Experimental Gerontology 175 (2023) 112149

Contents lists available at ScienceDirect

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

Effect of a dietary intervention based on the Mediterranean diet on the

quality of life of patients recovered from depression: Analysis of the
PREDIDEP randomized trial
Beatriz M. Cabrera-Suárez a, Francisca Lahortiga-Ramos b, c, Carmen Sayon-Orea d,
Jose L. Hernández-Fleta a, Ana González-Pinto d, e, Patricio Molero b, c, Rosario Vega-Pérez a,
Almudena Sánchez-Villegas c, d, f, *, **, ***, PREDI-DEP investigators
a
Psychiatry and Clinical Psychology Service, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
b
Department of Psychiatry and Medical Psychology, University Clinic of Navarra, Pamplona, Spain
c
IdiSNA, Instituto de Investigación Sanitaria de Navarra, Spain
d
Centro de Investigación Biomédica en Red (CIBER), Instituto de Salud Carlos III, Madrid, Spain
e
BIOARABA, Hospital Universitario de Alava, UPV/EHU, Spain
f
ISFOOD - Institute for Innovation & Sustainable Development in Food Chain, Universidad Pública de Navarra (UPNA), Spain

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

Keywords: Introduction: There is substantial evidence supporting that improving diet quality leads to improved health-
Mediterranean diet related quality of life (HRQoL). Our major aim was to assess the effectiveness of a Mediterranean diet–based
Quality of life nutritional intervention to improve HRQoL in the context of a secondary prevention trial of depression.
Depression
Secondarily to assess its effectiveness among adults aged 60 or more years.
Olive oil
Methods: The PREDIDEP study is a 2-year multicentre, randomized, single-blinded nutritional trial. At baseline
Clinical trial
and at 1-year and 2-year follow-up, SF-36 health survey questionnaire was collected to evaluate participants'
HRQoL (total and specific range for each of the 8 dimensions: 0 to 100 points). Mixed effect linear models were
used to assess changes in HRQoL according to adherence to the Mediterranean diet. The trial was registered at
ClinicalTrials.gov NCT03081065.
Results: After 2 years of intervention, the Mediterranean Diet intervention group compared to control group
(without nutritional intervention, only usual clinical care) showed an improvement in some dimensions of
HRQoL such as Mental Health (7.22; 95 % CI = 2.22–12.22) (between-group difference: 6.79; 95 % CI
− 0.14–13.73, p = 0.055); Vitality (9.51; 95 % CI = 4.00–15.03) (between-group difference: 9.00; 95 % CI
1.75–16.25, p = 0.020); Mental Summary Component (2.83; 95 % CI = 0.55–5.11) (between-group difference:
1.17; 95 % CI = − 1.96–4.30, p = 0.462); and General Health (10.70; 95 % CI = 5.58–15.81) (between-group
difference: 6.20; 95 % CI = − 0.89–13.28, p = 0.086). Similar results were observed for participants aged 60 or
more years.
Conclusion: The intervention based on Mediterranean diet in patients with previous depression seems to be
effective in improving HRQoL, especially the mental dimensions. This effect is also observed among participants
aged 60 or more years.

Abbreviations: BMI, body mass index; BP, bodily pain; CIs, Confidence Intervals; DALYs, disability-adjusted life years; DS, standard deviation; GH, General Health;
HELFIMED, Mediterranean-style dietary intervention supplemented with fish oil; HRQoL, health-related quality of life; MEDAS, Mediterranean Diet Adherence
Screener; MET, metabolic equivalent; MH, Mental Health; MSC, Mental Summary Component; PF, physical functioning; PREDIDEP, Prevention of depression with
Mediterranean Diet (Prevención con Dieta Mediterránea de Depresión); PSC, Physical Summary Component; RE, role emotional; SDs, standard deviations; SF, social
functioning; SF-36, The Short Form-36 Health Survey; VT, vitality; YLD, Years Lived with Disability.
* Corresponding author at: IdiSNA, Instituto de Investigación Sanitaria de Navarra, Spain.
** Corresponding author at: ISFOOD - Institute for Innovation & Sustainable Development in Food Chain, Universidad Pública de Navarra (UPNA), Pamplona,
Spain.
*** Corresponding author at: Centro de Investigación Biomédica en Red (CIBER), Instituto de Salud Carlos III, Madrid, Spain.
E-mail address: [email protected] (A. Sánchez-Villegas).

https://doi.org/10.1016/j.exger.2023.112149
Received 13 December 2022; Received in revised form 11 March 2023; Accepted 14 March 2023
Available online 20 March 2023
0531-5565/© 2023 The Authors. 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/).
B.M. Cabrera-Suárez et al. Experimental Gerontology 175 (2023) 112149

1. Introduction been followed up for at least 2 years (n = 157). Among them, 134 had
successfully fulfilled the information about HRQoL collected in SF-36
The World Health Organization defines quality of life concept as questionnaires (Fig. 1).
individuals' perception of their position in life in the context of the Additional analyses were carried out to assess the role of the dietary
culture and value systems in which they live and in relation to their goals intervention in HRQoL among participants aged 60 or more years who
expectations, standards and concerns (World Health Organization completed the trial (n = 29 in the control group and n = 26 in the
Quality of Life assessment, 1995). Unipolar depression is a prevalent and intervention group).
disabling condition that negatively influences quality of life. Patients All procedures contributing to this work complied with the ethical
with depression are more vulnerable to have a poorer health-related standards of the relevant national and institutional committees on
quality of life (HRQoL) (Papakostas et al., 2004). Moreover, factors human experimentation and with the Helsinki Declaration of 1975, as
such as the age of onset of depression, lack of therapeutic adherence, the revised in 2008. The trial was registered at ClinicalTrials.gov
existence of comorbid diseases, poor social support, perceived self- NCT03081065. The Research Ethics Committees at each recruitment
stigma, and positive family history influence in depressed patients' centre approved the protocol. All participants provided written
HRQoL (Priebe et al., 2010). This situation is particularly dramatic in informed consent after they received the information sheet and an
older patients. In this population, severity of depression has been also additional verbal explanation of the study characteristics.
associated to poorer HRQoL, and this association has been found to be
stable over time (Sivertsen et al., 2015). Depression is one of the leading
global causes of quality of life impairment measured in disability- 2.2. Description of the intervention
adjusted life years (DALYs) and Years Lived with Disability (YLD)
(GBD 2019 Mental Disorders Collaborators, 2022). Quality of life is an The aim of the nutritional intervention of the PREDIDEP study was to
important component and prognostic indicator of mental illness, and it improve adherence to the Mediterranean diet in recovered depressed
is recommended to be integrated into the clinical assessment and in­ patients. In the PREDIDEP study, we used a remote nutritional inter­
terventions of people with severe mental illness. In depression, HRQoL is vention rather than an in-person approach. This remote intervention
affected by the nature of the symptoms (depressed mood, anhedonia, was conducted by a team of registered dietitians by phone and on the
apathy, low self-esteem, psychomotor retardation, among others), co­ internet, and participants had access to web-based information on a
morbid diseases, and social, occupational and cognitive deterioration website and printed materials. Each participant in the intervention
(ulHaq et al., 2016). group also received extravirgin olive oil for free. The nutritional inter­
There is substantial evidence supporting the relationship between vention has been described previously in detail elsewhere (Sánchez-
high adherence to Mediterranean diet and low risk for depression Villegas et al., 2019). Participants in the control group received usual
(Lassale et al., 2019) or improvement in HRQoL (Muñóz et al., 2009; clinical care but not a nutritional intervention.
Galilea-Zabalza et al., 2018). The specific biological mechanisms that
link depression, HRQoL, and diet are still unknown. It is a challenge for
Public Health policies to identify new strategies to increase depressed 2.3. Outcome assessment
patients' quality of life to reduce their substantial resource expenditure
and personal and familiar suffering. HRQoL was assessed at baseline and yearly during follow-up (by
The principal objective of this study was to assess the effect of 2-year phone or through the web page) with the validated Spanish version of
intervention with Mediterranean Diet enriched with extravirgin olive oil the SF-36 Health Survey. This instrument is useful to evaluate the
on HRQoL improvement in the context of a secondary prevention trial of relationship between lifestyle habits and non-disease-specific quality of
depression particularly among participants older than 60 years. life (Alonso et al., 1998).
This questionnaire contains 36 items, which measure eight multiitem
2. Material & methods dimensions of health status: physical functioning, role limitations
because of physical health problems (role-physical), bodily pain (toler­
2.1. Study population ance), general health perceptions, vitality, social functioning, role lim­
itations because of emotional problems (role emotional) and mental
The PREDIDEP study was a multicentre, randomized, controlled, health. The first four domains deal with physical aspects, and the next
single-blind trial. The study design and methodology has been described four reflect psychological features. For each dimension, the scores are
previously in detail elsewhere (Sánchez-Villegas et al., 2019). Briefly, coded, summed, and transformed to a scale from 0 (the worst possible
study participants were randomly assigned to one of two groups (Med­ condition) to 100 (the best possible condition) (Brazier et al., 1992).
iterranean diet or control) once their data were included in a centralized Change in HRQoL was measured for each dimension as the difference
data management system by the specialists. Various stratification factors between one-year follow-up and baseline scores (short-term change) or
were considered for randomization, sex, age group (<65 years or ≥65 two years follow-up and baseline scores (long-term change).
years), and recruitment centre. At baseline, psychiatrists and clinical
psychologists were blinded to the allocation of participants, following
the CONSORT guidelines for randomized trials to prevent information 2.4. Other covariate assessment
biases.
The PREDIDEP study included 52 men and 144 women between 18 At baseline, the dietitians also collected information about socio­
and 86 years old who had suffered at least one depression episode and demographic characteristics (education level, civil status, and working
who were in a stage of clinical remission. Between March 2017 and status), smoking habits, and anthropometric measurements (self-re­
December 2020, 222 patients from different Spanish regions or prov­ ported weight and height). During this phone call, information about
inces (Alava, Navarra, Madrid, and Las Palmas) were invited to partic­ physical activity was also collected with a physical activity question­
ipate in the study by their specialists. Of them, although 208 patients naire validated for the Spanish population (Martínez-González et al.,
were recruited and randomized, 196 started the intervention. The 2005).
number of dropouts was 17, and the retention rate was 92.9 % among Depressive symptoms were assessed through the Beck Depression
participants with follow-up over 12 months (182/196), and 91.3 % with Inventory. In case of suspected recurrence (score Beck Depression In­
follow-up over 24 months (179/196). ventory >18), participants were examined by care providers and they
In a secondary analysis, we included all participants who had already were excluded if they suffered a depression recurrence.

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B.M. Cabrera-Suárez et al. Experimental Gerontology 175 (2023) 112149

2.5. Sample size calculation and statistical analysis Quantitative variables were expressed as means and standard de­
viations (SDs), whereas categorical variables were described as number
To detect a mean yearly difference of 5 points in the physical and and percentages (n [%]). The Student t-test for continuous variables and
mental summary components with a standard deviation equal to 10 in the chi-square test for categorical variables were applied to test differ­
each group with a 5 % significance level and 80 % power, a sample size ences in baseline characteristics between the intervention groups.
of 126 participants was calculated. Considering an attrition of 15 %, the Mixed effects linear models were used to assess changes in HRQoL
final number of required participants was 150. from baseline to 12- and 24-month follow-up visits in all randomized
The main analysis of the study included all randomized participants participants and completer-only analyses. A 2-level mixed linear model
with baseline data, regardless of whether they had incomplete infor­ with random intercepts at the recruitment centre and participants was
mation at follow-up visits, with multiple imputation procedures for fitted.
missing data (intention to treat analysis). Multiple imputation methods The analyses were performed using STATA (v 12.0, StataCorp LP).
used an iterative Markov chain Monte Carlo method (STATA “mi” The significance level (2-tailed) was set at p values lower than 0.05.
command). We generated 20 imputations for each missing measure­
ment. Imputed missing values were used for follow-up data but not for 3. Results
baseline data. The imputation models included sex, age, smoking status,
body mass index (BMI), civil status, education level, total energy intake, Among the 196 patients who started the intervention, 73.5 % were
physical activity, depressive symptoms (baseline Beck score), interven­ women and the mean age was 51.1 years (SD 14.2). Table 1 shows the
tion group, and the baseline value of the variable that was imputed as a demographic, anthropometric, and lifestyle baseline characteristics of
predictor. Secondary analyses included only participants with complete participants according to the randomized groups (intervention or con­
information available at each follow-up visit (completers only). trol). No baseline significant differences between intervention groups

222 patients invited to participate

in the study

14 excluded - do not meet

inclusion criteria

12 participants declined to
participate 208 participants randomized 1:1

196 participants started the

intervention

Control group Intervention group

n = 93 participants n = 103 participants

81 participants 91 participants
follow-up 1 year follow-up 1 year
Dropouts (n=6) Dropouts (n=8)
Relapses (n=6) Relapses (n=4)

Final sample=69 participants

Final sample=65 participants
Dropouts (n=1)
follow-up 2 years
Relapses (n=7)
Dropouts (n=2)
Participants followed-up for less
Relapses (n=5) than 2 y (n=8)
Participants followed-up for less Participants without data of quality
than 2 y (n=8) of life in any of the periods
evaluated (n=3)

Fig. 1. Flow-chart of participant screening, recruitment, and randomization.

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B.M. Cabrera-Suárez et al. Experimental Gerontology 175 (2023) 112149

were found. When the analysis was restricted to those participants aged 2.22–12.22)], Vitality [9.51 (95 % CI = 4.00–15.03)], and Mental
60 years or more, baseline characteristics were also similar between Summary Component [2.83 (95 % CI = 0.55–5.11)] in the intervention
comparison groups (data not shown). group with Mediterranean Diet enriched with extravirgin olive oil, with
no changes in control group. In addition, significant differences between
3.1. HRQoL changes by intervention groups groups were observed for Vitality (between-group difference: 9.00; 95 %
CI = 1.75–16.25, p = 0.015). In the analyses including only completers,
The effect of dietary intervention on changes in mental dimensions of the results did not substantially differ also finding a significant differ­
HRQoL is shown in Table 2. ence between groups in Mental Health after two years of intervention
After one year of follow-up, the intervention group showed a sig­ (between-group difference: 7.37; 95 % CI = 0.82–13.92, p = 0.027).
nificant increase in Vitality [mean absolute 1-y change for this domain The effect of the nutritional intervention on the physical dimensions
was 5.41 points (95 % CI = 0.51–10.31)] and in Mental Summary of HRQoL is showed in Table 3. After one year of follow-up, intervention
Component [2.48 (95 % CI = 0.54–4.41)], with no mean absolute group showed a significant improvement in General Health [5.05 (95 %
changes in the control group. However, between group differences did CI = 0.63–9.47)] and Role physical [14.00 (95 % CI = 2.88–25.11)] with
not reach statistical significance. The results for Vitality and Mental no changes in control group. After two years of intervention, there was a
Summary Component were similar in the analyses including only significant increase in General Health [10.70 (95 % CI = 5.58–15.81)] in
completers. the intervention group with Mediterranean Diet enriched with extra­
After two years of intervention, there was a significant increase in virgin olive oil, with no changes in control group. Results were very
Mental Health [mean absolute 2-y change was 7.22 (95 % CI = similar in the analysis including only completers.
Results for the analysis restricted to older participants were similar
(Supplemental Tables 1 and 2). Among participants that completed the
Table 1
Baseline characteristics of the participants in the prevention of recurrent overall follow-up period, those assigned to the Mediterranean dietary
depression with Mediterranean diet trial. pattern showed a significant increment in the Vitality dimension (10.49;
95 % CI = 1.96–19.03) and in the Mental Summary Component (3.50;
Characteristics Control (n = Intervention (n = p
93) 103) value* 95 % CI = 0.79–6.21) after two years of follow-up although, in these
cases, the differences between groups were not significant. Regarding
Age, years, mean (SD) 51.48 (14.7) 51.16 (13.79) 0.8647
Sex, n (%) 0.588
physical dimensions, important increment in General Health was
Men 23 (24.73) 29 (28.16) observed for participants assigned to the Mediterranean diet at short
Women 70 (75.27) 74 (71.84) term (one year of intervention): increment in 7.19 points (95 % CI =
Depressive episodes, n (%) 0.28–14.10) and at long term (two years of intervention): increment in
1 42 (45.16) 35 (33.98) 0.274
11.41 points (95 % CI = 2.46–20.37), although only significant differ­
2 21 (22.58) 27 (26.21)
3 or more 30 (32.26) 41 (39.81) ences between groups were observed for this dimension after one year of
Somatic diseases, n (%) 28 (30.43) 26 (25.24) 0.419 follow up (9.27; 95 % CI = 1.07–17.46).
Antidepressants use, n (%) 70 (75.27) 81 (78.64) 0.575
Civil status, n (%) 0.558
3.2. Adverse effects
Single 33 (35.87) 34 (33.01)
Married 37 (40.22) 49 (47.57)
Others 22 (23.91) 20 (19.41) Regarding the possible adverse effect, we did not find any harm or
Education, n (%) 0.613 unintended effects in the group assigned to Mediterranean diet supple­
Secondary or less 48 (52.17) 50 (48.54) mented with extravirgin olive oil.
University 44 (47.82) 53 (51.45)
Working status, n (%) 0.826
Working 39 (42.39) 47 (45.63) 4. Discussion
Retired 16 (17.39) 19 (18.45)
Others 37 (40.22) 37 (35.92) 4.1. Principal findings
BMI (kg/m2) 26.04 (5.29) 26.09 (4.78) 0.945
Smoking status, n (%) 24 (26.09) 24 (23.30) 0.457
Illegal drugs, n (%) 8 (8.6) 9 (8.74) 0.973
This trial is, to our knowledge, the first multiprofessional interven­
Beck score 5.78 (5.24) 6.41 (5.84) 0.428 tion study which has evaluated the effect of a remote dietary interven­
Physical activity (MET-hours/ 16.30 (19.19) 18.13 (24.99) 0.5694 tion based on the Mediterranean diet enriched with extravirgin olive oil
week) in increasing HRQoL in recovered depressed patients. This dietary
MEDAS score (14 items) 7.01 (2.1) 7.04 (1.97) 0.8959
intervention was specifically designed for patients in clinical remission
HRQoL mental dimensions
- MSC 37.07 (7.13) 37.85 (7.00) 0.4462 who had suffered at least one depression episode and was based on
- MH 62.70 (1.99) 67.02 (1.81) 0.1090 personalized nutritional information through different remote access
- VT 53.10 (2.30) 54.02 (2.16) 0.7705 routes, in coordination with face-to-face interventions, carried out by
- SF 75.54 (3.29) 81.74 (2.90) 0.1582 psychiatrists and psychologists.
- RE 29.35 (4.40) 23.53 (3.90) 0.3219
HRQoL physical dimensions
The intervention based on Mediterranean diet resulted in an
- PSC 47.81 (7.35) 48.36 (7.21) 0.6002 improvement in quality of life, especially in General Health and in the
- GH 60.67 (2.64) 60.62 (2.54) 0.9878 mental domains of HRQoL: Mental Health and Vitality, as well as in
- BP 70.11 (2.95) 73.04 (2.85) 0.4761 Mental Summary Component. When the analyses were restricted to
- PF 88.26 (1.78) 90.00 (1.60) 0.4676
participants aged 60 or more years the results were consistent with
- RP 21.74 (4.00) 20.34 (3.71) 0.7982
Energy intake (kcal/day) 2531 (809) 2683 (874) 0.2094 significant increment in Vitality, Mental Summary Component and
General Health after two years of intervention with Mediterranean diet.
BMI: body mass index; BP: Bodily pain; GH: General Health; HRQoL: Health
Furthermore, it should be highlighted the great magnitude of the
Related Quality of Life; MET: Metabolic equivalent; MEDAS: Mediterranean Diet
increment observed for Vitality and General Health scores after two
Adherence Screener; MH: Mental Health; MSC: Mental Summary Component;
PF: Physical functioning; PSC: Physical Summary Component; RE: Role years of intervention, higher than 8 points in both the overall sample
emotional; RP: Role physical; SF: Social functioning; VT: Vitality. and in the sub-analysis including only participants aged 60 or more
*
p-value obtained through the Student's t-test (quantitative variables) or the years. There is a debate on how to define meaningful differences on the
Chi-square (qualitative variables). SF-36 scores in a clinical setting. Even absolute differences from 3 to 10
points have been suggested as relevant (Samsa et al., 1999; Norman

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B.M. Cabrera-Suárez et al. Experimental Gerontology 175 (2023) 112149

Table 2
Changes in the mental dimensions of the HRQoL at 12- and 24-month follow-up visits of all randomized PREDIDEP participants according to randomized treatment
group.
HRQoL mental and Control group, mean change (CI 95 %) Intervention group, mean change (CI 95 Control vs. Intervención
physical dimensions %)
Between-group difference

Intention-to- Completers-onlyb Intention-to- Completers-onlyb Intention-to-treatc p Completers-onlyc p

treata (n = 65) treata (n = 69) (MI) valued valued
(n = 93) (n = 103)

Mental Health
1-year change − 2.43 − 2.30 2.73 2.87 5.16 0.115 5.17 0.089
(− 7.13–2.27) (− 6.30–1.70) (− 1.63–7.09) (− 1.55–7.28) (− 1.26–11.59) (− 0.79–11.12)
2-year change 0.43 0.23 7.22 7.60 6.79 0.055 7.37 (0.82–13.92) 0.027
(− 4.38–5.23) (− 4.28–4.74) (2.22–12.22) (2.85–12.36) (− 0.14–13.73)

Vitality
1-year change − 0.53 − 0.56 5.41 5.37 5.94 0.106 5.93 0.096
(− 5.81–4.75) (− 5.54–4.42) (0.51–10.31) (0.47–10.27) (− 1.27–13.16) (− 1.06–12.92)
2-year change 0.43 − 0.22 9.51 8.78 9.09 (1.42–16.75) 0.020 9.00 (1.75–16.25) 0.015
(− 4.90–5.76) (− 5.18–4.74) (4.00–15.03) (3.49–14.06)

Social functioning
1-year change 2.09 2.12 1.62 1.35 − 0.47 0.930 − 0.77 0.881
(− 5.69–9.88) (− 5.59–9.83) (− 5.64–8.88) (− 5.16–7.86) (− 11.13–10.18) (− 10.87–9.32)
2-year change 1.35 1.28 3.95 4.47 2.60 0.653 3.19 0.566
(− 6.54–9.25) (− 7.08–9.64) (− 4.15–12.06) (− 2.49–11.42) (− 8.75–13.96) (− 7.69–14.06)

Role emotionale
1-year change 4.65 4.48 7.13 6.38 2.48 0.747 1.89 0.798
(− 6.42–15.72) (− 6.08–15.04) (− 3.25–17.52) (− 3.53–16.28) (− 12.61–17.57) (− 12.58–16.37)
2-year change 7.58 7.44 − 3.38 − 3.39 − 10.96 0.176 − 10.83 0.182
(− 3.50–18.66) (− 4.53–19.40) (− 14.93–8.16) (− 13.87–7.09) (− 26.86–4.93) (− 26.73–5.07)

Mental Summary Component

1-year change 0.54 0.55 2.48 (0.54–4.41) 2.36 (0.55–4.17) 1.94 (− 0.98–4.77) 0.180 1.81 (− 0.81–4.43) 0.176
(− 1.52–2.60) (− 1.35–2.45)
2-year change 1.66 1.57 2.83 (0.55–5.11) 2.84 (0.73–4.94) 1.17 (− 1.96–4.30) 0.462 1.26 (− 1.81–4.33) 0.421
(− 0.51–3.82) (− 0.66–3.81)

CI: Confidence Interval. HRQoL: Health-Related Quality of Life.

a
Calculated using multiple imputation method with 20 imputations for each missing measurement.
b
Calculated using mixed-effect models with centre as random factor.
c
Calculated using mixed-effect models with site and intracluster correlations (couples) as random factors.
d
p value between group intervention difference.
e
Role emotional: convergence not achieved with the original model; thus, for this variable, the imputation model included sex, age, smoking status, body mass index
(BMI), total energy intake, physical activity, depressive symptoms (baseline Beck score), intervention group, and the baseline value of role emotional. Marital status
and education were excluded from the imputation method.

et al., 2003). Therefore, our results could be considered clinically HRQoL in those individuals with greater adherence to the Mediterra­
significant. nean diet pattern. This universality also goes beyond issues such as
population age profile. The evidence has been also replicated with these
improvements in the adolescent (Costarelli et al., 2013) and elderly
4.2. Comparison with prior work populations (Govindaraju et al., 2018).
However, we cannot forget that our study is based on adults affected
The benefits of a high adherence to the Mediterranean Diet are more by a medical condition, depression. Other studies have determined the
than those which evidence has already demonstrated for the general benefits of high adherence to a Mediterranean diet on HRQoL for other
health population or in the prevention and prognosis of different kinds pathologies, such as type 2 diabetes mellitus (Alcubierre et al., 2016)
of pathologies (Sánchez-Sánchez et al., 2020). During the last years, the metabolic syndrome (Galilea-Zabalza et al., 2018) or individuals at
benefit of Mediterranean diet has been the focus on its relationship with cardiovascular risk (Sanchez-Aguadero et al., 2016). In these pathol­
quality of life. In fact, there are several studies that have analyzed the ogies, improvements were found for both mental and physical di­
relationship between Mediterranean Diet and HRQoL. A recent meta- mensions of HRQoL. Depression shares with all of them a common
analysis (Vajdi and Farhangi, 2020) evaluated 13 studies with a total pathophysiological process that makes them susceptible to all potential
of 43,445 subjects. It determined that both a “healthy” and a “Medi­ benefits of Mediterranean diet, such as a low-grade inflammatory state
terranean” diet pattern were related to better HRQoL scores. mediated by the gut microbiota (Hills et al., 2019).
The perceived benefits found for Mediterranean diet have been Nevertheless, unlike the results of the aforementioned studies, in our
consolidated in culturally diverse populations and countries, such as analysis we observed benefits especially for the mental domains of
Italy (Bonaccio et al., 2013) and Spain (Galilea-Zabalza et al., 2018), HRQoL. Our participants are individuals with a potential risk of pre­
Greece, and the United Kingdom (Klonizakis et al., 2019), or the United senting a new depressive episode whose most affected HRQoL domains
States (Gigic et al., 2018), with improvements in various dimensions of

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Table 3
Changes in the physical dimensions of the HRQoL at 12- and 24-month follow-up visits of all randomized PREDIDEP participants according to randomized treatment
group.
HRQoL mental and Control group, mean change (CI 95 %) Intervention group, mean change (CI 95 %) Control vs. Intervención
physical dimensions
Between-group difference

Intention-to-treata Completers-onlyb Intention-to-treata Completers-onlyb Intention-to- p Completers-onlyc p

(n = 93) (n = 65) (n = 103) (n = 69) treatc (MI) valued value

General Health
1-year change 0.67 (− 4.08–5.41) 0.88 (− 3.19–4.96) 5.05 (0.63–9.47) 5.88 (1.92–9.83) 4.39 0.185 4.99 0.085
(− 2.11–10.88) (− 0.69–10.68)
2-year change 4.50 (− 0.41–9.41) 4.76 (− 0.29–9.82) 10.70 10.92 6.20 0.086 6.15 0.093
(5.58–15.81) (5.83–16.00) (− 0.89–13.28) (− 1.02–13.32)

Bodily pain
1-year change ¡7.90 (¡14.84 to ¡7.51 (¡13.28 to ¡9.20 (¡15.64 to ¡9.11 (¡15.67 to − 1.31 0.787 − 1.60 0.720
¡0.96) ¡1.73) ¡2.77) ¡2.54) (− 10.78–8.17) (− 10.34–7.14)
2-year change ¡11.67 (¡18.72 ¡11.40 (¡18.22 − 3.77 − 3.72 7.90 0.131 7.68 0.117
to ¡4.61) to ¡4.57) (− 11.15–3.62) (− 10.47–3.03) (− 2.36–18.16) (− 1.92–17.28)

Physical functioning
1-year change − 2.33 − 2.48 − 2.05 − 1.88 0.29 0.898 0.61 0.785
(− 5.55–0.88) (− 5.39–0.43) (− 5.02–0.93) (− 5.22–1.36) (− 4.11–4.68) (− 3.75–4.96)
2-year change ¡3.83 (¡7.03 to ¡3.97 (¡7.05 to ¡3.50 (¡6.77 to ¡3.03 (¡5.84 to 0.33 0.888 0.94 0.657
¡0.63) ¡0.90) ¡0.23) ¡0.22) (− 4.26–4.92) (− 3.22–5.10)

Role physical
1-year change 7.30 (− 4.65–19.24) 6.89 (− 3.11–16.89) 14.00 14.01 6.70 0.422 7.13 0.351
(2.88–25.11) (2.87–25.16) (− 9.65–23.05) (− 7.85–22.10)
2-year change 14.79 13.54 5.07 4.60 − 9.72 0.266 − 8.94 0.283
(2.77–26.82) (1.52–25.55) (− 7.32–17.47) (− 6.42–15.62) (− 26.87–7.43) (− 25.25–7.37)

Physical Summary Component

1-year change − 0.54 − 0.49 − 0.18 − 0.03 0.36 0.115 0.46 0.681
(− 2.26–1.18) (− 1.99–1.01) (− 1.78–1.43) (− 1.60–1.53) (− 2.00–2.73) (− 1.71–2.63)
2-year change − 0.47 − 0.56 0.54 (− 1.24–2.31) 0.47 (− 1.19–2.14) 1.01 0.055 1.04 0.402
(− 2.22–1.27) (− 2.33–1.20) (− 1.49–3.50) (− 1.39–3.47)

CI: Confidence Interval. HRQoL: Health-Related Quality of Life.

a
Calculated using multiple imputation method with 20 imputations for each missing measurement.
b
Calculated using mixed-effect models with centre as random factor.
c
Calculated using mixed-effect models with site and intracluster correlations (couples) as random factors.
d
p value between group intervention difference.

are mental dimensions. Thus, we consider that the observed results are and MEDAS, respectively, which were assessed at baseline and during
of special importance in the management of this kind of patients. the intervention. Thereby, the precision of the analyses and temporal
However, to our knowledge, only one previous study, the HELFIMED consistency of the results are guaranteed.
study, has directly evaluated changes in HRQoL in an intervention with Likewise, to evaluate low/high adherence to the Mediterranean diet
a Mediterranean diet in patients with depression, with a shorter sample according to MEDAS, we have used a widely used reference point for
size and duration (Parletta et al., 2019). Similar to our results, this study Spanish population (García-Conesa et al., 2020), which allows us to
concluded that the intervention with Mediterranean diet supplemented obtain comparable results with other populations. Finally, some ana­
with fish oil improved Mental Health dimensions of HRQoL. We also lyses have been adjusted for a wide range of baseline characteristics that
found improvements in Vitality, Total Mental Score and General Health could have interfered with the results.
parameters in HRQoL. However, the results obtained in our study might not be applicable to
the general population. Our study is based on patients with depression,
4.3. Strengths and limitations who present worse HRQoL baseline scores (Papakostas et al., 2004).
Another possible limitation of this study is that SF-36 questionnaire
There are several strengths and limitations of this study that should is a self-reported measure, which is susceptible to information bias. It is
be considered when interpreting the results. possible that the association reflects a tendency to report outcomes as
The main strength of this study is that, as far as we know, this is the more favourable than they actually are (social desirability bias). Like­
first trial including such a high number of participants and that it has wise, if there had been an information bias, this would be a non­
evaluated the effect of a dietary intervention based on the principles of differential one; and it would have biased the results towards null (lack
the Mediterranean diet on the HRQoL of individuals recovered from of effectiveness). Therefore, it would be expected that the difference
depression for a large period of time, up to 2 years. That long duration obtained would be even greater than that observed. Furthermore, the
has allowed us to accurately evaluate the medium-long-term effects of use of validated questionnaire such as SF-36 (Brazier et al., 1992) to
adherence to the Mediterranean diet on HRQoL. Moreover, HRQoL and assess information minimizes this possibility.
adherence to Mediterranean diet-related data were evaluated by SF-36

6
B.M. Cabrera-Suárez et al. Experimental Gerontology 175 (2023) 112149

5. Conclusion Health and Quality of Life Outcomes 14, 69. https://doi.org/10.1186/s12955-016-

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Funding
PREDIMED-PLUS trial. PLoS One 13 (6), e0198974. https://doi.org/10.1371/
journal.pone.0198974 eCollection 2018.
This study was externally funded by the Spanish Ministry of Science García-Conesa, M.T., Philippou, E., Pafilas, C., Massaro, M., Quarta, S., Andrade, V.,
Jorge, R., Chervenkov, M., Ivanova, T., Dimitrova, D., Maksimova, V., Smilkov, K.,
and Innovation (Carlos III National Health Institute-ISCIII), PI16/01274.
Ackova, D.G., Miloseva, L., Ruskovska, T., Deligiannidou, G.E., Kontogiorgis, C.A.,
The Interprofesional del Aceite de Oliva-Aceites de Oliva de España Pinto, P., 2020. Exploring the validity of the 14-item Mediterranean Diet Adherence
(Madrid, Spain) donated the olive oil used in the study. Screener (MEDAS): a cross-national study in seven european countries around the
None of the funding sources played a role in the design, collection, Mediterranean Region. Nutrients 12 (10), 2960. https://doi.org/10.3390/
nu12102960.
analysis, or interpretation of the data or in the decision to submit the GBD 2019 Mental Disorders Collaborators, 2022. Global, regional, and national burden
manuscript for publication. of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic
analysis for the global burden of disease study 2019. Lancet Psychiatry 9 (2),
137–150. https://doi.org/10.1016/S2215-0366(21)00395-3.
CRediT authorship contribution statement Gigic, B., Boeing, H., Toth, R., Böhm, J., Habermann, N., Scherer, D., Schrotz-King, P.,
Abbenhardt-Martin, C., Skender, S., Brenner, H., Chang-Claude, J., Hoffmeister, M.,
Almudena Sánchez-Villegas: Conceptualization. Syrjala, K., Jacobsen, P.B., Schneider, M., Ulrich, A., Ulrich, C.M., 2018. Associations
between dietary patterns and longitudinal quality of life changes in colorectal cancer
Beatriz M Cabrera-Suárez, Francisca Lahortiga-Ramos, Jose L patients: the ColoCare study. Nutr. Cancer 70 (1), 51–60. https://doi.org/10.1080/
Hernández-Fleta, Ana González-Pinto, Patricio Molero, Rosario Vega- 01635581.2018.1397707.
Pérez: Data curation. Govindaraju, T., Sahle, B.W., TA, McCaffrey, McNeil, J.J., Owen, A.J., 2018. Dietary
patterns and quality of life in older adults: a systematic review. Nutrients 10 (8),
Beatriz M Cabrera-Suárez; Carmen Sayon-Orea: Formal analysis. 971. https://doi.org/10.3390/nu10080971, 2018.
Almudena Sánchez-Villegas: Funding acquisition. Hills Jr., R.D., Pontefract, B.A., Mishcon, H.R., Black, C.A., Sutton, S.C., Theberge, C.R.,
Almudena Sánchez-Villegas, Beatriz M Cabrera-Suárez, Francisca 2019. Gut microbiome: profound implications for diet and disease. Nutrients 11 (7),
1613. https://doi.org/10.3390/nu11071613.
Lahortiga-Ramos, Jose L Hernández-Fleta, Ana González-Pinto, Patricio
Klonizakis, M., Grammatikopoulou, M.G., Theodoridis, X., Milner, M., Liu, Y.,
Molero, Rosario Vega-Pérez: Methodology. Chourdakis, M., 2019. Effects of long-versus short-term exposure to the
Beatriz M Cabrera-Suárez, Almudena Sánchez-Villegas: Roles/ Mediterranean diet on skin microvascular function and quality of life of healthy
Writing - original draft. adults in Greece and the UK. Nutrients 11 (10), 2487. https://doi.org/10.3390/
nu11102487.
All authors: Writing - review &editing. Lassale, C., Batty, G.D., Baghdadli, A., Jacka, F., Sánchez-Villegas, A., Kivimäki, M.,
Akbaraly, T., 2019. Healthy dietary indices and risk of depressive outcomes: a
systematic review and meta-analysis of observational studies. Mol. Psychiatry 24 (7),
Declaration of competing interest
965–986. https://doi.org/10.1038/s41380-018-0237-8.
Martínez-González, M.A., López-Fontana, C., Varo, J.J., Sánchez-Villegas, A.,
The authors have no relevant financial or non-financial interests to Martinez, J.A., 2005. Validation of the spanish version of the physical activity
questionnaire used in the Nurses' health study and the health professionals' follow-up
disclose.
study. Public Health Nutr. 8 (7), 920–927. https://doi.org/10.1079/phn2005745.
Muñóz, M.A., Fíto, M., Marrugat, J., Covas, M.I., Schröder, H., REGICOR and HERMES
Data availability investigators, 2009. Adherence to the Mediterranean diet is associated with better
mental and physical health. British Journal of Nutrition 101. https://doi.org/
10.1017/S0007114508143598, 1821–182.
Data will be made available on request. Norman, G.R., Sloan, J.A., Wyrwich, K.W., 2003. Interpretation of changes in health-
related quality of life: the remarkable universality of half a standard deviation. Med.
Acknowledgments Care 41 (5), 582–592. https://doi.org/10.1097/01.MLR.0000062554.74615.4C.
Papakostas, G.I., Petersen, T., Mahal, Y., Mischoulon, D., Nierenberg, A.A., Fava, M.,
2004. Quality of life assessments in major depressive disorder: a review of the
The authors are grateful to the PREDIDEP study participants. literature. Gen. Hosp. Psychiatry 26 (1), 13–17. https://doi.org/10.1016/j.
genhosppsych.2003.07.004.
Parletta, N., Zarnowiecki, D., Cho, J., Wilson, A., Bogomolova, S., Villani, A.,
Appendix A. Supplementary data Itsiopoulos, C., Niyonsenga, T., Blunden, S., Meyer, B., Segal, L., Baune, B.T.,
O'Dea, K., 2019. A Mediterranean-style dietary intervention supplemented with fish
Supplementary data to this article can be found online at https://doi. oil improves diet quality and mental health in people with depression: a randomized
controlled trial (HELFIMED). Nutr. Neurosci. 22 (7), 474–487. https://doi.org/
org/10.1016/j.exger.2023.112149. 10.1080/1028415X.2017.1411320.
Priebe, S., Reininghaus, U., McCabe, R., Burns, T., Eklund, M., Hansson, L., Junghan, U.,
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