PharmaNutrition 19 (2022) 100288

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PharmaNutrition
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The impact of functional food in prevention of malnutrition

Mukhtar H. Ahmed a, *, Dávid Vasas b, Arez Hassan c, Judit Molnár b
a
Sisaf Nanotechnology Drug Delivery, Ulster University, BT370QB, Belfast, UK
b
Széchenyi István University - Faculty of Agricultural and Food Sciences, 9200, Mosonmagyaróvár, Hungary
c
School of Medicine, Queen’s University, BT9 7BL, Belfast, UK

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Malnutrition is a serious condition that develops when the human body is deprived of or does not
Nutrition obtain the right amount of vital nutrients like vitamins, minerals, proteins, carbohydrates, lipids and some other
Malnutrition essential substances that the body needs to function. It can have a significant impact on people’s health including
Diet
stunted growth, low body weight and muscle wasting.
Functional foods
Healthy foods
Purpose: This study is aimed to determine the factors that could cause malnutrition in humans, something that is
considered as a major global issue nowadays and is associated with negative aspects on patient’s activities.
Methods: Electronic searches were conducted on the Google Scholar database, Medline and PubMed up to the
11of December 2021. All studies reporting an association between foods and malnutrition were included.
Results: The search yielded 637 references, included 52 clinical trials, 11 meta-analysis, 45 randomised clinical
trials (RCT) and 201 reviews. Among the manuscripts, 25 studies provided evidence for the association between
malnutrition and micronutrients. The results showed that in addition to insufficient intake of the essential
nutrient, several chronic diseases including gastrointestinal tract diseases, cancer and sometimes post-surgery
complications are also associated with malnutrition.
Conclusion: Only a limited number of studies reported a direct link between functional foods and malnutrition,
which all agree that there is clear evidence in favour of functional foods being effective in preventing and
reducing the impact of malnutrition. Other studies looked at for this review would suggest that they may even be
effective in improving the quality of life.

1. Introduction
The general term of malnutrition can be defined as a serious condi­
tion that arises when our diet does not contain the right amount of
nutrition. This can be in both ways; overnutrition - which is when we get
extra amounts of nutrition, and undernutrition which is described as not
getting enough amounts of nutrition.
Despite developed world economic growth in recent decades,
including in some of the poorest countries, millions of people still go to
bed hungry every night. In addition to long-term health status and body
function caused by ageing, there are several different factors which
cause malnutrition. Suboptimal dietary intake, which is a primary
contributing factor to undernutrition, there are some other factors like
education, health state, food security, economic and environmental
condition, and political situation also play a significant role.
Food insecurity affects people’s ability to obtain the amount of food
needed to meet their physical calories needs. Therefore, without
adequate calorie intake, a person may not be able to build energy or
strength to carry out activities of daily living [1]. Poverty and food
insecurity are strongly related to each other, as poverty may negatively
affect the social determinants of health and may create adverse condi­
tions in which people might experience unreliable food supply [2].
While people living in poverty may need more food than they currently
have, it is important to keep in mind that adequate intake of nutrients
and quality of food is equally important. Moreover, other research has
found deficiencies of iodine and iron, together with stunting, can
contribute to children not reaching their developmental potential.
Undernutrition results in a poor quantity or insufficient quality of
nutritional intake [3,4]. Therefore, body weight and body function are
below normal, which in turn carries the development of many diseases.
On the other hand, as a result of the world population ageing at a
rapid rate, malnutrition is a threat to elderly people as they become
more vulnerable. Some countries have a high level of risks of under­
nutrition associated with some circumstances like their lifestyle,

* Corresponding author.
E-mail address: ahmed-m@email.ulster.ac.uk (M.H. Ahmed).

https://doi.org/10.1016/j.phanu.2022.100288
Received 8 September 2021; Received in revised form 12 January 2022; Accepted 13 January 2022
Available online 15 January 2022
2213-4344/Crown Copyright © 2022 Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
M.H. Ahmed et al.
environment, and resources. This is a result of several pandemic diseases
which cause loss of life and increase the mortality rate.
There is an increased risk of malnutrition among children and the
elderly. It has been shown that deficiencies of vitamin A and zinc result
in deaths [5]. Moreover, other studies have found that deficiencies of
iodine and iron are a leading cause of delayed growth and mental
development in children [6,7]. It also results in deteriorating health,
increased morbidity, and mortality in elderly and chronically ill patients
[8]. Functional foods offer a potential opportunity to fully meet food
needs [9,10]. Alternative protein sources are also part of functional
foods. This article focuses on the determinants of undernutrition, diag­
nosis, causes, symptoms, treatment of undernutrition and the impact of
functional foods in the treatment.
Even though there are a number of social and economic factors
which cause undernutrition, this review focuses on the main biological
factors that lead to malnutrition such as those who are chronically ill or
the elderly.
2. Methods
Electronic searches were conducted on Google Scholar database,
Medline and PubMed. A further search was conducted on the World
Health Organization’s research article database Cochrane Library
database in English. The literature search was performed on the webs up
to the 11th of December 2021. The search items included were malnu­
trition, undernutrition, healthy and unhealthy diets, supplements,
nutrition and immune system. This review performed is to analyse the
recent literature to show the reasons, symptoms, treatments of malnu­
trition and the impact of superfoods in preventing diseases caused by
malnutrition.
3. Results and discussion
The search identified 637 articles, across five settings: clinical trials
(n = 52), randomized clinical studies (n = 45), meta-analysis (n = 11),
and the majority of the articles were reviews (n = 201). The research
found that there were fewer studies (n = 25) that focussed directly be­
tween the association of malnutrition and dietary micronutrients. The
papers showed concerns regarding the negative consequences related to
the deficiency of essential nutrients. The latter of the studies focussed
more on the importance of micronutrients and their biological functions
in the body.
Studies identified several factors related to malnutrition; the most
common factor being the lack of dietary intake or an inadequate diet.
This occurs due to a decrease in appetite which is sometimes related to
change in some hormones like glucocorticoids and insulin-like growth
factors. In addition, inflammatory cytokines can reduce appetite [11,
12]. Additionally, alcoholism also causes a lack of appetite as alcohol
contains high calories, which stops people from feeling hungry.
Furthermore, difficulties in digestion and absorption of food nutri­
tion across the gastrointestinal tract led to steatorrhea and abdominal
bloating are the most common symptoms of malabsorption [13].
Elevation in energy expenditure and urinary nitrogen excretion is also
related to malnutrition directly. This results in the rising of lipolysis,
gluconeogenesis and net breakdown of muscle protein so that energy
and substrates are mobilised to support the activation of an inflamma­
tory response [14]. Increased losses or altered requirements of micro­
nutrients is another contributing factor of malnutrition [15].
Malnutrition affects the whole-body system directly; it can impair
mobility and stamina as a consequence of muscle wasting. It also affects
wound healing and recovery time. Respiratory tract problems including
chest infections and difficulties in breathing are also affected by
malnutrition. Furthermore, the body is unable to maintain normal
temperature i.e. hypothermia, due to loss of muscle mass. Finally, the
immune system becomes slower, this might increase the risk of in­
fections and lead to fertility issues [16–18].
2
PharmaNutrition 19 (2022) 100288
In addition, the identification of patients at risk of malnutrition and
the early intervention with nutritional therapy is also important in a
wide range of ages (Table 1). It is important to detect malnutrition in the
early stages to avoid severe conditions. The common way to determine
malnutrition is by using the Malnutrition Universal Screening Tool
(MUST). This method is a simple rapid, and easy way to measure
malnutrition, which includes the following steps:
The first step is to detect malnutrition through calculating the adult
nutritional status so-called body mass index (BMI), which relates to the
weight in kilogram/ (height in metric)2 [15]. Based on the BMI data
below, 18.0 is considered as malnutrition (undernutrition) [19]. The
second step for detecting malnutrition is unexplained weight loss:
reduction of the >5% of initial body weight during 3–6 months is
defined as malnutrition [20,21]. Step three; Acute disease effect. Any
underlying disease notices that there will be no nutrition intake for five
days or more [22]. Step four is adding the scores obtained from the
above steps one, two and three, to calculate the overall risk of malnu­
trition. The last step is management guidelines based on the followed
policy. This can be defined as a low, medium, and high risk of malnu­
trition based on the obtained scores [23].
The treatment of malnutrition depends on the severity or the con­
dition of the cases. Researchers have suggested that the best way to
prevent the risk of malnutrition is providing food supplements with
some essential minerals like iron, iodine, and zinc [27]. In addition to
that, being active and having a healthy diet can also prevent malnutri­
tion at any age.
While detecting malnutrition, the treatment should be programmed
as it can lead to various physiological adaptations and metabolic
changes associated with reducing the function of many organs and tracts
like the liver, kidney, heart, and digestive tract [28]. In the case of severe
malnutrition, the treatment includes stabilisation for the first week and
rehabilitation for the next five weeks [29]. Children with severe
malnutrition should have an intake of 120− 150 kcal/kg/day to obtain
the appropriate weight gain [30].
The treatment methods involve oral nutrition, enteral nutrition and
parenteral nutrition, each method of treatment depends on the patient’s
circumstance and severity of malnutrition. In the initial malnutrition,
the fortified foods and drinks with supplements are given to patients
through oral intake. When patients have mild difficulties with the
gastrointestinal tract or problems with the gullet and mouth, the food
can be delivered to the stomach directly via a special tube. The duration
of this method depends on the patient’s recovery.
While in the case of gut failure and other severe internal diseases, the
nutritional solution is administered into the superior vena cava or
another main vein. The solution contains essential nutrients like pro­
teins, glucose, vitamins, and minerals with lipids [31,32].
Following carbohydrate and fat, protein is the essential macronu­
trient, which the body requires in large amounts. It is an essential factor
for growth, repair of the body and maintenance of health. All the pro­
teins in nature are made up of the same 20 amino acids and they
Table 1
Negative impacts of malnutrition on the human body in different ages (Children
and older people).
Malnutrition in The negative effect of the human body References
different ages
Increased susceptibility to inflammation and
infectious diseases.
Decrease motor, sensory, cognitive, social, and
Children emotional development, greater risk of [6,7,24]
developing diseases and early death.
Negative energy and nutrient balance and a
high rate of weight loss.
Physiological and social changes in the body.
Older people
A leading cause of morbidity and mortality.
[4,25,26]
Causes negative effects on tissue, body form
and function of organs.
M.H. Ahmed et al.
determine the nutrition values of protein. The essential amino acids
(valine, leucine, isoleucine, phenylalanine, tryptophan, lysine, histidine,
methionine, and threonine) cannot be synthesized in the human body
they must be obtained from our diet [33].
Biochemically, protein digestion begins in the stomach and con­
tinues in the lumen of the intestine and so the proteins are degraded into
mono and diamino acids, which then are absorbed in the intestine by the
presence of specific transporters. After this, they are released into the
blood for use by other tissues. These are considered as the fundamental
building blocks of proteins in the body, and they serve as the nitroge­
nous backbones for compounds like neurotransmitters, enzymes, and
hormones [34,35]. Both plant and animal proteins contain the same
amino acids and therefore are similar in components, however, animal
proteins contain all the essential amino acids, whereas plant protein
only contains some of the essential amino acids [33]. In general, the
body needs between 1.0 g–1.5 g of protein for each kilogram of weight in
children and adults respectively [36], and if there is an insufficient
amount of protein in the diet this could cause kwashiorkor, a severe form
of malnutrition [37]. Some studies included in this review highlighted
that functional food or food products resulted in better clinical benefits
than counselling and intake of supplements due to the fact that vitamins
and minerals found in food sources are easier to absorb than those in
supplement form [38].
3.1. Functional foods
Functional foods can be considered as primary prevention for
malnutrition at all ages. Functional foods are ingredients that offer
health benefits that extend beyond their nutritional value. The current
definition of functional food is “Natural, modified or processed foods
that contain the biologically active compounds claiming to improve
health and well-being [39]. The concept of functional food was intro­
duced for the first time in Japan in 1984. Functional foods can be natural
food, in which nutrients and ingredients have been added or removed
using biotechnological processes. They have physiological health ben­
efits and higher capacities to decrease the risk of chronic illness. Bio­
logical active compounds (or Bioactive) are an essential factor for the
effective positioning of functional foods. They include
anti-inflammatories, antioxidants, antifungal, vitamins, and minerals
[40].
Functional foods have a significant impact on optimizing human
health as a part of a person’s everyday healthy diet, thus the global
demand for functional foods has been growing by 8% annually [41].
Food experts also estimate that it needs to produce between (30–70) %
more food in 2050 compared to current production, as it is shaping the
future of the food industry at large.
The most beneficial effects of the functional foods may meet the
following criteria: strengthening of biological defence mechanisms, re­
covery from some illnesses, helping to protect against some specific
diseases, delaying the ageing process and could act to prevent mental
health issues. Recently, the International Life Science Institute has
proposed the biological advantages of functional foods into some wide
groups, such as substrate metabolism, gastrointestinal physiology,
development and growth, the cardiovascular system, behaviour and
psychological functions, and physical disorders [9,42].
Functional foods can be eaten as part of daily food. Food experts
would prefer and suggest that consuming functional foods in some
specific physiological states like lactation, pregnancy and during phys­
ical activity are better for health [43]. Furthermore, functional foods can
be provided to people who have food intolerances, sensitivities, and
allergies through diet [44]. Functional foods can be consumed daily to
reduce the risk of diseases including metabolic syndrome, diabetes,
cardiovascular disease, osteoporosis, etc. [41]. In these cases, eating
some specific bioactive components is preferable to provide some
beneficial impacts on health. However, functional foods cannot be used
as a disease therapy for patients, as the daily health benefit is associated
3
PharmaNutrition 19 (2022) 100288
with longer-term health objectives [45]. In addition to providing the
necessary nutrition, the new strategy of functional foods is also targeted
to people with specified requirements like low sugar, salt, or gluten and
lactose-free alternatives. Thus, functional foods can be a treatment for
severe malnutrition.
Most micronutrients are necessary to healthy development with
several vitamins and minerals being vital, some of these include vitamin
A, vitamin C, zinc, iodine, flavonoids, and omega-3 polyunsaturated
fatty acid [46]. These are the most essential nutrients that our body
needs to function optimally. These nutrients possess great potential to
improve overall health, for instance, preventing malnutrition, and pro­
tecting against chronic diseases.
3.1.1. (n-3) Fatty Acids or (ω − 3 fatty acids)
n-3 Fatty Acids are polyunsaturated fatty acids (PUFA) associated
with several health benefits and are primarily identified by the position
of the double bond three carbons away from the methyl group at the end
of the chain (ω) (1).
(1) The chemical structure of fatty acids
The most positive impacts of n-3 fatty acids on metabolic, immu­
nological events might be involved in regulating the blood pressure and
nervous system, hematic clotting plus protecting from cardiovascular
disease (CVD), Alzheimer’s, and rheumatoid. In addition, they act as an
anti-inflammatory potent [47].
Since our bodies do not produce omega-3 fatty acids, we must obtain
them through food. It has been investigated that Eicosapentaenoic acid
(EPA; 20:5, n-3), Docosahexaenoic acid (DHA; 22:6, n-3) and alpha
Linoleic acid (ALA;18:3, n-3) are the three main omega-3 fatty acids (2).
Both EPA and DHA are abundant in fish oil, and many other kinds of
seafood, while ALA can be obtained from plant sources [48].
(2) The chemical structure of Eicosapentaenoic Acid (EPA) and Do­
cosahexaenoic Acid (DHA) and alpha Linoleic acid (ALA).
3.1.2. Polyphenols and flavonoids
Flavonoids are a large family of polyphenolic compounds produced
by plants. The main structure of flavonoids consists of a fifteen-carbon
skeleton called flavan, two benzene rings (A and B) connected with a
heterocyclic ring called pyran (C) (3). Due to their properties, flavonoids
possess potent physiological activities such as anti-bacterial, anti-in­
flammatory, antioxidant and immunomodulatory abilities [49]. This has
a great ability to exert several biological effects that are potentially
useful for human health and are therefore important functional food in
our daily diet. Previous literature has shown that flavonoid consumption
may play a significant role in health through the regulation of weight,
metabolism, cell proliferation and chronic disease [50].
Similarly, polyphenols, as well as carotenoids, exhibit prooxidant
activity (electron acceptors) in normal tissues at normal daily doses.
[51]. Moreover, it has also been reported that polyphenol com­
pounds can act as prooxidants under certain conditions such as high pH,
the presence of oxygen molecules and high concentrations of transition
metal ions like Fe and Cu [52]. A prooxidant effect has been associated
with a proapoptotic function of these compounds in various types of
tumour cells [53].
The prospective mechanisms of pro-oxidant property of polyphenol
compounds are based on the direct formation of labile aroxil complex
M.H. Ahmed et al.
with a transition metal cation (Fe+3 or Cu+2). This radical compound
(aroxil) reacts with the oxygen molecule (O2) forming an ( O2− ) radical
•
[54], and indirect activation of intracellular production of reactive ox­
ygen species by NADPH oxidase [55].
This process has been shown to increase ROS production and sub­
sequently, DNA damage. As seen from the structure of flavonoids, there
is an association between prooxidant potential and the presence of hy­
droxyl group in B-ring and a double bond in pyran (ring -C).
(3) Basic structure with prooxidant activity in flavonoids [56].
Recent studies found that daily eating foods rich in flavonoids pro­
tect against several serious diseases such as diabetes, cardiovascular
complications, certain cancers, gastrointestinal problems, pancreatitis,
lung damage, osteoporosis and neurodegenerative diseases [57,58]. The
dominant explanation for these benefits all goes back to the
structure-activity relationship.
Proanthocyanidins, quercetin, myricetin and epicatechin are the
most affective flavonoid compounds. Chocolate, red wine, tea, cherries,
berries, apples and citrus fruits are the main sources of flavonoids [59].
Flavonoids have excellent preventive effects against atherosclerosis,
coronary heart disease and cancer [60,61].
3.1.3. Vitamin A (Retinol)
Vitamin A [C20H30O] (4), is an essential fat-soluble nutrient that has
physiological effects on various biological responses. It cannot be syn­
thesised in the body so must be consumed through foods. Vitamin A
deficiency can be resulted from inadequate intake, poor absorption or
chronic liver disease [62].
(4) Vitamin A (Retinol)
Protein-energy malnutrition is likely to be associated with vitamin A
intake deficiency and/or suppressed synthesis of retinol-binding protein
due to protein deficiency results in decreased retinol uptake [63]. Lack
of vitamin A causes anaemia by immobilizing ionic iron (Fe+3) in the
reticuloendothelial system, specifically, the spleen and liver [64].
Deficiency of vitamin A is a leading cause of xerophthalmia, impaired
immunity, haematopoiesis and increased risk of mortality in children
and pregnant women [65]. Vitamin A deficiency is also related to
stunted growth and bone development in children and teenagers, as well
infertility and miscarriage [66].
3.1.4. Ascorbic acid (Vitamin C)
Ascorbic acid or (vitamin C) is a water-soluble micronutrient, (the
chemical formula C6H8O6) that has a potential biological activity in the
human body. As an electron donor, ascorbic acid acts as a cofactor for
several enzymes that mediate a variety of essential biological functions
[67]. Furthermore, their activity is not only intracellular, but vitamin C
is also responsible for immune activation following exposure to chemi­
cal and biological toxins. Another biochemical role of ascorbic acid is to
act as an antioxidant (a reducing agent) by donating electrons to various
enzymatic and non-enzymatic reactions. Several clinical studies have
demonstrated the ability of vitamin C to increase serum concentrations
of iron and haemoglobin [68]. Accordingly, it might be logical to infer
that maintaining sufficient levels of vitamin C in the plasma either by the
4
PharmaNutrition 19 (2022) 100288
continuous uptake through the diet or supplement could effectively
protect against infection [69]. Therefore, vitamin C supplements can
boost the immune system and taking natural foods rich in vitamin C such
as fresh vegetables and fruits like citrus fruits, strawberries, kiwi and
cauliflower might be worthwhile [70]. In adults, the requirement for
vitamin C is 75− 90 mg per day.
3.1.5. Zinc
Zinc is considered an essential trace mineral in the human body
followed by iron. It is a crucial cofactor for the synthesis and functioning
of various proteins. It also possesses potent anti-inflammatory, anti­
apoptotic and antioxidant stress agent activity [71].
Zinc deficiency resulted in a serious alteration of lung epithelial cell
function [72]. Recent investigations demonstrated that zinc is strongly
involved in the modification and posttranslational process of proteins
[73]. Zinc deficiency appears to be a public health problem in almost all
ages. Zinc deficiency is associated with growth retardation (height and
weight), impaired immune function, recurrent infections, delayed sex­
ual and bone maturation, dermatitis, diarrhoea, eating disorder and
serious mental health disturbance [74,75].
Investigations have reported that dietary zinc deficiency negatively
affects the absorption of other nutrients and causes loss of appetite and
body weight. The study documented that, there is a significant rela­
tionship between low protein intake and zinc deficiency, which also
proved that one of the negative impacts of protein-energy malnutrition
is an alteration in the small intestinal mucosal absorptive capacity for
zinc [76].
Mossink et al. suggested that increasing the level of zinc in the diet in
all ages, could play a significant role in supporting immune function and
promoting healthy life [77].
3.1.6. Iodine
Iodine also plays a vital part in maintaining a good level of all-around
health and will avoid malnutrition. It is an essential micronutrient that
the human body needs to produce thyroid hormones [triiodothyronine
(T3) and thyroxine (T4)]. Both T3 and T4, play a significant role in
metabolic homeostasis in humans and as well Thyroid hormone is
essential for brain and bone development in infants and normal growth
in childhood and adolescence. [78].
The average daily recommended amounts of iodine intake for chil­
dren and adults can range from100 and 150 micrograms/day [79].
Iodine deficiency can cause serious problems which include the mental
and physical development of children as well as effects on reproductive
in adults [80].
4. Conclusion
Malnutrition is the most common global problem and has wide-
ranging effects on physiological function, as well as being associated
with more severe diseases in patients. Poor diet, mental health prob­
lems, mobility problems, digestive disorders, stomach conditions and
alcoholism etc, are all potential causes of malnutrition. It was also found
that loss of weight, difficulty in respiration and health complications are
the main signs and symptoms of malnutrition.
Eating a balanced diet that contains the recommended number of
fruits, vegetables, grains and protein-rich foods is the best way to pre­
vent malnutrition. Receiving a supplement and the addition of micro­
nutrients or fortified foods into diets can also help prevent malnutrition.
It is observed that the increase consumption of functional food, partic­
ularly in the future, will provide the major nutrients which are essential
for normal body function and is critically important, particularly in
older adults. Thus, functional food can possess a key role in protection
against malnutrition. Furthermore, the evolution of functional foods
could be a simple way to improve people’s health and wellbeing,
particularly in regions of high malnutrition and low food availability.
M.H. Ahmed et al. PharmaNutrition 19 (2022) 100288

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