Vitamins C, D, E and K, and minerals

Vitamins are organic compounds that act as co‑enzymes or cofactors. They are classified as fat‑soluble (A, D, E, K) or water‑soluble (B‑complex, C). Minerals such as iron, magnesium and zinc are inorganic elements that participate in enzymatic reactions, structural roles and ion transport.

The body cannot synthesise most vitamins; they must be obtained from diet or, for vitamin D, from cutaneous synthesis under ultraviolet light.

Scurvy is caused by a severe lack of vitamin C (ascorbic acid). The classic triad—bleeding gums, perifollicular haemorrhages and poor wound healing—develops after prolonged deficiency. Prior to these, patients often report non‑specific symptoms such as fatigue, irritability and muscle pain. ^[2]

Vitamin D is central to calcium and phosphorus homeostasis and skeletal integrity. It is also involved in numerous extra‑skeletal processes, including immune modulation and cell proliferation. Serum 25‑hydroxyvitamin D [25(OH)D] is the standard marker of vitamin D status.

• Deficiency: serum 25(OH)D < 20 ng/mL ^[1]
• Insufficiency: serum 25(OH)D < 30 ng/mL ^[1]

Vitamin D deficiency is common in chronic kidney disease (CKD) and end‑stage renal disease (ESRD), with a higher prevalence in haemodialysis patients. The degree of deficiency correlates inversely with kidney function, and low levels are linked to worsening renal outcomes and higher morbidity and mortality in CKD populations. Experimental models show that vitamin D deficiency can aggravate contrast‑induced nephropathy, a frequent cause of acute renal failure in hospitals. ^[1]

Vitamin E (α‑tocopherol) is a lipid‑soluble antioxidant that protects cell membranes from oxidative damage. It also modulates immune responses and platelet aggregation. Deficiency is rare but can occur in malabsorption syndromes, leading to neurological deficits such as ataxia, peripheral neuropathy and myopathy. ^[1]

Vitamin K exists in two main forms: K1 (phylloquinone) from green leafy vegetables and K2 (menaquinones) from fermented foods and bacterial synthesis. Its primary role is the γ‑carboxylation of glutamic acid residues on clotting factors II, VII, IX and X, enabling calcium binding and coagulation. Vitamin K deficiency manifests as prolonged clotting times and bleeding diathesis, especially in newborns and patients on long‑term antibiotics or fat‑malabsorption therapies. ^[1]

Both vitamins are essential for maintaining vascular health; vitamin K is required for matrix Gla‑protein activation, which inhibits vascular calcification, while vitamin E reduces oxidative stress that can promote atherosclerosis.

Vitamin K is the most well‑known example. It is required for γ‑carboxylation of clotting factors II, VII, IX and X. Warfarin and other vitamin K antagonists inhibit this process, so dietary vitamin K intake can blunt their effect. In patients on warfarin, a sudden increase in vitamin K intake (e.g. from leafy greens or supplements) can raise the international normalised ratio (INR) and reduce anticoagulant activity, whereas a decrease can precipitate thrombosis. Clinicians therefore advise stable vitamin K consumption and monitor INR closely when dietary changes occur.

Other vitamins and minerals may also influence anticoagulation indirectly. Vitamin C, for instance, is a potent antioxidant that can reduce oxidative stress and may affect platelet function. However, evidence for a clinically significant interaction between vitamin C and warfarin is limited and inconsistent. Likewise, high‑dose vitamin E has been reported to possess antiplatelet properties, potentially increasing bleeding risk when combined with antiplatelet agents or anticoagulants, but definitive data are lacking.

In summary, the only vitamin with a robust, clinically relevant anticoagulant interaction is vitamin K, and its effect is well characterised in the context of warfarin therapy.

Zinc is a catalytic cofactor for over 300 enzymes, including DNA polymerases and superoxide dismutase. It is essential for immune function, wound healing and neurocognitive processes. Low dietary zinc or low serum zinc is linked to depression in adults and the elderly, with a relative risk of 0.67 for depression when intake is high. Zinc overload can also be harmful; in Alzheimer disease, excessive zinc may promote β‑amyloid aggregation and neurodegeneration. ^[2]

Selenium is incorporated into selenoproteins such as glutathione peroxidases (GSH‑Px), which neutralise hydrogen peroxide and protect cells from oxidative stress. In chronic kidney disease (CKD) and end‑stage renal disease (ESRD), selenium deficiency is common due to reduced absorption and dialysis loss, leading to lower GSH‑Px activity. Selenium supplementation restores GSH‑Px levels and may improve oxidative balance. ^[1]

Iodine is indispensable for the synthesis of thyroid hormones (T₃ and T₄). Adequate iodine intake prevents goitre, cretinism and cognitive deficits. Iodine deficiency remains a public health issue in regions with low soil iodine. The recommended daily allowance (RDA) for adults is 150 µg, and deficiency can be diagnosed by urinary iodine excretion <100 µg/L. ^[2]

Iron is a core component of haemoglobin, myoglobin and numerous enzymes. It is essential for oxygen transport, DNA synthesis and mitochondrial respiration. However, excess iron catalyses the Fenton reaction, producing hydroxyl radicals that damage lipids, proteins and DNA. Tight regulation of iron homeostasis prevents overload, but in pathological states iron can accumulate and contribute to neurodegeneration.

Iron deficiency is the most common nutritional deficiency worldwide and is a major cause of anaemia. In young premenopausal women with non‑anaemic iron deficiency, iron supplementation (80 mg elemental iron daily for 12 weeks) reduced fatigue complaints by more than 60 %. Iron status also influences cognition: low ferritin is associated with poorer performance on memory and intelligence tests in young adults. ^[2]

Copper is a cofactor for cytochrome c oxidase, lysyl oxidase and ceruloplasmin. It is required for energy production, connective tissue formation and iron metabolism. Both copper deficiency and excess can cause neurological and hematological disorders. In deficiency, ceruloplasmin activity falls, impairing iron mobilisation and leading to microcytic anaemia. Excess copper, as seen in Wilson’s disease, accumulates in the liver and brain, causing hepatotoxicity and neuropsychiatric symptoms.

Protein‑energy malnutrition (PEM) remains a major public‑health problem in many low‑income settings, despite global progress in nutrition. PEM is characterised by a deficiency of both protein and energy, but the clinical manifestations differ according to the pattern of nutrient loss. Two classic phenotypes are recognised: kwashiorkor and marasmus.

Kwashiorkor presents after a period of adequate caloric intake that is suddenly interrupted by a protein‑deficient diet. The hallmark features are oedema, especially in the lower limbs, a distended abdomen, skin changes (hyper‑pigmentation, dermatitis), hair colour changes and a characteristic “moon face”. The oedema is largely due to hypo‑albuminaemia, which reduces plasma oncotic pressure and allows fluid to leak into interstitial spaces. The skin lesions reflect impaired collagen synthesis and altered immune function. Children with kwashiorkor often have a normal or only slightly reduced weight‑for‑height z‑score, but a markedly reduced weight‑for‑age z‑score.

Marasmus, by contrast, results from a prolonged deficiency of both protein and energy. The clinical picture is characterised by severe wasting of both fat and lean body mass, a “skin‑tight” appearance, a sunken abdomen, and a very low weight‑for‑height z‑score. The child appears emaciated, with a thin, translucent skin and a prominent rib cage. Oedema is usually absent, and the child’s growth trajectory is markedly impaired. Marasmus is associated with a higher mortality rate than kwashiorkor, largely due to the profound depletion of body reserves and the increased susceptibility to infections.

Both conditions share common pathophysiological mechanisms: impaired protein synthesis, altered immune function, and increased catabolism. However, the relative contribution of protein versus energy deficiency determines the clinical phenotype. In kwashiorkor, the energy intake may be sufficient to maintain body weight, but the lack of protein leads to hypo‑albuminaemia and oedema. In marasmus, the combined deficit of protein and energy leads to a loss of both fat and lean tissue.

The diagnosis of PEM is based on anthropometric measurements, clinical examination, and laboratory investigations. Weight‑for‑height z‑score <−2 indicates moderate to severe acute malnutrition. Mid‑upper arm circumference (MUAC) <115 mm is a rapid screening tool for severe acute malnutrition. Laboratory tests may reveal hypo‑albuminaemia, low pre‑albumin, and altered lipid profiles. In practice, the presence of oedema, skin changes, and hair abnormalities should prompt a high index of suspicion for kwashiorkor, whereas a markedly low weight‑for‑height and a “skin‑tight” appearance suggest marasmus.

Management of PEM requires a staged approach. The first stage is re‑feeding, which must be gradual to avoid re‑feeding syndrome. The recommended energy intake is 75–100 kcal/kg/day for children with severe acute malnutrition, with a protein intake of 1.5–2 g/kg/day. Micronutrient supplementation, particularly zinc, vitamin A, and iron, is essential to optimise recovery. In kwashiorkor, albumin replacement is not routinely recommended; instead, careful monitoring of fluid balance and electrolytes is crucial. In marasmus, the focus is on restoring lean body mass and preventing catabolism. The second stage involves nutritional rehabilitation, with a gradual increase in caloric and protein intake, and the introduction of a balanced diet rich in fruits, vegetables, and dairy products. The third stage is the prevention of relapse, which includes community‑based management, education of caregivers, and monitoring of growth trajectories.

The prognosis of PEM depends on the severity of the condition, the presence of comorbidities, and the timeliness of intervention. Children who receive appropriate re‑feeding and micronutrient supplementation have a good chance of recovery, but long‑term neuro‑cognitive deficits may persist, especially if the malnutrition occurs during critical periods of brain development.

1. Under‑recognition of kwashiorkor – Because the child may maintain a normal weight, clinicians may miss the diagnosis if oedema and skin changes are not recognised.
2. Rapid re‑feeding – Initiating high‑calorie feeds too quickly can precipitate re‑feeding syndrome, characterised by hypophosphataemia, hypomagnesaemia, and cardiac arrhythmias.
3. Inadequate micronutrient coverage – Focusing solely on macronutrients can overlook deficiencies in zinc, vitamin A, and iron, which are critical for immune function and wound healing.
4. Failure to monitor fluid status – In kwashiorkor, aggressive fluid administration can worsen oedema and lead to pulmonary oedema.
5. Neglecting psychosocial factors – Stigma, food insecurity, and caregiver education are often overlooked but are essential for sustainable recovery.

Protein‑energy malnutrition is most frequently encountered in humanitarian settings, refugee camps, and low‑income communities where food security is precarious. In high‑income countries, PEM is rare but can occur in institutionalised settings, among children with eating disorders, or in chronic illnesses that impair nutrient absorption.

Clinical practice guidelines recommend a systematic approach to screening, diagnosis, and management. In acute care, the World Health Organization (WHO) recommends the use of MUAC and weight‑for‑height z‑scores for rapid assessment. Community‑based management programmes, such as the Community‑Based Management of Acute Malnutrition (CMAM), use ready‑to‑use therapeutic foods (RUTF) to provide high‑energy, high‑protein nutrition without the need for complex preparation.

In hospital settings, specialised nutrition support teams assess caloric needs, monitor biochemical markers, and tailor supplementation. The use of micronutrient‑enriched formulations is common, especially in children with kwashiorkor, to address the high prevalence of zinc and vitamin A deficiencies.