2.4 3.

Article

Impact of Vitamin D Deficiency on

Mental Health in University
Students: A Cross-Sectional Study

Mansour Almuqbil, Moneer E. Almadani, Salem Ahmad Albraiki, Ali Musharraf Alamri,
Ahmed Alshehri, Adel Alghamdi, Sultan Alshehri and Syed Mohammed Basheeruddin Asdaq

Special Issue
The Role of Nutrition in Healthcare
Edited by
Prof. Dr. George Moschonis and Dr. Anj Reddy

https://doi.org/10.3390/healthcare11142097
 healthcare
Article
Impact of Vitamin D Deficiency on Mental Health in University
Students: A Cross-Sectional Study
Mansour Almuqbil 1, *, Moneer E. Almadani 2 , Salem Ahmad Albraiki 3 , Ali Musharraf Alamri 3 ,
Ahmed Alshehri 4 , Adel Alghamdi 5 , Sultan Alshehri 6 and Syed Mohammed Basheeruddin Asdaq 7, *

1 Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
2 Department of Clinical Medicine, College of Medicine, AlMaarefa University, Riyadh 13713, Saudi Arabia;
[email protected]
3 Department of Pharmacy, King Abdulaziz Medical City, Riyadh 14611, Saudi Arabia;
[email protected] (S.A.A.); [email protected] (A.M.A.)
4 Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University,
King Faisal Road, Dammam 31441, Saudi Arabia; [email protected]
5 Department of Pharmaceutical Chemistry, Faculty of Clinical Pharmacy, Al-Baha University,
Al Baha 65528, Saudi Arabia; [email protected]
6 Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University,
Riyadh 13713, Saudi Arabia; [email protected]
7 Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Riyadh 13713, Saudi Arabia
* Correspondence: [email protected] (M.A.); [email protected] or [email protected] (S.M.B.A.)

Abstract: Students pursuing a university education are vulnerable to psychological burdens such as
depression, anxiety, and stress. The frequency of vitamin D deficiency, on the other hand, is extensively
recognized worldwide, and vitamin D regulates various neurological pathways in the brain that control
psychological function. Therefore, the goal of this cross-sectional study was to determine the relationship
between vitamin D deficiency and psychological burden among university students in Riyadh, Saudi
Arabia. During March–May 2021 in Riyadh, a cross-sectional comparative study survey was delivered to
university students. The DASS-21 scale was used to determine the severity of the psychological burden.
Citation: Almuqbil, M.; Almadani,
Both univariate and binomial regression analyses were conducted to analyze the level of significance
M.E.; Albraiki, S.A.; Alamri, A.M.;
and influence of several factors on the development of psychological burden. The data were analyzed
Alshehri, A.; Alghamdi, A.; Alshehri,
S.; Asdaq, S.M.B. Impact of Vitamin
with SPSS-IBM, and a p value of <0.05 was considered significant. Of the 480 students recruited for the
D Deficiency on Mental Health in study, 287 (59.79%) had a vitamin D deficiency. Significantly (p = 0.048), a high proportion of the vitamin
University Students: A D-deficient students attained a low or moderate GPA compared to the control cohort. The prevalence of
Cross-Sectional Study. Healthcare depression, anxiety, and stress among the vitamin D-deficient students was 60.35%, 6.31%, and 75.08%,
2023, 11, 2097. https://doi.org/ respectively, which was significantly (p < 0.05) different from the control group. The odds of developing
10.3390/healthcare11142097 depression (OR = 4.96; CI 2.22–6.78; p < 0.001), anxiety (OR = 3.87; CI 2.55–6.59; p < 0.001), and stress
Academic Editors: George Moschonis
(OR = 4.77; CI 3.21–9.33; p < 0.001) were significantly higher in the vitamin D-deficient group. The
and Anj Reddy research shows a strong association between psychological stress and vitamin D deficiency. To promote
the mental health and psychological wellbeing of university students, it is critical to create awareness
Received: 4 July 2023
about the adequate consumption of vitamin D. Additionally, university students should be made aware
Revised: 19 July 2023
of the likelihood of a loss in academic achievement owing to vitamin D deficiency, as well as the cascade
Accepted: 21 July 2023
effect of psychological burden.
Published: 23 July 2023

Keywords: anxiety; depression; psychological burden; mental health; Riyadh; Saudi Arabia; stress;
university students; vitamin D deficiency
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and 1. Introduction
conditions of the Creative Commons
Vitamin D, a fat-soluble vitamin, plays a key role in maintaining healthy bones [1].
Attribution (CC BY) license (https://
Vitamin D is formed in large amounts by sun exposure. Foods including liver, tuna, and
creativecommons.org/licenses/by/
salmon contain a modest quantity of vitamin D [2]. Researchers have shown a correlation
4.0/).

Healthcare 2023, 11, 2097. https://doi.org/10.3390/healthcare11142097 https://www.mdpi.com/journal/healthcare

Healthcare 2023, 11, 2097 2 of 16

between vitamin D deficiency and mortality, heart failure, and myocardial infarction [3]. A
lack of vitamin D has been linked to a number of health issues, including cancer, osteoporo-
sis, autoimmune illnesses, mental disorders, respiratory problems, and osteomalacia [4–6].
The extensive expression of vitamin D receptors in many organ systems has been implicated
in the widespread systemic effects of vitamin D [4,7].
Lower serum vitamin D levels have been linked in several studies to psychological
distress [8]. Multiple studies have indicated that vitamin D has beneficial effects on
neurocognitive function [9,10]. The prevalence of vitamin D deficiency has been estimated
to be over one billion persons worldwide [11]. However, the incidence varies greatly from
one country to another. It is also of remarkable importance throughout the Middle East
and Asia, despite the region’s year-round sunshine [12,13].
Numerous studies have assessed the significant prevalence of vitamin D deficiency
among Saudi individuals. Elshafie et al. [14] carried out a study on vitamin D deficiency
in Saudi Arabia among 50 Saudi married couples and found that 70% of women had the
condition compared to 40% of males. Another study [15] revealed that 71% of female
medical students were vitamin D deficient. However, research from the Qassim Region of
Saudi [16] found that just 28% of the population was vitamin D deficient.
Psychological distress and mood swings are just two of the many elements that make
up mental distress. As defined by the American Psychiatric Association in its 1994 Diagnostic
and Statistical Manual of Mental Disorders, depression is characterized by a persistent and
pervasive state of sadness or a lack of interest or pleasure in virtually all activities for at
least two weeks. The pathophysiology of mental disorders has been poorly understood
because of the wide variety of clinical presentations and underlying causes [17]. According
to Vieth et al. [18], mental disorders are complicated illnesses with a variety of subtypes
and causes, including a potential vitamin D role. Numerous areas of the brain have been
shown to contain vitamin D receptors. These receptors have developed in parts of the brain
that are connected to the onset of psychological illness. Because of this, vitamin D has been
connected to mental health issues [19].
The pathogenesis of psychological distress is not clearly known, and it is likely that
several diverse mechanisms are at play despite the biological, psychological, and envi-
ronmental explanations that have been put forward [20–23]. Wilkins et al. [24] and May
et al. [25] found a significant association between low vitamin D levels and psychological
distress; however, Chan et al. [26] and Pan et al. [27] found no association.
Przybelski and Binkley’s [28] retrospective chart review study revealed the effects
of vitamin D deficiency on memory function and cognitive decline. Despite numerous
research studies claiming a link between vitamin D shortage and cognitive impairment,
there is currently a lack of data demonstrating that a lack of vitamin D has any impact on
academic performance [29]. However, a recent study [30] refutes the association between
low vitamin D levels and academic performance.
Numerous research studies have linked vitamin D deficiency to psychological distur-
bance, as was previously indicated. However, there is not a study in the literature that
looks at how these two variables relate to university students in Riyadh, Saudi Arabia.
With that in mind, the current study sought to employ a standardized, validated DASS
scoring system to better understand how vitamin D deficiency affects the mental health of
students at AlMaarefa University, Riyadh, Saudi Arabia.

2. Materials and Methods

2.1. Study Design
This research was conducted using a cross-sectional comparative study design with a
validated questionnaire carried out among students from AlMaarefa University, Riyadh,
from March to May 2021. The time corresponded to the period when students returned to
the on-campus education system from the COVID-19-mediated virtual system of teaching.
It involved a comparison of the psychological burden with vitamin D deficiency status
based on their affiliated college and socio-demographic features.
Healthcare 2023, 11, 2097 3 of 16

2.2. Sampling
The participants in our study were AlMaarefa University students affiliated with any
of the three colleges (College of Medicine, College of Pharmacy, and College of Applied Sci-
ence), aged above 18 years, who had provided consent to participate. They were recruited
using simple random sampling; the randomly selected subjects were approached, and the
interviewer administered questionnaires to those who consented to participate in the study.
Participation in this study survey was entirely voluntary, and complete confidentiality and
anonymity were maintained, with no identifying information being recorded in the survey
results. A consent form was added at the beginning of the questionnaire explaining the
purpose of the study, the objectives, a description of the research project, and a request
for their participation. To confirm the patients’ vitamin D status, the subjects’ vitamin D
levels were measured using an enzyme-linked immunosorbent assay (ELISA) machine
from BioTek and a vitamin D 25-OH ELISA assay kit from Calbiotech Incorporation. In
this study, participants were deemed to be vitamin D-deficient if their 25(OH)D levels were
under 20 ng/mL [16]. The Institutional Review Board of AlMaarefa University, Riyadh,
approved the study protocol (202/12/RC, 19 September 2020).

2.3. Study Questionnaire

The data for the study were gathered using a validated structured questionnaire.
The questionnaire was developed after extensive literature research and consulting with
specialists. Following the validation process, the questionnaire was used in a pilot study
involving thirty independent study samples. The questionnaire was refined and fine-tuned
based on comments from pilot research participants. There were three sections to the
questionnaire. The demographic information in the first section included the age, gender,
colleges/departments, study level, and nationality of the participants. The GPA of the
enrolled students was obtained from the university register.
The second section of the questionnaire included items that evaluated students’ overall
characteristics. Recent weight changes, self-perception of body shape, level and duration
of physical activity, sun exposure, presence or absence of vitamin D deficiency, use of sun
protection, use of artificial vitamin D sources such as tanning beds, vitamin D intake from
food, risk factors for depression, and use of antidepressants were all examined.
To determine the prevalence of psychological load among research participants, a
depression, anxiety, and stress scale that had undergone extensive international testing
and approval was used. The severity of several symptoms that are typical of depression,
anxiety, and stress was evaluated using a 21-item self-report questionnaire called the DASS
21. Items of the DASS-21 mentioned at positions 3, 5, 10, 13, 16, 17, and 21 were meant
to assess the depression status, while item numbers 2, 4, 7, 9, 15, 19, and 20 were able
to detect anxiety in the respondents. Furthermore, 7 other items (1, 6, 8, 11, 12, 14, and
18) were used to determine the level of stress in the surveyors. The person needed to
mention whether a symptom was present throughout the previous week when completing
the DASS. Each item was given a score between 0 (which did not apply to the participant
over the last week) and 3 (meaning it did apply to the participant frequently). The answers
were based on a Likert scale with 0 referring to “never”, 1 referring to “sometimes”,
2 referring to “often”, and 3 referring to “almost always”. After reducing the traditional
scale of 42 items, this section now featured 21 items. To obtain the final score, the ratings of
depression, anxiety, and stress scores were added together and multiplied by two. Henry
and Crawford [31] divided the scales into mild, moderate, and severe categories to rate
each state’s severity. For mild, moderate, and severe depression, the cutoff values were 10,
14, and 21, respectively. For mild, moderate, and severe anxiety, the cutoffs were 8, 10, and
15, respectively. Finally, the cutoff values for mild, moderate, and severe stress were 15, 19,
and 26, respectively [32]. Similarly, scores of 10, 8, and 15 in their respective items were
regarded as signs of depression, anxiety, and stress, respectively [33].
To ease the understanding of the questionnaire, the validated English questionnaire
was translated into Arabic using a forward–backward method with the help of subject
Healthcare 2023, 11, 2097 4 of 16

experts with good command over both languages. The validated Arabic version of the
DASS-21 items was included in the bilingual form of the questionnaire [34]. The Arabic
version was translated back to English to ensure the accuracy and uniformity of the
questionnaire contents in both languages.

2.4. Data Collection

The data collection team consisted of the Pharm.D program students from the College of
Pharmacy, AlMaarefa University, Riyadh, supported by senior faculty members. This team
was trained in introducing the study subject to the randomized participants, presenting them
with the bilingual survey forms, and collecting their responses. The participants were briefed
about the purpose, procedures, and potential risks in the Arabic language, and they consented
by ticking the “agree to participate” column on the first page of the questionnaire.

2.5. Statistical Analysis

Statistical Software for Social Science, version 23 (IBM SPSS Inc., Chicago, IL, USA),
was used to enter and analyze the acquired data. Frequencies and percentages were used
appropriately to present the data. Academic achievement and the students’ answers to
questions about their vitamin D status were compared. To further investigate the role
of vitamin D insufficiency in the development of psychological distress, the DASS score
was compared with vitamin D deficiency status. To determine the statistical significance
of variations in proportions of categorical data, Pearson’s Chi-square and Fisher’s exact
test (two-tailed, if appropriate) were performed. To examine the association between
sociodemographic factors, vitamin D deficiency status, and different forms of psychological
burdens, binary logistic regression analysis was carried out to obtain the odds ratios (ORs)
and 95% confidence intervals (CIs). p values lower than 0.05 were regarded as significant.

3. Results
3.1. Demographic Characteristics
The study included 480 university students, and a significantly (p = 0.032) high proportion
(Table 1) was between the ages of 20 and 22 years. Compared to their male counterparts, a
slightly higher proportion of female students (46% vs. 54%) was included in the study. The
number of students enrolled from the university’s three colleges was similar, while the number
of students from the College of Medicine was slightly less than that from the other two colleges.
The proportion of students in the middle level of their studies (5th to 7th level) was 39.37%,
which was not statistically different than the other levels (1–4 level and 8 level). The institution
offers two semesters in a single academic year (except the summer semester, typically chosen by
repeaters), with each level of study offered in a single semester. Most of the respondents who
participated in our research were Saudi nationals (81.45%), and a significantly high number of
the participants had grades ranging from 1.5 to 3.4 on a four-point scale.

3.2. General Characteristics of the Participants

A large percent (60%) of participants reported having their body weight significantly
fluctuate over the preceding three months (weight loss: 32.08%; weight gain: 28.54%),
whereas 39.37% of participants believed they maintained the same body shape. The
percentage of students who thought of themselves as slim, normal, and obese was 18.13%,
48.13%, and 33.75%, respectively. Regarding physical activity, fairly similar percentages
were found for people who engaged in physical activity (48.13%) and those who did not
(51.88%). Of the 48.13% of people who exercised physically, 23.33%, 25.83%, and 8.96%
of people exercised one to two days per week, three to four days per week, and more
than four days per week, respectively. Participants’ descriptions of the physical activity
patterns ranged from vigorous for at least 20 min (27.5%) to moderate for at least 30 min
(14.38%) to walking for at least 30 min (6.25%). Most individuals (48.13%) spent less than
one hour outside each day, whereas 25.42% spent between one and two hours outside each
day. Furthermore, 16.9% of people spent 2–4 h outside daily compared to 7% who spent
Healthcare 2023, 11, 2097 5 of 16

between 4 and 6 h outside daily. A significantly (p = 0.021) high percentage (59.79%) of

the individuals reported having vitamin D deficiency, whereas the remaining 40% either
did not have or did not know if they had any vitamin D deficit. A very small percentage
of participants (37.92%) were using vitamin D supplements or multivitamins containing
vitamin D, compared to a large proportion (62.08%) who denied taking any vitamin D
supplements. Most students who participated in the study said they had not used sun
protection cream in the previous 12 months (63.33%) or tanning beds (66.25%). Many
students (391, 81.46%) who participated in our survey denied using any antidepressant
medication, while just 18.54% were taking antidepressants (Table 2).

Table 1. Demographic characteristics of the participants.

Characteristics Variables Frequency (n = 480) Percentage p Value

20–22 years 245 51.04%
Age 23–25 years 134 27.91% 0.032
>25 years 101 21.04%
Male 221 46.04%
Gender 0.654
Female 259 53.95%
College of Medicine 135 28.12%
College College of Pharmacy 182 37.91% 0.078
College of Applied Science 163 33.95%
1–4 122 25.41%
Study level 5–7 189 39.37% 0.754
≥8 169 35.20%
0–1.5 137 28.54%
GPA (in a scale of 4) 1.51–3 215 44.79% 0.048
3.1–4 128 26.66%
Saudi 391 81.45%
Nationality 0.001
Non-Saudi 89 18.54%

Table 2. General characteristics of the subjects.

Characteristics Variables Frequency Percentage p Value

Weight loss 154 32.08%
Did you gain or lose body weight during the last Maintaining 189 39.37% 0.432
three months?
Weight gain 137 28.54%
Lean (slim) 87 18.13%
Your perceived body shape Normal 231 48.13% 0.094
Obese 162 33.75%
Yes 231 48.13%
Do you practice physical exercise? 0.765
No 249 51.88%
1–2 days per week 112 23.33%

How many times do you do physical exercise per 3–4 days per week 76 15.83%
0.065
week? More than 4 days per week 43 8.96%
Not applicable 249 51.88%
Healthcare 2023, 11, 2097 6 of 16

Table 2. Cont.

Characteristics Variables Frequency Percentage p Value

Intense physical activity for at least
132 27.50%
20 min

What is your duration of physical exercise per Moderate physical activity for at
69 14.38% 0.076
week? least 30 min
Walking at least 30 min 30 6.25%
Not applicable 249 51.88%
Less than 01 h/day 231 48.13%
1–2 h/day 122 25.42%
Including exercise, how many hours do you spend
outside during daylight hours? 2–4 h/day 81 16.88% 0.034
4–6 h/day 38 7.92%
More than 6 h 8 1.67%
Yes 287 59.79%
Do you have vitamin D deficiency? No 98 20.42% 0.021
I do not know 95 19.79%

Do you take vitamin D supplement or a Yes 182 37.92%

0.038
multivitamin that includes vitamin D? No 298 62.08%

Have you used sunscreen/sun protective cream Yes 176 36.67%

0.041
in the last 12 months? No 304 63.33%
Yes 162 33.75%
Did you ever try tanning beds/tanning booths? 0.042
No 318 66.25%

Do you currently take an antidepressant Yes 89 18.54%

0.001
medication? No 391 81.46%

3.3. Vitamin D Status and Academic Performance

Table 3 shows that there was a significant (p = 0.048) association between vitamin D
deficiency and the academic achievement of the student. When compared to students who did
not have any known vitamin D deficiency or who did not use vitamin D supplements, students
with known vitamin D deficiencies had significantly (p = 0.017) poor GPAs. GPA and the study
participants’ use of tanning beds or sunblock were not shown to be significantly correlated with
one another.

Table 3. Association between vitamin D status and academic performance based on student GPA
(grade point average).

GPA, n (Percentage)
Questions Variables p Value
Low Moderate High
102 115 70
Yes
(74.45) (53.48) (54.68)
Do you have vitamin D deficiency? 0.048
35 100 58
No, or not sure
(25.54) (46.51) (45.31)
98 45 39
Yes
(71.53) (20.93) (30.46)
Do you take vitamin D supplement or multivitamin
0.017
that includes vitamin D? 39 170 89
No
(28.46) (79.06) (69.53)
75 52 49
Yes
(54.74) (24.18) (38.28)
Have you used sunscreen/sun protective cream in the
0.082
last 12 months? 62 163 79
No
(45.25) (75.81) (61.71)
65 58 39
Yes
(47.44) (26.97) (30.46)
Did you ever try a tanning bed/tanning booth? 0.076
72 157 89
No
(52.55) (73.02) (69.53)
Healthcare 2023, 11, 2097 7 of 16

3.4. Symptoms of Vitamin D Deficiency

The potential signs and symptoms that a vitamin D deficiency can produce are shown
in Figure 1. Vitamin D deficiency is just one of many potential explanations for these
symptoms; yet, in some cases, the development of these symptoms may lead to the un-
expected diagnosis of vitamin D deficiency. Muscle weakness and chronic fatigue are the
most observed symptoms. These symptoms necessitate the investigation of other potential
causes and evaluating vitamin D levels to rule out deficiency.

Experience bone fracture 3%

Experience bone deformity 4%

Experience inflammatory bowel diseases 8%

Experience Profile

Experience recall events difficulty 10%

Experience chest pain 11%

Experience breathlessness 16%

Experience frequent tiredness 25%

Experience muscle weakness 28%

0% 5% 10% 15% 20% 25% 30%

Percentage

Figure 1. Experience profile of vitamin D-deficient participants in the last 12 months.

3.5. Dietary Status of Participants

Figure 2 shows the percentage preference for diets rich in vitamin D among our study
samples with vitamin D deficiency. Cheese was the dominant selection for a diet rich in
dairy products, which was followed by fatty fish and egg yolk. People with a regular intake
tt
of vitamin D-rich food may not develop vitamin D deficiency and its complications.

Cheese 39%

Dairy products 39%

Fatty fish 35%

Food types

Egg yolks 34%

Soy milk 12%

Cereals 11%

Beef liver 10%

0% 5% 10% 15% 20% 25% 30% 35% 40% 45%

Percentage

Figure 2. Common food habits of vitamin D-deficient participants.

Healthcare 2023, 11, 2097 8 of 16

3.6. Risk Factors for Depression

Figure 3 depicts the possible risk factors for the induction of depression. Excessive
academic demand (21%) was seen as the most common risk factor, followed by a family
background of psychological burden (18%). Other factors selected by our study participants
were thyroid diseases (14%), heart diseases (11%), the recent death of someone in the family
(11%), and social isolation (9%). Some participants selected factors such as job loss, cancer,
family disputes, drug abuse, and chronic injury.

Excessive academic demand 21%

Possible factors for psychological burden

Family member with psychological burden 18%

Thyroid disease 14%
Heart disease 11%
Recent death of a close relative 11%
Social isolation 9%
Losing a job or taking a new job 6%
Cancer 6%
Disputes in the family 5%
Drug abuse 5%
Chronic injury 3%

0% 5% 10% 15% 20% 25%

Percentage

Figure 3. Common depression determinants in vitamin D-deficient participants.

3.7. Drug Use Profile That May Cause Vitamin D Deficiency

Figure 4 depicts the profile of responders exposed to medicines or agents that could
cause vitamin D deficiency. An extremely low proportion of respondents said they rou-
tinely use one of the listed agents. Isotretinoin had the most significant percentage (8.9%),
and given that most individuals were within an age range where acne is typically more
prevalent, it may have been recommended for treating acne. Since more than 33% of
research participants were obese, 3.8% of surveyors acknowledged using statins. Among
the respondents, only 3.1% reported using opioids, beta-blockers, or benzodiazepines.
Varenicline (a smoking cessation medication) and alcohol were utilized by only 2.1% of the
students. Only 1.7% of the subjects reported using calcium channel blockers or nuvaring
(to manage pregnancy). Acyclovir, interferon, and anticonvulsants were only used by 0.3%
of those surveyed.

3.8. Analysis of Psychological Burden Using DASS-21

Table 4 compares the profile of psychological burden of participants with vitamin D
deficiency with the control group. The DASS-21 was used as a scoring system for deter-
mining the prevalence of psychological burden. A significantly (p = 0.042) high percentage
of the vitamin D-deficient students was found with depression (60.35%) compared to the
control group (47.66%). Overall, 55% of those surveyed in this study were diagnosed with
having depression symptoms. Further, Table 4 shows that the prevalence of anxiety in
our sample of students was 60.83%. There was a significant (p = 0.031) difference between
the vitamin D-deficient and the control groups regarding the prevalence rate of anxiety.
Additionally, DASS-21 helped measure the status of stress among the participants. The
percentage of vitamin D-deficient patients (75.08%) under mental stress was significantly
Healthcare 2023, 11, 2097 9 of 16

more than the control group (58.03%). The overall stress prevalence was 67.91% among the
students included in the study.

Isotretinoin 8.90%
Statin 3.80%
Opioids 3.10%
Beta blockers 3.10%
Benzodiazepine 3.10%
Drug use profile

Varenicline 2.10%
Alcohol 2.10%
Nuvaring 1.70%
Calcium channel blocker 1.70%
Acyclovir 0.30%
Interferon Alfa 0.30%
Anticonvulsant 0.30%
Barbiturates 0%

0% 1% 2% 3% 4% 5% 6% 7% 8% 9% 10%
Percentage

Figure 4. Drug use profile for causing vitamin D deficiency.

‐
Table 4. Prevalence of depression, anxiety, and stress among participants with vitamin D deficiency
and control groups.

Vitamin D
Control Total
Categories Deficient p Value *
(N = 193) (N = 480)
(N = 285)
Depression (n) 172 92 264
ff 0.042
Prevalence (%) 60.35% 47.66% 55%
Anxiety (n) 189 103 292
0.031
Prevalence (%) 66.31% 53.36% 60.83%
Stress (n) 214 112 326
0.001
Prevalence (%) 75.08% 58.03% 67.91%
* Pearson Chi-square test (2-sided).

3.9. Level of Severity of Psychological Burden among Participants

As shown in Table 5, around 70% of the vitamin D-deficient participants in our study
were suffering from either moderate or severe forms of depression (p = 0.032) compared
to the control, which was only 53%. Further, a severe form of anxiety was significantly
(p = 0.012) more common (13.75%) in vitamin D-deficient students compared to the control
cohort (5.82%). Significantly (p = 0.011) a higher proportion of the vitamin D-deficient stu-
dents was found with either moderate (59.2%) or severe (15.88%) forms of stress compared
to the control group of the participants.
Healthcare 2023, 11, 2097 10 of 16

Table 5. Level of severity of depression, anxiety, and stress among participants with vitamin D
deficiency and control groups.

Vitamin D
Categories Control Total p Value *
Deficient
Depression, n (%) 172 (65.15) 92 (34.84) 264 (100)
Mild 51 (29.65) 42 (45.65) 93 (35.22)
0.032
Moderate 87 (50.58) 43 (46.73) 130 (49.24)
Severe 34 (19.76) 7 (7.60) 41 (15.53)
Anxiety, n (%) 189 (64.72) 103 (35.27) 292 (100)
Mild 82 (43.38) 42 (40.77) 124 (42.46)
0.021
Moderate 81 (42.85) 55 (53.39) 136 (46.57)
Severe 26 (13.75) 6 (5.82) 32 (10.95)
Stress, n (%) 214 (65.64) 112 (34.35) 326 (100)
Mild 64 (29.90) 54 (48.21) 118 (36.19)
0.011
Moderate 116 (54.20) 44 (39.28) 160 (49.07)
Severe 34 (15.88) 14 (12.5) 48 (14.72)
* Pearson Chi-square test (2-sided).

3.10. Regression Analysis for Depression

As per the details given in Table 6, the risk estimate to develop depression was highest due
to vitamin D deficiency (OR = 4.96, CI 2.22–6.78, p = 0.001), being female (OR = 3.45), experiencing
muscle pain (OR = 3.21), frequent tiredness (OR = 2.98), excessive academic demand (OR = 2.87),
family history of psychological burden (OR = 2.76), obesity (OR = 2.67), and use of anti-acne
medicine (isotretinoin) (OR = 2.34) were other significant factors that influenced the chances
of developing depression among the study participants. Using statin showed a decreased risk
(OR = 0.342) for developing depression, whereas 20–22 years and early study level (between 1
and 4) had increased odds of depression of 1.67 and 1.32 times, respectively.

Table 6. Logistic regression analysis of factors associated with depression in study participants.

Confidence Interval (95%)

Categories Odds Ratio p Value
Lower Upper
Vitamin D deficient 4.96 2.22 6.78 0.001
Female 3.45 1.99 4.14 0.011
Experience muscle pain 3.21 2.490 5.01 0.021
Frequent tiredness 2.98 1.311 4.61 0.011
Excessive academic demand 2.87 1.76 3.98 0.001
Family history of psychological burden 2.76 1.98 4.02 0.025
Obesity 2.67 1.87 4.32 0.034
Use of isotretinoin 2.34 1.88 4.56 0.022
Age between 20 and 22 years 1.67 1.23 2.87 0.039
Study level (1–4) 1.32 1.01 2.43 0.028
Use of statins 0.342 0.121 0.98 0.013
Healthcare 2023, 11, 2097 11 of 16

3.11. Regression Analysis for Anxiety

As depicted in Table 7, a family history of psychological burden showed the highest
risk (OR = 4.55, CI 2.25–8.65, p = 0.001) for developing anxiety among the study partici-
pants. Further, patients who experienced frequent tiredness, and those who used anti-acne
medicine (isotretinoin), experienced increased odds of anxiety development of 4.21 and
4.01 times, respectively. Vitamin D deficiency was found to be the fourth risk factor
(OR = 3.87, CI 2.55–6.59, p = 0.001) for anxiety in our study samples. Excessive academic
demand (OR = 3.56), the experience of muscle pain (OR = 3.22), female gender (OR = 3.21),
obesity (OR = 3.11), age group 20–22 years (OR = 2.13), and early study level (1–4 level)
(OR = 1.32) were other significant factors that increased the risk for the development of
anxiety among the surveyed university students. Interestingly, the use of statin (OR = 0.54),
benzodiazepines (OR = 0.44), and beta blockers (OR = 0.32) showed significantly less risk
for anxiety compared to those who were not using those medicines.

Table 7. Logistic regression analysis of factors associated with anxiety in study participants.

Confidence Interval (95%)

Categories Odds Ratio p Value
Lower Upper
Family history of psychological burden 4.55 2.25 8.65 0.001
Frequent tiredness 4.21 2.56 7.98 0.001
Use of isotretinoin 4.01 2.87 7.76 0.001
Vitamin D deficient 3.87 2.55 6.59 0.001
Excessive academic demand 3.56 2.11 7.65 0.001
Experience muscle pain 3.22 2.05 6.85 0.001
Female 3.21 2.15 6.87 0.001
Obesity 3.11 2.11 5.96 0.001
Age between 20 and 22 years 2.13 1.85 4.21 0.032
Study level (1–4) 1.32 1.04 2.76 0.022
Use of statins 0.54 0.23 0.98 0.019
Use of benzodiazepine 0.44 0.18 0.76 0.019
Use of beta-blockers 0.32 0.10 0.65 0.010

3.12. Regression Analysis for Stress

Family history of psychological burden had the highest risk (OR = 5.67, CI 2.071–9.32,
p = 0.001) of causing stress among the study participants (Table 8). Anti-acne medicine
(isotretinoin) was associated with the second highest risk (OR = 4.87, CI 2.98–8.64, p = 0.001)
of developing stress among the university students who participated in this study. The odds
of having stress were greater in vitamin D-deficient individuals by 4.77 times, whereas obese
individuals had an increased risk of stress by 4.21 times. Experiencing frequent tiredness
(OR = 3.44), excessive academic demands (OR = 3.21), experiencing muscle pain (OR = 2.45),
female gender (OR = 2.33), study level (1–4) (OR = 2.31), and age (20–22 years) (OR = 1.32)
were significantly associated with an increased chance of developing stress among our study
samples. Those participants who were using statins (OR = 0.89), benzodiazepines (OR = 0.87),
and beta blockers (OR = 0.56) had a lower chance of stress induction compared to those who
were not using these medicines.
Healthcare 2023, 11, 2097 12 of 16

Table 8. Logistic regression analysis of factors associated with stress in study participants.

Confidence Interval (95%)

Categories Odds Ratio p Value
Lower Upper
Family history of psychological burden 5.67 2.071 9.32 0.001
Use of isotretinoin 4.87 2.98 8.64 0.001
Vitamin D deficient 4.77 3.21 9.33 0.001
Obesity 4.21 2.52 8.48 0.001
Frequent tiredness 3.44 2.11 9.21 0.001
Excessive academic demand 3.21 1.98 8.61 0.001
Experience muscle pain 2.45 1.21 6.54 0.001
Female 2.33 1.76 5.43 0.001
Study level (1–4) 2.31 1.73 6.21 0.001
Age between 20 and 22 years 1.32 0.98 3.22 0.032
Use of statins 0.89 0.32 1.34 0.021
Use of benzodiazepine 0.87 0.43 1.81 0.011
Use of beta-blockers 0.56 0.23 1.01 0.034

4. Discussion
This study was conducted to determine the association between deficiency in vitamin
D and psychological burden in university students of Riyadh, Saudi Arabia. Further
research was conducted to ascertain the association between academic achievement and
the status of vitamin D deficiency. We also investigated additional variables that affect
the emergence of psychological loads and compared their impact with that of vitamin D
deficiency. The results of the inferential analysis point to a considerable impact of vitamin
D shortage on the occurrence of depression, anxiety, and stress, as well as a clear correlation
between vitamin D deficiency and a decline in academic performance.
The prevalence of vitamin D deficiency in the current study (59.794%) is lower than
that reported by the authors [15], where (70.7%) of their sample reported having a vitamin
D level below 20 ng/mL, even though the sample also included healthcare students, as in
our study. In addition, most participants in our study (62.08%) denied taking vitamin D
supplements. This difference in vitamin D deficiency prevalence could be related to the
participants’ healthy lifestyle choices; a sizable portion of our study samples (39.37%) had
a normal body shape and exercised regularly (48.13%), at least 1–2 days per week.
We found in our study that there was an association between vitamin D deficiency
and academic achievement, where we found that there was significantly low academic
achievement among vitamin D-deficient students. These results contrast with a study that
found no connection between low vitamin D levels and academic performance [29]; how-
ever, another study found that over 90% of students who did not consume enough vitamin
D were more likely to perform slightly less well academically than those who consumed
adequate amounts of vitamin D and other dietary sources [30]. A recent study [35] con-
ducted in Saudi Arabia demonstrated that there was a drop in the academic performance of
health science university students in the presence of vitamin D deficiency. Therefore, as our
study participants are mostly health science students, it is possible that subject overload
in health science programs is further increasing the workload on the already-vulnerable
vitamin D-deficient students, thereby resulting in a significant decrease in the academic
attainment of our study participants.
Although bone fracture is one of the main symptoms of vitamin D deficiency [36],
it was the least noticeable symptom in our study populations. The participants’ ages
ranged from 20 to 26 years, and bone fractures are less obvious in young people than in the
elderly, which may account for the notable difference in results between these symptoms.
According to Feskanish et al. [37], hormonal changes that may decrease bone density may
Healthcare 2023, 11, 2097 13 of 16

cause bone fractures to occur more frequently in elderly women (postmenopausal women)
with vitamin or calcium deficiencies than in younger women.
The majority of the participants’ diets consisted of cheese and other dairy items,
followed by diets rich in fatty fish and egg yolk. People who consume these diets on a
regular basis may not develop vitamin D deficiency, and this may be one of the possible
reasons for having a relatively lower percentage of vitamin D-deficient individuals, as
demonstrated previously by a systemic review study conducted by Bolland [38].
In addition to being a food, vitamin D is also a hormone that has receptors in almost all the
body’s cells and tissues. It has been demonstrated that vitamin D supports healthy physical,
mental, and immunological system function and has a wide range of effects on systemic
health. Correlational scientific evidence continually demonstrates an adverse association
between low vitamin D levels and mental health issues, including depression and anxiety,
across all age groups [39]. The findings in our study show that there is a significant influence
of vitamin D deficiency on developing depression, anxiety, and stress among young university
students. The risk of depression increased by five times in vitamin D-deficient students
compared to the control cohort. These findings are in agreement with a meta-analysis of
31,424 participants, which showed a significantly high risk of depression in participants who
had lower than normal vitamin D levels [21]. Another study with 7970 participants indicated
that the odds ratio for depressive episodes is considerably higher in those with serum vitamin
D levels below 20 ng/mL compared to those with levels above 30 ng/mL [40]. In addition to
depression, the risk of anxiety increased by 3.87 times, and the odds of stress were enhanced
by 4.77 times in vitamin D-deficient patients compared to the normal participants.
The hypothalamus pituitary adrenal (HPA) axis is a dynamic feedback loop between
the central nervous system and the endocrine system that is activated in response to stress.
Anxiety and mood disorders, as well as other mental health problems, have been linked to
the malfunctioning HPA axis. When exposed to UVB light, the skin has a systemic effect on
the HPA axis, ensuring appropriate vitamin D levels [41,42]. Studies conducted in vitro and
on animals have demonstrated that skin exposure to UVB light causes the expression of all
HPA axis components, including corticotropin-releasing hormone, proopiomelanocortin,
adrenocorticotropic hormone, beta-endorphin with associated receptors, the glucocorti-
coidogenic pathway, and the glucocorticoid receptor [41]. Dysfunction of this activation
may result in a variety of mental stresses and the development of anxiety, so vitamin D
deficiency is eventually a cause of psychological distress. It is also important to note that
calcitriol, the active form of vitamin D, drives gene transcription in the brain that functions
to both induce serotonin synthesis and block reuptake, likely increasing serotonin levels in
the central nervous system [43,44]. Therefore, it is thought that maximizing vitamin D may
aid in preventing and reducing the severity of brain dysfunction.
One of the major contributing factors to the development of psychological burden in
our study samples was the female gender. There are several reports that validate the rela-
tionship between the female population and the occurrence of psychological burdens [45].
According to a study conducted in Egypt, girls are more likely than boys to experience sig-
nificant levels of depression and anxiety [46]. A study conducted in Saudi Arabia reported
that the prevalence rate of psychiatric disorders is in the range of 30 to 46% [47]. Further,
we found that vitamin D deficiency was strongly associated with the female gender in our
study samples, which is similar to earlier reports [8,48], and we attribute this to prevalent
local cultural norms that limit skin exposure to sunlight [49]. Therefore, with vitamin D
deficiency, women are more likely to develop psychological distress. This was confirmed by
Bassil et al. [8] in a systematic review of vitamin D prevalence and predictors in the Middle
East and North Africa region. They concluded that despite the region’s high sunshine
levels, hypovitaminosis D is extremely common, with a prevalence of between 30% and
90%, and adult risk factors include older age, female sex, multiparty, the season of the year,
style of clothing, socioeconomic status, and residence (urban rather than rural). Therefore,
there is a need for necessary steps to improve the vitamin D level, which will considerably
improve the mental status of the population in general and females in particular.
Healthcare 2023, 11, 2097 14 of 16

The use of statins, benzodiazepines, and beta blockers was inversely correlated with
the occurrence of psychological burden in the study population. Our findings are congruent
with a meta-analysis that reported statistically significant improvements in mood scores
among the 2105 participants [50]. The benefit of statin could be attributed to its anti-
inflammatory, antioxidant, and cardioprotective properties [51]. Benzodiazepines are
psychoactive agents known for their anxiolytic effects [52], and hence we found in our
study samples a decreased correlation between stress and anxiety with the use of this drug.
Nevertheless, the use of this drug was found with only 3.1% of the population, which
indicates the cautious approach of our study participants to deal with this drug due to its
drug dependence and side effects. Further, the use of beta-blockers was associated with
decreased vulnerability to stress and anxiety among the students who participated in this
study. Our findings are similar to those of an earlier study [53], where they observed links
between beta-blockers and lower psychological distress.
Despite some intriguing findings, our study has several limitations. First, because
it was cross-sectional, we were unable to determine causality. Additionally, this could
have exposed the study to sources of bias due to disparities in the participants’ cultural
backgrounds, ages, and socioeconomic levels, as well as bias originating from the way study
subjects were recruited. However, as a sizable portion of the students attending AlMaarefa
University are from other parts of the country, the participants in the current study were
not restricted to the capital city of Riyadh. This renders the selection of cases impartial and
perhaps representative of Saudi society. Second, we conducted our research from March to
May of 2021, which is the start of the summer. The research area’s temperature is generally
always between 25 and 35 degrees Celsius during this time, and the sun is not as intense as
it is from June to August; nevertheless, considering the availability of sunshine nearly all
year, seasonality may not be a relevant effect in our instance.

5. Conclusions
Even though there is ample sunlight in Saudi Arabia, vitamin D deficiency is widespread
among the population. The need for increased vitamin D awareness, particularly among
university students, and the integration of vitamin D testing in primary healthcare facilities,
vitamin supplements, and foods fortified with vitamin D are necessary, particularly for
people who are dealing with psychological burdens such as depression, anxiety, and stress.
Controlling vitamin D levels not only helps to control the wide range of psychological burdens
but also helps to improve the academic performance of the students. It is especially critical to
provide additional coverage for the female population to combat the high frequency of both
psychological discomfort and vitamin D deficiency.

Author Contributions: Under the supervision of S.M.B.A., M.A., M.E.A., S.A.A. and A.M.A. carried
out the data collection, cleaning, and filtration. A.A. (Ahmed Alshehri) and A.A. (Adel Alghamdi) were
responsible for the formal analysis and interpretation of the work. S.A. participated in writing the original
draft of the manuscript. M.E.A. administered the project, and S.M.B.A. was instrumental in reviewing and
editing the manuscript. All authors have read and agreed to the published version of the manuscript.
Funding: This research was funded by the Researchers Supporting Project number (RSP2023R115)
from King Saud University, Riyadh, Saudi Arabia. The authors also thank AlMaarefa University,
Riyadh, Saudi Arabia, for extending financial support for this research.
Institutional Review Board Statement: The study was conducted in accordance with the Declaration
of Helsinki and approved by the Institutional Review Committee of AlMaarefa University, Riyadh,
Saudi Arabia (202/12/RC, 19 September 2020).
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Data Availability Statement: Data is contained within the article.
Acknowledgments: This research was funded by the Researchers Supporting Project number
(RSP2023R115) from King Saud University, Riyadh, Saudi Arabia.
Conflicts of Interest: The authors declare no conflict of interest.
Healthcare 2023, 11, 2097 15 of 16

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