Vegetarian and vegan diets and the risk of cardiovascular disease, ischemic heart disease and stroke: a systematic review and meta-analysis of prospective cohort studies.

PURPOSE: Vegetarian diets have been associated with reduced risk of ischemic heart disease (IHD). However, results regarding cardiovascular disease (CVD) overall and stroke are less clear. We conducted a systematic review and meta-analysis of prospective cohort studies on CVD, IHD and stroke risk among vegetarians or vegans versus nonvegetarians to clarify these associations. METHODS: PubMed and Ovid Embase databases were searched through August 12, 2021. Prospective cohort studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for incidence or mortality from CVD, IHD and stroke, comparing vegetarians and vegans to nonvegetarians were included. Risk of bias (RoB) was assessed using ROBINS-I and the strength of evidence was assessed using World Cancer Research Fund (WCRF) criteria. Summary RRs (95% CIs) were estimated using a random effects model. RESULTS: Thirteen cohort studies (844,175 participants, 115,392 CVD, 30,377 IHD, and 14,419 stroke cases) were included. The summary RR for vegetarians vs. nonvegetarians was 0.85 (95% CI: 0.79-0.92, I2 = 68%, n = 8) for CVD, 0.79 (95% CI: 0.71-0.88, I2 = 67%, n = 8) for IHD, 0.90 (95% CI: 0.77-1.05, I2 = 61%, n = 12) for total stroke, and for vegans vs. nonvegetarians was 0.82 (95% CI: 0.68-1.00, I2 = 0%, n = 6) for IHD. RoB was moderate (n = 8) to serious (n = 5). The associations between vegetarian diets and CVD and IHD were considered probably causal using WCRF criteria. CONCLUSIONS: Vegetarian diets are associated with reduced risk of CVD and IHD, but not stroke, but further studies are needed on stroke. These findings should be considered in dietary guidelines. REVIEW REGISTRATION: No review protocol registered.

Precision patients: Selection practices and moral pathfinding in experimental oncology.

This paper addresses selection practices in a Danish phase 1 unit specialised in precision medicine in the field of oncology. Where precision medicine holds the ambition of selecting genetically fit medicine for the patient, we find that precision medicine in the early trial setting is oriented towards selecting clinically and genetically fit patients for available treatment protocols. Investigating how phase 1 oncologists experience and respond to the moral challenges of selecting patients for early clinical trials, we show that inclusion criteria and patient categories are not always transparent to patients. Lack of transparency about inclusion criteria has been interpreted as morally problematic. Yet drawing on social science studies of 'unknowing', we argue that silence and non-transparency in interactions between oncologists and patients are crucial to respect the moral agency of patients at the edge of life and recognise them as belonging to the public of Danish health care. In the discussion, we consider the practice of placing 'unfit' patients on a waiting list for trial participation. Rather than representing an ethical and political problem, we argue, the waiting list can act as a valve enabling oncologists to navigate the scientific and as well as the moral uncertainties in phase 1 oncology.

Taming Time: Configuring Cancer Patients as Research Subjects.

This article explores how incurable cancer patients in the affluent Danish welfare state are recruited to clinical trials. We show that patients' impending death constitutes their potential for being configured as research subjects. To produce valuable data, patients who enroll in trials and health care professionals must engage in daily "time practices" that prolong the threshold between life and death. When death becomes inevitable, the limit of configuring dying cancer patients as research subjects is reached. Navigating this temporal logic, health care professionals balance the boundary between patients' instrumental worth as research subjects and their intrinsic worth as dying cancer patients. Whereas previous studies have critically uncovered how clinical trials operate at socioeconomic margins, we point to the ways in which clinical trials operate through temporal margins. We argue that clinical trials are dependent on configuring marginal societal spaces and marginal bodies from which to produce knowledge.

Diet, eating behaviour and weight gain in men and women with overweight/obesity receiving varenicline for smoking cessation.

Because trying to quit smoking and not gain weight requires changes in two major behaviours simultaneously we explored eating behaviour in smokers with overweight/obesity making a quit attempt using guideline-based treatment. Participants were randomized to a carbohydrate-reduced or fat-reduced diet. The Three Factor Eating Questionnaire and Binge Eating Scale were completed by 48 of 64 participants in the low-carbohydrate and 47 of 58 in the fat-reduced group at randomization, after 6 and 14 weeks. At 6 weeks, no between group differences were seen in eating behaviour scores thus, we combined the sample for further analyses. In the combined sample, restraint increased (3.94 [95% CI 3.05, 4.83]), disinhibition (uncontrolled eating) decreased (-0.86 [95% CI-1.31, -0.41]) and binge eating decreased (-1.95 [95% CI -2.83, -1.06]), while hunger scores did not change (-0.43 [95% CI -0.89, 0.03]) after 14 weeks. In a general linear model, increase in dietary restraint (P = .012) and decrease in binge eating (P = .040) were associated with lower weight gain (model R2 adj = .147). In a smoking cessation program, dietary support regardless of diet was associated with increased dietary restraint and reduced binge eating. Because smoking cessation causes weight gain these results indicate that dietary support leads to eating behaviour changes that may prevent weight gain.

Mouse avatars of human cancers: the temporality of translation in precision oncology.

Patient-derived xenografts (PDXs) are currently promoted as new translational models in precision oncology. PDXs are immunodeficient mice with human tumors that are used as surrogate models to represent specific types of cancer. By accounting for the genetic heterogeneity of cancer tumors, PDXs are hoped to provide more clinically relevant results in preclinical research. Further, in the function of so-called "mouse avatars", PDXs are hoped to allow for patient-specific drug testing in real-time (in parallel to treatment of the corresponding cancer patient). This paper examines the circulation of knowledge and bodily material across the species boundary of human and personalized mouse model, historically as well as in contemporary practices. PDXs raise interesting questions about the relation between animal model and human patient, and about the capacity of hybrid or interspecies models to close existing translational gaps. We highlight that the translational potential of PDXs not only depends on representational matching of model and target, but also on temporal alignment between model development and practical uses. Aside from the importance of ensuring temporal stability of human tumors in a murine body, the mouse avatar concept rests on the possibility of aligning the temporal horizons of the clinic and the lab. We examine strategies to address temporal challenges, including cryopreservation and biobanking, as well as attempts to speed up translation through modification and use of faster developing organisms. We discuss how featured model virtues change with precision oncology, and contend that temporality is a model feature that deserves more philosophical attention.

BMI modifies the effect of dietary fat on atherogenic lipids: a randomized clinical trial.

BACKGROUND: SFA intake increases LDL cholesterol whereas PUFA intake lowers it. Whether the lipid response to dietary fat differs between normal-weight and obese persons is of relevance to dietary recommendations for obese populations. OBJECTIVES: We compared the effect of substituting unsaturated fat for saturated fat on LDL cholesterol and apoB concentrations in normal-weight (BMI ≤ 25 kg/m2) and obese (BMI: 30-45) subjects with elevated LDL cholesterol. METHODS: We randomly assigned 83 men and women (aged 21-70 y) stratified by BMI (normal: n = 44; obese: n = 39) and elevated LDL cholesterol (mean ± SD, normal weight 4.6 ± 0.9 mmol/L; obese 4.4 ± 0.8 mmol/L) to either a PUFA diet enriched with oil-based margarine ( n = 42) or an SFA diet enriched with butter (n = 41) for 6 wk. RESULTS: Seven-day dietary records showed differences of ∼9 energy percent (E%) in SFA and ∼4 E% in PUFA between the SFA and PUFA groups. In the total study population, the PUFA diet compared with the SFA diet lowered LDL cholesterol (-0.31 mmol/L; 95% CI: -0.47, -0.15 mmol/L, compared with 0.32 mmol/L; 95% CI: 0.18, 0.47 mmol/L; P < 0.001) and apoB (-0.08 g/L; 95% CI: -0.11, -0.05 g/L, compared with 0.07 g/L; 95% CI: 0.03, 0.10 g/L; P < 0.001). Tests of the BMI × diet interaction were significant for total cholesterol, LDL cholesterol, and apoB ( P values ≤ 0.009). In normal-weight compared with obese participants post-hoc comparisons found that the respective changes in LDL cholesterol were 9.7% (95% CI: 5.3%, 14.2%) compared with 5.3% (95% CI: -0.7%, 11.2%), P = 0.206, in the SFA group, and -10.4% (95% CI: -15.2%, -5.7%) compared with -2.3% (95% CI: -7.4%, 2.8%), P = 0.020, in the PUFA group. ApoB changes were 7.5% (95% CI: 3.5%, 11.4%) compared with 3.0% (95% CI: -1.7%, 7.7%), P = 0.140, in the SFA group, and -8.9% (95% CI: -12.6%, -5.2%) compared with -3.8% (95% CI: -6.3%, -1.2%), P = 0.021, in the PUFA group. Responses to dietary fat were not associated with changes in polyprotein convertase subtisilin/kexin type 9 concentrations. CONCLUSIONS: BMI modifies the effect of PUFAs compared with SFAs, with smaller improvements in atherogenic lipid concentrations in obese than in normal-weight individuals, possibly supporting adjustment of dietary recommendations according to BMI. This trial was registered with www.clinicaltrials.gov as NCT02589769.

Low Carbohydrate and Moderately Fat-Reduced Diets Similarly Affected Early Weight Gain in Varenicline-Treated Overweight or Obese Smokers.

INTRODUCTION: Weight gain is common when stopping smoking. This study compared the effect of advising smokers to follow a diet low in carbohydrates versus a usual fat-reduced diet on weight gain and nicotine withdrawal. METHODS: In a randomized clinical trial, 122 men and women smokers with body mass index 25-40kg/m(2) were assigned low-carbohydrate versus moderately fat-reduced diets. Within a week thereafter all participants started treatment with a 12-week course of varenicline 10 days prior to the target quit date. Brief dietary and motivational counseling was given at all visits. Self-reported abstinence was validated. RESULTS: Protein intake in the low-carbohydrate versus fat-reduced diets was 26.4% of total energy versus 20.0%, fat 38.2% versus 30.1%, and carbohydrates 29.0% versus 41.7% (all P < .001). Mean weight changes for the low-carbohydrate versus fat-reduced groups were -1.2 (SD 2.2) versus -0.5 (SD 2.0) kg, -0.2 (SD 3.3) versus 0.5 (SD 2.6) kg, and 2.2 (SD 4.5) versus 2.1 (SD 3.9) kg at 4, 12, and 24 weeks after the target quit date, respectively (not statistically significant). Smoking abstinence rates did not differ between diets. In the combined groups, point prevalence abstinence rates were 71.0% at 12 weeks and 46.3% at 24 weeks. The Minnesota Nicotine Withdrawal Symptoms score was lower in the fat-reduced group compared with the low-carbohydrate group at weeks 4 and 12. CONCLUSIONS: In overweight or obese smokers using varenicline a low-carbohydrate diet was no better than a fat-reduced diet in reducing weight gain but may result in more severe nicotine withdrawal symptoms. Compared to previous studies, cessation rates with varenicline were not impaired by dietary counseling. IMPLICATIONS: The study implies that a popular low-carbohydrate diet does not result in greater weight loss than a moderately fat-reduced diet in overweight and obese smokers who are attempting to quit smoking with the aid of varenicline. Dietary counseling combined with varenicline treatment did not appear to unfavorably influence quit rates compared to previous studies in smokers not selected for overweight or obesity. Notably, the withdrawal symptoms score was lower in the fat-reduced dietary group than the low-carbohydrate group, suggesting a venue for further study.

Authoring experience: the significance and performance of storytelling in Socratic dialogue with rehabilitating cancer patients.

This article examines the storytelling aspect in philosophizing with rehabilitating cancer patients in small Socratic dialogue groups (SDG). Recounting an experience to illustrate a philosophical question chosen by the participants is the traditional point of departure for the dialogical exchange. However, narrating is much more than a beginning point or the skeletal framework of events and it deserves more scholarly attention than hitherto given. Storytelling pervades the whole Socratic process and impacts the conceptual analysis in a SDG. In this article we show how the narrative aspect became a rich resource for the compassionate bond between participants and how their stories cultivated the abstract reflection in the group. In addition, the aim of the article is to reveal the different layers in the performance of storytelling, or of authoring experience. By picking, poking and dissecting an experience through a collaborative effort, most participants had their initial experience existentially refined and the chosen concept of which the experience served as an illustration transformed into a moral compass to be used in self-orientation post cancer.

Beyond weight reduction: improvements in quality of life after an intensive lifestyle intervention in subjects with severe obesity.

INTRODUCTION: We examined the effects of 10-14 weeks of inpatient intensive lifestyle intervention (ILI), including a minimum of 90 minutes of adapted physical activity 5 days/week, with regard to changes in quality of life and associations with weight loss in subjects with severe obesity. METHODS: A total of 100 severely obese subjects (BMI 42.6 ± 5.3 kg/m(2); 42.7 ± 10.6 years) were included. Quality of life was assessed by Binge Eating Scale, Hospital Anxiety, and Depression Scale, and SF- 36. The ILI group completed the questionnaires at inclusion, after 10-14 weeks and 12 months, and controls at inclusion and after 10-14 weeks. RESULTS: Compared to controls, self-reported binge eating (-6.4, P < 0.0001), anxiety (-1.7, P = 0.005), and depression (-3.0, P < 0.0001) were reduced, and physical (8.0, P < 0.0001) and mental (7.6, P < 0.0001) health increased in the ILI group. After 12 months, reduction in self-reported binge eating (-7.2, P < 0.0001) and depression (-3.4, P < 0.0001) and increase in physical (8.9, P < 0.0001) and mental (3.6, P = 0.035) health were maintained. Decreased self-reported binge eating (ß = 0.555, P = 0.010) and increased physical health (ß = -0.554, P = 0.003) were associated with weight loss. CONCLUSION: ILI including a high volume of physical activity in subjects with severe obesity improved quality of life by favorable changes in self-reported binge eating, depression, and mental and physical health. Improvements in binge eating and physical health were associated with weight loss.

Changes in body composition, cardiovascular disease risk factors, and eating behavior after an intensive lifestyle intervention with high volume of physical activity in severely obese subjects: a prospective clinical controlled trial.

We examined the effects of a 10-14-weeks inpatient lifestyle modification program, including minimum 90 min of physical activity (PA) five days/week, on body composition, CVD risk factors, and eating behavior in 139 obese subjects (BMI 42.6 ± 5.2 kg/m²). Completion rate was 71% (n = 71) in the intensive lifestyle intervention (ILI) group and 85% (n = 33) among waiting list controls. Compared to controls body weight (-17.0 (95% CI: -18.7, -15.3) kg, P < 0.0001), fat mass (-15.2 (95% CI: -17.4, -13.1) kg, P < 0.0001), fat free mass (-1.2 (95% CI: -2.2, -0.2) kg, P = 0.016) and visceral fat (-86.6(95% CI: -97.4, -75.7) cm², P < 0.0001) were reduced in the ILI-group after 10-14 weeks. Within the ILI-group weight loss was -23.8 (95% CI: -25.9, -21.7) kg, P < 0.0001 and -20.3 (95% CI: -23.3, -17.3) kg, P < 0.0001, after six and 12 months, respectively. Systolic BP, glucose, triglycerides, and LDL-C were reduced, and HDL-C was increased (all P ≤ 0.006) after 10-14 weeks within the ILI group. The reduction in glucose and increase in HDL-C were sustained after 12 months (all P < 0.0001). After one year, weight loss was related to increased cognitive restraint and decreased uncontrolled eating (all P < 0.05). Thus, ILI including high volume of PA resulted in weight loss with almost maintenance of fat-free mass, favorable changes in CVD risk factors, and eating behavior in subjects with severe obesity.

Compliance, tolerability and safety of two antioxidant-rich diets: a randomised controlled trial in male smokers.

It has been suggested that antioxidants attenuate oxidative stress and prevent oxidative stress-related diseases. Paradoxically, randomised controlled trials (RCT) using pharmacological doses of antioxidant supplements have demonstrated harmful effects in smokers. The aim of the present study was to test the compliance, tolerability and safety of two food-based antioxidant-rich diets in smokers. One of the diets provided antioxidants at levels similar to that used in RCT using supplements which previously have generated harmful effects. The present study followed a randomised, parallel-arm dietary intervention for 8 weeks (n 102) in male smokers (age ≥ 45 years). Participants were randomised to either antioxidant-rich diet, kiwi fruit or control groups. The antioxidant-rich foods provided about 300 mmol antioxidants/week from a wide range of plant-based food items. The kiwi fruit group consumed three kiwi fruits/d. Compliance to both diets was good. Only mild, undesirable events were reported by a minority of the participants. The safety of both diets was demonstrated as no potentially harmful or pro-oxidative effects were observed. In the antioxidant-rich diet group, the mean intake of antioxidants increased from 30 mmol/d at baseline to 62 mmol/d during the intervention. In conclusion, we have demonstrated that male smokers can comply with two food-based antioxidant-rich diets. Furthermore, the present study is the first to demonstrate the tolerability and safety of dietary antioxidants at levels similar to dosages provided in RCT using supplements. Such diets may be useful in future studies investigating whether dietary antioxidants may reduce oxidative stress and related diseases.

Blood cell gene expression associated with cellular stress defense is modulated by antioxidant-rich food in a randomised controlled clinical trial of male smokers.

BACKGROUND: Plant-based diets rich in fruit and vegetables can prevent development of several chronic age-related diseases. However, the mechanisms behind this protective effect are not elucidated. We have tested the hypothesis that intake of antioxidant-rich foods can affect groups of genes associated with cellular stress defence in human blood cells. TRIAL REGISTRATION NUMBER: NCT00520819 http://clinicaltrials.gov. METHODS: In an 8-week dietary intervention study, 102 healthy male smokers were randomised to either a diet rich in various antioxidant-rich foods, a kiwifruit diet (three kiwifruits/d added to the regular diet) or a control group. Blood cell gene expression profiles were obtained from 10 randomly selected individuals of each group. Diet-induced changes on gene expression were compared to controls using a novel application of the gene set enrichment analysis (GSEA) on transcription profiles obtained using Affymetrix HG-U133-Plus 2.0 whole genome arrays. RESULTS: Changes were observed in the blood cell gene expression profiles in both intervention groups when compared to the control group. Groups of genes involved in regulation of cellular stress defence, such as DNA repair, apoptosis and hypoxia, were significantly upregulated (GSEA, FDR q-values < 5%) by both diets compared to the control group. Genes with common regulatory motifs for aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (AhR/ARNT) were upregulated by both interventions (FDR q-values < 5%). Plasma antioxidant biomarkers (polyphenols/carotenoids) increased in both groups. CONCLUSIONS: The observed changes in the blood cell gene expression profiles suggest that the beneficial effects of a plant-based diet on human health may be mediated through optimization of defence processes.

Validation of ActiReg to measure physical activity and energy expenditure against doubly labelled water in obese persons.

ActiReg is an instrument that uses combined recordings of body position and motion to calculate energy expenditure (EE) and physical activity (PA). The aim of the study was to compare mean total energy expenditure (TEE) measured by ActiReg and doubly labelled water (DLW) in obese subjects. TEE was measured by the DLW method during a period of 14 d in fifty obese men and women with metabolic risk factors. During the same period ActiReg recordings were obtained for 7 d. RMR was measured by indirect calorimetry and also estimated by standardized equations. Because EE may be disproportionately increased in obese subjects during weight-bearing activities, we established a new set of physical activity ratios (PAR). These ratios were based on oxygen uptake measurements during treadmill walking. The mean TEE according to the DLW was 13.94 (sd 2.47) MJ/d. Mean TEE calculated from the ActiReg data and measured RMR was 13.39 (sd 2.26) MJ/d, an underestimation of 0.55 MJ (95 % CI 0.13, 0.98; P = 0.012) or 3.9 %. RMR derived from standard equations based on weight, age and sex were overestimated while the RMR based on fat-free mass values in addition was underestimated. Despite slight underestimation ActiReg may be used to measure TEE in obese subjects on two premises: RMR should be measured, and the increased EE during weight-bearing activities in obese subjects should be considered.

The social life of genetic knowledge: a case-study of choices and dilemmas in cancer genetic counselling in Denmark.

This article explores the social life of genetic knowledge in the context of cancer genetic counselling in Denmark. I focus on a specific case that occurred during my study of the processes through which genetic risk profiles are produced and through which knowledge of genes and kinship comes to appear both meaningful and contestable to counsellees. The analysis illuminates how participants in cancer genetic counselling experience gaps between, on the one hand, genetic information about kinship and predispositions to hereditary disease and, on the other hand, social experiences of kinship and risks. I argue that this gap constitutes a space for agency in which people make their own connections and interpretations. It is in this space that new social relations and understandings of bodies, health and kinship are crafted. Following the social life of genetic knowledge highlights how knowledge is practiced through social relations and how knowing is grounded in particular interactions and situated concerns.

[Social and family considerations in genetic counselling]. / Sociale og familiemaessige problemstillinger ved genetisk rådgivning.

Genetic knowledge can be viewed as an important tool in the prevention of hereditary disease. This article discusses the social issues that the link between genetics and prevention raises in cancer genetic counselling and testing. In particular, the moral dilemmas which health professionals and patients face in relation to disclosing genetic information to kin are described. The authors argue that questions about disclosing information and balancing autonomy and responsibility are not only ethical questions but biopolitical issues.

Genetics and prevention: a policy in the making.

This article explores the process through which the advances of genetic research are incorporated into public health care in Denmark. Drawing on ethnographic fieldwork in cancer genetic counselling, the implementation of new medical advances is investigated by following the establishment of a policy on informing relatives at risk of hereditary cancer. This case material provides the occasion to examine how policies are shaped in a governmental process through which different actors seek to establish a common goal for a specific health practice. The struggle to define such a goal implies a struggle to define where to draw the line between health and disease and what makes up a healthy person in the context of genetic knowledge. The authors argue that in the process of establishing a policy in the field of cancer genetics the imperative of prevention comes to provide the framework within which an ethics of rights and responsibilities is constituted and the target group of cancer genetic counselling defined. This ethics is not determined by or inherent in genetic technology itself, but constituted in a social process and therefore negotiated within pre-existing frameworks of understanding in professional practice.

Premature coronary heart disease, cigarette smoking, and the metabolic syndrome.

The metabolic syndrome and cigarette smoking each increase the risk of a recurrent event in patients with premature coronary heart disease. We explored the association between cigarette smoking and the metabolic syndrome by examining 705 men aged < 55 years and 296 women < 65 years within 6 to 12 months of a major coronary heart disease event. Most were taking statins (96%) and antihypertensive drugs (88%). Nearly 1/3 of the subjects had the full metabolic syndrome, as defined by the National Cholesterol Education Program criteria. These subjects were less likely to be nonsmokers than were those with < or = 2 components of the metabolic syndrome (13.2% vs 24.2%, p < 0.0001). After adjustment for age, educational attendance, and alcohol consumption, the odds ratio (OR) for the metabolic syndrome was doubled in men who smoked cigarettes daily (OR 2.2, 95% confidence interval 1.3 to 3.7) or who were ex-smokers (OR 2.3, 95% confidence interval 1.4 to 3.9) compared with nonsmokers. Female ex-smokers had an increased risk compared with nonsmokers (OR 2.0, 95% confidence interval 1.0 to 3.9). Ex-smokers were more likely to meet the metabolic syndrome cutoff levels for waist circumference and high-density lipoprotein cholesterol (p < or = 0.01) than were nonsmokers. Also, male ex-smokers were more likely to exceed the cutoff level for triglycerides (p = 0.004). These findings indicate that although smoking cessation is imperative for patients with premature CHD, the metabolic risks associated with overweight and obesity after cessation need to be addressed.

Providing solutions--defining problems: the imperative of disease prevention in genetic counselling.

Common sense states that problems make people look for solutions. This article proposes the contrary, i.e. that solutions provide the framework within which certain problems can be stated and handled. Drawing on observations of cancer genetic counselling in Denmark and official recommendations concerning the practice of genetic counselling, this article explores how the new prophylactic possibilities become the lens through which risk factors are identified and defined as problems that require action. In particular, the question of how new possibilities to prevent hereditary disease challenge the traditional non-directive ethos of clinical genetics provides the occasion to analyse governmentality processes in clinical genetic dialogues. The article argues that an imperative of choosing disease prevention in genetic counselling transforms the notion of non-directiveness as well as the notions of autonomy and informed consent. The transforming event is the transmission of expert knowledge on genetic risk from counsellor to counsellee. This process of knowledge transmission creates autonomous individuals who, through the medium of choice, consent voluntarily to take personal responsibility for themselves and their relatives. Conceived as a health technology, genetic counselling is a practice through which hegemonic knowledge claims about saving lives by acting responsibly is created. Disease prevention as the solution to increased risks comes to stand out as the right way of relating to oneself, the family, and society.