Vitamin c deficiency

Vitamin C deficiency, commonly known as scurvy in its severe form, is a nutritional disorder that arises from inadequate intake or absorption of ascorbic acid. This essential water-soluble vitamin plays a crucial role in collagen synthesis, antioxidant protection, and immune function. Understanding its deficiency is important for early diagnosis, prevention, and management of associated complications.

Definition and Overview

Meaning of Vitamin C Deficiency

Vitamin C deficiency refers to an insufficient level of ascorbic acid in the body, leading to impaired collagen formation, weakened connective tissue, and various systemic disturbances. As a vital micronutrient, vitamin C cannot be synthesized endogenously and must be obtained through dietary sources such as citrus fruits, berries, and leafy vegetables. A persistent lack of these sources results in reduced plasma and tissue levels, ultimately manifesting as clinical symptoms of deficiency.

Historical Background (Scurvy and its Discovery)

The history of vitamin C deficiency dates back several centuries, particularly among sailors during long sea voyages who subsisted on preserved foods devoid of fresh produce. The resulting condition, known as scurvy, was characterized by bleeding gums, fatigue, and poor wound healing. In the 18th century, British naval physician James Lind conducted experiments demonstrating that citrus fruits could prevent and cure scurvy, marking a pivotal moment in nutritional science. The identification of ascorbic acid as the active compound responsible for this effect occurred in the early 20th century, solidifying vitamin C’s role in human health.

Physiology of Vitamin C

Chemical Nature and Properties of Ascorbic Acid

Vitamin C, or ascorbic acid, is a six-carbon lactone structurally related to glucose. It functions as a potent reducing agent, readily donating electrons to neutralize reactive oxygen species. This antioxidant property is critical in protecting cellular components such as proteins, lipids, and DNA from oxidative stress. Ascorbic acid is also involved in several enzymatic reactions requiring metal cofactors like iron and copper.

Sources of Vitamin C

Vitamin C is widely distributed in plant-based foods, particularly in fresh fruits and vegetables. Heat, light, and prolonged storage can destroy vitamin C, making fresh consumption essential.

• Citrus fruits: oranges, lemons, and grapefruits
• Berries: strawberries, blackcurrants, and raspberries
• Vegetables: broccoli, bell peppers, tomatoes, and spinach
• Other sources: guava, kiwi, and amla (Indian gooseberry)

Absorption, Metabolism, and Excretion

Vitamin C is absorbed primarily in the small intestine through active transport and passive diffusion. Once absorbed, it circulates in the plasma and is concentrated in tissues such as the adrenal glands, pituitary gland, and leukocytes. The body maintains homeostasis through renal reabsorption, and excess amounts are excreted in urine. Absorption efficiency declines as intake increases, highlighting the importance of regular moderate consumption.

Physiological Roles and Functions

• Collagen synthesis: Acts as a cofactor for prolyl and lysyl hydroxylases, essential for stabilizing collagen structure.
• Antioxidant defense: Protects cells from free radicals and regenerates other antioxidants like vitamin E.
• Iron absorption: Enhances intestinal absorption of non-heme iron by reducing ferric (Fe³⁺) to ferrous (Fe²⁺) form.
• Immune function: Supports leukocyte activity, wound healing, and resistance against infections.
• Neurotransmitter synthesis: Participates in the biosynthesis of norepinephrine and other catecholamines.

Etiology (Causes of Vitamin C Deficiency)

Dietary Deficiency

The most common cause of vitamin C deficiency is inadequate dietary intake. Populations with limited access to fresh fruits and vegetables, such as those in low-income or remote areas, are particularly at risk. Prolonged cooking and food processing can also destroy vitamin C, further reducing its availability in the diet. Individuals relying on unbalanced or restrictive diets, such as those low in plant-based foods, are more likely to develop deficiency symptoms.

Increased Requirement Conditions

Certain physiological and pathological conditions elevate the body’s demand for vitamin C. Growth, pregnancy, lactation, and periods of intense physical activity increase metabolic requirements. Chronic diseases such as infections, malignancies, and inflammatory disorders also heighten oxidative stress, necessitating higher antioxidant intake to maintain tissue integrity and immune defense.

Malabsorption Syndromes

Diseases affecting the gastrointestinal tract, including Crohn’s disease, celiac disease, and chronic diarrhea, can interfere with the absorption of vitamin C. Surgical resection of portions of the intestine or chronic use of medications that alter gastric pH may also reduce its bioavailability, predisposing individuals to deficiency despite adequate intake.

Alcoholism and Drug Interference

Chronic alcohol consumption impairs nutrient absorption and increases urinary excretion of vitamin C. Certain medications, such as oral contraceptives, corticosteroids, and some antibiotics, may alter vitamin metabolism or increase oxidative stress, thereby depleting vitamin C reserves. Smokers are also at higher risk due to increased oxidative turnover of the vitamin.

Socioeconomic and Environmental Factors

Low-income populations, individuals living in institutional settings, and those with poor dietary diversity are particularly susceptible. Environmental factors, such as limited access to fresh produce and reliance on preserved foods, contribute to the global burden of deficiency, especially in developing regions.

Pathophysiology

Role of Vitamin C in Collagen Synthesis

Vitamin C is an essential cofactor for the enzymes prolyl and lysyl hydroxylase, which catalyze the hydroxylation of proline and lysine residues in collagen. This modification stabilizes the collagen triple helix structure, ensuring proper cross-linking and tensile strength of connective tissues. In the absence of sufficient vitamin C, collagen fibers become unstable and weak, resulting in tissue fragility and impaired wound healing.

Impact on Connective Tissue Integrity

Deficiency disrupts the formation of healthy connective tissue in the skin, gums, bones, and blood vessels. Capillary walls become fragile, leading to petechiae and ecchymoses, while gum tissues become swollen and prone to bleeding. Poor collagen synthesis also affects bone matrix formation, causing pain and delayed fracture healing.

Effects on Capillary Fragility and Hemostasis

Vitamin C deficiency leads to increased capillary permeability and fragility due to defective collagen in the vascular basement membrane. This results in spontaneous bleeding under the skin and mucous membranes. Additionally, impaired platelet function and altered hemostasis exacerbate bleeding tendencies, contributing to classic signs such as bleeding gums and subcutaneous hemorrhages.

Influence on Iron Absorption and Antioxidant Defense

Vitamin C enhances non-heme iron absorption by reducing ferric ions to their ferrous form in the intestine. Deficiency may therefore contribute to microcytic anemia, particularly in individuals with low iron intake. Furthermore, the reduced antioxidant capacity leads to increased oxidative stress, damaging cellular components and impairing immune defense mechanisms. This vulnerability contributes to fatigue, poor resistance to infections, and delayed recovery from illness.

Clinical Manifestations

General Symptoms

Vitamin C deficiency manifests initially with nonspecific symptoms that reflect the body’s declining metabolic efficiency. Fatigue, malaise, and generalized weakness are often the earliest complaints. These arise from impaired energy metabolism, oxidative stress, and the weakened structural integrity of tissues dependent on collagen.

• Fatigue and malaise: Result from decreased carnitine synthesis and reduced energy production within cells.
• Weakness and weight loss: Develop due to anorexia, muscle atrophy, and poor nutrient utilization.

Specific Signs

As deficiency progresses, more distinctive clinical signs become apparent, primarily due to defective collagen formation and capillary fragility. These manifestations are characteristic and aid in clinical diagnosis.

• Oral Manifestations: The gums become swollen, spongy, and prone to bleeding. Gingival overgrowth and tooth loosening may occur in severe cases due to weakening of periodontal connective tissue.
• Dermatological Signs: The skin may exhibit petechiae, ecchymoses, and perifollicular hemorrhages. A hallmark feature is the presence of corkscrew hairs, resulting from defective keratin synthesis and follicular hemorrhage.
• Musculoskeletal Symptoms: Joint pain and muscle tenderness occur because of bleeding within muscles and joints. Subperiosteal hemorrhages may cause bone pain and restricted movement, particularly in children.
• Delayed Wound Healing: Impaired collagen deposition results in prolonged healing time and susceptibility to wound dehiscence or reinjury.
• Anemia and Immune Dysfunction: Anemia develops due to both decreased iron absorption and chronic blood loss from fragile capillaries. Immune weakness increases susceptibility to infections.

Severe Deficiency: Scurvy

Prolonged vitamin C deficiency leads to scurvy, a systemic condition marked by profound connective tissue breakdown and hemorrhagic manifestations. Classical scurvy presents with swollen, bleeding gums, joint effusions, anemia, and marked fatigue. In advanced cases, patients may develop poor wound healing, ulcerations, and secondary infections. Without intervention, complications such as severe anemia or cardiac failure can occur, though these are rare in modern medicine.

Diagnosis

Clinical Assessment and History

Diagnosis begins with a detailed dietary history, focusing on fruit and vegetable intake, along with risk factors such as alcohol use or malabsorption disorders. Symptoms like bleeding gums, bruising, and delayed wound healing raise clinical suspicion. A history of poor nutrition or socioeconomic constraints often supports the diagnosis.

Physical Examination Findings

On examination, findings may include perifollicular petechiae, ecchymoses, hyperkeratotic papules, and gingival hypertrophy. Children may present with limb tenderness and difficulty walking due to subperiosteal hemorrhages. In severe cases, pseudoparalysis can occur, mimicking rheumatologic or orthopedic conditions.

Laboratory Investigations

• Plasma Ascorbic Acid Levels: The most direct diagnostic test. Levels below 11 µmol/L (0.2 mg/dL) are diagnostic of deficiency.
• Complete Blood Count (CBC): May show normocytic or microcytic anemia due to reduced iron absorption and chronic bleeding.
• Iron Studies: Often indicate secondary iron deficiency with low serum iron and ferritin levels.
• Inflammatory Markers: Elevated ESR and CRP may be present in cases complicated by infection or inflammation.

Radiological and Imaging Features (if applicable)

In pediatric scurvy, X-rays may reveal characteristic findings such as a dense white line at the metaphysis (Frankel’s line), a lucent zone of bone resorption (Trümmerfeld zone), and subperiosteal hemorrhages. These findings are rare in adults but remain diagnostic indicators in severe deficiency.

Differential Diagnosis

Vitamin C deficiency should be distinguished from other causes of bleeding or connective tissue disorders. The following table summarizes key differentiating features:

Condition	Distinguishing Features
Vitamin K deficiency	Prolonged clotting time, normal collagen synthesis, bleeding primarily due to coagulation defect
Hemophilia	Inherited clotting disorder, joint hemorrhages without skin petechiae
Protein-calorie malnutrition	Generalized wasting and edema without characteristic gum or skin findings
Vasculitis	Inflammatory skin lesions, positive autoimmune markers, often painful purpura

Complications

Hematological Complications

Vitamin C deficiency contributes to the development of various hematological abnormalities, primarily anemia. This occurs through several mechanisms, including reduced iron absorption, chronic blood loss due to fragile capillaries, and decreased folate metabolism. The resulting anemia often manifests as fatigue, pallor, and shortness of breath, which can exacerbate the patient’s overall weakness.

• Iron deficiency anemia: Caused by impaired intestinal absorption of non-heme iron.
• Hemorrhagic anemia: Arises from recurrent bleeding into tissues and mucous membranes.
• Folate-related anemia: Due to decreased stability and utilization of folic acid in deficiency states.

Musculoskeletal and Connective Tissue Disorders

The integrity of the musculoskeletal system depends heavily on collagen synthesis. In the absence of adequate vitamin C, connective tissue becomes weak and unstable, leading to pain and structural deformities. Subperiosteal hemorrhages and bone tenderness are particularly pronounced in children, often causing reluctance to walk or pseudoparalysis.

• Osteopenia and bone pain: Due to defective bone matrix formation and cortical thinning.
• Joint effusions and hemorrhage: Lead to painful swelling and limited mobility.
• Delayed fracture healing: Collagen deficiency prolongs the repair process following injury.

Infectious Susceptibility

Vitamin C plays a significant role in immune defense by enhancing leukocyte function and supporting epithelial barrier integrity. Deficiency weakens these protective mechanisms, leading to an increased frequency and severity of infections. Respiratory and periodontal infections are particularly common in individuals with chronic deficiency.

Maternal and Infant Health Implications

In pregnant women, low vitamin C levels are associated with adverse outcomes such as preterm labor, low birth weight, and premature rupture of membranes. In infants, deficiency can lead to impaired growth, irritability, and bone deformities resembling rickets. Breastfed infants of deficient mothers are especially vulnerable due to low vitamin content in breast milk.

Treatment and Management

Vitamin C Supplementation: Dosage and Routes

Treatment of vitamin C deficiency involves replenishing ascorbic acid stores through oral or, in severe cases, parenteral supplementation. The dose depends on the severity of deficiency and the presence of clinical symptoms. Mild cases respond well to oral therapy, while scurvy may require higher doses for rapid correction.

• Mild deficiency: 100–250 mg orally once or twice daily for one to two weeks.
• Scurvy: 500–1000 mg daily for at least two weeks, followed by maintenance dosing.
• Parenteral route: Used in patients with malabsorption or inability to tolerate oral medication.

Dietary Modifications and Nutritional Counseling

Long-term management includes adopting a diet rich in fresh fruits and vegetables to prevent recurrence. Nutritional counseling should emphasize the importance of consuming raw or minimally cooked produce to preserve vitamin content.

• Include citrus fruits, berries, and guava regularly in meals.
• Incorporate vitamin C–rich vegetables such as bell peppers, tomatoes, and broccoli.
• Advise minimal boiling and prolonged storage of food to prevent nutrient loss.

Management of Underlying Causes

Identifying and addressing contributing factors is crucial for sustained recovery. Conditions such as alcoholism, malabsorption syndromes, or chronic illness should be treated concurrently. Supplementation may be extended in patients with increased metabolic demand or chronic disease states.

Monitoring and Follow-Up

Clinical improvement is typically observed within days of initiating treatment, with bleeding and fatigue resolving rapidly. Gums and skin lesions heal progressively over weeks. Follow-up includes dietary assessment and periodic monitoring of plasma ascorbic acid levels, especially in high-risk populations.

Prevention

Recommended Dietary Allowances (RDA)

Preventing vitamin C deficiency involves ensuring adequate daily intake through a balanced diet. The recommended dietary allowances vary according to age, gender, and physiological status. Increased intake is necessary during periods of stress, infection, pregnancy, and lactation due to higher metabolic demands.

Group	Recommended Dietary Allowance (mg/day)
Infants (0–12 months)	40–50
Children (1–8 years)	15–25
Adolescents (9–18 years)	45–65
Adults (Men)	90
Adults (Women)	75
Pregnant women	85
Lactating women	120
Smokers	+35 (additional to base requirement)

Public Health Measures and Awareness

Community-level interventions and awareness programs play a crucial role in reducing the prevalence of vitamin C deficiency. Educational initiatives can promote the consumption of vitamin-rich foods and highlight the dangers of dietary neglect. Public health nutrition campaigns should focus on at-risk groups such as children, pregnant women, and the elderly.

• Promotion of local cultivation and availability of vitamin C–rich produce.
• Inclusion of nutrition education in school curricula and community outreach programs.
• Encouraging healthy food preparation methods that preserve nutrient value.

Fortification and Supplement Programs

Food fortification with vitamin C is an effective preventive strategy, especially in regions where access to fresh produce is limited. Supplementation programs in healthcare facilities and community centers can also ensure adequate intake among vulnerable populations.

• Fortification of juices, cereals, and processed foods with ascorbic acid.
• Distribution of vitamin supplements in maternal and child health programs.
• Routine supplementation during recovery from illness or surgery to enhance tissue repair.

Prognosis

Recovery and Reversibility of Symptoms

Vitamin C deficiency has an excellent prognosis when diagnosed and treated early. Most symptoms begin to improve within days of initiating supplementation, with complete recovery in a few weeks. Gingival swelling, bleeding, and fatigue resolve rapidly, while musculoskeletal symptoms and anemia may take longer to normalize. Early intervention prevents irreversible tissue damage and secondary complications.

Long-Term Outcomes if Untreated

Without treatment, chronic deficiency can lead to severe systemic effects, including persistent anemia, chronic pain, and impaired wound healing. In advanced cases of scurvy, internal hemorrhage, secondary infections, and cardiac complications may occur. Untreated deficiency in children can result in stunted growth and bone deformities. However, in modern healthcare settings, fatal outcomes are extremely rare due to early recognition and effective supplementation.

Vitamin C Deficiency in Special Populations

Infants and Children

Infants and growing children are particularly vulnerable to vitamin C deficiency due to their rapid metabolic rate and higher nutritional needs relative to body weight. Exclusive feeding on pasteurized milk, which contains minimal vitamin C, or delayed introduction of fruits and vegetables can precipitate deficiency. In children, scurvy presents with irritability, loss of appetite, and painful swelling of the limbs due to subperiosteal hemorrhages. Growth retardation and delayed bone formation are common findings, and radiographic changes such as cortical thinning and metaphyseal lucent zones may be evident.

• Encourage early introduction of vitamin-rich weaning foods.
• Promote breastfeeding alongside supplementation for at-risk infants.
• Monitor growth patterns and dietary diversity during pediatric checkups.

Pregnant and Lactating Women

Pregnancy increases the demand for vitamin C to support fetal growth, placental function, and maternal tissue expansion. Deficiency during this period can lead to complications such as premature rupture of membranes, preterm labor, and anemia. In lactating mothers, inadequate vitamin C intake reduces the concentration of ascorbic acid in breast milk, increasing the risk of deficiency in infants. Supplementation during pregnancy and breastfeeding ensures adequate nutrient transfer to the developing child and maintains maternal health.

• Provide prenatal supplements containing 85–120 mg of vitamin C daily.
• Encourage dietary sources like citrus fruits, amla, and leafy greens.
• Conduct routine nutritional screening during antenatal visits.

Elderly Individuals

The elderly population often exhibits reduced dietary intake and poor absorption of vitamin C due to age-related physiological changes. Dental issues, decreased appetite, limited access to fresh produce, and chronic illnesses further increase vulnerability. Deficiency in older adults can exacerbate wound healing delays, increase infection risk, and impair mobility through musculoskeletal pain. Maintaining adequate intake through fresh foods or supplements significantly improves quality of life in this age group.

Individuals with Chronic Diseases or Malnutrition

Patients with chronic illnesses such as diabetes, renal failure, malignancies, or inflammatory diseases experience increased oxidative stress and metabolic demand for vitamin C. Similarly, malnourished individuals, alcoholics, and those with eating disorders frequently suffer from deficiency due to inadequate intake and absorption. Regular monitoring and targeted supplementation are essential to prevent complications and enhance immune and tissue repair functions in these populations.

Recent Research and Advances

Role of Vitamin C in Immunity and Chronic Diseases

Recent studies highlight vitamin C’s crucial role in immune regulation and chronic disease prevention. Ascorbic acid enhances the function of neutrophils, promotes lymphocyte proliferation, and reduces oxidative stress during infections. Evidence suggests that adequate vitamin C intake may reduce the severity and duration of respiratory infections and improve outcomes in patients with sepsis and critical illness. Additionally, its antioxidant properties contribute to reducing the risk of chronic diseases such as cardiovascular disorders, diabetes, and certain cancers by mitigating oxidative damage.

Emerging Studies on Antioxidant and Anti-Inflammatory Effects

Modern research explores vitamin C’s potential beyond traditional deficiency correction. Clinical trials are investigating high-dose intravenous vitamin C as an adjunctive therapy in conditions involving systemic inflammation and oxidative stress, such as COVID-19, sepsis, and cancer therapy. Its synergistic action with other micronutrients like vitamin E and zinc is also under study for optimizing antioxidant defense. While these findings are promising, further large-scale studies are required to establish definitive therapeutic roles and dosing protocols.

References

1. Gorton HC, Jarvis K. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. J Manipulative Physiol Ther. 1999;22(8):530-533.
2. Naidu KA. Vitamin C in human health and disease is still a mystery? An overview. Nutr J. 2003;2(1):7.
3. Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin Care. 2002;5(2):66-74.
4. Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999;281(15):1415-1423.
5. Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press; 2000.
6. Padayatty SJ, Katz A, Wang Y, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. 2003;22(1):18-35.
7. World Health Organization. Vitamin and mineral requirements in human nutrition. 2nd ed. Geneva: WHO; 2004.
8. Figueroa-Méndez R, Rivas-Arancibia S. Vitamin C in health and disease: its role in the metabolism of cells and redox state in the brain. Front Physiol. 2015;6:397.
9. Carr AC, Maggini S. Vitamin C and immune function. Nutrients. 2017;9(11):1211.
10. Hemilä H. Vitamin C and infections. Nutrients. 2017;9(4):339.