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A dietary intervention for postmenopausal hot flashes: A potential role of gut microbiome. An exploratory analysis.
Kahleova, H, Holtz, DN, Strom, N, La Reau, A, Kolipaka, S, Schmidt, N, Hata, E, Znayenko-Miller, T, Holubkov, R, Barnard, ND
Complementary therapies in medicine. 2023;79:103002
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Postmenopausal vasomotor symptoms not only lead to discomfort and reduced quality of life but also signal an increased risk of cardiovascular disease and diabetes. Nutrition is an important modifying factor and may be helpful in alleviating vasomotor symptoms. The aim of this study was to test the effects of a low-fat plant-based diet, including daily consumption of soybeans, on the gut microbiome composition, particularly the equol-producing gut bacteria, and their association with changes in postmenopausal vasomotor symptoms. This study was a secondary exploratory analysis of a randomised controlled trial were participants were randomly assigned to the intervention or control group. Results showed that the dietary intervention led to a 95 % reduction in total hot flashes, and a 96 % decrease in moderate-to-severe hot flashes. Daytime and night-time hot flashes were reduced by 96 % and 94 %, respectively. Even though in the intervention group there were significant changes in gut microbiome after 12 weeks, changes in the equol-producing bacteria were not significant. Authors conclude that their findings revealed potential associations between changes in vasomotor symptoms in response to a diet change and changes in the gut microbiome.
Abstract
OBJECTIVE This study examined the role of gut microbiome changes in mediating the effects of a dietary intervention on the frequency and severity of postmenopausal vasomotor symptoms METHODS Postmenopausal women (n = 84) reporting ≥2 moderate-to-severe hot flashes daily were randomly assigned, in 2 successive cohorts, to an intervention including a low-fat, vegan diet and cooked soybeans (½ cup [86 g] daily) or to stay on their usual diet. Over a 12-week period, frequency and severity of hot flashes were recorded with a mobile application. In a subset of 11 women, gut microbiome was analyzed at baseline and after 12 weeks of the dietary intervention (low-fat vegan diet with soybeans), using deep shotgun metagenomic sequencing. Differences in the microbiome between baseline and 12 weeks were assessed by comparing alpha diversity with Wilcoxon signed rank tests, beta diversity with permanovaFL, and taxon abundance with Wilcoxon signed rank tests. Pearson correlations were used to assess the association between changes in hot flashes and gut bacteria. RESULTS In the subset for which microbiome testing was done, total hot flashes decreased by 95 % during the dietary intervention (p = 0.007); severe hot flashes disappeared (from 0.6 to 0.0/day; p = 0.06); and moderate-to-severe hot flashes decreased by 96 % (p = 0.01). Daytime and nighttime hot flashes were reduced by 96 % (p = 0.01) and 94 % (p = 0.004), respectively. Alpha and beta diversity did not significantly differ in the intervention group between baseline and 12 weeks. Two families (Enterobacteriaceae and Veillonellaceae), 5 genera (Erysipelatoclostridium, Fusicatenibacter, Holdemanella, Intestinimonas, and Porphyromonas), and 6 species (Clostridium asparagiforme, Clostridium innocuum, Bacteroides thetaiotaomicron, Fusicatenibacter saccharivorans, Intestinimonas butyriciproducens, Prevotella corporis, and Streptococcus sp.) were differentially abundant, but after correction for multiple comparisons, these differences were no longer significant. Changes in the relative abundance of Porphyromonas and Prevotella corporis were associated with the reduction in severe day hot flashes both unadjusted (r = 0.61; p = 0.047; and r = 0.69; p = 0.02), respectively), and after adjustment for changes in body mass index (r = 0.63; p = 0.049; and r = 0.73; p = 0.02), respectively). Changes in relative abundance of Clostridium asparagiforme were associated with the reduction in total severe hot flashes (r = 0.69; p = 0.019) and severe night hot flashes (r = 0.82; p = 0.002) and the latter association remained significant after adjustment for changes in body mass index (r = 0.75; p = 0.01). CONCLUSIONS This exploratory analysis revealed potential associations between changes in vasomotor symptoms in response to a diet change and changes in the gut microbiome. Larger randomized clinical trials are needed to investigate these findings.
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A dietary intervention for vasomotor symptoms of menopause: a randomized, controlled trial.
Barnard, ND, Kahleova, H, Holtz, DN, Znayenko-Miller, T, Sutton, M, Holubkov, R, Zhao, X, Galandi, S, Setchell, KDR
Menopause (New York, N.Y.). 2023;30(1):80-87
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Postmenopausal vasomotor symptoms cause recurrent discomfort, disrupt sleep, and reduce quality of life. A role for nutritional factors in vasomotor symptoms was suggested by their low prevalence in areas where traditional dietary staples included grains, legumes, vegetables, and other plant-derived foods. The aim of this study was to investigate the effects of a dietary intervention on vasomotor symptoms and menopause-related quality of life. This study is a randomised controlled study. Eighty-four participants were randomly assigned, in two cohorts; the intervention or control group. Results show that the dietary intervention led to clinically important reductions in menopausal symptoms. In fact, there was an 88% reduction in moderate-to-severe vasomotor events among participants in the intervention-group, accompanied by weight loss and improvements in physical, psychosocial, and sexual domains. Authors conclude that a dietary intervention, combining a reduced-fat vegan diet and daily soybeans, was associated with a marked reduction in postmenopausal vasomotor events, significant weight loss, and reductions in physical and sexual symptoms.
Abstract
OBJECTIVE Postmenopausal vasomotor symptoms disrupt quality of life. This study tested the effects of a dietary intervention on vasomotor symptoms and menopause-related quality of life. METHODS Postmenopausal women (n = 84) reporting at least two moderate-to-severe hot flashes daily were randomly assigned, in two successive cohorts, to an intervention including a low-fat, vegan diet and cooked soybeans (½ cup [86 g] daily) or to a control group making no dietary changes. During a 12-week period, a mobile application was used to record hot flashes (frequency and severity), and vasomotor, psychosocial, physical, and sexual symptoms were assessed with the Menopause-Specific Quality of Life questionnaire. Between-group differences were assessed for continuous ( t tests) and binary ( χ2 /McNemar tests) outcomes. In a study subsample, urinary equol was measured after the consumption of ½ cup (86 g) of cooked whole soybeans twice daily for 3 days. RESULTS In the intervention group, moderate-to-severe hot flashes decreased by 88% ( P < 0.001) compared with 34% for the control group ( P < 0.001; between-group P < 0.001). At 12 weeks, 50% of completers in the intervention group reported no moderate-to-severe hot flashes at all. Among controls, there was no change in this variable from baseline ( χ2 test, P < 0.001). Neither seasonality nor equol production status was associated with the degree of improvement. The intervention group reported greater reductions in the Menopause-Specific Quality of Life questionnaire vasomotor ( P = 0.004), physical ( P = 0.01), and sexual ( P = 0.03) domains. CONCLUSIONS A dietary intervention consisting of a plant-based diet, minimizing oils, and daily soybeans significantly reduced the frequency and severity of postmenopausal hot flashes and associated symptoms.
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Nutrition in the prevention and treatment of endometriosis: A review.
Barnard, ND, Holtz, DN, Schmidt, N, Kolipaka, S, Hata, E, Sutton, M, Znayenko-Miller, T, Hazen, ND, Cobb, C, Kahleova, H
Frontiers in nutrition. 2023;:1089891
Abstract
Endometriosis is characterized by the presence of endometrial tissues outside the uterine lining, typically on the external surface of the uterus, the ovaries, fallopian tubes, abdominal wall, or intestines. The prevalence of endometriosis in North America, Australia, and Europe is ~1-5% in women of reproductive age. Treatment options for endometriosis are limited. While over-the-counter medications may be used to reduce acute pain, hormonal treatments are common and may interfere with fertility. In more severe cases, laparoscopic excision procedures and even hysterectomies are used to treat the pain associated with endometriosis. Nutritional interventions may be helpful in the prevention and treatment of endometriosis and associated pain. Reducing dietary fat and increasing dietary fiber have been shown to reduce circulating estrogen concentrations, suggesting a potential benefit for individuals with endometriosis, as it is an estrogen-dependent disease. Meat consumption is associated with greater risk of developing endometriosis. Anti-inflammatory properties of plant-based diets may benefit women with endometriosis. Additionally, seaweed holds estrogen-modulating properties that have benefitted postmenopausal women and offers potential to reduce estradiol concentrations in pre-menopausal women. Furthermore, consumption of vitamin D has been shown to reduce endometrial pain via increased antioxidant capacity and supplementation with vitamins C and E significantly reduced endometriosis symptoms, compared with placebo. More randomized clinical trials are needed to elucidate the role of diet in endometriosis.
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Dietary advanced glycation end-products and postmenopausal hot flashes: A post-hoc analysis of a 12-week randomized clinical trial.
Kahleova, H, Znayenko-Miller, T, Uribarri, J, Schmidt, N, Kolipaka, S, Hata, E, Holtz, DN, Sutton, M, Holubkov, R, Barnard, ND
Maturitas. 2023;:32-38
Abstract
OBJECTIVE Postmenopausal hot flashes are associated with an increased risk of cardiovascular disease and diabetes. Because dietary advanced glycation end-products (AGEs) may act as endocrine disruptors, this study examined the potential association of modifications to the intake of dietary AGEs with the frequency and severity of postmenopausal hot flashes. METHODS Postmenopausal women (n = 84) reporting ≥2 moderate-to-severe hot flashes daily were randomly assigned to either the intervention group or the control group. The former were asked to follow a low-fat, vegan diet, including cooked soybeans (1/2 cup [86 g]/day) for 12 weeks, and the latter continued their usual diets for 12 weeks. Frequency and severity of hot flashes were recorded with a mobile application. Three-day diet records were analyzed using the Nutrition Data System for Research software and dietary AGEs were estimated, using a database. Seventy-one participants completed the whole study and 63 provided complete hot flash and dietary data for the AGEs analysis (n = 31 in the intervention and n = 24 in the control group). Pearson correlations were used to assess the association between changes in hot flashes and dietary AGEs. RESULTS Dietary AGEs decreased in the intervention group by 73 %, that is by 5509 ku/day on average (95 % -7009 to -4009; p < 0.001), compared with the control group (+458; 95 % CI -835 to +1751; p = 0.47; treatment effect -5968 ku/day [95 % CI -7945 to -3991]; Gxt, p < 0.001). Severe hot flashes decreased by 92 % (p < 0.001) and moderate-to-severe hot flashes decreased by 88 % in the intervention group (p < 0.001). Changes in dietary AGEs correlated with changes in severe (r = +0.39; p = 0.002) and moderate hot flashes (r = +0.34; p = 0.009) and remained significant after adjustment for changes in energy intake (r = +0.45; p < 0.001; and r = +0.37; p = 0.004, respectively) and changes in body mass index (r = +0.37; p = 0.004; and r = +0.27; p = 0.04, respectively). The reduction in dietary AGEs required to achieve a predicted reduction in hot flashes by 1/day was 6933 ku/day for severe and 4366 ku/day for moderate-to-severe hot flashes. CONCLUSIONS The reduction in dietary AGEs with a low-fat plant-based diet was associated with a significant reduction in the frequency of severe and moderate-to-severe postmenopausal hot flashes, independent of changes in energy intake and weight loss. Plant-based diets could be used not only to alleviate vasomotor symptoms in postmenopausal women, but also to reduce other health risks associated with AGEs. TRIAL REGISTRATION ClinicalTrials.gov, NCT04587154.
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Not all very-low-carbohydrate diets are created equal. Reply to Conte C, Camajani E, Lai A, Caprio M [letter].
Reynolds, AN, Kahleova, H, Uusitupa, M, Hermansen, K, Aas, AM, Schwab, U, Lean, MEJ, Pfeiffer, A, Salas-Salvadó, J, Mann, JI
Diabetologia. 2023;(9):1754-1755
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Can a plant-based diet help mitigate Covid-19?
Kahleova, H, Barnard, ND
European journal of clinical nutrition. 2022;(7):911-912
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A Mediterranean Diet and Low-Fat Vegan Diet to Improve Body Weight and Cardiometabolic Risk Factors: A Randomized, Cross-over Trial.
Barnard, ND, Alwarith, J, Rembert, E, Brandon, L, Nguyen, M, Goergen, A, Horne, T, do Nascimento, GF, Lakkadi, K, Tura, A, et al
Journal of the American Nutrition Association. 2022;(2):127-139
Abstract
Objective: Evidence suggests that both Mediterranean and vegan diets improve body weight and cardiometabolic risk factors, but their relative efficacy has not been compared in a randomized trial.Methods: In a randomized crossover trial, 62 overweight adults were randomly assigned to a Mediterranean or vegan diet for a 16-week period. Body weight, plasma lipids, blood pressure, and body composition (dual X-ray absorptiometry) were measured. Secondary measures included insulin resistance (Homeostasis Model Assessment, HOMA-IR), oral glucose insulin sensitivity (OGIS), and predicted insulin sensitivity (PREDIM) indices. Thereafter, participants were asked to return to their baseline diets for 4 weeks, after which they began the opposite diet for 16 weeks. The same parameters were measured before and after this 2nd 16-week period.Results: Overall net weight changes were 0.0 (Mediterranean) and -6.0 kg (vegan), (treatment effect -6.0 kg [95% CI -7.5 to -4.5]; p < 0.001). HOMA-IR decreased and OGIS increased on the vegan diet with no significant change on the Mediterranean diet (treatment effect -0.7 [95% CI, -1.8 to +0.4]; p = 0.21; and +35.8 mL/min/m2 [95% CI, +13.2 to +58.3]; p = 0.003, respectively). PREDIM did not change significantly in either group. Among participants with no medication changes, total and LDL-cholesterol decreased 18.7 mg/dL (0.5 mmol/L) and 15.3 mg/dL (0.4 mmol/L), respectively, on the vegan diet, compared with no significant change on the Mediterranean diet (treatment effect -15.6 [-24.6 to -6.6]; p = 0.001 and -14.8 [-23.5 to -6.2]; p = 0.001, respectively); systolic and diastolic blood pressure decreased 9.3 and 7.3 mmHg on the Mediterranean diet, compared with 3.4 and 4.1 mmHg on the vegan diet (treatment effect +5.9 [95% CI +1.0 to +10.9]; p = 0.02; and +1.8 [95% CI -4.6 to +8.1]; p = 0.58, respectively).Conclusions: A low-fat vegan diet improved body weight, lipid concentrations, and insulin sensitivity, both from baseline and compared with a Mediterranean diet. Blood pressure decreased on both diets, more on the Mediterranean diet.Clinical trial registration: ClinicalTrials.gov number, NCT03698955 https://clinicaltrials.gov/ct2/show/NCT03698955?term=NCT03698955&draw=2&rank=1.
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Temporal Patterns of Glucagon and Its Relationships with Glucose and Insulin following Ingestion of Different Classes of Macronutrients.
Göbl, C, Morettini, M, Salvatori, B, Alsalim, W, Kahleova, H, Ahrén, B, Tura, A
Nutrients. 2022;(2)
Abstract
BACKGROUND glucagon secretion and inhibition should be mainly determined by glucose and insulin levels, but the relative relevance of each factor is not clarified, especially following ingestion of different macronutrients. We aimed to investigate the associations between plasma glucagon, glucose, and insulin after ingestion of single macronutrients or mixed-meal. METHODS thirty-six participants underwent four metabolic tests, based on administration of glucose, protein, fat, or mixed-meal. Glucagon, glucose, insulin, and C-peptide were measured at fasting and for 300 min following food ingestion. We analyzed relationships between time samples of glucagon, glucose, and insulin in each individual, as well as between suprabasal area-under-the-curve of the same variables (ΔAUCGLUCA, ΔAUCGLU, ΔAUCINS) over the whole participants' cohort. RESULTS in individuals, time samples of glucagon and glucose were related in only 26 cases (18 direct, 8 inverse relationships), whereas relationship with insulin was more frequent (60 and 5, p < 0.0001). The frequency of significant relationships was different among tests, especially for direct relationships (p ≤ 0.006). In the whole cohort, ΔAUCGLUCA was weakly related to ΔAUCGLU (p ≤ 0.02), but not to ΔAUCINS, though basal insulin secretion emerged as possible covariate. CONCLUSIONS glucose and insulin are not general and exclusive determinants of glucagon secretion/inhibition after mixed-meal or macronutrients ingestion.
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A plant-based meal reduces postprandial oxidative and dicarbonyl stress in men with diabetes or obesity compared with an energy- and macronutrient-matched conventional meal in a randomized crossover study.
Malinska, H, Klementová, M, Kudlackova, M, Veleba, J, Hoskova, E, Oliyarnyk, O, Markova, I, Thieme, L, Hill, M, Pelikanova, T, et al
Nutrition & metabolism. 2021;(1):84
Abstract
BACKGROUND Increased oxidative/dicarbonyl stress and chronic inflammation are considered key pathophysiological mediators in the progression of complications in obesity and type 2 diabetes (T2D). Lifestyle and diet composition have a major impact. In this study, we tested the effects of a vegan (V) and a conventional meat containg (M) meal, matched for energy and macronutrients, on postprandial oxidative and dicarbonyl stress, inflammatory markers and appetite hormones. METHODS A randomised crossover design was used to evaluate T2D, obese with normal glucose tolerance and control participants (n = 20 in each group), with serum concentrations of analytes determined at 0, 120 and 180 min. Repeated-measures ANOVA was used for statistical analysis. RESULTS In T2D subjects, we observed decreased postprandial concentrations of oxidised glutathione (p ˂ 0.001) and increased glutathione peroxidase activity (p = 0.045) after the V-meal consumption, compared with the M-meal. In obese participants, V-meal consumption increased postprandial concentrations of reduced glutathione (p = 0.041) and decreased methylglyoxal concentrations (p = 0.023). There were no differences in postprandial secretion of TNFα, MCP-1 or ghrelin in T2D or obese men, but we did observe higher postprandial secretion of leptin after the V-meal in T2D men (p = 0.002) compared with the M-meal. CONCLUSIONS The results show that a plant-based meal is efficient in ameliorating the postprandial oxidative and dicarbonyl stress compared to a conventional energy- and macronutrient-matched meal, indicating the therapeutic potential of plant-based nutrition in improving the progression of complications in T2D and obese patients. Registered under ClinicalTrials.gov Identifier No. NCT02474147.
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A plant-based meal affects thalamus perfusion differently than an energy- and macronutrient-matched conventional meal in men with type 2 diabetes, overweight/obese, and healthy men: A three-group randomized crossover study.
Kahleova, H, Tintera, J, Thieme, L, Veleba, J, Klementova, M, Kudlackova, M, Malinska, H, Oliyarnyk, O, Markova, I, Haluzik, M, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1822-1833
Abstract
BACKGROUND & AIMS Reward circuitry in the brain plays a key role in weight regulation. We tested the effects of a plant-based meal on these brain regions. METHODS A randomized crossover design was used to test the effects of two energy- and macronutrient-matched meals: a vegan (V-meal) and a conventional meat (M-meal) on brain activity, gastrointestinal hormones, and satiety in participants with type 2 diabetes (T2D; n = 20), overweight/obese participants (O; n = 20), and healthy controls (H; n = 20). Brain perfusion was measured, using arterial spin labeling functional brain imaging; satiety was assessed using a visual analogue scale; and plasma concentrations of gut hormones were determined at 0 and 180 min. Repeated-measures ANOVA was used for statistical analysis. Bonferroni correction for multiple comparisons was applied. The Hedge's g statistic was used to measure the effect size for means of paired difference between the times (180-0 min) and meal types (M-V meal) for each group. RESULTS Thalamus perfusion was the highest in patients with T2D and the lowest in overweight/obese individuals (p = 0.001). Thalamus perfusion decreased significantly after ingestion of the M-meal in men with T2D (p = 0.04) and overweight/obese men (p = 0.004), and it decreased significantly after ingestion of the V-meal in healthy controls (p < 0.001; Group x Meal x Time: F = 3.4; p = 0.035). The effect size was -0.41 (95% CI, -1.14 to 0.31; p = 0.26) for men with diabetes; -0.72 (95% CI, -1.48 to 0.01; p = 0.05) for overweight/obese men; and 0.82 (95% CI, 0.09 to 1.59; p = 0.03) for healthy men. Postprandial secretion of active GLP-1 increased after the V-meal compared with the M-meal by 42% (95% CI 25-62%; p = 0.003) in men with T2D and by 41% (95% CI 24-61%; p = 0.002) in healthy controls. Changes in thalamus perfusion after ingestion of both test meals correlated with changes in satiety (r = +0.68; p < 0.01), fasting plasma insulin (r = +0.40; p < 0.01), C-peptide (r = +0.48; p < 0.01) and amylin (r = +0.55; p < 0.01), and insulin secretion at 5 mmol/l (r = +0.77; p < 0.05). CONCLUSIONS The higher postprandial GLP-1 secretion after the V-meal in men with T2D, with concomitant greater satiety and changes in thalamus perfusion, suggest a potential use of plant-based meals in addressing the key pathophysiologic mechanisms of food intake regulation. Trial registration ClinicalTrials.gov number, NCT02474147.