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Abstract

Lifestyle risk factors for erectile and sexual function include smoking, excessive alcohol consumption, lack of physical activity, psychological stress, and adherence to unhealthy diets. In the present study, we evaluated the effects of mixed nuts supplementation on erectile and sexual function. Eighty-three healthy male aged 18-35 with erectile function assessment were included in this FERTINUTS study sub-analysis; a 14-week randomized, controlled, parallel feeding trial. Participants were allocated to (1) the usual Western-style diet enriched with 60 g/day of a mixture of nuts (nut group; n = 43), or (2) the usual Western-style diet avoiding nuts (control group; n = 40). At baseline and the end of the intervention, participants answered 15 questions contained in the validated International Index of Erectile Function (IIEF), and peripheral levels of nitric oxide (NO) and E-selectin were measured, as surrogated markers of erectile endothelial function. Anthropometrical characteristics, and seminogram and blood biochemical parameters did not differ between intervention groups at baseline. Compared to the control group, a significant increase in the orgasmic function (p-value = 0.037) and sexual desire (p-value = 0.040) was observed during the nut intervention. No significant differences in changes between groups were shown in peripheral concentrations of NO and E-selectin. Including nuts in a regular diet significantly improved auto-reported orgasmic function and sexual desire.
nutrients
Article
Eect of Nut Consumption on Erectile and Sexual
Function in Healthy Males: A Secondary Outcome
Analysis of the FERTINUTS Randomized
Controlled Trial
Albert Salas-Huetos 1,2,3,, Jananee Muralidharan 1,2, Serena Galiè1,2,
Jordi Salas-Salvadó1,2,3,4,* and Mònica Bulló1,2,3,*
1Human Nutrition Unit, Biochemistry and Biotechnology Department, Faculty of Medicine and Health
Sciences, Universitat Rovira i Virgili (URV), 43201 Reus, Spain; albert.salas@utah.edu (A.S.-H.);
jananee.muralidharan@estudiants.urv.cat (J.M.); serena.galie@outlook.it (S.G.)
2Institut d’InvestigacióSanitària Pere i Virgili (IISPV), 43204 Reus, Spain
3Consorcio CIBER, M.P., Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos
III (ISCIII), 28029 Madrid, Spain
4Hospital Universitari Sant Joan de Reus (HUSJR), 43204 Reus, Spain
*Correspondence: jordi.salas@urv.cat (J.S.-S.); monica.bullo@urv.cat (M.B.);
Tel.: +34-977-75-93-12 (J.S.-S. & M.B.); Fax: +34-977-75-93-22 (J.S.-S. & M.B.)
Current aliation: Andrology and IVF Laboratory, Division of Urology, Department of Surgery, University
of Utah, Salt Lake City, UT 84180, USA.
Received: 8 May 2019; Accepted: 17 June 2019; Published: 19 June 2019


Abstract:
Lifestyle risk factors for erectile and sexual function include smoking, excessive alcohol
consumption, lack of physical activity, psychological stress, and adherence to unhealthy diets.
In the present study, we evaluated the eects of mixed nuts supplementation on erectile and sexual
function. Eighty-three healthy male aged 18–35 with erectile function assessment were included
in this FERTINUTS study sub-analysis; a 14-week randomized, controlled, parallel feeding trial.
Participants were allocated to (1) the usual Western-style diet enriched with 60 g/day of a mixture of
nuts (nut group; n=43), or (2) the usual Western-style diet avoiding nuts (control group; n=40).
At baseline and the end of the intervention, participants answered 15 questions contained in the
validated International Index of Erectile Function (IIEF), and peripheral levels of nitric oxide (NO) and
E-selectin were measured, as surrogated markers of erectile endothelial function. Anthropometrical
characteristics, and seminogram and blood biochemical parameters did not dier between intervention
groups at baseline. Compared to the control group, a significant increase in the orgasmic function
(p-value =0.037) and sexual desire (p-value =0.040) was observed during the nut intervention.
No significant dierences in changes between groups were shown in peripheral concentrations of
NO and E-selectin. Including nuts in a regular diet significantly improved auto-reported orgasmic
function and sexual desire.
Keywords: nuts; RCT; erectile function; sexual desire; orgasmic function; nitric oxide; E-selectin
1. Introduction
National Institutes of Health (NIH) define erectile dysfunction (ED) as a persistent diculty
achieving and maintaining an erection sucient for satisfactory sexual intercourse [
1
]. The prevalence
of ED ranged from 2% in men younger than 40 years old, around 52% in men aged 40–70 years, and
more than 85% in men with 80 years and older [
2
,
3
]. Although significant advances in the field were
made, primary prevention research on this condition is very preliminary. Lifestyle risk factors for
Nutrients 2019,11, 1372; doi:10.3390/nu11061372 www.mdpi.com/journal/nutrients
Nutrients 2019,11, 1372 2 of 13
ED include smoking, excessive alcohol consumption, lack of physical activity, psychological stress,
overweight or obesity, and adherence to unhealthy diets, among others [47].
Lifestyle factors may influence ED through the vascular and nervous system. Because adequate
arterial supply is critical for erection, any disorder that impairs blood flow may be implicated in the
etiology of erectile failure. However, a wide variety of psychological problems can influence the
male erectile response because, in a vascular event initiated by neuronal action, it is maintained by a
complex interplay between vascular, neurological events and other comorbidities [
7
,
8
]. Moreover, it is
generally accepted that nitric oxide (NO) is the principal agent responsible for relaxation/erection of
penile smooth muscle.
Mediterranean diet and some components of the Mediterranean diet have been inversely related
to erectile and sexual dysfunction [
9
] but also a better endothelial function [
10
]. This is the case of
nuts that its consumption has consistently demonstrated beneficial eects on endothelial function [
11
].
In fact, in a recent study, it has demonstrated that pistachio consumption improves erectile function,
probably because it contains (as other types of nuts [
12
]) several antioxidants, and arginine, a precursor
of nitric oxide (NO), a powerful compound that increases vasodilatation [13].
To demonstrate that a dietary pattern or a food group can not only modulate the erectile function,
but also the sperm function increasing the chances of fertility is of great interest mainly in developed
countries where male infertility seems to have fallen drastically [
14
], and the psychological stress seems
to be more prevalent [15].
Therefore, in order to elucidate the possible role of nut consumption in the primary prevention of
ED, we explored using a randomized controlled trial (RCT), the eects of nuts supplementation on
erectile function determined by the International Index of Erectile Function, but also the endothelial
function by measuring peripheral concentrations of NO and E-selectin.
2. Materials and Methods
2.1. Study Design
The study design of the FERTINUTS trial has been reported previously [
16
]. The trial was
registered in ISRCTN registry with identifier ISRCTN12857940. Briefly, FERTINUTS was a 14-week
(wk) randomized, controlled, two-interventions parallel, clinical trial conducted in healthy males
who reported a Western-style diet. The trial was conducted between 2015 and 2017, and included
participants who were randomly assigned (1:1) to one of the following two interventions: (1) enriching
the usual Western-style diet with 60 g/d of a mixture of raw walnuts, almonds, and hazelnuts (nut
group); or (2) following the usual Western-style diet avoiding nuts (control group). The protocol was
approved by the Institutional Review Board of the Hospital Universitari Sant Joan de Reus in October
2015. All the participants provided a written informed consent.
Eligible participants were healthy men aged 18–35 years old. The following exclusion criteria
were applied: frequent consumption of nuts or a known history of allergy; use of plant sterol or fish oil
supplements and multivitamins, vitamin E or other antioxidant supplements; history of reproductive
disorders or vasectomy; current smokers; medications for chronic illness consumption; or use of illegal
drugs. More detailed criteria for enrolment have been reported elsewhere [16].
The eect of the interventions on several cardiovascular risk factors and sperm parameters have
been reported previously [
16
18
]. We report here the eect of the interventions on auto-reported
erectile function parameters and the concentrations of peripheral endothelial biomarkers over 14-wk
as a secondary outcome.
2.2. Anthropometric, Dietary, Blood Parameters, and Seminogram Measurements
Trained nurses, biologists, or dietitians directly recall all the general participants’ information and
conduct anthropometric measurements. The initial assessment of individuals was conducted with
a 15-item dietary screener modified from Mart
í
nez-Gonz
á
lez et al., 2012 [
19
] to verify the presence
Nutrients 2019,11, 1372 3 of 13
of a Western-style diet adherence. Participants in the nut group received at no cost, every month,
pre-weighed packs for the consumption of 60 g of nuts per day (30 g of walnuts, 15 g of almonds,
and 15 g of hazelnuts). Participants in both groups received detailed dietary instructions in order to
increase the adherence to the assigned intervention.
At baseline, participants completed a general questionnaire with a medical history, reproductive
history, use of medication, and a 143-item semi-quantitative validated food frequency questionnaire
(FFQ) [20] in a face-to-face interview.
During the 14-wk follow-up (with four in-site visits), weight, height, and waist circumference
were recorded using a high-precision electronic scale (TANITA TBF-300, Tanita). Blood pressure
was measured at rest in duplicate with a 5 minutes interval between each measurement by using
a semiautomatic oscillometer (Omron HEM-705CP, Netherlands). Furthermore, all the participants
completed a specific questionnaire reporting any adverse eects related or not related to the intervention,
and a 3-day dietary record (3DDR) in a face-to-face interview with an expert dietitian in order to
measure the compliance with the dietary intervention. Energy and nutrient intake were calculated
using Spanish food composition tables [
21
,
22
]. Adherence to the intervention was also assessed by
counting the empty sachets of nuts returned in each visit.
At baseline and at the end of the intervention, blood samples in 12 h fasting conditions and semen
samples after 3 days of sexual abstinence were collected. Fasting glucose, total cholesterol, HDL
cholesterol, LDL cholesterol, VLDL cholesterol, triglycerides, insulin, C-reactive protein (CRP), and
folate were determined (COBAS; Roche Diagnostics Ltd, UK) in blood. Semen volume and pH, sperm
count and concentration, sperm motility, sperm viability, and sperm morphology were assessed in
semen following the 2010 WHO criteria and the Björndahl checklist [23,24].
2.3. Erectile Function Questionnaire
The main outcome in the present analysis was the erectile function. To evaluate the influence
of nuts on erectile function, participants answered to the 15 questions contained in the validated
International Index of Erectile Function (IIEF) [
25
] at baseline and the end of the intervention. The
IIEF-15 permits to detect treatment-related changes [
25
,
26
]. The questionnaire of IIEF-15 addresses the
relevant domains of male sexual function: erectile function (EF: 0–6 severe dysfunction, 7–12 moderate
dysfunction, 13–18 mild to moderate dysfunction, 19-24 mild dysfunction, 25–30 no dysfunction),
orgasmic function (OF: 0–2 severe dysfunction, 3-4 moderate dysfunction, 5–6 mild to moderate
dysfunction, 7–8 mild dysfunction, 9–10 no dysfunction), sexual desire (SD: 0–2 severe dysfunction, 3–4
moderate dysfunction, 5–6 mild to moderate dysfunction, 7–8 mild dysfunction, 9–10 no dysfunction),
intercourse satisfaction (IS: 0–3 severe dysfunction, 4–6 moderate dysfunction, 7–9 mild to moderate
dysfunction, 10–12 mild dysfunction, 13–15 no dysfunction), and overall satisfaction (OS: 0–2 severe
dysfunction, 3–4 moderate dysfunction, 5–6 mild to moderate dysfunction, 7–8 mild dysfunction,
9–10 no dysfunction).
2.4. Surrogated Measures of Erectile Endothelial Function
At baseline and end of the trial the peripheral concentrations of endothelial function markers, NO
and E-selectin, were measured by Enzyme-Linked Immunosorbent Assay (ELISA) procedures according
to the manufacturer instructions. Briefly, the NO assay kit (ThermoFisher Scientific) determines nitric
oxide composition through measurement of nitrate (NO
3
) and nitrite (NO
2
) levels, while the E-selectin
assay kit (ThermoFisher Scientific) determines the soluble E-selectin. Samples were read at 540 nm
absorbance in the case of NO assay, and 450 nm absorbance in the case of E-selectin assay (TECAN,
Sunrise). A polynomial curve was used as the standard. Laboratory technicians were blinded to
group assignments.
Nutrients 2019,11, 1372 4 of 13
2.5. Statistical Analyses
The sample size for the FERTINUTS trial was calculated to detect significant dierences in the
viability after nut consumption based on the results of Robbins et al., 2012 [
27
]. However, taking
into account EF changes reported in a previous similar trial [
9
], a total sample size of 54 (27 per
arm) was estimated to provide sucient statistical power (more than 80%) to assess the eects of nut
supplementation on erectile function parameters assuming two-sided 95% confidence interval.
Kolmogorov–Smirnov and Levene’s test were used in order to check the normal distribution
and homogeneity, respectively. The data are shown as means
±
standard deviation (SD) for normally
distributed variables, and median
±
interquartile rank (IQR) for non-normal continuous variables.
Non-parametric statistical Mann–Whitney for non-paired data and Wilcoxon tests for paired data
were used to assess dierences within each intervention. ANCOVA models were applied to assess
dierences in changes between intervention groups after adjusting for baseline values. Spearman
correlation coecients were used to calculate pair-wise correlations, and Benjamini-Hochberg false
discovery rate (FDR) correction was used for multiple comparisons. Statistical analyses were conducted
using per protocol approaches, including all randomized participants fulfilling all baseline and final
measurements. p-values of <0.05 were considered statistically significant. Statistical analyses were
carried out using the freely available R statistical computing environment v.2.14.2 (www.r-project.
org) [28] and the additional package Deducer for R (http://www.deducer.org/) [29].
3. Results
In the FERTINUTS trial, we assessed 244 subjects for eligibility. Of these, 57 subjects declined to
participate and 68 did not meet the inclusion criteria. Thus, 119 participants were included in the trial
and were randomly assigned to one of the two intervention groups: 61 in the nuts group and 58 in the
control group. A total 98 participants successfully completed the study, and finally, 83 participants
were included in this secondary analysis (those subjects who fulfilled the International Index of Erectile
Function questionnaire): 43 in the nuts supplemented group and 40 in the control group (Figure 1).
Baseline characteristics (age, weight, height, BMI, waist circumference, systolic and diastolic blood
pressure, fasting glucose, serum total cholesterol, HDL cholesterol, LDL cholesterol, VLDL cholesterol,
triglycerides, insulin, C-reactive protein and folate, and main sperm parameters) are detailed in Table 1.
No significant dierences were observed in these baseline parameters agreeing to the sequence of
randomization. Participants in the two groups reported similar adherence to the Western-style diet at
baseline according to the 15-item dietary screener.
Compliance with the intervention, as assessed by counting the empty sachets of nuts returned
by the participants, was high (>95% of empty sachets returned). According to the 3DDR data,
significant between-group dierences in nut intake was shown through the study. This was
associated with an increase in the intake total fat (p-value <0.001), MUFA (p-value<0.001), PUFA
(p-value <0.001), magnesium (p-value <0.001), vitamin E (p-value =0.014), omega-3 fatty acids
(p-value <0.001),
α
-Linolenic acid (ALA) (p-value <0.001), and omega-6 fatty acids (p-value =0.016)
in the nut-supplemented group. The intake of energy (p-value =0.029) and fiber (p-value =0.002)
experienced a smaller decrease in the nut-supplemented group compared with the control group
(Table 2).
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Nutrients 2018, 10, x FOR PEER REVIEW 5 of 14
Figure 1. Flow diagram of the FERTINUTS sub-analysis. * 68 participants did not meet the
inclusion criteria (ascribed to a non-Western style diet, n = 37; smoking, n = 21; or other
minor reasons, n = 10) and 57 subjects declined to participate (lack of interest, n = 34;
impossible to contact with them, n = 18; and for non-economic compensation, n = 5).
Baseline characteristics (age, weight, height, BMI, waist circumference, systolic and diastolic
blood pressure, fasting glucose, serum total cholesterol, HDL cholesterol, LDL cholesterol, VLDL
cholesterol, triglycerides, insulin, C-reactive protein and folate, and main sperm parameters) are
detailed in Table 1. No significant differences were observed in these baseline parameters agreeing
to the sequence of randomization. Participants in the two groups reported similar adherence to the
Western-style diet at baseline according to the 15-item dietary screener.
Table 1. Baseline characteristics of the study population (general characteristics, blood, and
semen parameters).
Variable
Nuts Group (n = 43)
Control Group (n = 40)
P-Value
General characteristics; mean (SD)
Age (years)
24.05 (4.82)
25.83 (4.58)
0.066
Weight (kg)
73.44 (10.16)
76.82 (12.04)
0.270
Height (cm)
176.46 (6.21)
177.73 (6.66)
0.409
BMI (kg/m2)
23.53 (2.59)
24.33 (3.64)
0.379
Figure 1.
Flow diagram of the FERTINUTS sub-analysis. * 68 participants did not meet the inclusion
criteria (ascribed to a non-Western style diet, n=37; smoking, n=21; or other minor reasons, n=10)
and 57 subjects declined to participate (lack of interest, n=34; impossible to contact with them, n=18;
and for non-economic compensation, n=5).
Nutrients 2019,11, 1372 6 of 13
Table 1.
Baseline characteristics of the study population (general characteristics, blood, and
semen parameters).
Variable Nuts Group (n=43) Control Group (n=40) p-Value
General characteristics; mean
(SD)
Age (years) 24.05 (4.82) 25.83 (4.58) 0.066
Weight (kg) 73.44 (10.16) 76.82 (12.04) 0.270
Height (cm) 176.46 (6.21) 177.73 (6.66) 0.409
BMI (kg/m2)23.53 (2.59) 24.33 (3.64) 0.379
Waist circumference (cm) 79.98 (7.41) 83.26 (8.98) 0.067
Systolic blood pressure (mmHg)
129.38 (11.37) 126.50 (11.79) 0.425
Diastolic blood pressure
(mmHg) 73.34 (7.90) 70.90 (8.49) 0.174
Score for adherence to
Western-style diet a8.11 (2.16) 8.80 (2.26) 0.182
Blood parameters; median (IQR)
Fasting plasma glucose (mg/dl) 87.0 (82.0, 93.5) 85.5 (81.5, 91.0) 0.384
Total cholesterol (mg/dl) 167.0 (149.5, 188.5) 173.5 (150.0, 196.0) 0.374
HDL-c (mg/dl) 58.0 (49.5, 66.5) 55.5 (50.0, 67.0) 0.736
LDL-c (mg/dl) 87.0 (74.5, 105.5) 98.0 (77.8, 119.3) 0.202
VLDL-c (mg/dl) 13.0 (12.0, 19.0) 13.0 (9.0, 17.3) 0.240
Triglycerides (mg/dl) 66.0 (59.0, 95.5) 64.0 (47.0, 85.0) 0.258
Fasting plasma insulin
(mcUl/ml) 5.40 (2.60, 8.60) 5.20 (2.75, 6.80) 0.654
C-Reactive protein (mg/dl) 0.20 (0.20, 0.20) 0.20 (0.13, 0.20) 0.144
Folate (ng/ml) 6.30 (4.80, 8.70) 6.30 (4.88, 7.80) 0.616
Semen characteristics; median
(IQR)
pH 8.0 (8.0, 8.5) 8.0 (8.0, 8.5) 0.940
Volume (mL) 3.50 (1.95, 4.55) 3.40 (2.50, 5.13) 0.179
Total spermatozoa (×106)75.20 (28.10, 104.50) 72.05 (40.90, 125.50) 0.497
Spermatozoa concentration
(×106)25.20 (14.50, 41.80) 19.80 (9.70, 37.95) 0.402
Viability (%) 78.68 (70.26, 82.52) 80.21 (73.66, 85.87) 0.257
Total motility (progressive and
non-progressive motility) (%) 64.66 (45.91, 71.34) 70.11 (62.73, 78.56) 0.097
Progressive motility (%) 44.67 (28.27, 53.97) 49.72 (35.39, 61.67) 0.086
Non-progressive motility (%) 13.26 (9.79, 16.15) 11.64 (7.58, 14.31) 0.103
Immotile spermatozoa (%) 35.33 (28.58, 52.06) 29.89 (21.44, 37.27) 0.094
Normal forms (%) 6.33 (4.91, 8.17) 6.27 (5.23, 7.57) 0.935
Abnormal head (%) 52.59 (43.06, 66.28) 55.07 (41.22, 67.81) 0.771
Abnormal midpiece (%) 10.71 (8.63, 15.05) 12.71 (8.46, 14.23) 0.705
Abnormal principal piece (%) 12.94 (5.44, 29.66) 9.46 (4.53, 25.27) 0.529
Combined abnormality (%) 8.40 (6.49, 12.88) 7.85 (6.71, 14.07) 0.985
Data are given as mean and standard deviation (SD) or medians and Interquartile ranges (IQRs). All the
analyses were assessed by non-parametric tests (the Mann–Whitney for non-paired data) for normality distribution
reasons. Equivalences: 1 mg/dl plasma glucose =18.018 mmol/l, 1 mg/dl total cholesterol=38.610 mmol/l.
a
The score for adherence to the Western-style diet is based on a 15-item dietary screener (a score of zero indicates
minimum adherence, a score of 15 indicates maximum adherence). Abbreviations: BMI, body mass index; HDL,
high-density lipoprotein; IQR, interquartile rank; LDL, low-density lipoprotein; SD, standard deviation; VLDL,
very-low-density lipoprotein.
Nutrients 2019,11, 1372 7 of 13
Table 2. Nutrient intake at baseline and changes by intervention group.
Variables Nut Group (n=43) Control Group (n=40) Treatment Eect
Baseline Changes Baseline Changes p-Value
Energy
Energy intake
(kcal/d)
2699.13 (994.43)
145.19 (31.74)
2359.57 (565.72)
215.22 (18.18) 0.029
Macronutrients
Proteins (g/d) 112.20 (39.37) 7.68 (1.44) 103.13 (22.51) 10.45 (0.34) 0.065
Carbohydrates
(g/d) 305.24 (134.16) 50.48 (4.83) 254.34 (63.04) 11.21 (0.05) 0.333
Simple
carbohydrates (g/d)
112.70 (79.80) 13.47 (3.33) 92.54 (28.75) 6.31 (0.06) 0.696
Complex
carbohydrates (g/d)
176.44 (68.26) 34.36 (0.84) 145.29 (46.70) 12.09 (1.30) 0.604
Total fat (g/d) 106.89 (40.75) 12.19 (0.66) 97.98 (30.47) 11.95 (0.92) <0.001
MUFA (g/d) 42.87 (18.36) 5.89 (0.32) 37.97 (15.82) 6.14 (0.48) <0.001
SFA (g/d) 33.33 (17.87) 3.19 (0.21) 31.17 (10.64) 3.67 (0.04) 0.589
PUFA (g/d) 13.51 (6.41) 11.03 (0.27) 11.37 (4.50) 2.60 (0.23) <0.001
Cholesterol (mg/d) 426.64 (253.96) 70.48 (8.95) 386.09 (131.85) 56.08 (2.37) 0.745
Fiber (g/d) 24.69 (11.21) 0.77 (0.39) 19.84 (9.45) 2.39 (0.41) 0.002
Alcohol (g/d) 9.43 (14.01) 2.79 (0.73) 7.91 (13.14) 2.25 (0.89) 0.693
Glycemic load 172.69 (75.43) 31.38 (2.55) 141.20 (37.69) 5.52 (0.32) 0.384
Glycemic index 56.16 (4.50) 1.48 (0.18) 55.13 (5.45) 0.29 (0.08) 0.346
Micronutrients
Sodium (mg/d) 3452.88
(1455.36) 407.37 (26.13)
3178.08 (958.75)
174.95 (23.37) 0.743
Potassium (mg/d) 3639.91
(1624.75) 217.88 (58.80)
3126.17 (968.16)
140.77 (21.62) 0.289
Linoleic (g/d) 26.08 (26.64) 4.79 (1.35) 31.40 (31.79) 4.66 (1.24) 0.311
Magnesium (mg/d)
407.62 (199.96) 32.17 (7.96) 329.53 (108.61) 16.92 (0.93) <0.001
Calcium (mg/d) 987.45 (514.83) 98.27 (2.79) 898.70 (324.53) 51.64 (13.16) 0.843
Iron (mg/d) 20.27 (14.55) 2.04 (0.60) 18.35 (13.33) 0.11 (0.47) 0.864
Selenium (mg/d) 222.04 (162.30) 48.94 (13.01) 209.25 (140.86) 46.06 (11.51) 0.563
β-carotene
equivalents (µg/d)
4711.11
(5096.91)
1008.75
(348.71)
3913.42
(4116.64) 22.34 (72.89) 0.642
Retinol (µg/d)
592.05 (1409.67)
230.55
(169.57) 402.76 (166.28) 141.07 (141.29) 0.254
Vitamin D (µg/d) 7.37 (13.90) 0.55 (0.31) 5.05 (5.65) 4.50 (3.67) 0.606
Vitamin E (µg/d) 13.18 (5.12) 6.10 (1.20) 15.19 (18.38) 3.03 (0.93) 0.014
Vitamin K (µg/d) 130.94 (163.71) 10.50 (0.30) 115.38 (111.22) 32.51 (6.99) 0.213
Omega-3 (g/d) 1.72 (0.89) 1.53 (0.02) 1.68 (0.73) 0.10 (0.02) <0.001
ALA (g/d) 1.10 (0.61) 1.55 (0.02) 1.00 (0.39) 0.22 (0.02) <0.001
EPA (g/d) 0.51 (2.74) 0.02 (0.00) 1.03 (3.96) 0.65 (0.12) 0.236
DHA (g/d) 0.15 (0.19) 0.02 (0.01) 0.21 (0.31) 0.10 (0.03) 0.161
Omega-6 (g/d) 18.03 (14.80) 10.27 (0.08) 24.64 (23.36) 3.76 (0.94) 0.016
Dataare given as meansand SD for baselinevalues, and mean and SE for changes. Inbold the significant values. ANCOVA
models were used to assess differences between intervention groups. Changes in variables were adjusted for baseline
values of each variable. Abbreviations: ALA:
α
-Linolenic acid, DHA: docosahexaenoic acid, EPA: eicosapentaenoic acid,
MUFA: monounsaturated fatty acids, PUFA: polyunsaturated fatty acids, SFA: saturated fatty acids.
No significant between-group dierences were observed in erectile function parameters at
baseline. However, compared to the control group, a significant increase in the orgasmic function (OF;
p-value =0.037) and sexual desire (SD; p-value =0.040) was observed in the nut-supplemented group
during the intervention. No significant between-group dierences in changes during the intervention
were found in erectile function (EF; p-value =0.192), intercourse satisfaction (IS; p-value =0.473), and
overall satisfaction (OS; p-value =0.333) (Figure 2). No significant correlations were found between
changes in ED parameters and changes in biochemical parameters during the intervention.
Nutrients 2019,11, 1372 8 of 13
Nutrients 2018, 10, x FOR PEER REVIEW 9 of 14
Nutrients 2018, 10, x; doi: FOR PEER REVIEW www.mdpi.com/journal/nutrients
Figure 2. Box plot of the differences between the control group and the nut-supplemented group in the erectile function parameters (IIEF-15). ANCOVA
models were used to assess differences between intervention groups. Changes were adjusted for baseline values. A horizontal line in the boxplot illustrates
the median value. The upper and lower bars indicate the third and first percentiles, respectively. Outliers are plotted as individual circles. Abbreviations:
IIEF: International Index of Erectile Function.
Figure 2.
Box plot of the dierences between the control group and the nut-supplemented group in the erectile function parameters (IIEF-15). ANCOVA models were
used to assess dierences between intervention groups. Changes were adjusted for baseline values. A horizontal line in the boxplot illustrates the median value.
The upper and lower bars indicate the third and first percentiles, respectively. Outliers are plotted as individual circles. Abbreviations: IIEF: International Index of
Erectile Function.
Nutrients 2019,11, 1372 9 of 13
Moreover, no significant dierences in changes between intervention groups were shown in
peripheral concentrations of NO (p-value =0.737) (Figure 3A) or E-selectin (p-value =0.347) (Figure 3B).
Nutrients 2018, 10, x FOR PEER REVIEW 10 of 14
Nutrients 2018, 10, x; doi: FOR PEER REVIEW www.mdpi.com/journal/nutrients
Moreover, no significant differences in changes between intervention groups were shown in
peripheral concentrations of NO (p-value = 0.737) (Figure 3A) or E-selectin (p-value = 0.347) (Figure
3B).
Figure 3. Box plot of the differences between the control group and the nut group in the
concentrations of nitric oxide (A) and E-selectin (B) erectile function markers. ANCOVA
models were used to assess differences between intervention groups. Changes were
adjusted for baseline values. A horizontal line in the boxplot illustrates the median value.
The upper and lower bars indicate the third and first percentiles, respectively. Outliers are
plotted as individual circles. In this analysis 3 participants (2 participants in the nut group
and 1 in the control group) had missing values for NO or E-selectin (see Figure 1).
4. Discussion
Herein we report that adding 60 g/d of mixed raw nuts to a Western-style diet for 14-wk
improved the auto-reported orgasmic function and sexual desire parameters in a group of healthy
reproductive-aged participants compared with an age-matched control group. In the present study,
Figure 3.
Box plot of the dierences between the control group and the nut group in the concentrations
of nitric oxide (
A
) and E-selectin (
B
) erectile function markers. ANCOVA models were used to assess
dierences between intervention groups. Changes were adjusted for baseline values. A horizontal
line in the boxplot illustrates the median value. The upper and lower bars indicate the third and first
percentiles, respectively. Outliers are plotted as individual circles. In this analysis 3 participants (2
participants in the nut group and 1 in the control group) had missing values for NO or E-selectin (see
Figure 1).
4. Discussion
Herein we report that adding 60 g/d of mixed raw nuts to a Western-style diet for 14-wk
improved the auto-reported orgasmic function and sexual desire parameters in a group of healthy
reproductive-aged participants compared with an age-matched control group. In the present study,
Nutrients 2019,11, 1372 10 of 13
none of the possible mechanisms explored (NO and E-selectin as surrogated markers of endothelial
function) seem to explain the beneficial eects observed on orgasmic function and sexual desire.
Interestingly, our findings in healthy young males are pretty consistent with the only previous
clinical study reporting an increase of all the five IIEF-15 domains after 100 g/day pistachio consumption
for 3 weeks [
13
], although this study was conducted in patients with erectile dysfunction at baseline.
Therefore, our study extends the findings to a healthy population without erectile dysfunction
supplemented with a mixture of nuts like hazelnuts, almonds, and walnuts.
Nuts are nutrient-dense foods with a special nutrient content, a key component of several healthy
dietary patterns and recommendations, and its consumption is associated with improvements in some
cardiovascular disease risk factors [
30
32
]. Specifically, hazelnuts, almonds and walnuts contain high
amounts of vegetable protein and fat (mainly unsaturated fatty acids), are dense in antioxidants and
vitamins (e.g., folic acid, niacin, tocopherols, and vitamin B6, among others) and some minerals (e.g.,
calcium, magnesium, phosphorous and potassium), and also rich =in dietary fiber and many other
bioactive constituents (e.g., phytosterols and phenolic compounds) (Supplementary Materials Table
S1 [33]).
In addition, nuts had a relatively high amount of the nonessential amino acid arginine, a
precursor of NO, that is a potent vasoactive neurovascular, nonadrenergic, noncholinergic (NANC)
neurotransmitter that plays an important role in erectile action through the corpora cavernosa [
34
].
The results from our study do not demonstrate that Arginine-NO pathway act as the unique player
modulating erectile function. However, we cannot discard a lack of statistical power to demonstrate
dierences between intervention groups in relation to these subrogated markers of endothelial function,
because the sample size of the present sub-analysis was estimated using the IIEF as the main outcome.
Another promising serum biomarker for erectile function is serum E-selectin [
35
]. In that case,
E-selectin, because it is an endothelial dysfunction marker, seems more useful in patients diagnosed
with diabetes mellitus [
36
]. E-selectin is a cell adhesion molecule activated by cytokines that plays an
important role in inflammation. Because consuming between 60 and 90 g of nuts has proven eective
improving inflammation [
37
] it could have been reasonable to detect some dierences in this marker
due to the nut’s supplementation. Nonetheless, our study does also not confirm any eect on this
endothelial marker. This lack of eect could be explained not only because of a lack of power but also
because our participants were healthy and therefore without having type 2 diabetes.
Because we detected an improvement in the auto-reported orgasmic function and sexual desire
parameters, maybe other mechanisms beyond those mentioned above may be implicated. It is
interesting to mention that erectile (dys)function and atherogenesis share common pathways [
38
]. For
that reason, several antioxidants (e.g., polyphenols) and vitamins, that are present in nuts, have been
suggested to be eective treatments for ED and at the same time are beneficial for the cardiovascular
system [
38
]. Previous studies reported that chronic consumption of nuts has proven eective for
lowering LDL cholesterol [
32
] and improving glucose metabolism [
39
], among other cardiovascular
risk factors, decreasing the incidence of major cardiovascular events [
17
]. Therefore, we strongly
believe in the necessity to develop similar trials with participants at high cardiovascular risk and
erectile dysfunction to accurately establish an eect of nut consumption on erectile function and
cardiovascular risk.
Our study has several strengths. This is the largest and unique RCT to date analyzing the eect of
nut supplementation on erectile and sexual function in healthy participants. Moreover, the present
analysis has theoretically enough statistical power to detect eects on erectile function measured
by a validated International Index of Erectile Function. Although several questionnaires have been
developed to objectively evaluate EDs, the validated International Index of Erectile Function (IIEF)
questionnaire is considered a valuable tool for defining the area of sexual dysfunction that may be
incorporated as part of the clinical history to document the degree of dysfunction and gauge response
to therapy [
25
]. Moreover, having detailed information on medical and reproductive history allowed
us to reduce bias by excluding participants with chronic and reproductive diseases that may influence
Nutrients 2019,11, 1372 11 of 13
diet, seminogram or erectile function. The main strength of the present study is the design because
RCTs represent the cornerstone of evidence-based medicine.
However, the following limitations need to be highlighted. The present study is based on a
secondary outcome analysis of the FERTINUTS trial. Second, our study was conducted in apparently
healthy and fertile participants limiting the extrapolation of the results to other populations, for example
with erectile dysfunction, the inclusion of a group of subjects suering from erectile dysfunction could
help us to extend the results obtained. Third, reproductive hormonal (e.g., testosterone, prolactin, FSH,
estradiol) values, which could aect erectile and sexual function are not reported. Finally, our study
did not provide enough evidence to support the main mechanism for these improvements, however,
an absence of evidence does not mean evidence of no eect [
40
]. Only equivalence trials are properly
suited to demonstrate the equality of eects. For that reason, other RCT focused on markers of erectile
endothelial function as possible mechanisms of the eect as main outcomes, are warranted in the future
to increase the scientific evidence in the field.
5. Conclusions
In conclusion, our study suggests that compliance with a healthy diet supplemented with mixed
nuts may help to improve erectile and sexual desire. Large studies are warranted in the future to
confirm these results and elucidate possible mechanisms implicated on these benefits.
Supplementary Materials:
The following are available online at http://www.mdpi.com/2072-6643/11/6/1372/s1,
Table S1: Average nutrient composition of studied nuts (per 100 g).
Author Contributions:
A.S.-H. and J.S.-S. initiated the idea of the trial. A.S.-H., J.S.-S., and M.B. were involved in
study concept and design. A.S.-H. was involved in study execution, acquisition of data, analyzed of data, wrote
the manuscript and had primary responsibility for final content; J.M. and S.G. were involved in erectile function
markers analysis. J.S.-S., and M.B. supervised the analysis and critically revised the manuscript. All authors
provided substantial intellectual contributions and approved the final version of the manuscript.
Funding:
This work was partially supported by the International Nut and Dried Fruit Council (INC) with the
Grant No. 2015 INC Research Grant (PV15110S) and by Human Nutrition Unit funds. INC is a non-profit entity
registered at the Register of Foundations of Catalonia, Spain. Nuts were supplied by Crisolar, Spain.
Acknowledgments:
We thank all the FERTINUTS participants for their enthusiastic collaboration. The authors
gratefully acknowledge Santiago Dom
í
nguez for nursery assistance, Roc
í
o Moraleda for dietary assessment and
some primary data collection, and Susana Benigno and Carles Munn
é
for their help as editor assistance. Consorcio
CIBER, M.P., Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III (ISCIII). The Plan
Nacional de Investigaci
ó
n Cient
í
fica, Desarrollo e Innovaci
ó
n Tecnol
ó
gica, the Instituto de Salud Carlos III - Fondo de
Investigación Sanitaria (PI12/0153). The Fondo Europeo de Desarrollo Regional (FEDER).
Conflicts of Interest:
J.S.-S. is a nonpaid member of the Scientific Advisory Council of the INC. M.B. has
received research funds through her Institution from Pistachio Growers. No other potential conflicts of interest
were reported.
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©
2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
... One study investigated the effects of pistachio nuts on International Index of Erectile Function (IIEF) scores, penile color Doppler ultrasound (PCDU). To evaluate the influence of nuts on erectile function, participants answered to the 15 questions contained in the validated IIEF [59] at baseline and the end of the intervention [60]. ...
... The International Index of Erectile Function (IIEF) questionnaire was used [59]. Compared to the control group, a significant increase in the orgasmic function and sexual desire was observed in the nutsupplemented group during the intervention [60]. ...
... Mots-clés: Régime, Régime à base de Végétaux, Dysfonction érectile, Fonction érectile, Testostérone Background Diet modification, proved by several well-designed studies, is considered as a potentially important method for cancer prevention and chronic non-communicable diseases control [1][2][3]. In light of these findings, participation in diet modification, especially the plant-based diet has grown swiftly in recent years. ...
... Furthermore, some prospective studies and randomized controlled trials (RCTs) indicated that weight loss through low-fat diets in obese ED patients could improve IIEF-5 scores [24,25]. Other diet compositions, like organic diet and ingredient supplement diet, like nuts, were also reported related to improved IIEF-5 scores [3,26]. When it comes to plant-based diet, a previous study conducted by Liu et al. indicated that adequate fruit and vegetable intakes were not associated with improved ED [27]. ...
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Background Diet, one of the components of lifestyle, has been believed to have associations with erectile dysfunction (ED). However, whether there is an association between plant-based diet and ED is remains to be explored. Thus, we conducted the nested case-control study to investigate the relationship between the plant-based diet and ED in China. Results ED group (92 subjeczts) and ED free group (92 subjects) were similar in terms of basic features ( P > 0.05), except for lifestyle ( P < 0.05). The plant-diet index (PDI) and healthy plant-diet index (hPDI) in the ED group were significantly lower than those in the control group ( P < 0.001). Adjusted multivariate analysis indicated that the presence of ED was negatively associated with nitric oxide levels, PDI, and hPDI (all P < 0.05), and was positively related to body mass index, metabolic syndrome, and E-selectin levels. Furthermore, both the PDI and hPDI increased significantly as the International Index of Erectile Function (IIEF-5) scores increased within the ED group ( P < 0.05). Multi-model multivariate analysis indicated the robustness of results. Conclusions More plant-based diet intake was associated with a reduced presence of ED and less severe ED in China. Committing to plant-based diet can be encouraged for many health benefits and to lower ED burden. Further well-designed studies are warranted to validate our findings.
... In a recent study, Salas-Huetos et al. (2019) reported that the consumption of walnuts increased sexual function. Indeed, a secondary outcome analysis of the FERTINUTS study, a 14-week randomized controlled trial with 83 subjects consuming a Western-style diet, reported that consuming 60 g/day of nuts was associated with increased orgasmic function and sexual desire compared with the control group (avoiding nuts), but no significant differences in erectile function were observed [36]. ...
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Interest in the role of dietary patterns has been consistently emerging in recent years due to much research that has documented the impact of metabolism on erectile dysfunction (ED) and/or benign prostatic hyperplasia (BPH). We conducted a non-systematic review of English articles published from 1964 to September 2021. The search terms were: (“dietary patterns” OR “diet”) AND/OR (“erectile dysfunction”) AND/OR (“benign prostatic hyperplasia”). In the present review, we have highlighted how the association between dietary patterns and two of the most frequent pathologies in urology, namely erectile dysfunction and benign prostatic hyperplasia, is present in the literature. The data suggested that a diet that is more adherent to the Mediterranean diet or that emphasizes the presence of vegetables, fruits, nuts, legumes, and fish or other sources of long-chain (n-3) fats, in addition to reduced content of red meat, may have a beneficial role on erectile function. At the same time, the same beneficial effects can be transferred to BPH as a result of the indirect regulatory effects on prostatic growth and smooth muscle tone, thus determining an improvement in symptoms. Certainly, in-depth studies and translational medicine are needed to confirm these encouraging data.
... Сложно однозначно утверждать о пользе только снижения массы тела пациентов, поскольку оно, как правило, сопряжено и с другими качественными изменениями образа жизни [18,19]. А учитывая комплексное влияние лираглутида, в том числе за счет изменения пищевого поведения, трудно выделить ведущую причину положительных изменений спермограммы: это может быть изменение образа жизни, уменьшение жировой массы или непосредственное влияние самой молекулы. ...
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Background: Considering the influence of visceral obesity on male infertility, the investigation of ejaculate quality indicators under obesity treatment is relevant. Objective: Evaluation of ejaculate quality indicators by obesity treatment with liraglutide in andrologically healthy men with infertility and post-pubertal visceral obesity. Methods: Infertile men with post-pubertal alimentary visceral obesity were included in a pilot observational prospective study. All patients were given recommendations for body weight loss (hypocaloric diet, daily aerobic physical activity) as well as an average daily dose of liraglutide 2.4 [2.4; 3.0] mg. Evaluation of waist circumference, antioxidant activity of ejaculate, spermogram was carried out initially and after 6 months. The differences were considered statistically significant at p <0.005. Results: The body weight decrease was -11.7 [12.4; 11.0]%, the waist circumference decrease was 8 [12; 7] cm. In dynamics, increased content of living sperm in ejaculate from 92 [90; 95]% to 95 [92; 98]%, morphologically normal forms from 5 [3; 6]% to 6 [3; 8]%, mobility of A + B from 25 [15; 36] to 35 [19; 52]%, seminal antioxidant capacity, a decrease in reactive oxygen forms in the neat ejaculate were statistically significant. Increasing the sperm count in 1 ml and decreasing reactive oxygen forms in the washed ejaculate did not reach statistical significance. Conclusion: Ejaculate quality indicators improved by the complex obesity therapy with liraglutide in young andrologically healthy men with postpubertal visceral obesity.
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Common nuts (tree nuts and peanuts) are energy-dense foods that nature has gifted with a complex matrix of beneficial nutrients and bioactives, including monounsaturated and polyunsaturated fatty acids, high-quality protein, fiber, non-sodium minerals, tocopherols, phytosterols, and antioxidant phenolics. These nut components synergize to favorably influence metabolic and vascular physiology pathways, ameliorate cardiovascular risk factors and improve cardiovascular prognosis. There is increasing evidence that nuts positively impact myriad other health outcomes as well. Nut consumption is correlated with lower cancer incidence and cancer mortality, and decreased all-cause mortality. Favorable effects on cognitive function and depression have also been reported. Randomized controlled trials consistently show nuts have a cholesterol-lowering effect. Nut consumption also confers modest improvements on glycemic control, blood pressure (BP), endothelial function, and inflammation. Although nuts are energy-dense foods, they do not predispose to obesity, and in fact may even help in weight loss. Tree nuts and peanuts, but not peanut butter, generally produce similar positive effects on outcomes. First level evidence from the PREDIMED trial shows that, in the context of a Mediterranean diet, consumption of 30 g/d of nuts (walnuts, almonds, and hazelnuts) significantly lowered the risk of a composite endpoint of major adverse cardiovascular events (myocardial infarction, stroke, and death from cardiovascular disease) by ≈30% after intervention for 5 y. Impressively, the nut-supplemented diet reduced stroke risk by 45%. As they are rich in salutary bioactive compounds and beneficially impact various health outcomes, nuts can be considered natural pleiotropic nutraceuticals.
... This diet is rich in seeds and nuts, olive oil, seafood, whole grains and fruits and vegetables [108]. In this context, the intervention of nuts (raw walnuts, almonds, and hazelnuts) over 2 weeks improved the Orgasmic Function and Sexual Desire domains of the IIEF compared to a standard Western diet devoid of nuts [50]. Furthermore, dietary based weight loss in obese and diabetic men also improved sexual and endothelial function [109,110], where a high protein, moderate carbohydrate and low-fat diet further improved systemic inflammation [110]. ...
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Objectives: To systematically review and discuss the current evidence from placebo-controlled clinical trials that investigated the use of alternative medicines and herbal remedies in the management of erectile dysfunction (ED). Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-based systematic review using specific keyword combinations was conducted on the PubMed and Scopus databases. Randomised controlled trials investigating herbal medicine in at least one group and using the International Index of Erectile Function (IIEF) as an outcome in patients primarily diagnosed with ED were included for review. Results: Following the literature search, screening and eligibility analysis, a total of 42 articles were included. The 42 articles were categorised as single herb extractions (n = 14), combination herbal formula (n = 5), combination of herbal formula and non-herbal nutraceuticals (n = 7), non-herbal nutraceuticals (n = 5), acupuncture and moxibustion (n = 2), diet and nutrition (n = 3), exercise (n = 5), and topical treatments (n = 1). Based on the results, Korean ginseng, Pygnogenol and Prelox, Tribulus terrestris, Lepidium meyenii, L-arginine, acupuncture and lifestyle interventions were the more predominantly investigated treatments interventions for ED. Conclusions: Panax ginseng, Pygnogenol, Prelox and Tribulus terrestris have promising evidence as herbal products, alongside L-arginine as a nutritional supplement, for ED based on IIEF outcomes, and warrant further clinical investigation. The mechanisms of action remain unclear, but each of these appears to in part increase nitric oxide synthesis. Importantly, improved diet and exercise should be considered, particularly in patients with obesity or diabetes mellitus.
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In an era of ever-increasing healthcare expenditures, yet simultaneously worsening outcomes, many of our patients choose between traditional medical care or often unproven alternative therapies. While the recognition of lifestyle change in addressing cardiovascular and metabolic disease grows, there is less understanding of the impact of lifestyle change on issues facing women every day. Millions of women around the globe struggle with infertility, cancer, sexual dysfunction, and dermatologic needs. Yet, research on the benefits of lifestyle change on these conditions is scarce, and gaps exist both in our understanding of evidence-based approaches to address these issues, as well as adequate provider education when evidence exists. The Women’s Health Member Interest Group convened medical experts in these areas that affect women’s lives to provide insights and meaningful education applicable not only for our patients, but also in our own lives.
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Plants and plant materials have been used for thousands of years to treat and control erectile dysfunction in men. This practice has spanned many cultures and traditions around the world, with the therapeutic effects of many plants attributed to their phytochemical constituents. This review explains how polyphenols (including phenolic acids, flavonoids, terpenoids, carotenoids, alkaloids and polyunsaturated fatty acids) in plants and plant food products interact with key enzymes (phosphodiesterase-5 [PDE-5], angiotensin-converting enzyme [ACE], acetylcholinesterase [AChE], adenosine deaminase [ADA] and arginase) associated with erectile dysfunction. By modulating or altering the activity of these physiologically important enzymes, various bioactive compounds from plants or plant products can synergistically or additively provide tremendous protection against male erectile problems.
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Erectile dysfunction (ED) is a common condition that affects a large percentage of men and can have a significant impact on the patient’s quality of life. In addition to nonmodifiable risk factors, such as age, genetics, hormones, and inflammatory responses, Several modifiable risk factors have been associated with ED, including diet, exercise, tobacco use, and alcohol consumption. Despite this modifiable component in the pathophysiology of ED, research into diet and lifestyle interventions for this condition has been fairly limited. This chapter will focus on the modifiable aspects of ED, including dietary components, such as dietary fats, sodium, red meat, vegetables, fruit, and nuts.
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The study was designed and conducted to evaluate the plant‐based diet status and its association with erectile function (EF) in Chinese young healthy men. From July 2018 to May 2020, 116 objectively proved physically and psychologically healthy men were selected. Clinical questionnaires, detailed physical examinations and blood tests were all assessed. An overall plant‐based diet index (PDI) and a healthful plant‐based diet index (hPDI) were developed from each participant to measure plant‐based diet quantitatively. The EF was measured by both the International Index of Erectile Function‐5 (IIEF‐5) and the surrogated measures of endothelial function, peripheral levels of nitric oxide (NO) and E‐selectin. In subjects, the mean PDI and hPDI were 53.8 ± 8.2 and 54.7 ± 8.9 respectively. Results of multivariate analysis showed that both PDI and hPDI were negatively associated with BMI (all p < .05), but had no relationships with NO, E‐selectin, TT levels and IIEF‐5 scores (all p > .05). In a subgroup of male population, Chinese young healthy men, the plant‐based diet, measured by PDI and hPDI, was not related to erectile function. The population can adhere to plant‐based diet to keep healthy without concerns of negative influence on erectile function.
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Background Male infertility is a widespread condition among couples. In about 50% of cases, couple infertility is attributable to the male partner, mainly due to a failure in spermatogenesis. In recent times, the crucial role that modifiable lifestyle factors play in the development of infertility have generated a growing interest in this field of study, i.e. aging, psychological stress, nutrition, physical activity, caffeine, high scrotal temperature, hot water, mobile telephone use. Several studies have investigated associations between semen quality and the presence of lifestyle stressors i.e. occupational, life events (war, earthquake, etc.) or couple infertility; overall, these studies provide evidence that semen quality is impaired by psychological stress. In this review, we will discuss the impact of quality of life (modifiable lifestyle factors) and psychological stress on male fertility. In addition, the role that increased scrotal temperature along with inappropriate nutritional and physical exercise attitudes exert on male fertility will be presented. Conclusion The decline of male fertility, particularly associated with advancing age, incorrect lifestyles and environmental factors plays an important role on natality, and its consequences on the future on human population makes this an important public health issue in this century. Thus, modification of lifestyle through a structured program of educational, environmental, nutritional/physical exercise and psychological support, combined with the use of nutraceutical antioxidants can prevent infertility and therefore, may help couples to obtain better quality of life and improved possibility to conceive spontaneously or optimize their chances of conception.
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Objective: The long-term impact of intentional weight loss on cardiovascular events remains unknown. We describe 12-month changes in body weight and cardiovascular risk factors in PREvención con DIeta MEDiterránea (PREDIMED)-Plus, a trial designed to evaluate the long-term effectiveness of an intensive weight-loss lifestyle intervention on primary cardiovascular prevention. Research design and methods: Overweight/obese adults with metabolic syndrome aged 55-75 years (n = 626) were randomized to an intensive weight-loss lifestyle intervention based on an energy-restricted Mediterranean diet, physical activity promotion, and behavioral support (IG) or a control group (CG). The primary and secondary outcomes were changes in weight and cardiovascular risk markers, respectively. Results: Diet and physical activity changes were in the expected direction, with significant improvements in IG versus CG. After 12 months, IG participants lost an average of 3.2 kg vs. 0.7 kg in the CG (P < 0.001), a mean difference of -2.5 kg (95% CI -3.1 to -1.9). Weight loss ≥5% occurred in 33.7% of IG participants compared with 11.9% in the CG (P < 0.001). Compared with the CG, cardiovascular risk factors, including waist circumference, fasting glucose, triglycerides, and HDL-cholesterol, significantly improved in IG participants (P < 0.002). Reductions in insulin resistance, HbA1c, and circulating levels of leptin, interleukin-18, and MCP-1 were greater in IG than CG participants (P < 0.05). IG participants with prediabetes/diabetes significantly improved glycemic control and insulin sensitivity, along with triglycerides and HDL-cholesterol levels compared with their CG counterparts. Conclusions: PREDIMED-Plus intensive lifestyle intervention for 12 months was effective in decreasing adiposity and improving cardiovascular risk factors in overweight/obese older adults with metabolic syndrome, as well as in individuals with or at risk for diabetes.
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Background Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk. Methods In a multicenter trial in Spain, we assigned 7447 participants (55 to 80 years of age, 57% women) who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). After a median follow-up of 4.8 years, the trial was stopped on the basis of a prespecified interim analysis. In 2013, we reported the results for the primary end point in the Journal. We subsequently identified protocol deviations, including enrollment of household members without randomization, assignment to a study group without randomization of some participants at 1 of 11 study sites, and apparent inconsistent use of randomization tables at another site. We have withdrawn our previously published report and now report revised effect estimates based on analyses that do not rely exclusively on the assumption that all the participants were randomly assigned. Results A primary end-point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intention-to-treat analysis including all the participants and adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for a Mediterranean diet with nuts, as compared with the control diet. Results were similar after the omission of 1588 participants whose study-group assignments were known or suspected to have departed from the protocol. Conclusions In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. (Funded by Instituto de Salud Carlos III, Spanish Ministry of Health, and others; Current Controlled Trials number, ISRCTN35739639.)
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Aims/hypothesis: In line with current advice, we assessed the effect of replacing carbohydrate consumption with mixed nut consumption, as a source of unsaturated fat, on cardiovascular risk factors and HbA1c in type 2 diabetes. The data presented here are from a paper that was retracted at the authors' request ( https://doi.org/10.2337/dc16-rt02 ) owing to lack of adjustment for repeated measures in the same individual. Our aim, therefore, was to fix the error and add new complementary data of interest, including information on clotting factors and LDL particle size. Methods: A total of 117 men and postmenopausal women with type 2 diabetes who were taking oral glucose-lowering agents and with HbA1c between 47.5 and 63.9 mmol/mol (6.5-8.0%) were randomised after stratification by sex and baseline HbA1c in a parallel design to one of three diets for 3 months: (1) 'full-dose nut diet' (n = 40): a diet with 2.0 MJ (477 kcal) per 8.4 MJ (2000 kcal) energy provided as mixed nuts (75 g/day); (2) 'full-dose muffin diet' (n = 39): a diet with 1.97 MJ (471 kcal) per 8.4 MJ (2000 kcal) energy provided as three whole-wheat muffins (188 g/day), with a similar protein content to the nuts, and the same carbohydrate-derived energy content as the monounsaturated fatty acid-derived energy content in the nuts; or (3) 'half-dose nut diet' (n = 38): a diet with 1.98 MJ (474 kcal) per 8.4 MJ (2000 kcal) energy provided as half portions of both the nuts and muffins. The primary outcome was change in HbA1c. The study was carried out in a hospital clinical research centre and concluded in 2008. Only the statistician, study physicians and analytical technicians could be blinded to the group assessment. Results: A total of 108 participants had post-intervention data available for analysis (full-dose nut group, n = 40; full-dose muffin group, n = 35; half-dose nut group, n = 33). Compared with the full-dose muffin diet, the full-dose nut diet provided 9.2% (95% CI 7.1, 11.3) greater total energy intake from monounsaturated fat. The full-dose nut diet (median intake, 75 g/day) also reduced HbA1c compared with the full-dose muffin diet by -2.0 mmol/mol (95% CI -3.8, -0.3 mmol/mol) (-0.19% [95% CI -0.35%, -0.02%]), (p = 0.026). Estimated cholesterol levels in LDL particles with a diameter <255 ångström [LDL-c<255Å]) and apolipoprotein B were also significantly decreased after the full-dose nut diet compared with the full-dose muffin diet. According to the dose response, the full-dose nut diet is predicted to reduce HbA1c (-2.0 mmol/mol [-0.18%]; p = 0.044), cholesterol (-0.25 mmol/l; p = 0.022), LDL-cholesterol (-0.23 mmol/l; p = 0.019), non-HDL-cholesterol (-0.26 mmol/l; p = 0.020), apolipoprotein B (-0.06 g/l, p = 0.013) and LDL-c<255Å (-0.42 mmol/l; p < 0.001). No serious study-related adverse events occurred, but one participant on the half-dose nut diet was hospitalised for atrial fibrillation after shovelling snow. Conclusions/interpretation: Nut intake as a replacement for carbohydrate consumption improves glycaemic control and lipid risk factors in individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT00410722 FUNDING: The study was funded by the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Loblaw Companies and the Canada Research Chairs Program of the Government of Canada.
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Objectives To examine the effect of nut consumption on inflammatory biomarkers and endothelial function. Design A systematic review and meta-analysis. Data sources MEDLINE, PubMed, Cumulative Index to Nursing and Allied Health Literature and Cochrane Central Register of Controlled Trials (all years to 13 January 2017). Eligibility criteria Randomised controlled trials (with a duration of 3 weeks or more) or prospective cohort designs conducted in adults; studies assessing the effect of consumption of tree nuts or peanuts on C-reactive protein (CRP), adiponectin, tumour necrosis factor alpha, interleukin-6, intercellular adhesion molecule 1, vascular cell adhesion protein 1 and flow-mediated dilation (FMD). Data extraction and analysis Relevant data were extracted for summary tables and analyses by two independent researchers. Random effects meta-analyses were conducted to explore weighted mean differences (WMD) in change or final mean values for each outcome. Results A total of 32 studies (all randomised controlled trials) were included in the review. The effect of nut consumption on FMD was explored in nine strata from eight studies (involving 652 participants), with consumption of nuts resulting in significant improvements in FMD (WMD: 0.79%(95% CI 0.35 to 1.23)). Nut consumption resulted in small, non-significant differences in CRP (WMD: −0.01 mg/L (95% CI −0.06 to 0.03)) (26 strata from 25 studies), although sensitivity analyses suggest results for CRP may have been influenced by two individual studies. Small, non-significant differences were also found for other biomarkers of inflammation. Conclusions This systematic review and meta-analysis of the effects of nut consumption on inflammation and endothelial function found evidence for favourable effects on FMD, a measure of endothelial function. Non-significant changes in other biomarkers indicate a lack of consistent evidence for effects of nut consumption on inflammation. The findings of this analysis suggest a need for more research in this area, with a particular focus on randomised controlled trials. PROSPERO registration number CRD42016045424.
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Background: Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality. Objective and rationale: To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group. Search methods: PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981-2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973-2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group ('Unselected by fertility' versus 'Fertile'), geographic group ('Western', including North America, Europe Australia and New Zealand versus 'Other', including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models. Outcomes: SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models -0.70 million/ml/year; 95% CI: -0.72 to -0.69; P < 0.001; slope in adjusted meta-regression models = -0.64; -1.06 to -0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (-1.38; -2.02 to -0.74; P < 0.001) and among Fertile Western (-0.68; -1.31 to -0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (-5.33 million/year, -7.56 to -3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (-2.06 million/ml, -3.38 to -0.74; P = 0.004 and -8.12 million, -13.73 to -2.51, P = 0.006, respectively). Wider implications: This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50-60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed.
Article
Introduction Erectile dysfunction (ED) is a major health care problem that has implications for quality of life. Aim This umbrella review sought to synthesize all meta-analytic research on risk factors, treatment, and prevalence of ED. Methods 8 electronic databases were searched for relevant meta-analyses in June 2018. The evidence was graded with 2 measures that use quantitative criteria to establish the quality of report writing and confidence in the effect size reported. Main Outcome Measures Lifestyle factors, genetic markers, medical conditions, treatments. Results In total, 98 meta-analyses were identified that included 421 meta-analytic effects, 4,188 primary-effects, and 3,971,122 participants. Pooled estimates showed that an unhealthy lifestyle, genetic markers, and medical conditions were associated with an increased risk of ED. Testosterone therapy and phosphodiesterase type 5 inhibitors showed the greatest treatment efficacy, with mild adverse events observed across treatments. Psychological and behavior change interventions produced effect sizes that were comparable to medication but had greater imprecision in effect sizes. There was little evidence that combined treatments were more efficacious than single treatments. Meta-analyses of prevalence estimates showed consistent age trends but were limited to particular regions or clinical samples, meaning that global estimates of ED are difficult to determine. Clinical Implications The umbrella review synthesized findings for many treatment options that might aid evidence-based clinical decision-making. Based on prevalence estimates, we recommend that primary care physicians take a proactive approach and enquire about erectile problems in all men over age 40 displaying any health-related issue (eg, overweight, cigarette smoking). Strengths & Limitations Strengths include the calculation and comparison of summary estimates across multiple meta-analyses. Limitations include heterogeneity in research quality across research themes limiting effect size comparisons. Conclusion The review provides summary estimates for 37 risk factors and 28 treatments. Meta-analyses of risk factors often did not control for important confounders, and meta-analyses of randomized trials were not exclusive to double-blinded trials, active placebo controls, or tests of long-term effects. We recommend further meta-analyses that eliminate lower quality studies and further primary research on behavioral and combined treatments. Allen MS, Walter EE. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. J Sex Med 2019;16:531–541.
Article
Background: Human semen quality has declined in industrialized countries. Pollution, smoking, and the consumption of a Western-style diet are all hypothesized as potential causes. Objective: We evaluated the effect of chronic consumption of nuts on changes in conventional semen parameters and the potential mechanisms implicated. Design: The FERTINUTS study was a 14-wk randomized, controlled, parallel trial. A total of 119 healthy men, aged 18-35 y, were allocated to 1 of 2 intervention groups: one group was fed the usual Western-style diet enriched with 60 g of a mixture of nuts/d (nut group), and the other was fed the usual Western-style diet avoiding nuts (control group). Semen and blood samples were collected at baseline and at the end of the intervention. Dietary information was recorded throughout the trial. Changes in conventional semen parameters (pH, volume, sperm count and concentration, motility, and morphology) were determined as primary outcomes. The effect of nut consumption on sperm DNA fragmentation (SDF), reactive oxygen species (ROS) production, chromosome anomalies (X, Y, and 18), total DNA methylation, and microRNA expression were measured in sperm samples as potential causes of the changes in the seminogram. Results: Compared with the control group, improvements in total sperm count (P = 0.002) and vitality (P = 0.003), total motility (P = 0.006), progressive motility (P = 0.036), and morphology of sperm (P = 0.008) were observed in the nut group. Participants in the nut group showed an increase in the consumption of total fat, monounsaturated fatty acids, polyunsaturated fatty acids, magnesium, vitamin E, α-linolenic acid, total omega-3 (n-3) and ω-3:ω-6 ratio intake during the intervention. Participants in the nut group showed a significant reduction in SDF (P < 0.001) and in the expression of hsa-miR-34b-3p (P = 0.036). No significant changes in ROS, sperm chromosome anomalies, or DNA methylation were observed between groups. Conclusions: The inclusion of nuts in a Western-style diet significantly improves the total sperm count and the vitality, motility, and morphology of the sperm. These findings could be partly explained by a reduction in the sperm DNA fragmentation. This trial was registered at ISRCTN as ISRCTN12857940.
Article
Introduction Erectile dysfunction (ED) is a common complication in patients with diabetes mellitus (DM). However, the utility of serum biomarkers as clinical surrogates for the development and/or progression of ED is unknown. Aim To summarize the current literature for serum biomarkers for ED in DM and emphasize areas for future research. Main Outcome Measures Human subject data demonstrating the utility of serum markers for the development and progression of ED in patients with DM. Methods We performed a systematic PubMed-Medline search in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement using Medical Subject Headings (MeSH) for articles published from January 1, 2000 through December 31, 2016 of serum biomarkers for development or progression of ED in patients with DM using erectile dysfunction [MeSH] AND (biomarkers [MeSH] or inflammation mediators [MeSH] or intercellular signaling peptides and proteins [MeSH] or cell adhesion molecules [MeSH]). A thorough review of these studies was completed. Results Of the 327 abstracts screened, 12 full-text studies were assessed and 1 study was excluded. Eleven studies assessing serum biomarkers for ED in patients with DM were included in this review. The most studied serum biomarkers for ED in men with DM included endothelial dysfunction markers such as serum E-selectin, endothelial progenitor cells, and endothelial microparticles and specific markers of inflammation such as interleukin-10, ratio of tumor necrosis factor-α to interleukin-10, and reactive oxygen species such as nitric oxide and malondialdehyde. Reliable serum biomarkers will enable earlier diagnosis and objective monitoring of disease progression and responses to treatment in patients with ED. Conclusion Serum biomarkers for ED in men with DM are very limited. Future longitudinal studies with uniform patient characteristics are needed to evaluate the potential clinical use of serum biomarkers in men with DM for the development and progression of ED. Patel DP, Craig JR, Myers JB, et al. Serum Biomarkers of Erectile Dysfunction in Diabetes Mellitus: A Systematic Review of Current Literature. Sex Med Rev 2017:5:339–348.