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Mixed Tree Nuts, Cognition, and Gut Microbiota: A 4-Week, Placebo-Controlled, Randomized Crossover Trial in Healthy Nonelderly Adults.
Haskell-Ramsay, CF, Dodd, FL, Smith, D, Cuthbertson, L, Nelson, A, Lodge, JK, Jackson, PA
The Journal of nutrition. 2023;152(12):2778-2788
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Cognitive impairment is a growing worldwide health concern as our population ages. In the absence of effective pharmaceutical treatments, modifiable lifestyle factors such as nutrition represent crucial targets in preventing cognitive decline. The aim of this study was to investigate the cognitive and mood effects of mixed tree nut supplementation in healthy non-elderly adults aged 18 to 49 years. This study is a randomised, placebo-controlled, double-blind, counterbalanced crossover design. Participants (n = 81) were randomly assigned to one of the two groups; the treatment or placebo group. Results showed that nut consumption led to improved picture recognition in terms of increased accuracy and faster reaction time. Furthermore, there was an enrichment of an unclassified type of bacterial community (Lachnospiraceae) but limited changes to the urinary metabolome. On the other hand, supplementation with mixed nuts failed to evince effects on mood. Authors conclude by pointing out that their findings are attributed to a sample of healthy and nonelderly participants. Thus, more profound effects may be shown with higher quantities of nuts or in those at risk, such as those experiencing cognitive decline or in those suffering gut dysbiosis.
Abstract
BACKGROUND Beneficial effects of nut supplementation on cognitive function have previously been demonstrated in young and older adults. Alterations to gut microbiota have also been shown following tree nut consumption. However, no data exists on the effects of nuts on cognition and intestinal microbial communities assessed within the same study. OBJECTIVES The study aimed to examine the effects of daily consumption of tree nuts for 4 wk on cognitive function (primary outcome), mood, metabolomics, and gut microbial species (secondary outcomes) in healthy, nonelderly adults. METHODS This randomized, placebo-controlled, double-blind, counterbalanced crossover study assessed the effects of 4 wk of supplementation with 30 g/d mixed tree nuts versus placebo on cognition and mood in 79 healthy adults aged 18-49 y. Metabolic responses, gut bacterial community structure, and the potential for these to impact cognition were explored using a multi-omic approach. Bacterial community analysis was conducted in Quantitative Insights Into Microbial Ecology 2 (QIIME2). RESULTS Mixed model analysis indicated that nut consumption led to significant improvements to accuracy (placebo M = 92.2% compared with NUTS M = 94.5%; P = 0.019) and speed of response (placebo M = 788 ms compared with NUTS M = 757 ms; P = 0.004) on a picture recognition task. No significant changes to bacterial community α or β diversity were observed when comparing nut consumption to the placebo arm. However, an unclassified Lachnospiraceae amplicon sequence variant (ASV) was significantly enriched in participants when supplemented with nuts (P = 0.015). No correlations were observed between the changes to picture recognition and the changes to the unclassified Lachnospiraceae ASV. There were no significant changes to the urinary metabolome. CONCLUSIONS These findings indicate a positive effect of nut on cognition following only 4 wk of consumption in a healthy nonelderly sample, as well as upregulation of a microbial taxa associated with gut health. The effects appear to be independent of one another, but further exploration is required in those experiencing cognitive decline and/or gut dysbiosis.
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The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial.
Yaskolka Meir, A, Keller, M, Hoffmann, A, Rinott, E, Tsaban, G, Kaplan, A, Zelicha, H, Hagemann, T, Ceglarek, U, Isermann, B, et al
BMC medicine. 2023;21(1):364
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Biological age differs from chronological age and is determined by assessing our DNA, this is known as mAge. A healthy lifestyle and weight loss have been shown to be of benefit to mAge. The Mediterranean (MED) diet includes ingredients such as vitamins and naturally occurring chemicals, known as polyphenols, which may alter biological age. This randomised control trial of 256 aimed to determine the effects of a MED diet richer in green vegetables and lower in meat (Green-MED) compared to the MED diet and recommendations for healthy eating. The results showed that after 18 months of healthy eating and weight loss, none of the diets was able to lower the biological age, however the Green-MED diet and in particular the intake of green tea and the vegetable Mankai were associated with slower biological ageing compared to the other two diets. The polyphenol tyrosol was also associated with slower biological ageing. It was concluded that the diets were unable to reverse biological ageing, but a GreenMed diet rich in polyphenols, may be able to slow it. This study could be used by healthcare professionals to understand that as higher biological age is associated with poorer health outcomes, a diet rich in polyphenols may have additional benefits beyond just weight loss.
Abstract
BACKGROUND Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined. METHODS We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3-4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight). RESULTS Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e - 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = - 0.41, p = 0.004 and beta = - 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = - 1.8; p = 0.061) and green tea (beta = - 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02). CONCLUSIONS This study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging. To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging. TRIAL REGISTRATION ClinicalTrials.gov, NCT03020186.
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Wild blueberry (poly)phenols can improve vascular function and cognitive performance in healthy older individuals: a double-blind randomized controlled trial.
Wood, E, Hein, S, Mesnage, R, Fernandes, F, Abhayaratne, N, Xu, Y, Zhang, Z, Bell, L, Williams, C, Rodriguez-Mateos, A
The American journal of clinical nutrition. 2023;117(6):1306-1319
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The risk of developing both cardiovascular and neurodegenerative diseases increases with aging. Growing evidence from epidemiological and human intervention trials indicates that (poly)phenols may have cardioprotective properties as well as the ability to improve cognitive function. The aim of this study was to investigate the effects of daily wild blueberry (WBB) (poly)phenol consumption on vascular function and cognitive performance in healthy older individuals. This study was a randomised, double-blinded, placebo-controlled parallel design study. A total of 61 healthy older individuals were recruited and randomly assigned to one of the two arms; placebo intervention or blueberry intervention group. Results showed that long-term consumption of a dietary achievable amount of WBB enhanced vascular and cognitive function in older adults. Authors conclude that gut microbiota and vascular blood flow may play important roles in mediating the cognitive benefits shown by the consumption of (poly)phenol-rich foods.
Abstract
BACKGROUND Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown. METHODS A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography-mass spectrometry. RESULTS A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P < 0.001; -3.59 mmHg; 95% CI: -6.95, -0.23, P = 0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task was also found following WBB treatment compared with placebo (P < 0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared with placebo. No changes in the CBF or gut microbiota composition were found. CONCLUSIONS Daily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function and decreases 24 h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future CVD risk in an older population and may improve episodic memory processes and executive functioning in older adults at risk for cognitive decline. Clinical Trial Registration number in clinicaltrials.gov: NCT04084457.
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A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study.
Vauzour, D, Scholey, A, White, DJ, Cohen, NJ, Cassidy, A, Gillings, R, Irvine, MA, Kay, CD, Kim, M, King, R, et al
The American journal of clinical nutrition. 2023;118(2):369-381
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At a population level, interventions that delay the onset of dementia by 2 years are predicted to reduce the number of dementia patients by 20%. Prospective cohort studies have consistently reported cognitive and neurophysiological benefits of the fish-derived omega-3 long-chain polyunsaturated fatty acids (PUFAs), EPA, and DHA and plant-derived flavanols (FLAVs). This study hypothesised that 12-month administration of a combination of 500 mg cocoa FLAVs with 1.5g omega-3 long-chain PUFAs would improve cognitive function in a mixed subjective cognitive impairment and mild cognitive impairment cohort. This study is based on the results of the CANN randomised controlled trial. A total of 258 participants were recruited and randomised to control or test intervention. Following baseline measurements, 125 participants were randomised into the active OM3FLAV intervention group and 121 into the control group. Results showed that the 1-year intervention with EPA and DHA and cocoa FLAVs did not improve cognition or protect the brain against atrophy in older adults with evidence of memory deficits. Authors concluded that given the complexity of neuropathological processes underpinning cognitive decline and dementia risk, multidomain, multinutrient, or whole diet approaches may be needed to positively impact the cognitive trajectory in the medium term (months to 3 years).
Abstract
BACKGROUND There is evidence that both omega-3 long-chain polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and cocoa flavanols can improve cognitive performance in both healthy individuals and in those with memory complaints. However, their combined effect is unknown. OBJECTIVES To investigate the combined effect of EPA/DHA and cocoa flavanols (OM3FLAV) on cognitive performance and brain structures in older adults with memory complaints. METHODS A randomized placebo-controlled trial of DHA-rich fish oil (providing 1.1 g/d DHA and 0.4 g/d EPA) and a flavanol-rich dark chocolate (providing 500 mg/d flavan-3-ols) was conducted in 259 older adults with either subjective cognitive impairment or mild cognitive impairment. Participants underwent assessment at baseline, 3 mo, and 12 mo. The primary outcome was the number of false-positives on a picture recognition task from the Cognitive Drug Research computerized assessment battery. Secondary outcomes included other cognition and mood outcomes, plasma lipids, brain-derived neurotrophic factor (BDNF), and glucose levels. A subset of 110 participants underwent structural neuroimaging at baseline and at 12 mo. RESULTS 197 participants completed the study. The combined intervention had no significant effect on any cognitive outcomes, with the exception of reaction time variability (P = 0.007), alertness (P < 0.001), and executive function (P < 0.001), with a decline in function observed in the OM3FLAV group (118.6 [SD 25.3] at baseline versus 113.3 [SD 25.4] at 12 mo for executive function) relative to the control, and an associated decrease in cortical volume (P = 0.039). Compared with the control group, OM3FLAV increased plasma HDL, total cholesterol ratio (P < 0.001), and glucose (P = 0.008) and reduced TG concentrations (P < 0.001) by 3 mo, which were sustained to 12 mo, with no effect on BDNF. Changes in plasma EPA and DHA and urinary flavonoid metabolite concentrations confirmed compliance to the intervention. CONCLUSIONS These results suggest that cosupplementation with ω-3 PUFAs and cocoa flavanols for 12 mo does not improve cognitive outcomes in those with cognitive impairment. This trial was registered at clinicaltrials.gov as NCT02525198.
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A 2-yr Randomized Controlled Trial on Creatine Supplementation during Exercise for Postmenopausal Bone Health.
Chilibeck, PD, Candow, DG, Gordon, JJ, Duff, WRD, Mason, R, Shaw, K, Taylor-Gjevre, R, Nair, B, Zello, GA
Medicine and science in sports and exercise. 2023;55(10):1750-1760
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Osteoporosis is a bone disease that gradually develops when bone mineral density (BMD) or bone mass decreases and the quality of bone is impaired. This randomised controlled trial conducted over 2 years wanted to test the effects of creatine monohydrate supplementation on BMD at several bone sites during a supervised resistance training and walking program in post menopausal women. 120 were randomly allocated to creatine and 117 to placebo. All participants received a daily supplement of 500 mg of calcium and 10 μg -400 IU of vitamin D. The researchers were particularly interested in finding out whether the creatine group showed improved (BMD) at the femoral neck, lower spine and upper thigh bone also known as the proximal femur which connects the hip joint. Bone density scans, dual-energy X-ray’s and ultrasounds were used to measure BMD and assess areas of bone. Falls and fractures were recorded for a total of 3 years. Dietary intake and physical activity outside of study requirements was assessed using food frequency and exercise questionnaires. Fasting blood and urine analyses along with 24-h urine analysis were taken. The authors conclude that creatine supplementation during a resistance training and walking program had no effect on BMD at the femoral neck, total hip, or lower spine. They further acknowledge relatively low compliance with the creatine supplements, and exercise protocols, along with a high drop out rate. Further studies of larger sample sizes are needed.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Creatine supplementation may have beneficial effects on bone geometry at the proximal femur when combined with a resistance training program and walking programme in postmenopausal women.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This study aimed to determine the effects of creatine monohydrate supplementation and exercise on femoral neck bone mineral density (BMD), lumbar spine BMD and proximal femur geometric properties in postmenopausal women over 2 years.
Methods
- 237 postmenopausal women (mean age, 59 yr) were randomised into 2 groups across 2 sites.
- Participant inclusion criteria: no menstrual period for 2 years, and considered at “low” and “moderate” risk of fracture.
- Treatment group (n=120) received creatine monohydrate (0.14 g/kg−1 per day−1 mixed with 0.14 g·kg−1·d−1 maltodextrin) and supervised resistance training plus partially supervised walking.
- Placebo group (n=117) received 0.28 g·kg−1·d−1 maltodextrin and supervised resistance training plus partially supervised walking.
- All participants also received 500 mg of calcium and 10 μg (400 IU) of vitamin D per day.
- Resistance exercises and 20-30 mins of brisk walking were performed in-lab and supervised 3 days per week. 3 days of non- supervised 20-30 mins of brisk walking was undertaken outside of the lab.
Results
- Creatine monohydrate supplementation combined with resistance training and walking over 2 yr: i) had no effect on BMD at the femoral neck (P < 0.0001), total hip (P < 0.0001), or lumbar spine (P= 0.003); ii) increased lean tissue mass compared with placebo (P = 0.046); iii) preserved a number of geometric properties and may therefore help to maintain bone bending strength and cortical bending under compressive loads.
- The authors speculated that creatine supplementation stimulates remodeling of bone to alter geometric properties and whether bone formation or resorption predominates depends on the location of bone in the proximal femur.
Conclusion
- 2 years of creatine supplementation with resistance training and walking in postmenopausal women had no beneficial effects on BMD but did improve the proximal femur cortical thickness and section modulus bone geometry, and reduced SPW and buckling ratio that may be protective against hip fracture.
Adverse Events: The dose of creatine over 2 years resulted in minimal adverse events.
Limitation: Low compliance at 56%, and high attrition within the groups: creatine (n=86 of n=120) and placebo (n=88 of n=117) , 61% compliance for exercise sessions completed.
Clinical practice applications:
Creatine supplementation is effective for increasing lean tissue mass when combined with resistance training that may allow for increased mechanical stress on bone, stimulating a net bone formation.
Considerations for future research:
- Assess the mechanism of action of creatine supplementation on BMD.
- Longer term follow-up with larger sample sizes would be needed to confirm protection against hip fracture with creatine supplementation.
Abstract
PURPOSE Our purpose was to examine the effects of 2 yr of creatine monohydrate supplementation and exercise on bone health in postmenopausal women. METHODS Two hundred and thirty-seven postmenopausal women (mean age, 59 yr) were randomized to receive creatine (0.14 g·kg -1 ·d -1 ) or placebo during a resistance training (3 d·wk -1 ) and walking (6 d·wk -1 ) program for 2 yr. Our primary outcome was the femoral neck bone mineral density (BMD), with lumbar spine BMD and proximal femur geometric properties as the secondary outcomes. RESULTS Compared with placebo, creatine supplementation had no effect on BMD of the femoral neck (creatine: 0.725 ± 0.110 to 0.712 ± 0.100 g·cm -2 ; placebo: 0.721 ± 0.102 to 0.706 ± 0.097 g·cm -2 ), total hip (creatine: 0.879 ± 0.118 to 0.872 ± 0.114 g·cm -2 ; placebo: 0.881 ± 0.111 to 0.873 ± 0.109 g·cm -2 ), or lumbar spine (creatine: 0.932 ± 0.133 to 0.925 ± 0.131 g·cm -2 ; placebo: 0.923 ± 0.145 to 0.915 ± 0.143 g·cm -2 ). Creatine significantly maintained section modulus (1.35 ± 0.29 to 1.34 ± 0.26 vs 1.34 ± 0.25 to 1.28 ± 0.23 cm 3 (placebo), P = 0.0011), predictive of bone bending strength, and buckling ratio (10.8 ± 2.6 to 11.1 ± 2.2 vs 11.0 ± 2.6 to 11.6 ± 2.7 (placebo), P = 0.011), predictive of reduced cortical bending under compressive loads, at the narrow part of the femoral neck. Creatine reduced walking time over 80 m (48.6 ± 5.6 to 47.1 ± 5.4 vs 48.3 ± 4.5 to 48.2 ± 4.9 s (placebo), P = 0.0008) but had no effect on muscular strength (i.e., one-repetition maximum) during bench press (32.1 ± 12.7 to 42.6 ± 14.1 vs 30.6 ± 10.9 to 41.4 ± 14 kg (placebo)) and hack squat (57.6 ± 21.6 to 84.4 ± 28.1 vs 56.6 ± 24.0 to 82.7 ± 25.0 kg (placebo)). In the subanalysis of valid completers, creatine increased lean tissue mass compared with placebo (40.8 ± 5.7 to 43.1 ± 5.9 vs 40.4 ± 5.3 to 42.0 ± 5.2 kg (placebo), P = 0.046). CONCLUSIONS Two years of creatine supplementation and exercise in postmenopausal women had no effect on BMD; yet, it improved some bone geometric properties at the proximal femur.
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Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial.
Thomsen, MN, Skytte, MJ, Samkani, A, Carl, MH, Weber, P, Astrup, A, Chabanova, E, Fenger, M, Frystyk, J, Hartmann, B, et al
Diabetologia. 2022;65(3):506-517
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The carbohydrate restricted diet has been shown to be beneficial for Type 2 diabetes (T2D) management and reducing cardiovascular disease risk. This open-label, parallel randomised controlled trial involved Type 2 diabetic patients taking antidiabetic medications who restricted their energy intake by following either a carbohydrate-reduced high protein diet or a conventional diabetic diet. Participants in both groups had a 5.9% reduction in body weight, similar changes in fasting NEFA, apoB, apoA-1, total cholesterol, LDL-cholesterol, HDL-cholesterol, and non-HDL cholesterol, and a significant reduction in fasting glucose, insulin, C-peptide, and HOMA2-IR after 6 weeks of intervention. Carbohydrate-reduced high protein diet group showed a greater reduction in HbA1c and diurnal mean glucose, glycaemic variability, fasting triacylglycerol concentration and liver fat content. Carbohydrate-reduced high protein diet caused an adverse reaction in some patients, and those following a carbohydrate-reduced high protein diet excreted more urea than those eating a conventional diabetic diet. To confirm the results of this study, long-term robust studies are needed. This study can assist healthcare professionals in understanding the benefits of following a carbohydrate-reduced high protein diet in improving glycaemic control, triglyceride levels, and reducing body weight in Type 2 diabetes patients.
Abstract
AIMS/HYPOTHESIS Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes. METHODS This open-label, parallel RCT included adults with type 2 diabetes, HbA1c 48-97 mmol/mol (6.5-11%), BMI >25 kg/m2, eGFR >30 ml min-1 [1.73 m]-2 and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev). RESULTS Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m2 were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA1c (mean [95% CI] -1.9 [-3.5, -0.3] mmol/mol [-0.18 (-0.32, -0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] -0.8 [-1.2, -0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] -4.1 [-5.9, -2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] -18 [-29, -6]%, p < 0.01) and liver fat content (by mean [95% CI] -26 [-45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets. CONCLUSIONS/INTERPRETATION Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies. TRIAL REGISTRATION ClinicalTrials.gov NCT03814694. FUNDING The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg.
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The effects of Aronia berry (poly)phenol supplementation on arterial function and the gut microbiome in middle aged men and women: Results from a randomized controlled trial.
Le Sayec, M, Xu, Y, Laiola, M, Gallego, FA, Katsikioti, D, Durbidge, C, Kivisild, U, Armes, S, Lecomte, M, Fança-Berthon, P, et al
Clinical nutrition (Edinburgh, Scotland). 2022;41(11):2549-2561
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Over the last decades, Aronia melanocarpa, or black chokeberry, has gained increased attention for its high content of (poly)phenols, and potential protection against chronic diseases such as cardiovascular disease and diabetes. The aim of this study was to investigate the effects of 12-week aronia berry (poly)phenol consumption on cardiometabolic health and gut microbiome composition in prehypertensive middle-aged adults. This study was a 2-arm, double-blind, parallel randomised controlled trial. Participants (n = 102; 47 men and 55 women) were assigned randomly to Aronia or control groups. Results showed that there were no significant effects in blood pressure (primary outcome), endothelial function or blood lipids. However, there was a significant improvement in 24-hour ambulatory arterial indices and significant changes in gut microbiome richness, functions and composition between Aronia and control groups. Authors conclude that future studies should be conducted to investigate whether aronia supplementation may be effective in other at-risk populations such as hypertensives or people with cardiovascular disease risk.
Abstract
BACKGROUND AND AIMS Berry (poly)phenol consumption has been associated with cardioprotective benefits, however little is known on the role the gut microbiome may play on such health benefits. Our objective was to investigate the effects of aronia berry (poly)phenol consumption on cardiometabolic health and gut microbiome richness and composition in prehypertensive middle-aged men and women. METHODS A total of 102 prehypertensive participants were included in a parallel 12-week randomized double-blind placebo-controlled trial. Volunteers were randomly allocated to daily consume an encapsulated (poly)phenol-rich aronia berry extract (Aronia, n = 51) or a matched maltodextrin placebo (Control, n = 51). Blood pressure (BP) and arterial function (office and 24 h), endothelial function (measured as flow-mediated dilation), serum biochemistry (including blood lipids), plasma and urine (poly)phenol metabolites as well as gut microbiome composition through shotgun metagenomic sequencing were monitored over the study period. Relationships between vascular outcomes, (poly)phenol metabolites and gut microbiome were investigated using an integrated multi-levels approach. RESULTS A significant improvement in arterial indices measured as augmentation index (AIx) and pulse wave velocity (PWV) was found in the Aronia compared to Control group (awake Δ PWV = -0.24 m/s; 95% CI: -0.79, -0.01 m/s, P < 0.05; 24 h peripheral Δ AIx = -6.8; -11.2, -2.3, %, P = 0.003; 24 h central Δ AIx = -3.3; -5.5, -1.0, %, P = 0.006). No changes in BP, endothelial function or blood lipids were found following the intervention. Consumption of aronia (poly)phenols led to a significant increase in gut microbiome gene richness and in the abundance of butyrate-producing species such as Lawsonibacter asaccharolyticus and Intestinimonas butyriciproducens species, compared to Control group. Results from an approach including metabolomic, metagenomic and clinical outcomes highlighted associations between aronia-derived phenolic metabolites, arterial stiffness, and gut microbiome. CONCLUSIONS Aronia berry (poly)phenol consumption improved arterial function in prehypertensive middle-aged individuals, possibly via modulation of gut microbiome richness and composition based on the associations observed between these parameters. CLINICAL TRIAL REGISTRY The National Institutes of Health (NIH)-randomized trial records held on the NIH ClinicalTrials.gov website (NCT03434574). Aronia Berry Consumption on Blood Pressure.
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Fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), but not gluten, elicit modest symptoms of irritable bowel syndrome: a double-blind, placebo-controlled, randomized three-way crossover trial.
Nordin, E, Brunius, C, Landberg, R, Hellström, PM
The American journal of clinical nutrition. 2022;115(2):344-352
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Irritable bowel syndrome (IBS) is a chronic functional bowel disorder that is characterised by recurring abdominal pain over ≥3 months within a 6-month period in association with altered bowel habits. Symptomatic treatment of IBS includes dietary adaptation, with a focus on prebiotics, probiotics, gluten, and fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). The main aim of this study was to investigate the effects of weeklong interventions with high intakes of a wide range of FODMAPs, gluten, or a nonfermentable placebo in subjects with moderate to severe IBS. This study is a double-blind, placebo-controlled, randomised 3-way study with triple crossover design. One-hundred and ten participants were enrolled and randomly assigned for the study. Results show that a mixture of widely consumed FODMAPs caused only modest worsening of gastrointestinal symptoms compared with gluten and placebo. Authors conclude that there were interindividual variability in the intervention responses. Thus, future studies should investigate these differences to understand possible underlying disease mechanisms.
Abstract
BACKGROUND Irritable bowel syndrome (IBS) has been associated with diets rich in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), and gluten. Most previous studies have been single-blind and have focused on the elimination of FODMAPs or provocation with single FODMAPs. The effect of gluten is unclear, large trials isolating the effect of gluten from that of FODMAPs are needed. OBJECTIVES The aims of this study were to ensure high intakes of a wide range of FODMAPs, gluten, or placebo, and to evaluate the effects on IBS symptoms using the IBS-severity scoring system (IBS-SSS). METHODS The study was carried out with a double-blind, placebo-controlled, randomized 3-way crossover design in a clinical facility in Uppsala from September 2018 to June 2019. In all, 110 participants fulfilling the IBS Rome IV criteria, with moderate to severe IBS, were randomly assigned; 103 (90 female, 13 male) completed the trial. Throughout, IBS participants maintained a diet with minimal FODMAP content and no gluten. Participants were block-randomly assigned to 1-wk interventions with FODMAPs (50 g/d), gluten (17.3 g/d), or placebo, separated by 1-wk washout. All participants who completed ≥1 intervention were included in the intention-to-treat analysis. RESULTS In participants with IBS (n = 103), FODMAPs caused higher IBS-SSS scores (mean 240 [95% CI: 222, 257]) than placebo (198 [180, 215]; P = 0.00056) or gluten (208 [190, 226]; P = 0.013); no differences were found between the placebo and gluten groups (P = 1.0). There were large interindividual differences in IBS-SSS scores associated with treatment. No adverse events were reported. CONCLUSION In participants with IBS, FODMAPs had a modest effect on typical IBS symptoms, whereas gluten had no effect. The large interindividual differences in responses to the interventions warrant further detailed studies to identify possible underlying causes and enable individual prediction of responses. This trial was registered at www.clinicaltrials.gov as NCT03653689.
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The relationship between different iodine sources and nutrition in pregnant women and adults.
Sun, R, Fan, L, Du, Y, Liu, L, Qian, T, Zhao, M, Che, W, Liu, P, Sun, D
Frontiers in endocrinology. 2022;13:924990
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Iodine is one of the essential trace elements in human body, which can only be obtained from the diet. Pregnant women are a special population, and their iodine intake needs to not only meet their own health needs but also to supply the growth of the foetus. The main aim of this study was to compare the iodine supplement measures and dietary contribution between pregnant women and adults. This study is based on a multi-stage random sampling method with a total of 2,128 pregnant women and 1,493 adults. Results show that iodine nutrition of pregnant women and adults was adequate in the four provinces included in the study. The largest difference of iodine levels between these provinces was the use of iodine during food preparation and the amount of dietary iodine intake. Additionally, the dietary iodine intake of pregnant women was less than the recommended nutrition intake. Authors conclude that various factors may affect thyroid disease prevalence in pregnant women, such as habitation (urban/rural) and gestation. Furthermore, it is important to coordinate the relationship between iodine nutrition and low sodium diet.
Abstract
BACKGROUND Different iodine supplement measures emerge along with the economy development in China. The article objectives are to compare and explore the relationship between iodine sources and nutrition of pregnant women and adults. METHODS A total of 2,145 pregnant women and 1,660 adults were investigated by multi-stage random method. Questionnaire was used to collect basic information and the consumption of food, water, and iodine preparations. Household salt and individual urine and blood samples were collected, and thyroid function and morphology of pregnant women were measured. RESULTS The median urinary iodine concentration (MUIC) of pregnant women (164.49 μg/L) was lower than adults (187.30 μg/L, p < 0.05). Iodine supplement with IS (iodized salt) was the main measure for pregnant women and adults, and the difference was mainly on the consumption of iodine preparations between pregnant women (5.19%) and adults (0.85%). Moreover, adults' dietary iodine intake from food (100.6 μg/day), IS (140.8 μg/day), and drinking water (6.0 μg/day) was higher than those of pregnant women (86.5, 107.2, and 3.5 μg/day, respectively). Compared with iodine supplement with IS, ISFP (IS + iodine-rich food + iodine preparations) could reduce the risk of iodine deficiency for pregnant women. The MUICs for pregnant women and adults of iodine supplements with IF (iodine-rich food) and ISF (IS + iodine-rich food) were lower. For pregnant women, thyroid nodule (11.90%) and peroxidase antibody (TPOAb) positive (9.32%) were high prevalent thyroid diseases, and habitation (urban/rural), gestation, annual income, and drinking water type would affect them. CONCLUSION Pregnant women and adults had adequate iodine nutrition in four provinces. Their iodine supplement measures were different, the consumption of iodine preparations in pregnant women was higher, and their dietary iodine intake was lower than adults. ISFP was an effect measure for pregnant women to supplement iodine.
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10.
Consumption of flavonoids and risk of hormone-related cancers: a systematic review and meta-analysis of observational studies.
Liu, F, Peng, Y, Qiao, Y, Huang, Y, Song, F, Zhang, M, Song, F
Nutrition journal. 2022;21(1):27
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Hormone-related cancers (HRCs) are greatly influenced by hormone levels and generally respond to hormone regulation, which plays an indispensable role in tumour growth. Encouragingly, diets rich in vegetables, fruits and tea are found to reduce the cancer risk, having the potential to exert chemo-preventive effects with the presence of anticarcinogenic phytochemicals. The aim of this study was to elucidate the association between flavonoids intake and HRCs risk. This study is a meta-analysis of fifty-one studies. It consisted of 22 prospective cohort studies, 1 nested case–control study, 18 population-based case–control studies and 10 hospital-based case–control studies. Results show that higher consumption of total flavonoids was only associated with an increased risk of men-specific cancers, mainly prostate cancer. Furthermore, the subclasses, flavanols, flavones, and isoflavones, and the three main individual compounds of isoflavones (daidzein, genistein and glycitein) may have protective effects on women-specific cancers, whereas flavones and flavanones have been found to cause potentially dangerous effects in thyroid cancer. Additionally, there was no evidence in support of any role for anthocyanidins in HRCs. Authors conclude that there is a small amount of evidence that total flavonoids, flavanols, flavones, flavanones, flavan-3-ols and isoflavones may be associated with a lower or higher risk of certain HRCs, which may provide guidance for dietary guidelines to a certain extent in the future.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Dietary flavonoids are widely available in plant-based foods such as vegetables, citrus fruits, green tea and berries
- Menopausal status may be an important consideration for flavonoid intake when considering breast cancer risk
- Differences in results for Asians and non-Asians need to be considered for the use of flavonoids in women-specific hormonal cancers and prostate cancer in men
- Caution should be exercised when considering flavones and flavanones and thyroid cancer risk until further research is available
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Hormone-related cancers (HRCs) are the most frequently diagnosed cancers globally , accounting for more than a quarter of new cancer cases worldwide in 2018. They include breast, ovarian, endometrial, prostate, testicular and thyroid cancer which share a similar carcinogenic mechanism. Diets rich in vegetables, fruit, legumes and tea may reduce cancer risk due to anticarcinogenic phytochemicals, such as flavonoids. Flavonoids are claimed to have many different physiological and pathological functions in the cancer process, including tumour cell proliferation, inflammation, angiogenesis, invasion and metastasis.. This study aimed to summarise the relationships between consumption of flavonoids with the risk of HRC.
Methods:
The meta-analysis was carried out following PRISMA guidelines and registered on PROSPERO. A literature search in PubMed and Embase was conducted using the keywords flavonoids, flavanols and isoflavones and breast, ovarian, endometrial, prostate, testicular and thyroid cancer. 51 studies published between 1999 and 2022 consisted of 22 prospective cohort, 18 population-based and 10 hospital-based case-control studies. On the Newcastle-Ottawa Scale assessment all studies were of medium or high methodological quality.
Results:
Results were analysed using Stata 15.1 software and ORs with 95% CIs used to measure the association between flavonoid intake and HRCs risk. Statistical I2 evaluated heterogeneity among the studies.
Funnel plots were inspected for publication bias and calculated by Begg’s/Egger’s regression tests. Sensitivity analyses were performed to explore the source of heterogeneity. Subgroup analysis was performed on study design and region, as well as menopausal status.
Higher consumption of flavonoids was associated with a decreased risk of women-specific cancers but a significant elevated risk of prostate cancer as seen below.
Women specific cancers:
For flavonoid sub-classes, higher consumption of flavanols (OR=0.85; 95% CI, 0.76–0.94; I2=75.5%; p<0.001), flavones (OR=0.85; 95% CI, 0.77–0.95; I2=76.3%; p<0.001) and isoflavones (OR=0.87; 95% CI, 0.82–0.92; I2=73.8%; p<0.001) was associated with a decreased risk of women-specific cancers (breast, ovarian and endometrial), especially among the case–control studies. Similar results were seen in the main compounds of isoflavones: daidzen, genistein and glycitein. There were differences in the association between isoflavones in Asian and non-Asian regions.
Men-specific cancers:
The higher consumption of total flavonoids (OR=1.11; 95% CI, 1.02–1.21; I2 = 0%; p = 0.484) was associated with an increased risk of prostate cancer and this was only found in non-Asian populations.
Conclusion:
Despite limitations of the meta-analysis, such as the use of observational studies and small sample sizes of the included studies, this systematic review may provide some preliminary dietary evidence for the use of flavonoids in HRCs.
Clinical practice applications:
- The promotion of a plant-based diet, rich in vegetables, fruits, green tea and legumes may have protective effects on women-specific cancers due to the rich presence of flavanols, flavones and isoflavones, as well as the compounds genistein, glycitein and daidzein.
- Results show no associations between total flavonoids intake and women-specific cancer however, the sub-groups of flavanols, flavones and isoflavones were associated with a decreased risk in women-specific cancers. Similar results were seen in the individual compounds of isoflavones: genistein, glycitein and daidzein. These results may guide decision-making when recommending the inclusion of these compounds for protective benefits in women-specific cancers.
- The positive association between total flavonoids and prostate cancer risk was only seen in non-Asians, and between higher consumption of flavones and flavanones and thyroid cancer risk albeit in limited studies (n=3) may provide important guidelines when considering which foods to include from a plant-based diet.
Considerations for future research:
- Further meta-analysis of prospective studies with larger sample sizes
- The use of a validated and reliable questionnaire for measuring flavonoid intake
- Intervention studies evaluating flavonoid subclasses
- Comparisons between Asian and non-Asian populations
- Consideration of menopausal status as an effect modifier
Abstract
BACKGROUND Flavonoids seem to have hormone-like and anti-hormone properties so that the consumption of flavonoids may have potential effects on hormone-related cancers (HRCs), but the findings have been inconsistent so far. This meta-analysis was aimed to explore the association between flavonoids intake and HRCs risk among observational studies. METHODS Qualified articles, published on PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) from January 1999 to March 2022 and focused on relationships between flavonoids (total, subclass of and individual flavonoids) and HRCs (breast, ovarian, endometrial, thyroid, prostate and testicular cancer), were retrieved for pooled analysis. Random effects models were performed to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Funnel plots and Begg's/Egger's test were used to evaluate the publication bias. Subgroup analyses and sensitivity analyses were conducted to explore the origins of heterogeneity. RESULTS All included studies were rated as medium or high quality. Higher consumption of flavonols (OR = 0.85, 95% CI: 0.76-0.94), flavones (OR = 0.85, 95% CI: 0.77-0.95) and isoflavones (OR = 0.87, 95% CI: 0.82-0.92) was associated with a decreased risk of women-specific cancers (breast, ovarian and endometrial cancer), while the higher intake of total flavonoids was linked to a significantly elevated risk of prostate cancer (OR = 1.11, 95% CI: 1.02-1.21). A little evidence implied that thyroid cancer risk was augmented with the higher intake of flavones (OR = 1.24, 95% CI: 1.03-1.50) and flavanones (OR = 1.31, 95% CI: 1.09-1.57). CONCLUSIONS The present study suggests evidence that intake of total flavonoids, flavonols, flavones, flavanones, flavan-3-ols and isoflavones would be associated with a lower or higher risk of HRCs, which perhaps provides guidance for diet guidelines to a certain extent. TRIAL REGISTRATION This protocol has been registered on PROSPERO with registration number CRD42020200720 .