitamin C)
Collagen Synthesis	Stable triple-helix collagen formation via hydroxylation of proline and lysine.	Unstable, weak collagen production due to impaired hydroxylation.
Blood Vessels	Strong, elastic, and intact vessel walls, providing structural integrity.	Fragile capillaries prone to leakage, causing hemorrhages and bruising.
Wound Healing	Robust and rapid healing process with proper scar tissue formation.	Slowed and impaired healing, with potential reopening of old wounds.
Antioxidant Protection	Potent antioxidant activity protecting cells from free radical damage.	Compromised cellular protection, increasing oxidative stress and cell damage.
Iron Absorption	Enhanced absorption of nonheme iron, aiding red blood cell production.	Reduced iron absorption, contributing to anemia and associated fatigue.
Energy & Mood	Adequate carnitine and neurotransmitter synthesis for sustained energy and stable mood.	Fatigue, weakness, and depression linked to impaired carnitine and neurotransmitter synthesis.

Conclusion

The pathophysiology of vitamin C deficiency is a cascade of events triggered by the lack of ascorbic acid, with the defective synthesis of stable collagen as the central pillar. This primary defect leads to the hallmark signs of scurvy, including hemorrhages and compromised connective tissue integrity. Secondary to this, the loss of vitamin C's antioxidant properties, and its role as a cofactor in other metabolic processes, exacerbates symptoms like fatigue and anemia. The clinical manifestations are a direct reflection of these underlying biochemical failures throughout the body. Early diagnosis and supplementation with vitamin C are crucial for reversing these pathological changes and restoring proper bodily function. A balanced diet rich in fresh fruits and vegetables is the most effective preventative measure against this historically significant, yet still present, disease. For more detailed information on vitamin C's biochemistry and disease links, consult the article "Vitamin C: A Comprehensive Review of Its Role in Health and Disease" via the National Institutes of Health.

Frequently Asked Questions

The primary cause of symptoms is the body's inability to synthesize stable collagen due to a lack of vitamin C, leading to fragile connective tissues in blood vessels, skin, bones, and gums.

In vitamin C deficiency, blood vessels, particularly capillaries, become fragile and prone to leakage because their collagen structure is compromised. This results in hemorrhages, easy bruising, and petechiae.

Scurvy causes these dental issues because the connective tissues that support the gums and teeth rely on stable collagen for their strength. Without vitamin C, this collagen breaks down, making the gums swollen and prone to bleeding, and the teeth eventually loosen.

Wound healing is severely impaired because vitamin C is crucial for the synthesis of new collagen, which is needed to form scar tissue. In its absence, wounds heal slowly and poorly.

Yes, vitamin C deficiency can contribute to anemia. It impairs the body's absorption of nonheme iron from plant-based foods and also causes blood loss due to capillary hemorrhages.

Vitamin C's role as a potent antioxidant is diminished in deficiency, leaving cells more vulnerable to damage from oxidative stress. This can contribute to systemic issues like a weakened immune system and general malaise.

Fatigue and muscle weakness are linked to impaired carnitine and neurotransmitter synthesis. Vitamin C is a cofactor for these processes, which are essential for transporting fatty acids for energy and for nervous system function.