Understanding the Pathology of Vitamin C Deficiency (Scurvy)

December 24, 2025 •

4 min read

According to studies, vitamin C deficiency was once a major cause of death among sailors, with severe cases of scurvy claiming more lives than enemy action. Understanding the pathology of vitamin C, or ascorbic acid, reveals its critical role in key biological processes and how its absence leads to systemic tissue damage and impaired immune function.

Quick Summary

This article details the cellular mechanisms and systemic effects of vitamin C deficiency, examining its impact on collagen, the immune system, oxidative stress, and hematological health. It covers the progression of scurvy, from early symptoms to severe complications and tissue-level changes, providing a comprehensive overview of this nutritional disorder.

Key Points

Impaired Collagen Synthesis: Vitamin C deficiency leads to defective collagen due to a lack of crucial enzyme cofactors, resulting in systemic connective tissue weakness.
Vascular Fragility: Weak collagen causes capillary walls to become fragile, leading to widespread hemorrhages, bruising, and petechiae.
Immune Compromise: Deficiency impairs immune cell functions like phagocytosis and chemotaxis, and depletes antioxidant defenses, increasing susceptibility to infection.
Increased Oxidative Stress: As a potent antioxidant, vitamin C's absence leaves cells vulnerable to damaging free radicals, contributing to tissue damage.
Hematological Effects: Scurvy can cause anemia due to impaired iron absorption, bleeding, and poor folate utilization.
Musculoskeletal Abnormalities: Inadequate collagen affects bones, especially in children, leading to bone lesions and painful subperiosteal hemorrhages.

Core Pathological Mechanisms

Impaired Collagen Synthesis

At the heart of vitamin C deficiency pathology is its vital role as a cofactor for the enzymes prolyl and lysyl hydroxylase. These enzymes are crucial for stabilizing the triple-helix structure of collagen, the most abundant structural protein in connective tissues, skin, blood vessels, bone, and teeth.

When vitamin C levels are inadequate, the hydroxylation process fails, resulting in the production of weak, unstable collagen. This leads to a breakdown in structural integrity throughout the body, manifesting as the classic symptoms of scurvy:

Vascular Fragility: Weakened capillary walls rupture easily, causing widespread hemorrhages. Perifollicular hemorrhages (bleeding around hair follicles), petechiae (small red or purple spots from broken capillaries), and ecchymoses (larger bruises) are common, especially in the lower extremities.
Impaired Wound Healing: The body's inability to form stable connective tissue results in poor scar tissue formation. Existing wounds may break open, and new wounds heal poorly or not at all.
Gum Disease and Tooth Loss: Collagen weakness affects the gums and periodontal ligaments that hold teeth in place. Gums become swollen, purple, spongy, and prone to bleeding, eventually leading to tooth loss.
Musculoskeletal Issues: In infants and children, impaired bone growth and weakened osteoid formation lead to painful subperiosteal hemorrhages and bony lesions. Adults may experience joint pain, swelling, and hemarthrosis due to bleeding into the joints.

Compromised Immune Function

Vitamin C is actively accumulated by immune cells, such as neutrophils and phagocytes, reaching concentrations up to 100 times higher than in plasma. This indicates its significant role in supporting immune defense. The pathology of vitamin C deficiency undermines this system in several ways:

Weakened Physical Barriers: The impaired collagen synthesis weakens the skin and mucosal barriers, making the body more susceptible to pathogens.
Dysfunctional Phagocytes: Vitamin C enhances the chemotaxis (migration) of neutrophils and phagocytosis (engulfing of microbes). Deficiency impairs these functions, reducing the effectiveness of the innate immune response.
Oxidative Damage to Immune Cells: Phagocytes use reactive oxygen species (ROS) to kill microbes in a process known as an "oxidative burst". Vitamin C protects these cells from self-inflicted oxidative damage, and its deficiency leaves them vulnerable, prolonging inflammation and contributing to tissue damage.
Impaired Lymphocyte Function: Though less understood, vitamin C is known to influence the differentiation and proliferation of B- and T-cells, which are critical for adaptive immunity. Its deficiency hampers these processes, leaving the immune system compromised and increasing susceptibility to infection.

Oxidative Stress and Cellular Damage

As a powerful antioxidant, vitamin C helps protect important biomolecules (proteins, lipids, and DNA) from damage by free radicals generated during normal metabolism and from toxins. A deficiency disrupts this protective mechanism.

Inadequate Free Radical Scavenging: In the absence of sufficient vitamin C, the body's ability to neutralize harmful free radicals is significantly reduced. This leads to an increase in oxidative stress, which can damage cells throughout the body.
Epigenetic Alterations: Vitamin C is a cofactor for enzymes involved in the hydroxylation of DNA and histones, which regulates gene expression. Deficiency can lead to epigenetic changes, including hypermethylation, which inhibits the transcription of important genes, including those for collagen.

Hematological Abnormalities

The pathology of vitamin C deficiency extends to blood health, with several hematological consequences.

Anemia: Scurvy is often associated with anemia, which can result from multiple factors. Impaired iron absorption is one cause, as vitamin C facilitates the absorption of non-heme iron from plant-based foods. Hemorrhages in various tissues can also lead to chronic blood loss and anemia. In rare cases, changes to the stability of red blood cells due to collagen defects can contribute to intravascular hemolysis.
Impaired Folate Metabolism: Vitamin C is necessary for converting folic acid to its active metabolite, folinic acid. Deficiency can therefore contribute to folate deficiency and megaloblastic anemia.

Pathology of Vitamin C Deficiency: A Comparative View


Feature	Deficiency (Scurvy)	Sufficiency
Collagen Synthesis	Defective. Unstable triple-helix structure due to inactive hydroxylase enzymes.	Normal. Prolyl and lysyl hydroxylation stabilize collagen.
Vascular Health	Fragile capillaries and blood vessels lead to easy bruising, petechiae, and hemorrhages.	Strong, resilient vessel walls supported by stable collagen.
Immune Response	Impaired. Reduced phagocyte function, lowered resistance to infection, and increased inflammatory response.	Robust. Supports immune cell function and protects against self-inflicted oxidative damage.
Oxidative Stress	Increased cellular damage from free radicals due to weakened antioxidant defense.	Reduced. Potent antioxidant function protects macromolecules from damage.
Bone Structure	Impaired formation of intercellular cement substances. Leads to brittle bones, microfractures, and subperiosteal hemorrhages.	Normal. Essential for the health and repair of bone and cartilage.
Iron Metabolism	Reduced absorption of non-heme iron, potentially leading to iron deficiency anemia.	Enhanced absorption of non-heme iron.
Healing Process	Poor wound healing. Wounds may reopen due to unstable collagen formation.	Accelerated. Necessary for wound healing and scar tissue formation.
Epigenetic Regulation	Epigenetic DNA hypermethylation inhibits transcription of certain genes, including those for collagen.	Normal. Acts as a cofactor for enzymes that regulate gene expression through DNA and histone hydroxylation.

Conclusion

Vitamin C deficiency, leading to the clinical syndrome of scurvy, is a multi-systemic disease rooted in a few core pathological mechanisms. Its inability to act as a crucial enzymatic cofactor directly cripples collagen synthesis, resulting in the characteristic weakening of connective tissues seen in skin, gums, and blood vessels. This, combined with a compromised immune system and heightened oxidative stress, creates a cascade of systemic failures. Early diagnosis, often based on clinical signs and dietary history, is critical, as simple supplementation can reverse the condition, highlighting the profound impact of this single micronutrient on human health and disease. Vitamin C and Immune Function.

Frequently Asked Questions

The primary cause of scurvy is the failure of collagen synthesis. Vitamin C is a critical cofactor for enzymes needed to stabilize collagen, and without it, the body produces weak, defective collagen, leading to a breakdown of connective tissue throughout the body.

A deficiency in vitamin C compromises the collagen that forms the structural integrity of blood vessel walls. This makes capillaries and blood vessels fragile and prone to rupture, resulting in hemorrhages, bruising, and petechiae.

Yes, vitamin C deficiency can cause anemia through several mechanisms, including impaired absorption of non-heme iron, chronic blood loss from hemorrhages, and its role in activating folate, a vitamin also important for red blood cell formation.

Vitamin C is essential for immune function, supporting the activity of phagocytes and lymphocytes. It enhances microbial killing, protects immune cells from oxidative stress, and is depleted during infections, increasing susceptibility to illness.

As a primary antioxidant, vitamin C neutralizes harmful free radicals. In its absence, oxidative stress increases, leading to widespread cellular damage. This stress contributes to inflammation and cellular dysfunction in various organs.

Inadequate vitamin C leads to defective osteoid and dentin formation, impairing bone growth and causing weakened bone structures. In children, this can lead to painful bone lesions. It also causes swollen, bleeding gums and eventual tooth loss.

Although rare in developed countries, scurvy can still occur in individuals with poor dietary intake, such as those with alcoholism, restrictive diets due to allergies, mental illness, or malabsorptive disorders like Crohn's disease. Smoking and other conditions can also increase vitamin C requirements.