Overview

Malnutrition is one of the major public health concerns for children. It affects millions of kids worldwide, especially those living in countries with a low socioeconomic status. Severe malnutrition causes Kwashiorkor.¹ 

Kwashiorkor is usually observed in children aged 6 months to 5 years. The characteristics of this disease are reduced protein and micronutrient levels.² These lead to oxidative stress, poor nutrition, gut imbalance, and a weakened immune system in children, which in turn affects their growth.³ 

Research suggests that it can also decrease the efficiency of oral vaccines, which can make children prone to fatal secondary infections such as pneumonia, diarrhoea.⁴ 

This article explores the key micronutrient deficiencies and their roles in the manifestation of kwashiorkor.

Symptoms of kwashiorkor

Kwashiorkor developed due to a severe protein deficiency condition with varying symptoms. The most characteristic symptom of this disease is swelling in the face and legs, also known as pitting oedema.^2,5

Other symptoms include:

• Pale skin tone 
• Sores on the legs, groin area, and arms 
• Hair thinning 
• Enlargement of the liver⁶ 

In severe cases, swelling may develop in the whole body. Affected children often feel tired and lose their appetite. If these symptoms are neglected, this could result in coma, shock, or death.⁷

Pathophysiology of kwashiorkor

Kwashiorkor is mainly driven by severe protein deficiency.² This inadequate protein availability sets off a cascade of physiological reactions in the body.⁸ They include:

• Hypoalbuminemia or reduced hepatic albumin production
• Hepatic Steatosis or fatty liver
• Weakened Immune system
• Oxidative Stress and Inflammation
• Leaky gut

But Kwashiorkor is not just about low protein intake.  It is commonly observed that children with kwashiorkor are extremely deficient in micronutrients such as Iron, Zinc, Selenium, and Vitamin A.⁸ These deficiencies contribute significantly to Kwashiorkor’s pathophysiology and are observed to worsen the severity of the disease.⁷

The following sections explain how deficiencies in micronutrients such as iron, zinc, selenium, and vitamin A influence the clinical progression of kwashiorkor.

Role of micronutrient deficiencies in kwashiorkor

Iron

In Kwashiorkor, iron deficiency occurs due to a combination of factors that are linked to protein deficiency and other micronutritional imbalances.⁵ These include decreased iron absorption, increased iron losses, and the body's inability to efficiently use iron due to a lack of protein and other important nutrients.⁶,⁹ 

• Impaired Iron Absorption:
  • Kwashiorkor patients experience environmental enteric dysfunction (EED) (a chronic inflammation of the gut common in people from low-income settings), which damages the intestinal lining; this damage reduces dietary iron absorption^{9 13,10}
  • Protein deficiency in Kwashiorkor can affect the production of hydrochloric acid in the stomach, which is essential for converting iron into a form that can be absorbed in the intestines^9,10 
• Increased loss of Iron:
  • Kwashiorkor patients often suffer from secondary infections such as intestinal parasites, dysentery, and malaria, which can cause blood loss or inflammation and further reduce the body's iron levels⁵
• Inefficient Iron Utilisation:
  • Kwashiorkor causes Transferrin deficiency, affecting the body's ability to transport iron to the bone marrow for RBC production⁹ 
  • Folic acid deficiency in Kwashiorkor hinders the production of RBCs, leading to iron deficiency anaemia¹⁰ 
• Compromised Immune Function:
  • Iron deficiency state in Kwashiorkor patients reduces the number of circulating T cells, impairing production of cytokines such as IL-6, TNF-α, and IFN-γ. As a result, the body becomes more susceptible to secondary infections like pneumonia¹¹
  • The fine balance between Th1 and Th2 responses is altered due to Iron deficiency. This, in turn, affects the ability of the body to fight intracellular pathogens such as viruses and certain bacteria^2,13

In summary, iron deficiency in Kwashiorkor not only contributes to anaemia and growth delays but also plays a critical role in weakening immune defences and prolonging recovery.

Zinc

Zinc is an essential micronutrient for cell growth, immune function, and maintaining the gut lining.  Zinc deficiency is common in children with Kwashiorkor.⁵ The deficiency can be linked to several physiological and dietary factors.⁷ 

Physiologically, zinc deficiency occurs due to impaired absorption and altered metabolism.

• Impaired Zinc Absorption:
  • Due to protein deficiency in Kwashiorkor, the synthesis of proteins such as metallothionein and albumin is affected, both of which are essential for zinc absorption and transport¹⁴ 
  • In Kwashiorkor, the intestinal lining is damaged due to inflammation and malnutrition. As a result, there is increased intestinal permeability and nutrient loss. All these causes significantly affect zinc absorption¹⁵
• Altered Zinc Metabolism:
  • Kwashiorkor causes reduced synthesis of albumin, a protein that binds to zinc in the blood. This can reduce the transportation of zinc to the tissues 
  • Kwashiorkor also leads to increased loss of zinc through urine or faeces, further reducing zinc concentration
  • Oxidative stress, which is a classic Kwashiorkor symptom, can also further impair zinc absorption and utilisation

Also, consuming food that is low in zinc and heavy in phytate-rich foods such as legumes and cereals can lead to zinc deficiency, because phytates bind zinc in the stomach and stop its absorption.¹⁴ 

Hence, zinc deficiency in Kwashiorkor results from a combination of factors like improper zinc absorption, altered zinc metabolism, and reduced dietary zinc intake. It leads to gut damage, disrupts immune responses and increases vulnerability to secondary infections.

Selenium

Selenium is an essential micronutrient that helps the body’s antioxidant defence, thyroid hormone metabolism, and immune function.¹⁶ Selenium deficiency is frequently observed in children with Kwashiorkor.⁵ Causes include improper absorption of selenium due to a weakened gut barrier and other physiological mechanisms, which are still under investigation. It is also more prevalent in areas where the soil is low in selenium.^{7 17}

• Impaired selenium adsorption:  
  • In Kwashiorkor, protein deficiency causes damage to the gastrointestinal lining. This affects the uptake of selenium^6,7
• Geographical Influences:
  • Kwashiorkor is highly prevalent in Children from regions with low soil selenium levels, especially if their diet is primarily based on locally grown foods¹⁷

Selenium deficiency in Kwashiorkor can have several consequences, including weakened immune function, thyroid dysfunction, and potential contributions to the development of congestive heart failure or Keshan’s disease^{16 18}

Vitamin A

Vitamin A is an important micronutrient required for healthy vision, immune function, and maintenance of the gut lining.¹⁹ In Kwashiorkor, vitamin A deficiency results from poor dietary intake and improper absorption due to fat malabsorption, which is often seen when there is severe protein deficiency.²⁰

• Impaired Vitamin A Absorption and reduced reserves:
  • In Kwashiorkor, protein deficiency affects both the liver and the gut, reducing vitamin A storage in the liver and affecting its absorption in the intestine due to fat malabsorption²⁰
• Increased loss of vitamin A due to infections:
  • Kwashiorkor often leads to infections, like diarrhoea. These diseases can lead to vitamin A deficiency by impairing its absorption^{20 21}
• Dietary Factors:
  • Consuming diets based on starchy foods like maize, cassava, or rice also causes vitamin A deficiency^{20 22} 

Vitamin A deficiency in Kwashiorkor patients can lead to increased chances of secondary infections, delayed wound healing, and, in severe cases, vision problems such as night blindness and an increased risk of blindness.²⁰

When diagnosing Kwashiorkor, micronutrient deficiencies are neglected. Research has proved that each of these deficiencies can significantly affect the body’s immunological function and defence.

Therefore, treating Kwashiorkor requires more than just correcting protein deficiency. The important role played by micronutrients like vitamin A, iron, zinc, and selenium in maintaining overall health should also be considered.

Neglecting these deficiencies can result in chronic infections and delayed recovery. A complete nutritional plan that includes proteins and micronutrient supplements is essential for effective management of Kwashiorkor.

Summary

Kwashiorkor is a severe type of malnutrition commonly affecting children in low-income regions. While it is known to be associated with protein deficiency, recent research has highlighted the role of micronutrient deficiencies like iron, zinc, selenium, and vitamin A in its development. 

These micronutrients are important for immune function, to prevent oxidative stress, and to maintain gut lining. For example, iron deficiency affects T-cell function and cytokine production, zinc deficiency destroys the gut, selenium deficiency weakens redox function, and vitamin A deficiency affects vision and immunity. Despite their critical roles, these deficiencies are often neglected in diagnosis and treatment. 

Treatment thus requires a comprehensive nutritional plan that includes both macronutrient and micronutrient support. Early recognition and intervention with these considerations can help in recovery, reduce complications of secondary infections, and support long-term health in affected children.