Narrative Review of Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Health in People Living with Obesity.

Glucagon-like peptide-1 Receptor agonists (GLP-1Ras) such as liraglutide and semaglutide have been recently approved as medications for chronic weight management in people living with obesity (PwO); GLP-1 may enhance bone metabolism and improve bone quality. However, the effects of GLP-1Ras on skeletal health remain to be determined and that's the purpose of this narrative review. Nevertheless, bone consequences of intentional weight loss interventions in PwO are well known: (i) significant weight loss induced by caloric restriction and bariatric surgery results in accelerated bone turnover and bone loss, and (ii) unlike caloric restriction interventions, PwO experience a substantial deterioration in bone microarchitecture and strength associated with an increased risk of fracture after bariatric surgery especially malabsorptive procedures. Liraglutide seems to have a positive effect on bone material properties despite significant weight loss in several rodent models. However, most of positive effects on bone mineral density and microarchitecture were observed at concentration much higher than approved for obesity care in humans. No data have been reported in preclinical models with semaglutide. The current evidence of the effects of GLP-1Ra on bone health in PwO is limited. Indeed, studies on the use of GLP-1Ra mostly included patients with diabetes who were administered a dose used in this condition, did not have adequate bone parameters as primary endpoints, and had short follow-up periods. Further studies are needed to investigate the bone impact of GLP-1Ra, dual- and triple-receptor agonists for GLP-1, glucose-dependent insulin releasing polypeptide (GIP), and glucagon in PwO.

Environmental impact and nutritional quality of adult diet in France based on fruit and vegetable intakes.

PURPOSE: To describe the nutritional quality and environmental impact of self-selected diets of adults in France in relation to their fruit and vegetable (FV) intakes. METHODS: Estimates of food and nutrient intakes were taken from the national INCA3 Survey on food intakes carried out in France in 2014-2015. The population (n = 2121 adults) was split into five quintiles of FV intakes, in g/d (Q1 representing the lowest intake, and Q5 the highest). The nutritional quality of diets was assessed through 4 indicators: mean adequacy ratio (MAR), solid energy density, mean excess ratio (MER) and Programme National Nutrition Santé guideline score 2 (PNNS-GS2). The environmental impacts were measured with environmental footprint (EF) scores and 4 additional indicators: climate change, ozone depletion, fine particulate matter and water use. Indicators were compared between quintiles. Analysis was conducted on diets adjusted to 2000 kcal. RESULTS: MAR and PNNS-GS2 increased with increased FV quintiles, while solid energy density decreased. Fibre, potassium, vitamin B9 and vitamin C densities increased with increasing FV intakes. Climate change, ozone depletion and fine particulate matter impacts of diets decreased with increasing quintiles of FV consumption. Conversely, water use impact increased. CONCLUSION: Higher intake of FV is associated with higher nutritional quality of diets and lower environmental impact, except for water use. Given the benefits of fruit and vegetables for human health and the environment, their negative impact on water use could be improved by working on the agricultural upstream, rather than by changing individuals' food choices and reducing their consumption.

Dietary recommendations in the prevention and treatment of osteoporosis.

INTRODUCTION: This article presents the initial recommendations of the French Rheumatology Society (Société Française de Rhumatologie - SFR) and the Osteoporosis Research and Information Group (Groupe de Recherche et d'Informations sur les Ostéoporoses - GRIO) on the role of diet in the prevention and treatment of osteoporosis. METHODS: The recommendations were produced by a working group composed of rheumatologists, physician nutrition specialists and a geriatrician. Fifteen (15) questions pertaining to "daily practices" were preselected by the working group. For the literature review, the working group focussed mainly on the effects of diet on bone mineral density (BMD) and fractures, and primarily on meta-analyses of longitudinal studies and dietary intervention studies. RESULTS: A Mediterranean-type diet and the daily consumption of 2 to 3 dairy products are recommended. Together, these provide the calcium and "high quality" protein required to maintain a normal calcium-phosphorus balance and bone metabolism, and are associated with lower fracture risk. Conversely, unbalanced Western diets, vegan diets, weight-loss diets in non-overweight individuals, alcohol consumption and daily consumption of sodas are advised against. In terms of the beneficial effects on bone mineral density and fracture risk, current scientific data are either insufficient or too divergent to recommend increasing or restricting the consumption of tea or coffee, vitamins other than vitamin D, vitamin D-enriched or phytoestrogen-rich foods, calcium-enriched plant-based beverages, oral nutritional supplements, or dietary sources of prebiotics and probiotics. CONCLUSIONS: These are the first set of recommendations addressing the role of diet in the prevention and treatment of osteoporosis. More research is necessary to direct and support guidelines.

Comparison of pesticide residue and specific nutrient levels in peeled and unpeeled apples.

BACKGROUND: Studies have shown that the consumption of apples has a beneficial effect on cardiovascular diseases and some cancers, largely as a result of their micronutrient and phytoconstituent contents. Apple peel not only contains more polyphenols than the flesh, but also is likely to contain pesticide residues. The present study aimed to compare the contents of certain micronutrients and residual pesticide levels in peeled and unpeeled apples. RESULTS: Peeled apples contained fewer pesticide residues at lower concentrations than unpeeled apples. However, whether samples were peeled or not, the exposure values for pesticide residues in apples never exceeded the acceptable daily intake (ADI), but ranged between 0.04% and 2.10% of the ADI in adults for food intake estimated at the 95th percentile (277 g per person per day). Determination of polyphenol, fibre, magnesium and vitamin C levels showed that the nutritional differences observed between peeled and unpeeled apples were marginal. CONCLUSION: The consumption of apples, such as the apples tested in the present study, results in an exposure to pesticides that is low for unpeeled apples, and lower for peeled apples. Moreover, there was no significant loss of nutritional value from eating peeled apples based on the nutrients investigated. © 2022 Society of Chemical Industry.

Cholecalciferol (vitamin D3) must not be considered as an endocrine disruptor / Le cholécalciférol (la vitamine D3) ne doit pas être inclus dans la liste des perturbateurs endocriniens

A French ministerial decree planning to include cholecalciferol, i.e. vitamin D3 (VD3), in the endocrine disruptors (ED) list has generated a lot of concerns in French physicians and scientists. The aim of the present article was to discuss the scientific rationale that may support or not this decision, which seems to be due to the use of VD3 overdose as a rodenticide in some European countries. First, it is noticeable that cholecalciferol is not an "exogenous substance", a term used in all the definitions of ED, as it is largely synthesized in the skin after UVB rays exposure. Second, we did not find any published article that may support the inclusion of VD3 in the ED list. The request "vitamin D AND endocrine disruptor" reported 33 references in the PubMed database on March, 10, 2022, most of them discussing disturbances of vitamin D metabolism by EDs. Third, a large amount of studies conclude that VD3 has or may have beneficial effects on many functions that are known to be altered by EDs. In addition, we warn that learning that VD3 could be legally considered as a PE may cause the general public to mistrust vitamin D supplementation, which is not desirable in terms of public health as it may increase the already too high prevalence of vitamin D deficient individuals. We consider the aberrant decision of including cholecalciferol in the ED list should be rapidly invalidated before being effective in France and possibly disseminated in the European Union.

Un projet d'arrêté ministériel inscrivant le cholécalciférol, c'est-à-dire la vitamine D3 (VD3), dans la liste des perturbateurs endocriniens (PE) est à l'origine de débats en France. L'objectif de notre article était de préciser les arguments scientifiques pour et contre l'inscription de la VD3 dans la liste des PE, qui semble être initialement due à son utilisation à très forte dose comme raticide/rodenticide dans certains pays. Premièrement, le cholécalciférol ne peut être défini comme une substance exogène, terme utilisé dans les différentes définitions des PE, car il est largement synthétisé dans la peau suite à l'exposition aux UVB. Deuxièmement, il n'existe aucune publication dans la base de données PubMed en faveur d'une inscription de la VD3 dans la liste des PE. La requête « vitamin D AND endocrine disruptor ¼ retrouvait 33 références au 10 mars 2022, la plupart évoquant des perturbations du métabolisme de la vitamine D par les PE. Troisièmement, un grand nombre d'études concluent, au contraire, que la VD3 a des effets bénéfiques sur de nombreuses fonctions altérées par les PE. Plus largement, nous alertons sur le fait qu'apprendre que la VD3 pourrait être règlementairement considérée comme un PE pourrait occasionner, auprès du grand public, une défiance vis-à-vis de la supplémentation en vitamine D, ce qui n'est pas souhaitable en termes de santé publique car de nature à aggraver la prévalence déjà trop élevée des individus carencés en vitamine D. Il est encore temps d'éviter cette décision aberrante et non fondée.

Whole Exome/Genome Sequencing Joint Analysis of a Family with Oligogenic Familial Hypercholesterolemia.

Autosomal Dominant Hypercholesterolemia (ADH) is a genetic disorder caused by pathogenic variants in LDLR, APOB, PCSK9 and APOE genes. We sought to identify new candidate genes responsible for the ADH phenotype in patients without pathogenic variants in the known ADH-causing genes by focusing on a French family with affected and non-affected members who presented a high ADH polygenic risk score (wPRS). Linkage analysis, whole exome and whole genome sequencing resulted in the identification of variants p.(Pro398Ala) in CYP7A1, p.(Val1382Phe) in LRP6 and p.(Ser202His) in LDLRAP1. A total of 6 other variants were identified in 6 of 160 unrelated ADH probands: p.(Ala13Val) and p.(Aps347Asn) in CYP7A1; p.(Tyr972Cys), p.(Thr1479Ile) and p.(Ser1612Phe) in LRP6; and p.(Ser202LeufsTer19) in LDLRAP1. All six probands presented a moderate wPRS. Serum analyses of carriers of the p.(Pro398Ala) variant in CYP7A1 showed no differences in the synthesis of bile acids compared to the serums of non-carriers. Functional studies of the four LRP6 mutants in HEK293T cells resulted in contradictory results excluding a major effect of each variant alone. Within the family, none of the heterozygous for only the LDLRAP1 p.(Ser202His) variant presented ADH. Altogether, each variant individually does not result in elevated LDL-C; however, the oligogenic combination of two or three variants reveals the ADH phenotype.

A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus.

Chikungunya virus (CHIKV) infection causes acute disease characterized by fever, rash and arthralgia, which progresses to severe and chronic arthritis in up to 50% of patients. Moreover, CHIKV infection can be fatal in infants or immunocompromised individuals and has no approved therapy or prevention. This phase 1, first-in-human, randomized, placebo-controlled, proof-of-concept trial conducted from January 2019 to June 2020 evaluated the safety and pharmacology of mRNA-1944, a lipid nanoparticle-encapsulated messenger RNA encoding the heavy and light chains of a CHIKV-specific monoclonal neutralizing antibody, CHKV-24 ( NCT03829384 ). The primary outcome was to evaluate the safety and tolerability of escalating doses of mRNA-1944 administered via intravenous infusion in healthy participants aged 18-50 years. The secondary objectives included determination of the pharmacokinetics of mRNA encoding for CHKV-24 immunoglobulin heavy and light chains and ionizable amino lipid component and the pharmacodynamics of mRNA-1944 as assessed by serum concentrations of mRNA encoding for CHKV-24 immunoglobulin G (IgG), plasma concentrations of ionizable amino lipid and serum concentrations of CHKV-24 IgG. Here we report the results of a prespecified interim analysis of 38 healthy participants who received intravenous single doses of mRNA-1944 or placebo at 0.1, 0.3 and 0.6 mg kg-1, or two weekly doses at 0.3 mg kg-1. At 12, 24 and 48 h after single infusions, dose-dependent levels of CHKV-24 IgG with neutralizing activity were observed at titers predicted to be therapeutically relevant concentrations (≥1 µg ml-1) across doses that persisted for ≥16 weeks at 0.3 and 0.6 mg kg-1 (mean t1/2 approximately 69 d). A second 0.3 mg kg-1 dose 1 week after the first increased CHKV-24 IgG levels 1.8-fold. Adverse effects were mild to moderate in severity, did not worsen with a second mRNA-1944 dose and none were serious. To our knowledge, mRNA-1944 is the first mRNA-encoded monoclonal antibody showing in vivo expression and detectable ex vivo neutralizing activity in a clinical trial and may offer a treatment option for CHIKV infection. Further evaluation of the potential therapeutic use of mRNA-1944 in clinical trials for the treatment of CHIKV infection is warranted.

The ALGOVUE Clinical Trial: Effects of the Daily Consumption of Eggs Enriched with Lutein and Docosahexaenoic Acid on Plasma Composition and Macular Pigment Optical Density.

BACKGROUND: Carotenoids and docosahexaenoic acid (DHA) were identified as essential components for eye health and are both naturally present in eggs. OBJECTIVE: We aimed to evaluate the effect of the daily consumption of two eggs enriched with lutein/zeaxanthin and DHA on macular pigment optical density (MPOD) and on circulating xanthophyll and fatty acid concentrations in healthy participants. METHODS: Ninety-nine healthy volunteers consumed either two standard eggs or two enriched eggs per day for 4 months. MPOD was measured at baseline (V0) and at follow-up (V4) using a modified confocal scanning laser ophthalmoscope (primary outcome). Blood samples were collected to determine total plasma and lipoprotein fatty acids and lutein/zeaxanthin compositions at V0 and V4 (secondary outcomes). RESULTS: A slight but significant increase in MPOD was observed for all study participants consuming two eggs per day for 4 months at all eccentricities (0.5°, 1°, 2°, and 4°). Plasma and lipoprotein lutein, zeaxanthin, and DHA concentrations significantly increased in both groups but were greater in the enriched group (for the enriched group (V0 vs. V4): lutein, 167 vs. 369 ng/mL; zeaxanthin, 17.7 vs. 29.2 ng/mL; DHA, 1.89 vs. 2.56% of total fatty acids). Interestingly, lutein from high-density lipoprotein (HDL) was strongly correlated with MPOD at 0.5 and 1° eccentricities (rho = 0.385, p = 0.008, and rho = 0.461, p = 0.001, respectively). CONCLUSIONS: MPOD was slightly increased in both groups. Lutein, zeaxanthin, and DHA plasma concentrations were strongly enhanced in the enriched group compared with the standard group. A significant correlation was found between MPOD level and lutein concentration in HDL.

Processing in the food chain: do cereals have to be processed to add value to the human diet?

Cereals and cereal products have a long history of use by humans. Recently, there have been some discussions regarding level of processing as a descriptor to define food products, including cereal-based foods. This has led to a somewhat emotional debate on food processing. Given the widespread inclusion of cereals in the diet, this review highlights the history of cereal processing as well as their consumption by humans. It provides an evidence-based discussion on their production, contribution to human nutrition, benefits and disadvantages. The present review illustrates the impact of processing on nutrients, as well as non-nutrients specifically in bread and ready-to-eat breakfast cereals (RTEC), two cereal-based foods which are widely consumed and integral parts of food-based dietary guidelines globally. As a category, most cereals must be processed in some way to enable consumption by humans as we are not equipped to survive exclusively on raw grains. Even thousands of years ago, the processing of cereals was a common practice by humans, turning raw grains into palatable, safe and nutritious foods. Modern processes for cereal-based products are efficient in providing safe and good-quality products to satisfy population needs, as well as helping to meet consumer expectations by providing a range of foods that allows for a varied and balanced diet. Today, RTEC and bread make significant contributions to dietary energy and nutrient requirements and underpin food-based dietary guidance globally. They have been positively linked with intake of dietary fibre, vitamins and minerals, especially when consumed as whole grain.

Long term effect of spa therapy combined with patient education program on subjects with overweight and obesity - A controlled study.

The aim of this single center prospective controlled study in volunteers with obesity and overweight was to evaluate the effect of a patient therapeutic education program (PTE group) combined with spa therapy on weight, physical activity, eating habits and quality of life versus spa therapy alone (control group). The main endpoint was weight change at 5 months after the end of the program. The PTE group of 151 subjects with obesity or overweight followed a 3-week program combining patient education with spa therapy and 189 attended a course of spa therapy alone. At 5 months significant loss was observed in the PTE group compared to controls (-2.69kg vs -1.24kg, p=0.008), a relative weight loss of -2.8% vs -1.3%. At 11 months after spa therapy, only the PTE group maintained a weight loss in addition to the weight loss obtained during spa therapy. The control group returned to the weight they had at the end of spa therapy. In both groups, a significant increase in physical activity was observed at 5 (p<0.001) and 11 months (p<0.001) with a significant better improvement in the PTE group. In addition, while in both groups some quality of life parameters and dietary choices were improved, the improvement (more fruit, vegetables, fish and water) was significantly higher in the PTE group, at both 5 and 11 months after spa therapy. In conclusion, while spa therapy alone initiated positive changes in weight loss, physical activity and some quality of life parameters, the PTE program enhanced this effect.

Cholic acid as a treatment for cerebrotendinous xanthomatosis in adults.

Cerebrotendineous xanthomatosis (CTX) is an autosomal recessive disorder of bile acids synthesis. Patients may present with a variety of clinical manifestations: bilateral cataract and chronic diarrhea during childhood, then occurrence of neurological debilitating symptoms in adulthood (cognitive decline, motor disorders). Plasma cholestanol is used as a diagnostic marker of CTX, and to monitor the response to the treatment. Current treatment for CTX is chenodeoxycholic acid (CDCA), which was reported to improve and/or stabilize clinical status and decrease levels of plasma cholestanol. Rare published reports have also suggested a potential efficacy of cholic acid (CA) in patients with CTX. In this retrospective Franco-Belgian multicentric study, we collected data from 12 patients treated with CA, evaluating their clinical status, cholestanol levels and adverse effects during the treatment period. The population was divided in two subgroups: treatment-naive (who never had CDCA prior to CA) and non-treatment-naive patients (who had CDCA prior to CA introduction). We found that treatment with CA significantly and strongly reduced cholestanol levels in all patients. Additionally, 10 out of 12 patients clinically improved or stabilized with CA treatment. Worsening was noted in one treatment-naïve patient and one non-treatment-naïve patient, but both patients experienced similar outcomes with CDCA treatment as well. No adverse effects were reported from patients with CA treatment, whereas elevated transaminases were observed in some patients while they were treated with CDCA. In conclusion, these findings suggest that CA may be a suitable alternative treatment for CTX, especially in patients with side effects related to CDCA.

[Early prevention and nutritional education]. / Prévention précoce et éducation nutritionnelle.

To be effective, prevention must not remain a theoretical concept and its implementation must not be perceived negatively. Ignorance and prejudices need to be overcome. From conception to adolescence, simple and easy-to-follow nutritional education measures, as well as practical and concrete advice, can be easily applied. Caregivers have an important role to play in communicating these guidelines.

Whole dairy matrix or single nutrients in assessment of health effects: current evidence and knowledge gaps.

Foods consist of a large number of different nutrients that are contained in a complex structure. The nature of the food structure and the nutrients therein (i.e., the food matrix) will determine the nutrient digestion and absorption, thereby altering the overall nutritional properties of the food. Thus, the food matrix may exhibit a different relation with health indicators compared to single nutrients studied in isolation. The evidence for a dairy matrix effect was presented and discussed by an expert panel at a closed workshop, and the following consensus was reached: 1) Current evidence does not support a positive association between intake of dairy products and risk of cardiovascular disease (i.e., stroke and coronary heart disease) and type 2 diabetes. In contrast, fermented dairy products, such as cheese and yogurt, generally show inverse associations. 2) Intervention studies have indicated that the metabolic effects of whole dairy may be different than those of single dairy constituents when considering the effects on body weight, cardiometabolic disease risk, and bone health. 3) Different dairy products seem to be distinctly linked to health effects and disease risk markers. 4) Different dairy structures and common processing methods may enhance interactions between nutrients in the dairy matrix, which may modify the metabolic effects of dairy consumption. 5) In conclusion, the nutritional values of dairy products should not be considered equivalent to their nutrient contents but, rather, be considered on the basis of the biofunctionality of the nutrients within dairy food structures. 6) Further research on the health effects of whole dairy foods is warranted alongside the more traditional approach of studying the health effects of single nutrients. Future diet assessments and recommendations should carefully consider the evidence of the effects of whole foods alongside the evidence of the effects of individual nutrients. Current knowledge gaps and recommendations for priorities in future research on dairy were identified and presented.

Interindividual variability in the cholesterol-lowering effect of supplementation with plant sterols or stanols.

Low-density lipoprotein cholesterol (LDL-C) plays a causal role in atherosclerosis. One way to reduce LDL-C levels is to inhibit cholesterol absorption. Plant sterols and stanols compete with cholesterol for absorption in the intestine and induce an average decrease in LDL-C by 5% to 15% in a dose-dependent manner, but not in all individuals. This review focuses on the interindividual variability in response to dietary supplementation with plant sterols and stanols. Dietary plant sterols and stanols have no significant effects on LDL-C in substantial numbers of individuals. Higher responses, in absolute value and percentage of LDL-C, are observed in individuals with higher cholesterol absorption and a lower rate of cholesterol synthesis. Some data provide evidence of the influence of genetics on the response to plant sterols and stanols. Further studies in large populations are required to extend these conclusions about genetic influences.

[Should we prescribe statins for primary prevention of cardiovascular risk? Rather no] / Faut-il prescrire des statines en prévention primaire du risque cardiovasculaire ? Plutôt contre, si des modifications du mode de vie suffisent à réduire le risque.

Should we prescribe statins for primary prevention of cardiovascular risk ? Statins have their place in primary cardiovascular prevention but lifestyles changes are quite efficient and therefore are more important. However they are often neglected due to a lack of adherence by the patient and/or the physician. Drug therapy could be frequently avoided. In other cases it is still necessary but the adherence to a good nutrition allows to decrease the statins dosage: that induces a decrease in adverse events risk: muscular injury and dysglycemia. So the cost of the statin treatment is directly lower. The two, statins and lifestyle, are complementary, but the second must be the first. We have to convince everyone.

Faut-il prescrire des statines en prévention primaire du risque cardiovasculaire ? Les statines ont une place en prévention cardiovasculaire primaire mais les mesures hygiéno-diététiques sont très efficaces et sont donc plus importantes et souvent négligées par manque de motivation du patient et/ou du médecin. Dans bon nombre de cas le traitement médicamenteux pourrait être évité. Dans d'autres cas il reste nécessaire mais l'observance d'une bonne nutrition permet de diminuer les doses de statines, ce qui diminue le recours à des doses élevées, et donc le risque d'effets secondaires musculaires et de survenue d'un diabète ou d'une intolérance au glucose. Cela permet de réduire automatiquement le coût du traitement médicamenteux. Les deux, statines et mode de vie, sont donc complémentaires mais le second est prioritaire. Il faut s'efforcer d'accroître la motivation de tous.

The Contribution of Modern Margarine and Fat Spreads to Dietary Fat Intake.

The study of dietary fat consumption and its resultant effects on human health has been one of the most investigated topics in the field of human nutrition. Based on the results obtained from such studies, specific dietary recommendations on fat intake (both in terms of quantity and quality) have been established by health organizations around the globe. Among the various food industry sectors, the margarine manufacturers have also responded to these guidelines and now offer improved formulations with a desirable balance of fat contents and fat types. The main aim of this article is to provide an overview on how these modern margarines can contribute towards reaching the dietary guidelines relating to fat intake. In particular, the dietary recommendations with respect to the specific fatty acid types are comprehensively detailed along with an emphasis on the role of modern margarines in providing balanced fat types (more polyunsaturated fats, less saturated fats and a near-complete absence of trans fats) in the daily diet.

Involvement of dietary saturated fats, from all sources or of dairy origin only, in insulin resistance and type 2 diabetes.

Reducing the consumption of saturated fatty acids to a level as low as possible is a European public health recommendation to reduce the risk of cardiovascular disease. The association between dietary intake of saturated fatty acids and development and management of type 2 diabetes mellitus (T2DM), however, is a matter of debate. A literature search was performed to identify prospective studies and clinical trials in humans that explored the association between dietary intake of saturated fatty acids and risk of insulin resistance and T2DM. Furthermore, to assess whether specific foods, and not just the saturated fatty acid content of the food matrix, can have differential effects on human health, the relationship between consumption of full-fat dairy products, a main source of dietary saturated fatty acids, and risk of insulin resistance and T2DM was studied. There is no evidence that dietary saturated fatty acids from varied food sources affect the risk of insulin resistance or T2DM, nor is intake of full-fat dairy products associated with this risk. These findings strongly suggest that future studies on the effects of dietary saturated fatty acids should take into account the complexity of the food matrix. Furthermore, communication on saturated fats and their health effects should be prudent and well informed.