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Nature Communications Oct 2023Identifying oncological applications for drugs that are already approved for other medical indications is considered a possible solution for the increasing costs of...
Identifying oncological applications for drugs that are already approved for other medical indications is considered a possible solution for the increasing costs of cancer treatment. Under the hypothesis that nutritional stress through fasting might enhance the antitumour properties of at least some non-oncological agents, by screening drug libraries, we find that cholesterol biosynthesis inhibitors (CBIs), including simvastatin, have increased activity against cancers of different histology under fasting conditions. We show fasting's ability to increase CBIs' antitumour effects to depend on the reduction in circulating insulin, insulin-like growth factor-1 and leptin, which blunts the expression of enzymes from the cholesterol biosynthesis pathway and enhances cholesterol efflux from cancer cells. Ultimately, low cholesterol levels through combined fasting and CBIs reduce AKT and STAT3 activity, oxidative phosphorylation and energy stores in the tumour. Our results support further studies of CBIs in combination with fasting-based dietary regimens in cancer treatment and highlight the value of fasting for drug repurposing in oncology.
Topics: Simvastatin; Fasting; Diet; Insulin; Cholesterol
PubMed: 37907500
DOI: 10.1038/s41467-023-42652-1 -
The Journal of Nutrition Sep 2022The 2020-2025 Dietary Guidelines for Americans (2020 DGA) recommend 3 dietary patterns for Americans, including a Healthy Vegetarian Dietary Pattern (HVDP).
BACKGROUND
The 2020-2025 Dietary Guidelines for Americans (2020 DGA) recommend 3 dietary patterns for Americans, including a Healthy Vegetarian Dietary Pattern (HVDP).
OBJECTIVES
The objective of this study was to assess whether nutritionally adequate dairy-free and vegan adaptations to the HVDP can be modeled with foods already in the DGA.
METHODS
Using similar food pattern modeling procedures as the 2020 DGA, the nutrient composition of 2 alternative models-dairy-free and vegan-of the 1800-, 2000-, 2200-, and 2400-kcal/d HVDPs was assessed. The dairy food group was replaced with a dairy alternative group comprised of soy milk and soy yogurt fortified with calcium, vitamin A, and vitamin D. For the vegan model, eggs were replaced with equal proportions of vegetarian protein foods.
RESULTS
Dairy-free and vegan models required minimal changes to the HVDP. Cup-equivalents and/or ounce-equivalents of vegetables, fruits, grains, oils, and discretionary calories remained unchanged. Content of total fat, polyunsaturated fat, linoleic acid (18:2n-6), linolenic acid, iron, copper, vitamin D, riboflavin, vitamin B-12, and vitamin K increased in both models by ≥10% (all comparisons relative to the original HVDP). Choline increased ≥25% in the dairy-free models. Protein decreased 11% in both 1800-kcal/d models and 10% in both 2000-kcal/d models. Sodium, cholesterol, zinc, and phosphorus decreased across all energy levels in both models, and selenium decreased in the vegan model. Carbohydrate, fiber, saturated fat, EPA, DHA, calcium, magnesium, potassium, vitamin A, vitamin E, vitamin C, thiamin, folate, and vitamin B-6 changed ≤10%. Both models contained adequate nutrients to meet Dietary Reference Intakes (DRIs) for most age and sex groups for which 1800-, 2000-, 2200-, and 2400-kcal/d diets are appropriate. Zinc was the only nutrient below the DRI for males.
CONCLUSIONS
The dairy-free and vegan HVDP models could help adults who do not consume dairy foods and/or other animal products to meet nutrition recommendations.
Topics: Calcium; Calcium, Dietary; Diet; Diet, Vegetarian; Humans; Male; United States; United States Department of Agriculture; Vegans; Vitamin A; Vitamin D; Vitamins; Zinc
PubMed: 35485767
DOI: 10.1093/jn/nxac100 -
BMC Nephrology Jul 2020Dietary and lifestyle factors may play an important role in the increasing prevalence of nephrolithiasis. We aimed to review and quantify the associations between... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dietary and lifestyle factors may play an important role in the increasing prevalence of nephrolithiasis. We aimed to review and quantify the associations between lifestyle factors and incident nephrolithiasis and suggest lifestyle changes for the primary prevention of nephrolithiasis.
METHODS
PubMed, EMBASE, and Cochrane Library were searched up to May 2019, for observational studies and randomized controlled trials (RCTs) that assessed modifiable lifestyle factors and risk of nephrolithiasis in adults. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were computed using a random effects model. The I statistic was employed to evaluate heterogeneity. Subgroup analysis, sensitivity analysis and meta-regression were also conducted whenever possible.
RESULTS
Fifty relevant articles with 1,322,133 participants and 21,030 cases in total were identified. Prominent risk factors for incident stones were body mass index (1.39,1.27-1.52), dietary sodium (1.38, 1.21-1.56), fructose, meat, animal protein, and soda. In contrast, protective factors included fluid intake (0.55, 0.51-0.60), a Dietary Approaches to Stop Hypertension (DASH) style diet (0.69, 0.64-0.75), alcohol (0.69, 0.56-0.85), water, coffee, tea, vegetables, fruits, dietary fiber, dietary calcium (0.83, 0.76-0.90), and potassium. Vitamin D (1.22, 1.01-1.49) and calcium (1.16, 1.00-1.35) supplementation alone increased the risk of stones in meta-analyses of observational studies, but not in RCTs, where the cosupplementation conferred significant risk.
CONCLUSIONS
Several modifiable factors, notably fluid intake, dietary patterns, and obesity, were significantly associated with nephrolithiasis. Long-term RCTs are required to investigate the cost-effectiveness of dietary patterns for stone prevention. The independent and combined effects of vitamin D and calcium supplementation on nephrolithiasis need further elucidation.
Topics: Alcohol Drinking; Calcium, Dietary; Carbonated Beverages; Coffee; Diet; Dietary Approaches To Stop Hypertension; Dietary Fiber; Dietary Supplements; Drinking Behavior; Drinking Water; Fruit; Humans; Life Style; Nephrolithiasis; Potassium, Dietary; Primary Prevention; Tea; Vegetables; Vitamin D
PubMed: 32652950
DOI: 10.1186/s12882-020-01925-3 -
Advances in Nutrition (Bethesda, Md.) Sep 2023The Dietary Guidelines for Americans recommend two-and-a-half cup equivalents of low-fat and fat-free dairy foods per day for children 4-8 y and 3 cup equivalents per... (Review)
Review
The Dietary Guidelines for Americans recommend two-and-a-half cup equivalents of low-fat and fat-free dairy foods per day for children 4-8 y and 3 cup equivalents per day for adolescents aged 9-18 and adults. Currently, the Dietary Guidelines for Americans recognizes 4 nutrients as being of public concern because of suboptimal levels in the diet. These include calcium, dietary fiber, potassium, and vitamin D. In the American diet, dairy foods are leading contributors of calcium, vitamin D, and potassium. Milk, because of its unique nutrient package that provides shortfall nutrients to the diets of children and adolescents, remains an underpinning of dietary recommendations and is included with school meals. Despite this, milk consumption is declining, and >80% of Americans do not meet recommendations for dairy. Data indicate that children and adolescents who consume flavored milk are more likely to consume more dairy and adhere to healthier overall dietary patterns. Flavored milk, however, receives more scrutiny than plain milk because of its contribution of added sugar and calories to the diet and concerns over childhood obesity. Therefore, the purpose of this narrative review is to describe trends in beverage consumption in children and adolescents aged 5-18 y and highlight the science that has examined the impact of including flavored milk in overall healthy dietary patterns within this population.
Topics: Adult; Adolescent; Child; Humans; United States; Animals; Milk; Pediatric Obesity; Diet; Energy Intake; Flavoring Agents; Calcium, Dietary; Vitamins; Diet, Fat-Restricted; Vitamin D
PubMed: 37290718
DOI: 10.1016/j.advnut.2023.06.002 -
Cell Reports Jun 2023Intermittent fasting (IF) is an established intervention to treat the growing obesity epidemic. However, the interaction between dietary interventions and sex remains a...
Intermittent fasting (IF) is an established intervention to treat the growing obesity epidemic. However, the interaction between dietary interventions and sex remains a significant knowledge gap. In this study, we use unbiased proteome analysis to identify diet-sex interactions. We report sexual dimorphism in response to intermittent fasting within lipid and cholesterol metabolism and, unexpectedly, in type I interferon signaling, which was strongly induced in females. We verify that secretion of type I interferon is required for the IF response in females. Gonadectomy differentially alters the every-other-day fasting (EODF) response and demonstrates that sex hormone signaling can either suppress or enhance the interferon response to IF. IF fails to potentiate a stronger innate immune response when IF-treated animals were challenged with a viral mimetic. Lastly, the IF response changes with genotype and environment. These data reveal an interesting interaction between diet, sex, and the innate immune system.
Topics: Female; Mice; Animals; Interferon Type I; Gene-Environment Interaction; Gonadal Steroid Hormones; Fasting; Diet; Sex Characteristics
PubMed: 37243595
DOI: 10.1016/j.celrep.2023.112559 -
Annals of Nutrition & Metabolism 2022The rapid worldwide increase in the incidence of Alzheimer's disease is associated with changing nutrition patterns. Recently, some articles have highlighted the link... (Review)
Review
BACKGROUND
The rapid worldwide increase in the incidence of Alzheimer's disease is associated with changing nutrition patterns. Recently, some articles have highlighted the link between Alzheimer's disease and dietary cholesterol. It was found that elevated levels of some of its fractions in the brain and circulation affect metabolism.
SUMMARY
Previous studies have considered the relationship between Alzheimer's disease and oxidized cholesterol molecules in the brain. To date, there are limited data available on the relationship between oxidized cholesterol in the brain and Alzheimer's disease. There is a link between a diet high in cholesterol and its oxidized forms, leading to hypercholesterolemia, which is one of significant risk factors of dementia, and Alzheimer's disease. Oxidized cholesterol can be absorbed in the small intestine and cross the blood-brain barrier, leading to increased inflammation and endogenous oxidative process. Animal-origin foods are sources of oxidized cholesterol, with cholesterol oxidation beginning already after slaughter and occurring during storage and processing.
KEY MESSAGES
High-heat food preparation and storage of cooked products in the refrigerator followed by subsequent heating may significantly increase the amount of oxidized cholesterol products. Therefore, a diet low in cholesterol oxidation products and high in plants with antioxidative properties seems to be most preventable and should be implemented as early as possible.
Topics: Alzheimer Disease; Animals; Brain; Cholesterol; Diet; Humans; Oxysterols
PubMed: 35545012
DOI: 10.1159/000520514 -
Journal of Animal Science Jan 2023This study aimed to investigate the effects of diets supplemented with 25-hydroxycholecalciferol [25-(OH)D3] and additional vitamin E on growth performance, antioxidant...
This study aimed to investigate the effects of diets supplemented with 25-hydroxycholecalciferol [25-(OH)D3] and additional vitamin E on growth performance, antioxidant capacity, bone development, and carcass characteristics at different stocking densities on commercial broiler farms. A total of 118,800 one-day-old Arbor Acres broilers were assigned to a 2 × 2 factorial treatment consisting of two dietary vitamin levels (5,500 IU vitamin D3 and 60 IU vitamin E: normal diet, using half 25-(OH)D3 as a source of vitamin D3 and an additional 60 IU of vitamin E: 25-(OH)D3+VE diet) and two stocking densities (high density of 20 chickens/m2: HD and 16 chickens/m2: LD). The experiment lasted for 42 d. The results showed that high-density stocking negatively affected the growth performance of broilers during the first four weeks, whereas the vitamin diet treatment significantly improved the feed conversion ratios (FCR) during the last 2 wk. Vitamin diets increased catalase at 14 and 42 d, and the glutathione peroxidase (GSH-px) levels at 42 d in high-density-stocked broilers. The interaction showed that serum vitamin E levels were significantly improved at 28 d of age in high-density-stocked broilers as a result of the vitamin diets. Stocking density and dietary treatments were found to significantly affect bone development, with the vitamin diet significantly increasing metatarsal length and femoral bone strength in broilers from high-density stocking density at 28 d of age. High stocking density increased the proportion of leg muscles and meat yield per square meter. In general, 25-(OH)D3 and additional vitamin E suppressed oxidative stress and ameliorated the negative effects of high-density stocking on bone development in a commercial chicken farm setting. Vitamin diets improved the FCR of broilers, while high-density stocking resulted in better economic outcomes.
Topics: Animals; Calcifediol; Chickens; Antioxidants; Vitamin E; Diet; Dietary Supplements; Vitamins; Cholecalciferol; Bone Development; Animal Feed
PubMed: 37933958
DOI: 10.1093/jas/skad369 -
Nutrients Mar 2023The gut microbiome has been shown to play a role in the relationship between diet and cardiometabolic health. We sought to examine the degree to which key microbial...
The gut microbiome has been shown to play a role in the relationship between diet and cardiometabolic health. We sought to examine the degree to which key microbial lignan metabolites are involved in the relationship between diet quality and cardiometabolic health using a multidimensional framework. This analysis was undertaken using cross-sectional data from 4685 US adults (age 43.6 ± 16.5 years; 50.4% female) participating in the National Health and Nutrition Examination Survey for 1999-2010. Dietary data were collected from one to two separate 24-hour dietary recalls and diet quality was characterized using the 2015 Healthy Eating Index. Cardiometabolic health markers included blood lipid profile, glycemic control, adiposity, and blood pressure. Microbial lignan metabolites considered were urinary concentrations of enterolignans, including enterolactone and enterodiol, with higher levels indicating a healthier gut microbial environment. Models were visually examined using a multidimensional approach and statistically analyzed using three-dimensional generalized additive models. There was a significant interactive association between diet quality and microbial lignan metabolites for triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, insulin, oral glucose tolerance, adiposity, systolic blood pressure, and diastolic blood pressure (all < 0.05). Each of these cardiometabolic health markers displayed an association such that optimal cardiometabolic health was only observed in individuals with both high diet quality and elevated urinary enterolignans. When comparing effect sizes on the multidimensional response surfaces and model selection criteria, the strongest support for a potential moderating relationship of the gut microbiome was observed for fasting triglycerides and oral glucose tolerance. In this study, we revealed interactive associations of diet quality and microbial lignan metabolites with cardiometabolic health markers. These findings suggest that the overall association of diet quality on cardiometabolic health may be affected by the gut microbiome.
Topics: Humans; Adult; Female; Middle Aged; Male; Risk Factors; Nutrition Surveys; Cross-Sectional Studies; Cardiovascular Diseases; Diet; Obesity; Triglycerides; Cholesterol, HDL; Lignans
PubMed: 36986142
DOI: 10.3390/nu15061412 -
The British Journal of Nutrition Dec 2022Childbearing decreases HDL-cholesterol, potentially contributing to the increased risk of CVD in parous women. Large HDL particles (HDL-P) are associated with lower risk... (Randomized Controlled Trial)
Randomized Controlled Trial
Childbearing decreases HDL-cholesterol, potentially contributing to the increased risk of CVD in parous women. Large HDL particles (HDL-P) are associated with lower risk of CVD. In this secondary analysis of a randomised controlled trial, we investigated the effects of 12-week dietary and exercise treatments on HDL-P subclass concentration, size and apoA1 in lactating women with overweight/obesity. At 10-14 weeks postpartum, 68 women with pre-pregnant BMI 25-35 kg/m were randomised to four groups using 2 × 2 factorial design: (1) dietary treatment for weight loss; (2) exercise treatment; (3) both treatments and (4) no treatment. Lipoprotein subclass profiling by NMR spectroscopy was performed in serum at randomisation and after 3 and 12 months, and the results analysed with two-way ANCOVA. Lipid concentrations decline naturally postpartum. At 3 months (5-6 months postpartum), both diet ( = 0·003) and exercise ( = 0·008) reduced small HDL-P concentration. Concurrently, exercise limited the decline in very large HDL-P ( = 0·002) and the effect was still significant at 12 months (15 months postpartum) ( = 0·041). At 12 months, diet limited the decline in very large HDL-P ( = 0·005), large HDL-P ( = 0·001) and apoA1 ( = 0·002) as well as HDL size ( = 0·002). The dietary treatment for weight loss and the exercise treatment both showed effects on HDL-P subclasses in lactating women with overweight and obesity possibly associated with lower CVD risk. The dietary treatment had more effects than the exercise treatment at 12 months, likely associated with a 10 % weight loss.
Topics: Pregnancy; Female; Humans; Overweight; Lactation; Obesity; Diet; Weight Loss; Cholesterol, HDL; Cardiovascular Diseases
PubMed: 35067237
DOI: 10.1017/S0007114522000241 -
Nutrients Aug 2019Lifestyle is a well-known environmental factor that plays a major role in facilitating the development of metabolic syndrome or eventually exacerbating its consequences.... (Review)
Review
Lifestyle is a well-known environmental factor that plays a major role in facilitating the development of metabolic syndrome or eventually exacerbating its consequences. Various lifestyle factors, especially changes in dietary habits, extreme temperatures, unusual light-dark cycles, substance abuse, and other stressful factors, are also established modifiers of the endocannabinoid system and its extended version, the endocannabinoidome. The endocannabinoidome is a complex lipid signaling system composed of a plethora (>100) of fatty acid-derived mediators and their receptors and anabolic and catabolic enzymes (>50 proteins) which are deeply involved in the control of energy metabolism and its pathological deviations. A strong link between the endocannabinoidome and another major player in metabolism and dysmetabolism, the gut microbiome, is also emerging. Here, we review several examples of how lifestyle modifications (westernized diets, lack or presence of certain nutritional factors, physical exercise, and the use of cannabis) can modulate the propensity to develop metabolic syndrome by modifying the crosstalk between the endocannabinoidome and the gut microbiome and, hence, how lifestyle interventions can provide new therapies against cardiometabolic risk by ensuring correct functioning of both these systems.
Topics: Animals; Cannabinoids; Diet; Diet, High-Fat; Dietary Fiber; Endocannabinoids; Exercise; Gastrointestinal Microbiome; Humans; Life Style; Metabolic Syndrome; Nutritional Requirements; Receptors, Cannabinoid; Signal Transduction; Vitamin D
PubMed: 31434293
DOI: 10.3390/nu11081956