Compléments alimentaires : consommation et facteurs associés en population générale et dans des groupes spécifiques - modulation du risque de cancer

This thesis is structured in three parts. In the first part (descriptive epidemiology), we assessed dietary supplement use and associated factors in the general population and in specific subgroups (smokers, pregnant women and cancer survivors) of a large sample of French adults (the NutriNet-Santé cohort). Dietary supplement use was widespread, often in self-medication, particularly in pregnant women and in cancer survivors. Our findings suggest that the frequency of risky practices of dietary supplement use were su bstantial in several subgroups. In the second part (etiological epidemiology), we highlighted, for the first time, a potential modulatory effect of an antioxidant supplementation (SU.VI.MAX. trial) on prospective relationships between processed meat intake and breast cancer risk and between levels of plasma fatty acids and cancer risk (overall and breast), in line with mechanistic studies. Our results suggest that antioxidants may counteract the potential procarcinogenic effects of processed meat on breast cancer risk and may modify associations between fatty acids and cancer risk by counteracting the potential effects of these fatty acids on carcinogenesis. Finally, the third part of my thesis pertained to a methodological work in the field of e-epidemiology, related to computer literacy of participants of the NutriNet-Santé web-cohort. These results will be useful for optimizing descriptive and etiological epidemiological studies in nutritional e-epidemiology. Overall, these PhD findings underline the importance of taking into account dietary supplement use in epidemiological studies and contribute to a better understanding of cancer etiology. More general ly, they will also contribute to optimize nutritional recommendations for primary cancer prevention.Cette thèse s’articule autour de 3 parties. Dans la première (épidémiologie descriptive), nous avons évalué, sur un large échantillon d’adultes français (cohorte NutriNet-Santé), la prise de compléments alimentaires et les facteurs associés en population générale et dans des groupes spécifiques (fumeurs, femmes enceintes, sujets atteints de cancer). La prise de compléments, souvent en automédication, était très répandue, en particulier chez les femmes enceintes et les sujets atteints de cancer. Nos travaux suggèrent que les pratiques « à risque » de consommation de compléments alimentaires étaient loin d’être négligeables dans certains groupes. Dans la seconde partie (épidémiologie étiologique), nous avons mis en évidence, pour la première fois, un potentiel effet modulateur d’une supplémentation en antioxydants (essai randomisé SU.VI.MAX) sur les relations prospectives entre consommation de charcuteries et risque de cancer du sein d’une part et taux d’acides gras plasmatiques et risque de cancer (toutes localisations et du sein) d’autre part, en cohérence avec les études mécanistiques. Nos résultats suggèrent que les antioxydants pourraient contrecarrer certains effets potentiellement pro-cancérigènes des charcuteries sur le risque de cancer du sein, et pourraient modifier les associations acides gras – cancer en s’opposant aux effets potentiels des acides gras sur la carcinogénèse. Enfin, la troisième partie de ma thèse a consisté en des travaux méthodologiques transversaux en e-épidémiologie portant sur les compétences informatiques des participants à la web-cohorte NutriNet-Santé. Ces travaux méthodologiques sont nécessaires à la bonne conduite des études épidémiologiques descriptives ou étiologiques en e-épidémiologie nutritionnelle. Les résultats de cette thèse soulignent l’importance de la prise en compte des consommations de compléments alimentaires en épidémiologie et contribuent plus généralement à une meilleure connaissance de l’étiologie des cancers. Ils permettront, à terme, d’améliorer les recommandations en matière de prévention nutritionnelle des cancers

Saffron Extract-Induced Improvement of Depressive-Like Behavior in Mice Is Associated with Modulation of Monoaminergic Neurotransmission

Depressive disorders represent a major public health concern and display a continuously rising prevalence. Importantly, a large proportion of patients develops aversive side effects and/or does not respond properly to conventional antidepressants. These issues highlight the need to identify further therapeutic strategies, including nutritional approaches using natural plant extracts with known beneficial impacts on health. In that context, growing evidence suggests that saffron could be a particularly promising candidate. This preclinical study aimed therefore to test its antidepressant-like properties in mice and to decipher the underlying mechanisms by focusing on monoaminergic neurotransmission, due to its strong implication in mood disorders. For this purpose, the behavioral and neurobiochemical impact of a saffron extract, Safr’Inside™ (6.5 mg/kg per os) was measured in naïve mice. Saffron extract reduced depressive-like behavior in the forced swim test. This behavioral improvement was associated with neurobiological modifications, particularly changes in serotonergic and dopaminergic neurotransmission, suggesting that Safr’Inside™ may share common targets with conventional pharmacological antidepressants. This study provides useful information on the therapeutic relevance of nutritional interventions with saffron extracts to improve management of mood disorders

Acute Intake of a Grape and Blueberry Polyphenol-Rich Extract Ameliorates Cognitive Performance in Healthy Young Adults During a Sustained Cognitive Effort

Despite an increasing level of evidence supporting the individual beneficial effect of polyphenols on cognitive performance, information related to the potential synergistic action of these phytonutrients on cognitive performance during a prolonged cognitive effort is currently lacking. This study investigated the acute and sustained action of a polyphenols-rich extract from grape and blueberry (PEGB), on working memory and attention in healthy students during a prolonged and intensive cognitive effort. In this randomised, cross-over, double blind study, 30 healthy students consumed 600 mg of PEGB or a placebo. Ninety minutes after product intake, cognitive functions were assessed for one hour using a cognitive demand battery including serial subtraction tasks, a rapid visual information processing (RVIP) task and a visual analogical scale. Flow-mediated dilation (FMD) and plasma flavan-3-ols metabolites quantification were also performed. A 2.5-fold increase in serial three subtraction variation net scores was observed following PEGB consumption versus placebo (p < 0.001). A trend towards significance was also observed with RVIP percentage of correct answers (p = 0.058). No treatment effect was observed on FMD. Our findings suggest that consumption of PEGB coupled with a healthy lifestyle may be a safe alternative to acutely improve working memory and attention during a sustained cognitive effort

Nutrients

According to animal studies, saffron and its main volatile compound safranal may reduce biological and behavioral signs of acute stress. However, little is known about its impact in humans. This study investigated the acute effect of a saffron extract and safranal on the biological and psychological stress responses in healthy men experiencing a laboratory stress procedure. In this double-blind, placebo-controlled, randomized, cross-over study, 19 volunteers aged 18-25 received a single dose of 30 mg saffron extract (Safr'Inside, 0.06 mg synthetic safranal, or a placebo on three visits separated by a 28-day washout. Thirteen minutes after administration, participants were exposed to the Maastricht acute stress test (MAST). Salivary cortisol and cortisone were collected from 15 min before the MAST (and pre-dose), 3 min before the MAST, and then 15, 30, 45, 60, and 75 min after the MAST, and stress and anxiety were measured using visual analogic scales. Compared to the placebo, stress and anxiety were significantly toned down after Safranal and Safr'Inside administration and coupled with a delay in the times to peak salivary cortisol and cortisone concentrations ( < 0.05). Safr'Inside and its volatile compound seem to improve psychological stress response in healthy men after exposure to a lab-based stressor and may modulate the biological stress response

Front Psychol

Polyphenols are naturally occurring organic compounds found in plants. Research suggests that their intake reduces the risk of cognitive decline and related dementias. Grapes and blueberries are polyphenol-rich foods that have attracted attention for their potential cognitive-enhancing effects. Examine the effects of supplementation with a standardized and patented polyphenol-rich grape and blueberry extract (Memophenol™) on cognitive function in older adults with mild cognitive impairment. Two-arm, 6 month, parallel-group, randomized, double-blind, placebo-controlled trial. One hundred and forty-three volunteers aged 60 to 80 years with mild cognitive impairment were supplemented with either 150 mg of Memophenol™, twice daily or a placebo. Outcome measures included computer-based cognitive tasks, the Behavior Rating Inventory of Executive Function (BRIEF-A), the Cognitive Failures Questionnaire, and the CASP-19. Compared to the placebo, Memophenol™ supplementation was associated with greater improvements in the speed of information processing ( = 0.020), visuospatial learning ( = 0.012), and the BRIEF-A global score ( = 0.046). However, there were no other statistically significant between-group differences in the performance of other assessed cognitive tests or self-report questionnaires. Memophenol™ supplementation was well-tolerated with no reports of significant adverse reactions. The promising results from this trial suggest that 6-months of supplementation with Memophenol™ may improve aspects of cognitive function in adults with mild cognitive impairment. Further research will be important to expand on the current findings and identify the potential mechanisms of action associated with the intake of this polyphenol-rich extract

Mediterranean Diet Adherence and Risk of Depressive Symptomatology in a French Population-Based Cohort of Older Adults

Several foods from the Mediterranean Diet (MeDi) have already been characterized as beneficial for depression risk, while studies focusing on adherence to the overall MeDi are lacking among older adults at higher risk of depression. The aim of this study was to assess the association between MeDi adherence and the risk of depressive symptomatology (DS) in an older French cohort followed for 15 years. Participants from the Three-City Bordeaux cohort answered a food frequency questionnaire used to assess their MeDi adherence. The Center for Epidemiologic Studies Depression (CES-D) scale score of 16 or greater and/or use of antidepressant treatment ascertained at each visit defined incident DS. Random-effect logistic regression models were adjusted for potential confounders. Among 1018 participants, aged 75.6 years (SD 4.8 years) on average at baseline, 400 incident cases of DS were identified during the follow-up. Only when restricting the definition of DS to a CES-D score ≥ 16 was a borderline-significant trend towards a benefit of greater adherence to the MeDi with reduced odds of DS found (p-value = 0.053). In this large sample of older French adults, a potential benefit of greater adherence to the MeDi regarding the risk of DS would depend on the definition of DS

Effects of saffron extract supplementation on mood, well-being, and response to a psychosocial stressor in healthy adults: A randomized, double-blind, parallel group, clinical trial

Anxiety, stress, and low mood are closely related and may contribute to depressive symptoms. Among non-pharmacological solutions to improve subclinical mood symptoms and resilience to stress, natural products such as saffron—identified as promising following preliminary beneficial effects in major depressive disorder—represent a relevant strategy. This study aimed to assess the efficacy of 8 weeks' supplementation with 30 mg standardized saffron extract on emotional well-being in healthy adults with subclinical feelings of low mood and anxiety and/or stress and evaluate the acute effect of saffron in response to a lab-based psychosocial stressor. The study adopted a double-blind, randomized, parallel groups design in which 56 healthy male and female individuals (18–54 years) received either a saffron extract or a placebo for 8 weeks. Chronic effects of saffron on subjective anxiety, stress, and depressive feelings were assessed using a questionnaire battery [including Profile of Mood State-2, (POMS)] and acute effects in response to a lab-based psychosocial stressor were measured through psychological and physiological parameters. Urinary crocetin levels were quantified. Participants who received the saffron extract reported reduced depression scores and improved social relationships at the end of the study. Urinary crocetin levels increased significantly with saffron supplementation and were correlated with change in depression scores. The typical stress-induced decrease in heart rate variability (HRV) during exposure to the stressor was attenuated following acute saffron intake. Saffron extract appears to improve subclinical depressive symptoms in healthy individuals and may contribute to increased resilience against the development of stress-related psychiatric disorders. Clinical trials number: NCT03639831

BMC Cancer

BACKGROUND: Although some countries have observed a stabilization in the incidence of CNS, an increasing incidence has been reported from multiple studies. Recent observations point out to the heterogeneity of incidence trends according to histological subtypes, gender and age-groups. Using a high-quality regional CNS tumor registry, this article describes the trends of CNS tumor incidence for main histological subtypes, including benign and malignant tumors, in the French department of Gironde from 2000 to 2012. METHODS: Crude and age-standardized incidence rates were calculated globally, by histological subtypes, malignant status, gender and age groups. For trends, annual percent changes (APC) were obtained from a piecewise log-linear model. RESULTS: A total of 3515 CNS tumors was registered during the period. The incidence of overall CNS tumors was 19/100000 person-years (8.3/100000 for neuroepithelial tumors and 7.3/100000 for meningeal tumors). An increased incidence of overall CNS tumors was observed from 2000 to 2012 (APC = + 2.7%; 95%-confidence interval (CI): 1.8-3.7). This trend was mainly explained by an increase in the incidence of meningiomas over the period (APC = + 5.4%, 95%-CI: 3.8-7.0). The increased incidence rate of CNS tumors was more pronounced in female and in older patients even though the incidence rate increased in all age groups. CONCLUSIONS: Part of the temporal variation may be attributed to improvement in registration, diagnosis and clinical practices but also to changes in potential risk factors. Thus, etiological studies on CNS tumors are needed to clarify this rising trend

Dietary supplement use in the general population and in specific subgroups - modulation of cancer risk

Cette thèse s’articule autour de 3 parties. Dans la première (épidémiologie descriptive), nous avons évalué, sur un large échantillon d’adultes français (cohorte NutriNet-Santé), la prise de compléments alimentaires et les facteurs associés en population générale et dans des groupes spécifiques (fumeurs, femmes enceintes, sujets atteints de cancer). La prise de compléments, souvent en automédication, était très répandue, en particulier chez les femmes enceintes et les sujets atteints de cancer. Nos travaux suggèrent que les pratiques « à risque » de consommation de compléments alimentaires étaient loin d’être négligeables dans certains groupes. Dans la seconde partie (épidémiologie étiologique), nous avons mis en évidence, pour la première fois, un potentiel effet modulateur d’une supplémentation en antioxydants (essai randomisé SU.VI.MAX) sur les relations prospectives entre consommation de charcuteries et risque de cancer du sein d’une part et taux d’acides gras plasmatiques et risque de cancer (toutes localisations et du sein) d’autre part, en cohérence avec les études mécanistiques. Nos résultats suggèrent que les antioxydants pourraient contrecarrer certains effets potentiellement pro-cancérigènes des charcuteries sur le risque de cancer du sein, et pourraient modifier les associations acides gras – cancer en s’opposant aux effets potentiels des acides gras sur la carcinogénèse. Enfin, la troisième partie de ma thèse a consisté en des travaux méthodologiques transversaux en e-épidémiologie portant sur les compétences informatiques des participants à la web-cohorte NutriNet-Santé. Ces travaux méthodologiques sont nécessaires à la bonne conduite des études épidémiologiques descriptives ou étiologiques en e-épidémiologie nutritionnelle. Les résultats de cette thèse soulignent l’importance de la prise en compte des consommations de compléments alimentaires en épidémiologie et contribuent plus généralement à une meilleure connaissance de l’étiologie des cancers. Ils permettront, à terme, d’améliorer les recommandations en matière de prévention nutritionnelle des cancers.This thesis is structured in three parts. In the first part (descriptive epidemiology), we assessed dietary supplement use and associated factors in the general population and in specific subgroups (smokers, pregnant women and cancer survivors) of a large sample of French adults (the NutriNet-Santé cohort). Dietary supplement use was widespread, often in self-medication, particularly in pregnant women and in cancer survivors. Our findings suggest that the frequency of risky practices of dietary supplement use were su bstantial in several subgroups. In the second part (etiological epidemiology), we highlighted, for the first time, a potential modulatory effect of an antioxidant supplementation (SU.VI.MAX. trial) on prospective relationships between processed meat intake and breast cancer risk and between levels of plasma fatty acids and cancer risk (overall and breast), in line with mechanistic studies. Our results suggest that antioxidants may counteract the potential procarcinogenic effects of processed meat on breast cancer risk and may modify associations between fatty acids and cancer risk by counteracting the potential effects of these fatty acids on carcinogenesis. Finally, the third part of my thesis pertained to a methodological work in the field of e-epidemiology, related to computer literacy of participants of the NutriNet-Santé web-cohort. These results will be useful for optimizing descriptive and etiological epidemiological studies in nutritional e-epidemiology. Overall, these PhD findings underline the importance of taking into account dietary supplement use in epidemiological studies and contribute to a better understanding of cancer etiology. More general ly, they will also contribute to optimize nutritional recommendations for primary cancer prevention

Sociodemographic, lifestyle and dietary correlates of dietary supplement use in a large sample of French adults: results from the NutriNet-Sante cohort study

International audienceInformation on the determinants of dietary supplement (DS) use in France is largely lacking, especially in population subgroups such as smokers. Also, little is known about the role of health professionals in DS purchases. The aim of the present study was to describe DS use along with its sociodemographic, lifestyle and dietary correlates in a large sample of French adults (age 18+years) participating in the NutriNet-Sante cohort study. Data were collected by self-administered Internet questionnaires. Food intakes were assessed by 24 h dietary records. Data on DS use were available for 79 786 participants. Supplement users were compared with non-users by logistic regression. Current DS use at least three times/week was reported by 14.6% of men and 28.1% of women. Mg, and vitamins B-6 and C were the most frequently consumed nutrients. DS were prescribed or recommended by a physician in 54.9% of the cases. DS use was positively associated with knowledge of nutritional recommendations and organic product consumption, following a healthier diet and lifestyle (non-smoker, moderate leisure-time physical activity). Current smokers used less DS than did non-smokers, but their DS consumption was substantial (19.0%) and they were more likely to self-medicate. The present study provides updated and detailed information on DS use determinants in a large French cohort, including a focus on smokers, for whom the long-term effects of DS use are poorly documented and could represent a risk. These findings pave the way for future aetiological studies