The scourge of malnutrition: causes and consequences

Highlights:

• Malnutrition is a severe condition caused by a lack of nutrients, which includes both undernutrition and overnutrition
• Undernutrition impairs bodily functions, which may lead to immune system dysfunction, hormonal imbalance, and musculoskeletal problems
• Aging is a major risk factor for malnutrition 
• Nutritional management and prevention of malnutrition are one of the necessary steps for healthy aging

Introduction

Malnutrition is generally described as a condition of being poorly nourished, caused either by lack (undernutrition) or excess (overnutrition) of nutrients. Today, nearly one in three persons globally suffer from at least one form of malnutrition: wasting, stunting, vitamin and mineral deficiency, overweight or obesity, and diet-related NCDs (non-communicable diseases). In 2014, approximately 462 million adults worldwide were underweight, while 1.9 billion were overweight or obese. Women, children, and older adults are especially vulnerable to malnutrition. 

Diagnostic criteria

In 2019 more than 70 national scientific societies presented the Global Leadership Initiative on Malnutrition (GLIM) (1,2), aiming to develop malnutrition criteria that could be used in clinical settings. Three phenotypic criteria are considered:

• Weight loss,
• A low body mass index (BMI),
• A reduced muscle mass.

And additionally, two etiological criteria are included:

• A reduced food intake,
• Inflammation (chronic or acute).

The diagnosis requires the presence of at least one phenotypic and one etiological criterion. 

Types of weight loss

When discussing weight loss, four main types can be distinguished - wasting, stunting, cachexia, and sarcopenia. 

Wasting is related to an insufficient dietary intake, which leads to involuntary and severe weight loss. Wasting is characterized by a low weight-to-height ratio (3). 

Stunting is connected to chronic or recurrent undernutrition characterized by low height-for-age. It is primarily a child condition and prevents normal physical and cognitive development.

Cachexia is a condition of critical loss of a body mass that results from induced catabolic processes, with the production of pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), IL-6, and others playing a predominant role. The main consequence of cachexia is a reduction of lean mass and body cell mass (4).

Sarcopenia is an age-related condition defined by a loss of muscle mass combined with a loss of muscle strength or physical performance (5). The etiology is poorly understood, but the leading causes are thought to be physical inactivity, a pro-inflammatory response, and the dysregulation of anabolic hormones (such as testosterone or growth hormone) (6,7). Sarcopenia induced and accompanied by malnutrition led to the new term “malnutrition sarcopenia syndrome”.

Physiology and causes of malnutrition

The causes of malnutrition highly vary depending on the economic and social conditions. The main causes can be categorized into three main groups (8): 

Physiological causes:

• diseases (infectious, gastrointestinal, respiratory, endocrine, neurological, oncological, etc.),
• malabsorption,
• dysphagia,
• oral problems/loss of smell or taste,
• loss of autonomy,
• drug interactions,
• poor appetite and diet;

Psychological causes:

• depression,
• anxiety,
• dementia/confusion,
• alcoholism and other addictions;

Social causes:

• poverty,
• loneliness and isolation,
• inability to shop and/or prepare food.

Regarding nutrients, malnutrition can exist in two forms - protein-energy malnutrition and micronutrient malnutrition. Micronutrient malnutrition results from an insufficient intake of vitamins and minerals, the main deficiencies worldwide being iodine, vitamin A, and iron. Protein-energy malnutrition (PEM) involves protein deficiency of protein and micronutrients. There are two main types of PEM – kwashiorkor and marasmus, though they can coexist. Kwashiorkor is connected to insufficient protein consumption combined with high-energy food (i.e., a diet composed largely of carbohydrates). Marasmus is a similar condition, but in this case, low protein intake is combined with generally low-energy food. 

Research shows that undernourishment based on PEM greatly increases susceptibility to major human infectious diseases and has been causally linked to immunodeficiency (9). Chronic or acute PEM can affect various processes, including phagocytosis, inflammation, T cell activation and memory, cytokine secretion, leptin levels, and others. Moreover, infections themselves can contribute to malnutrition. Stimulation of an immune response by infection increases the demand for metabolically derived anabolic energy, which in case of malnutrition leads to a vicious cycle of a compromised nutritional state and consequently increased susceptibility to infection. Weakened immunity caused by malnutrition leads to decreased healing (10).

Malnutrition can also lead to protein catabolism (breakdown into smaller peptides and, finally, amino acids), resulting in a rapid wasting of muscle mass or decreased bone mineral mass (11). The result is impaired musculoskeletal function and reduced physical performance, leading to an increased risk of falling, osteoporosis, and osteoporotic fractures (12).

Malnutrition and obesity 

​​Malnutrition is frequently characterized by what is called a “double burden of malnutrition”, described by the WHO as “characterized by the coexistence of undernutrition, along with overweight, obesity or diet-related noncommunicable diseases, within individuals, households, and populations, and across the life-course” (13).  This phenomenon is common in highly developed countries. Diagnosing malnutrition in patients with obesity requires a complex assessment of nutrition, which includes dietary assessment (14). Many authors point out that this paradoxical state of malnutrition is caused by a shortage of individual microelements combined with excessive energy consumption (15). Frequently, malnutrition combined with obesity is connected to the incorrect implementation of a low-energy diet (16). Such microelement deficiency can significantly affect the cognitive and psychological state (17), as well as physical health (18).

Most common nutrient deficiencies associated with excessive body weight include vitamins A and C, and folic acid (19). Higher body weight resulting from increased body fat may lead to lower levels of serum vitamin D, B group vitamins, microbiota dysfunction, and thiamine deficiency.

Obesity is also known to be closely related to metabolic diseases, such as type 2 diabetes and atherosclerosis. Chronic and acute diseases add additional malnutrition burden on the nutritional state, and disease-related malnutrition requires specific attention in clinical settings (20). Malnutrition-related sarcopenia may occur in obese people showing the characteristic reduction of skeletal muscle mass and function.

Malnutrition and aging 

​​It is generally agreed that approximately 5–10% of community-dwelling older adults, 50% of those in rehabilitation, 20% in residential care, and 40% in the hospital are malnourished (21). Observations show that the PEM form of malnutrition prevails among older adults (22).

Older patients are at high risk of malnutrition due to multiple factors, including changes in metabolism, organ functionality, chronic diseases, and drug polypharmacy. Each of these factors can additionally decrease nutrient intake. 

Firstly, gastrointestinal aging is characterized by changes in motor function and, therefore, food transit, breakdown, and digestion. Reduction in digestive ability leads to further lack of adequate quantities of nutrients, potentially leading to malnutrition (23). Reduced stomach capacity and reduced number of taste buds can lead to a decreased appetite. Moreover, gastrointestinal aging is connected to structural alterations of mucosal defense (24), reduced immunity and disrupted gut microbiome (25), and increased inflammation. Secondly, age influences all the rest of organs and physiological processes, including balance of fluids, the density of bones, the flexibility of joints, metabolism (with increased risk of type 2 diabetes), cardiovascular system, and slower cell growth.

Malnutrition additionally burdens aging organisms and leads to a progressive deterioration of health (26). Particularly influenced are nervous, cardiovascular, immune systems, and skin. In the elderly, an association between cognitive deficits and depressive symptoms was linked to low levels of vitamin B6, folate, vitamin B12, and polyunsaturated fatty acids (27). Regarding the immune system, malnutrition reduces the total lymphocyte count, T cell proliferation, and interleukins. Malnutrition in the elderly is also linked to a reduced response to vaccines (28). Additionally, it increases the risk of the onset of pressure sores and infections, delaying wound healing as they prolong the inflammatory phase and alter the synthesis and proliferation of fibroblasts and collagen (29,30). 

Altogether, elderly patients with low BMI, weight loss, and insufficient food intake have consistently shown an association between mortality and malnutrition (31). A large inpatient study in France pinpoints malnutrition as an independent risk factor for hospital-acquired infections, which account for 6%–10% of all in-hospital deaths worldwide (26). 

Topics that have to be addressed

A range of yet unexplored research topics (9) concerning malnutrition has to be resolved for better understanding and treatment of malnutrition. The brief list is given below:

• Gut microbiome changes in malnutrition and influence of probiotics;
• Immune responses influence on energy regulation and food uptake;
• Role of cytokines in nutrient uptake;
• Crosstalk between immune (cytokines) and nutrition-related hormones;
• Tissue-specific loss of nutrients during infection and inflammation;
• Efficacy of vaccines and drugs under acute and chronic PEM conditions;
• Essential immunonutrients and food supplements easily accessible for societies with chronic PEM;
• Drinking water, nutritionally enhanced food, and food additives to prevent infection;
• Improved infrastructures for food distribution in developing countries.

Conclusions 

Malnutrition is a dangerous condition that influences both growing and aging. Healthy aging and longevity require special attention to balanced and sufficient nutrition. Accordingly, nutritive management has to become an elementary part of both daily routine and intensive health care. A range of related topics has to be further investigated to tackle the problem of malnutrition holistically, including social, psychological, and economical.

References 

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