Experimental Gerontology 172 (2023) 112072

Contents lists available at ScienceDirect

Experimental Gerontology
journal homepage: www.elsevier.com/locate/expgero

Review

The relationship between nutrition and depression in the life process: A

mini-review
Gülseren Nur Ekinci, Nevin Sanlier *
Ankara Medipol University, School of Health Science, Department of Nutrition and Dietetics, Ankara, Turkey

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

Section Editor: Jiankang Liu Depression is one of the leading health problems, and >300 million people have a major depressive disorder and
this number is getting increasing. Depression complicates the management of existing chronic diseases and the
Keywords: management of complications that may arise. A person's mental state can affect their food preferences, and food
Depression preferences can also affect their mental state. In this paper, depression and eating behavior, diet quality, folic
Nutrients
acid, vitamin B12, vitamin B6, vitamin D, omega-3 fatty acids, magnesium, selenium, zinc and copper, prebiotics
Minerals
and probiotics are discussed. Research on the subject emphasizes that diet quality may also affect the occurrence
Vitamins
Diet quality of depression. However, studies also indicated that dietary nutrients such as folic acid, vitamin B12, vitamin B6,
Prebiotic omega-3 fatty acids, zinc, selenium, and magnesium might be associated with the risk of depression.
Probiotic

1. Introduction fast food, snacks, low food quality, and high-energy foods. In addition,
individuals with severe depression have an unhealthy diet and a
The World Health Organization (WHO) stated that >300 million decrease in the consumption of vegetables, fruits, fish, chicken, milk,
people have major depressive disorder and depression is one of the and grains (Paans et al., 2019). Among the reasons for the relationship
leading mental problems (The World Health Organization, 2017). Major between depression and obesity; cigarette consumption, a decrease in
depressive disorder is responsible for approximately 800,000 suicides physical activity level, and bad eating habits are shown (Paans et al.,
per year (Cheung et al., 2019). It is known that depression complicates 2018b). While it is thought that excessive consumption of soft drinks
the management of existing chronic diseases and the management of may increase the risk of depression, it is thought that consumption of tea
complications that may occur in individuals. Depression is a risk factor and coffee is inversely proportional to the risk of depression, and sugary
for diabetes and chronic heart disease (Katon, 2022). It has been re­ drinks may increase the risk of depression (Y. Kang et al., 2018; Hu et al.,
ported to be associated with education level, body weight, and genetic 2019). In one study, it was seen that the risk of depression increased in
factors (Wray et al., 2018). women who consumed fast food, ketchup, mayonnaise, refined grains,
It is known that some foods and dietary habits affect mental health. and high amounts of sugar and fat. It was observed that the risk of
The situations of individuals can affect their nutritional status, as well as depression decreased in women with higher consumption of foods such
their food preferences, which can affect their mental state. Psychologi­ as vegetables, fruits, eggs, nuts, and olive oil (Saeidlou et al., 2021). In a
cal, physiological, genetic, and social functions affect the eating be­ study which is conducted on women with major depressive disorder or
haviors of people, food intake, and food preferences (Paans et al., anxiety disorder, the incidence of eating disorders was found to be four
2018a). times higher (Garcia et al., 2020). In another study, it was found that the
Subtypes of major depressive disorder could affect body weight and risk of depression was associated with poor food quality, inadequate
appetite. The atypical major depressive disorder causes an increase in protein intake, and irregular meals (Kim and Lee, 2022). In a study
appetite, body weight, and body mass index values, leading to an in­ examining individuals aged 45–75 with major or subclinical depression,
crease in chronic diseases. The melancholic major depressive disorder it was determined that the incidence of depressive symptoms decreased
causes a decrease in appetite and loss of body weight (Mills et al., 2020). as the rate of adherence to the Mediterranean Diet increased (Oliván-
Food preferences for increasing food intake due to depression consist of Blázquez et al., 2021). In another study, it was reported that the

* Corresponding author.
E-mail address: [email protected] (N. Sanlier).

https://doi.org/10.1016/j.exger.2022.112072
Received 10 December 2022; Accepted 20 December 2022
Available online 21 December 2022
0531-5565/© 2022 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
G.N. Ekinci and N. Sanlier Experimental Gerontology 172 (2023) 112072

incidence of depressive symptoms was higher in individuals with low schizophrenia, bipolar disorder, depression, and dementia. Docosahex­
fruit and vegetable consumption and that adequate fruit and vegetable aenoic acid and eicosapentaenoic acids play a role in the pathophysi­
consumption was associated with a decrease in the prevalence of ology of depression (Lange, 2020). The American Psychiatric
depression (Ju and Park, 2019; Wolniczak et al., 2017). In addition, it Association emphasizes that omega-3 fatty acids play a role in brain
has been reported that the increase in the frequency of eating with development and functioning due to their effects on serotonin and
family in elderly individuals reduces the risk of suicidal ideation and dopamine transmission (Clay, 2017). It also recommends giving omega-
depression and is inversely proportional (D. Kang et al., 2018). 3 fatty acid supplements for the treatment of depressive disorders,
psychotic disorders, and impulse control disorders (Nasir and Bloch,
2. Method 2019). In the Dutch Depression and Anxiety Study, lower levels of
omega-3 fatty acids and DHA were associated with higher rates of
The literature review was realized during the period of Februar­ depressive symptoms in individuals (Thesing et al., 2018). There was no
y–August 2022 through the chosen websites including the World Health significant difference in monounsaturated fatty acids, saturated fatty
Organization (WHO), Science Direct, PubMed, Google Scholar, acids, omega-3 fatty acids, and n− 3/n− 6 ratios between the group with
Cochrane Central, Web of Science, Embase, The MEDLINE, and www. and without major depression (Hamazaki et al., 2021).
ClinicalTrials.gov. The articles were searched using the keywords such The prevalence of depression was found to be lower in individuals
as “depression nutrition, depression and eating behavior, diet quality, consuming moderately fatty fish (about 20-30 g/day) or those with
nutrients health benefits/effects, folic acid, vitamin B12, vitamin B6, 0.5–0.15 g/day omega-3 fatty acid intake (Sánchez-Villegas et al.,
vitamin D, omega-3 fatty acids, magnesium, selenium, zinc and copper, 2018). In one study, it was stated that as the omega-3 fatty acid level
prebiotics and probiotics, minerals, vitamins”. Studies on depression decreases, the symptoms of depression increase (Milaneschi et al.,
nutrition have investigated clinical human, animal, in vitro and in vivo 2019). It is also thought that consuming 1 g daily of omega-3 fatty acids
studies. Articles published only in abstract form were excluded. The year with an EPA content of 60.0 % or more may have positive effects on
of publication was not restricted. Studies were identified by manually depression (Liao et al., 2019).
searching the reference lists of relevant original and review articles.
Inclusion criteria were as follows: the publication in peer-reviewed 3.2. Vitamin D
journals in English; specific consideration of nutrient intake concern­
ing depression outcomes. Articles published only in abstract form were It is known that there is a relationship between the development of
excluded. depression and vitamin D. Vitamin D plays a role in the production of
serotonin (Berridge, 2017). With the conversion of 7-dehydrocholesterol
3. The relationship of nutritional status to depression at all to vitamin D3, the synthesis of vitamin D begins in the skin. In the brain,
stages of the life cycle the vitamin D receptor regulates serotonin synthesis by genetic mecha­
nisms (Ceolin et al., 2021). While vitamin D induces the expression of
It is thought that diet quality is associated with the risk of depression, the tryptophan hydroxylase 2 gene, which is involved in serotonin
the mother's diet quality affects the child's mental health, and diet synthesis, it suppresses the expression of tryptophan hydroxylase 1.
quality is associated with depression at every stage of the life cycle Vitamin D is effective in preventing depression by keeping serotonin
(Marx et al., 2021). It was found that poor diet quality in older women levels at normal levels. High levels of reactive oxygen species and Ca+2
doubled the likelihood of depressive symptoms compared to men with in neuronal cells in those with vitamin D deficiency explain the rela­
poor diet quality (Gomes et al., 2018). A meta-analysis study concluded tionship between vitamin D and depression (Berridge, 2017). It is known
that diet quality, micronutrient intake, adherence to the Mediterranean that the risk of depression increases by 8.0 %–14 % in people with
Diet, and food choice may have effects on depression (Ljungberg et al., vitamin D deficiency (Fipps and Rainey, 2020). In a study, it was
2020). In another study, it was found that a strong association between observed that cholecalciferol vitamin D3 supplementation in a group for
adherence to the Mediterranean Diet and the risk of depression. It has three months decreased the depression score and increased serum se­
been observed that the severity of depression is lower in individuals with rotonin levels in individuals with moderate, severe, and extreme
high grain and vegetable consumption (Gibson-Smith et al., 2020). In depression according to the Beck Depression Scale (Alghamdi et al.,
older adults, alcohol consumption of <40 g/day for men and <24 g/day 2020). It was reported that older adults with low serum 25-hydroxyvita­
for women did not appear to have a protective effect on depression, min D levels have high depressive symptoms (De Oliveira et al., 2018).
consistent with the moderate Mediterranean Diet (García-Esquinas Besides, it was found that the risk of developing depression is 3.5 times
et al., 2018). As a result of the healthy nutrition program applied to higher in individuals with vitamin D deficiency (Sherchand et al., 2018).
young adults for 3 months, it was observed that there was a decrease in It was observed that vitamin D supplementation was moderately effec­
depression scores (Francis et al., 2019). In another study, it was deter­ tive in depression symptoms in individuals diagnosed with major
mined that the risk of depression was higher in the group with high depression (Vellekkatt and Menon, 2019). It was found that serum 25-
consumption of refined sugar and sweets, and low consumption of le­ hydroxyvitamin D levels are lower in obese individuals with depres­
gumes, vegetables, and fruits (Grases et al., 2019). Another study re­ sion (Kamalzadeh et al., 2021). In this study, it was observed that the
ported that high-quality carbohydrate consumption was effective in daily administration of 70 micrograms of vitamin D to people with
reducing the risk of depression (Sanchez-Villegas et al., 2018). Iron, folic depression did not cause any change in depression scores and symptoms
acid, omega-3 fatty acids, selenium, potassium, magnesium, vitamin A, of depression (Hansen et al., 2019).
vitamin B12, vitamin B6, and vitamin C, It is thought that the con­
sumption of foods containing thiamine and zinc will increase the Anti­ 3.3. Vitamin B12
depressant Nutrient Score designed for the prevention and treatment of
depression (LaChance and Ramsey, 2018). It is known that vitamin B12 deficiency may be associated with
depression. It was reported that the incidence of depression is higher in
3.1. Omega-3 fatty acids vegetarians due to insufficient intake of vitamin B12. In the case of
vitamin B12 deficiency, it is not sufficient to measure serum B12 levels
Omega-3 fatty acids have an important role in the functioning of the alone. Methylmalonic acid and homocysteine levels should also be
brain with their neuroinflammation, neurogenesis, and neurotransmis­ checked (Russell-Jones, 2022). Vitamin B12 deficiency plays a role in
sion effects. The deficiency of omega-3 fatty acids increases the risk of the formation of depression with its effects on the adrenergic system,
psychological disorders such as attention disorder, attention deficit, glutaminergic system, serotonin system, and dopamine system (Sangle

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G.N. Ekinci and N. Sanlier Experimental Gerontology 172 (2023) 112072

et al., 2020). People with B12 deficiency experience oxidative stress and mild stress, folic acid produced antidepressant-like effects through
changes in mitochondria tropic support, calcium buffering, and energy various pathways involving monoamine neurotransmitters (Zhou et al.,
supply. These changes cause depression by producing atrophy, death of 2020). It has been observed that oxidative damage and depressive be­
neurons, and decreased neurotransmitter signalling (Sangle et al., haviors caused by stress were prevented by folic acid given to mice daily
2020). It was found that serum B12 concentrations were lower in at 50 mg/kg (Réus et al., 2018).
omnivorous young people and the incidence of depression was 31.0 % in
the vegetarian group and 12.0 % in the omnivorous group (Kapoor et al.,
2017). It was observed that high serum B12 concentration in adults 3.6. Magnesium
increases the risk of depression (Huang et al., 2018). In a study, lasting 6
years in the elderly, it was concluded that there was no relationship Magnesium levels are very important for Alzheimer's, stroke, dia­
between serum vitamin B12 levels and depressive symptoms (Elstgeest betes, hypertension, attention deficit, hyperactivity, migraine, and
et al., 2017). In other study, no relationship was found between vitamin central nervous system functions (Wang et al., 2018). Magnesium is
B12 and depression (Markun et al., 2021). However, older adults with neurologically important because it plays a role in nerve conduction and
depressive symptoms were found to have lower serum vitamin B12 neuromuscular transmission. It has a protective effect against over­
levels, and B12 deficiency and low B12 levels were found to have a stimulation that leads to neuronal cell death (Kirkland et al., 2018).
significantly greater risk of depression four years later (Laird et al., Considering the relationship of magnesium with the limbic system, it is
2021). thought to affect the formation and progression of depression (Wang
et al., 2018). It is reported that magnesium has antidepressant properties
3.4. Vitamin B6 and increases the effectiveness of antidepressant drugs (Szewczyk et al.,
2018). As a result of a seven-year study, it was found that dietary
Vitamin B6 is a cofactor that can affect depression by affecting magnesium intake and the risk of depression were inversely related in
neurotransmitters such as serotonin and norepinephrine in the brain women, but not in men (Sun et al., 2019). In a study conducted with 60
(Mesripour et al., 2017). Pyridoxal phosphate vitamin, the active form of depressed people with hypomagnesemia, it was found that there was a
vitamin B6, plays an active role in plasma homocysteine concentration, significant improvement in serum magnesium levels and depression
decarboxylation reactions, and transamination reactions (Baradia et al., status in the intervention group given 500 mg magnesium oxide for 8
2018). In a study, it was stated that daily intake of vitamin B6 meets the weeks (Rajizadeh et al., 2017). In another study, it was reported that
daily recommended amount, but is not associated with the risk of there is a relationship between serum magnesium levels and depression
depression (Jahrami, 2021). In a study conducted by giving dexameth­ and that magnesium supplementation can improve depressive symp­
asone and 100 mg/kg vitamin B6 to mice for 7 days, it was found that toms in individuals with low serum magnesium levels (Tarleton et al.,
vitamin B6 prevented depression by showing an antidepressant effect 2019). According to the meta-analysis results of 17 epidemiological
(Mesripour et al., 2019). In another study, it was observed that in­ studies conducted to investigate the dose-response relationship between
dividuals with anxiety and depression had a lower intake of vitamin B6 magnesium intake and the risk of depression, it was concluded that 320
than healthy individuals. It was concluded that insufficient intake of mg/day of magnesium intake is effective in reducing the risk of
vitamin B6 may increase the possibility of developing depression depression (Z. Li et al., 2017; B. Li et al., 2017). In women, higher di­
(Kafeshani et al., 2019). It is known that women who use oral contra­ etary magnesium intake was associated with lower levels of anxiety. In
ceptives have low levels of vitamin B6. A 20.0 % decrease was found in addition, there was a significant inverse relationship between dietary
the Beck Depression Scale scores of 100 mg B6 daily for 4 weeks in magnesium intake and depression in overweight women and normal-
women using oral contraceptives (Curtin and Johnston, 2022). The weight men (Anjom-Shoae et al., 2018).
concentration of pyridoxal-5-phosphate, the active form of vitamin B6,
was measured in Latino adults in the 2nd and 5th years of the study, and
it was observed that depressive symptoms were higher in individuals 3.7. Selenium
with low values (Arévalo et al., 2019). It was found that there is an in­
verse relationship between only vitamin B6 and the risk of depression in Selenium plays an important role in antioxidant mechanisms in the
middle-aged and elderly women with moderate and severe depressive brain and nervous system by taking a role in the proper functioning of
symptoms and anxiety (Odai et al., 2020). Another study in adults re­ selenoproteins, and it also has an important role in thyroid metabolism.
ported an inverse relationship between vitamin B6 and stress (Mahda­ Thyroid diseases, on the other hand, are known to be associated with
vifar et al., 2021). mental disorders, and considering this effect on brain functions, it is
thought to be associated with depression. Selenium has a protective
3.5. Folic acid effect against the risk of depression with its effects on the prevention of
inflammation and modulation of serotonin, dopamine, and noradrena­
Irritability, anaemia, and behavioral disorders are seen in folic acid line (Wang et al., 2018). In a study, it was found that high doses of se­
deficiency. It is known that folic acid contributes to the recovery of lenium consumption and a 54.0 % reduction in the risk of depression
depression by increasing the effectiveness of antidepressant drugs occur (Ferreira de Almeida et al., 2021). Due to the anti-inflammatory
(Abdelmaksoud et al., 2019). In the body, folic acid is metabolized as S- and antioxidant properties of 3-((4-chlorophenyl)sulfanyl)-1-methyl-
adenosylmethionine (Bender et al., 2017). S-adenosylmethionine and 1H-indole (CMI), which contains selenium, its effects on depressive
folic acid are involved in the synthesis of serotonin, dopamine, behaviors in mice improve oxidative stress and impaired superoxide
epinephrine, and monoamine neurotransmitters (Bender et al., 2017; dismutase and catalase activity in the hippocampus reduced behaviors
Zheng et al., 2020). Folic acid deficiency is associated with decreased (Casaril et al., 2019). In another study, it is thought that there may be an
levels of serotonin, dopamine, and norepinephrine. Decreased levels of inverse relationship between dietary selenium intake and the risk of
norepinephrine, dopamine, and serotonin cause neurochemical deteri­ depression (Li et al., 2018). In the meta-analysis of fifteen studies, no
oration and cause depression (Abdelmaksoud et al., 2019; Halaris et al., significant difference was found between the serum selenium levels and
2021). Studies have shown that low folic acid levels are associated with depression scores of depressed and healthy individuals. It has been re­
depression. It is also known that the incidence of major depression is ported that high selenium intake is inversely associated with the risk of
lower in Asians with a high intake of folic acid. It has been observed that depression. It was concluded that depression symptoms decreased in
the efficacy of antidepressant drugs is lower in individuals with low folic individuals given additional selenium supplementation (Sajjadi et al.,
acid levels (Mikkelsen et al., 2017). In mice under chronic unpredictable 2022).

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G.N. Ekinci and N. Sanlier Experimental Gerontology 172 (2023) 112072

3.8. Zinc study investigating the relationship between dietary copper intake and
depression in adults, a negative relationship was found between copper
It is thought that zinc may be effective in neural transmission asso­ intake and depression (Li et al., 2018).
ciated with depression such as dopaminergic, serotonergic, and gluta­
matergic systems. Zinc shows antidepressant properties by modulating
N-methyl-D-aspartate receptors and serotonergic functions and 3.10. Major depressive disorder and prebiotic, probiotic
increasing brain-derived neurotrophic factor levels (Z. Li et al., 2017; B.
Li et al., 2017). The brain is known to have the highest level of zinc It is thought that there is a bidirectional interaction between major
compared to other organs. Therefore, zinc deficiency may cause depressive disorder and gut microbiota. The mechanisms that are
depression by causing changes in glutamatergic transmission in the thought to provide this communication between the brain and the gut
central nervous system, limbic system, and cerebral cortex (Styczeń are the autonomic, enteric, and central nervous systems, gastrointestinal
et al., 2017). There is a tendency for zinc deficiency to be seen in the systems, immune systems, and neuroendocrine systems. It has been re­
elderly population, and in a study, it was found that the majority of ported that major depressive disorder may be affected by possible
elderly individuals did not have sufficient dietary zinc intake, but there changes in the intestinal microbiota (Nikolova et al., 2019). It is known
was no relationship between depression and zinc intake (Anbari-Nogyni that probiotics produce anti-inflammatory and antioxidant compounds
et al., 2020). Another study observed that the serum zinc concentration and have anti-inflammatory, anti-infective, immune-supporting and
of individuals with depression was lower than that of healthy in­ oxidative stress-reducing effects. Probiotics are involved in the pro­
dividuals (Styczeń et al., 2017). It has been found that daily supple­ duction of fatty acids and amino acids, which are necessary for the
mentation of 30 mg of zinc for 70 days in the elderly leads to a synthesis of neurochemicals, which are inhibitory factors in the forma­
significant increase in serum zinc levels. This increase in serum zinc tion of depression (Gayathri and Rashmi, 2017). The mechanism of
levels was found to be associated with a decrease in depression and action of probiotics on depression is given in Fig. 1.
anxiety scores (Afzali et al., 2021). An inverse relationship was found GABA synthesized in the intestinal microbiota by probiotic bacteria
between dietary zinc intake and the risk of developing depression in plays a role in the synthesis of neurotransmitters such as serotonin,
female university students (Hajianfar et al., 2021). histamine, glutamate, dopamine, norepinephrine, and acetylcholine.
For example, probiotic bacteria Lactobacillus helveticus, Lactobacillus
plantarum, Lactobacillus casei, and Lactobacillus bulgaricus are involved in
3.9. Copper dopamine synthesis and play a role in the regulation of functions such as
concentration, motivation, mood, psychomotor speed, ability to enjoy
Copper is known to have energy metabolism, immune function, and (Yong et al., 2020). Antidepressant effects of probiotics; Lactobacillus
neurobehavioral effects. Copper can affect the regulation of neuro­ rhamnosus and Lactobacillus casei are involved in the production of GABA
transmitters and noradrenaline concentration and activation (Ni et al., neurotransmitters, which can affect the hypothalamic-pituitary-adrenal
2018). Cognitive, learning and memory processes, synaptogenesis, axis. Lactobacillus brevis probiotic bacteria, on the other hand, play a role
neuron growth, glycine receptors, catecholamine metabolism, regula­ in the secretion of GABA neurotransmitters that improve sleep quality.
tion of the immunological system and regulation of antioxidant pro­ Lactobacillus reuteri reduces the synthesis of proinflammatory cytokines
cesses, etc. copper is involved. It is thought that copper may play an by releasing histamine (Yong et al., 2020). Adults aged 18–65 years with
important role in the development of depression due to its effect on the major depressive disorder were given probiotic strains containing
conversion of dopamine to norepinephrine (Słupski et al., 2018). In a Lactobacillus helveticus and Bifidobacterium longum for 16 weeks, and

Fig. 1. Mechanism of action of probiotics on depression.

The image is adapted from Gayathri and Rashmi (2017).

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G.N. Ekinci and N. Sanlier Experimental Gerontology 172 (2023) 112072

symptoms of depression were reduced (Wallace et al., 2020). In the Data availability
meta-analysis study in which ten clinical studies were examined, it was
observed that probiotics were effective in reducing depressive symp­ No data was used for the research described in the article.
toms, but there was no significant change in the anxiety status of the
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Funding Gibson-Smith, D., Bot, M., Brouwer, I.A., Visser, M., Giltay, E.J., Penninx, B., 2020.
Association of food groups with depression and anxiety disorders. Eur. J. Nutr. 59
This research did not receive any specific grant from funding (2), 767–778. https://doi.org/10.1007/s00394-019-01943-4.
Gomes, A.P., Oliveira Bierhals, I., Goncalves Soares, A.L., Hellwig, N., Tomasi, E.,
agencies in the public, commercial, or not-for-profit sectors. Assunção, F., Gonçalves, H., 2018. Interrelationship between diet quality and
depressive symptoms in elderly. J. Nutr. Health Aging 22 (3), 387–392.
Grases, G., Colom, M.A., Sanchis, P., Grases, F., 2019. Possible relation between
Declaration of competing interest consumption of different food groups and depression. BMC Psychol. 7 (1), 14.
https://doi.org/10.1186/s40359-019-0292-1.

The authors declare no conflict of interest.

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