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Mediterranean and Western diet effects on Alzheimer's disease biomarkers, cerebral perfusion, and cognition in mid-life: A randomized trial.
Hoscheidt, S, Sanderlin, AH, Baker, LD, Jung, Y, Lockhart, S, Kellar, D, Whitlow, CT, Hanson, AJ, Friedman, S, Register, T, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022;18(3):457-468
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There is a current understanding that Alzheimer’s disease (AD) development is related to a high intake of saturated fat and simple carbohydrates, which are found in abundance in the so-called Western Diet (WD). In contrast the consumption of low saturated fat and simple carbohydrates characteristic of the Mediterranean Diet (MD), has been associated with a reduced risk for the development of AD. This study aimed to look at the association of the MD and WD with AD in a more robust way using the randomised control method in 84 individuals both with and without mild memory impairment. The results showed that depending on whether an individual has mild brain impairment determines their response to the MD or WD after 4 weeks. In those without brain impairment the adoption of the WD resulted in a shift towards increasing the risk for AD development and the reverse following the MD. Whereas in those with brain impairment, the adoption of the WD was protective against the development of AD and the MD moved individuals towards worse disease outcomes. It was concluded that diet can be of importance in the prevention or progression of AD and that further studies are required to determine the possible mechanisms through which these two diets can act differentially. This study could be used by health care professionals to understand that diet can have a large impact on AD.
Expert Review
Conflicts of interest:
None
Take Home Message:
- A Med-diet may be beneficial for supporting brain health, cognitive function. metabolic health and reduce the risk of an AD pathology in middle-aged adults with normal cognitive function
Evidence Category:
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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
Epidemiological studies have associated a Western diet (West-diet) with an increased risk of Alzheimer’s disease (AD) and other dementias. This study aimed to examine the impact of a Mediterranean-diet (Med-diet) versus a West-diet on AD pathology, cognition, vascular function and metabolic markers in middle aged adults with normal cognitive (NC) function compared to adults with mild cognitive impairment (MCI).
Methods
N=41 NC adult females completed the Med-diet and N=43 adult females with MCI completed the West-diet arm of this study. The average age of the participants was 56y. All participants received isocaloric diets which were either high or low in saturated fat, sodium and glycaemic index (GI) for 4 weeks. Statistical analyses were conducted per dietary arm as well as per cognitive function (NC vs MCI).
Results
- NC Participants were found to have decreased cerebro-spinal fluid (CSF) biomarkers (p=.026) following the Med-diet and increased levels following the West-diet. Whereas, cerebral perfusion increased following the med-diet and decreased after the West-diet (p=.003). These results indicate a reduced AD risk. The MCI group showed no changes to CSF or cerebral perfusion for either dietary group.
- Cognition tended to improve for the NC Med-diet and remain the same for the NC West-diet group. No changes were found for the MCI groups.
- Total cholesterol levels were increased following the West-diet and decreased following the Med-diet for both groups (p=0.0001).
- Glucose and HbA1C were unchanged in the NC group following the Med-diet, increased for the West-diet (p=.049) and decreased for the MCI group (p=<.001). whereas fasting insulin was increased in the NC Med-diet group and decreased in the MCI Med-diet (p=.0.12) and West diet groups.
Conclusion
The results of this study found that diet may modulate AD pathology, cognitive and metabolic function in middle-aged adults. A West-like diet may increase risk of AD through its effects on impairing cognitive function, reducing cerebral infusion and negatively influencing metabolic health in NC adults. Conversely, A Med-diet may promote brain function and metabolic health. However, surprisingly, in this study the results were reversed for MCI middle aged adults, the results showed improvement in metabolic and cerebrospinal fluid biomarkers for the West-diet. These results require further confirmation.
No conflicts of interest were declared.
Clinical practice applications:
- A Med-diet may be beneficial for supporting brain health, cognitive function, metabolic health and reducing the risk of an AD pathology in middle-aged adults with normal cognitive function but not for those with MCI.
Considerations for future research:
The authors acknowledged several limitations to this study.
- These results require further confirmation through longer and larger studies, particularly the surprising finding that a West-diet may confer beneficial effects on metabolic and brain health for middle-aged adults with MCI.
Abstract
INTRODUCTION Mid-life dietary patterns are associated with Alzheimer's disease (AD) risk, although few controlled trials have been conducted. METHODS Eighty-seven participants (age range: 45 to 65) with normal cognition (NC, n = 56) or mild cognitive impairment (MCI, n = 31) received isocaloric diets high or low in saturated fat, glycemic index, and sodium (Western-like/West-diet vs. Mediterranean-like/Med-diet) for 4 weeks. Diet effects on cerebrospinal fluid (CSF) biomarkers, cognition, and cerebral perfusion were assessed to determine whether responses differed by cognitive status. RESULTS CSF amyloid beta (Aβ)42/40 ratios increased following the Med-diet, and decreased after West-diet for NC adults, whereas the MCI group showed the reverse pattern. For the MCI group, the West-diet reduced and the Med-diet increased total tau (t-tau), whereas CSF Aβ42 /t-tau ratios increased following the West-diet and decreased following the Med-diet. For NC participants, the Med-diet increased and the West-diet decreased cerebral perfusion. DISCUSSION Diet response during middle age may highlight early pathophysiological processes that increase AD risk.
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Lipid Metabolism Links Nutrient-Exercise Timing to Insulin Sensitivity in Men Classified as Overweight or Obese.
Edinburgh, RM, Bradley, HE, Abdullah, NF, Robinson, SL, Chrzanowski-Smith, OJ, Walhin, JP, Joanisse, S, Manolopoulos, KN, Philp, A, Hengist, A, et al
The Journal of clinical endocrinology and metabolism. 2020;105(3)
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Following exercise, various metabolic changes occur which may be of benefit in fighting diseases such as type 2 diabetes and obesity. However, the degree of change may vary depending on whether the exercise has been performed pre or post meal consumption. This 6-week randomised crossover trial of 30 overweight or obese men aimed to determine the effect of exercising before or after breakfast on the use of fats and sugars by the body. The results showed that exercise before breakfast increased fat and sugar use in the body and also resulted in the alteration of eight genes associated with metabolism. Exercise before carbohydrate consumption also increased lipid use and improved insulin sensitivity, however body composition was similar regardless of when exercise was performed. It was concluded that exercising in the fasted state can optimise the body’s response without having to change intensity or effort. This study could be used by health care professionals to advise patients with obesity or overweight that exercising whilst in the fasted state could optimise their outcomes without having to increase exercise intensity or frequency.
Abstract
CONTEXT Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness. OBJECTIVE To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism. DESIGN (1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study). SETTING General community. PARTICIPANTS Men with overweight/obesity (mean ± standard deviation, body mass index: 30.2 ± 3.5 kg⋅m-2 for Acute Study, 30.9 ± 4.5 kg⋅m-2 for Training Study). INTERVENTIONS Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast (Acute Study) or carbohydrate (Training Study) ingestion. RESULTS Acute Study-exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I (net change: -3.44 ± 2.63% versus 1.44 ± 4.18% area lipid staining, P < 0.01) and type II fibers (-1.89 ± 2.48% versus 1.83 ± 1.92% area lipid staining, P < 0.05). Training Study-postprandial glycemia was not differentially affected by 6 weeks of exercise training performed before versus after carbohydrate intake (P > 0.05). However, postprandial insulinemia was reduced with exercise training performed before but not after carbohydrate ingestion (P = 0.03). This resulted in increased oral glucose insulin sensitivity (25 ± 38 vs -21 ± 32 mL⋅min-1⋅m-2; P = 0.01), associated with increased lipid utilization during exercise (r = 0.50, P = 0.02). Regular exercise before nutrient provision also augmented remodeling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (P < 0.05). CONCLUSIONS Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (ie, in the fasted state) may exert beneficial effects on lipid utilization and reduce postprandial insulinemia.
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Effects of Roux-en-Y Gastric Bypass on Osteoclast Activity and Bone Density in Morbidly Obese Patients with Type 2 Diabetes.
Tangalakis, LL, Tabone, L, Spagnoli, A, Muehlbauer, M, Omotosho, P, Torquati, A
Obesity surgery. 2020;30(1):290-295
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Gastric surgery and the resultant weight loss can improve an individual’s outcomes in a number of diseases, such as heart disease and type 2 diabetes, however an unfortunate side effect is bone loss. Roux-en-Y gastric bypass is a process whereby the size of your stomach is significantly reduced, and it is unclear as to the effect this type of surgery has on bone density. This cohort study of sixty-one individuals who underwent Roux-en-Y gastric bypass aimed to determine the effect on bone density one year post surgery. The results showed that following surgery, bone resorption was increased compared to control and although bone density was similar between the two groups, bone mineral content and bone surface area were decreased. Women who were post-menopausal demonstrated diminished bone health, although this was not significant. It was concluded that Roux-en-Y gastric bypass surgery results in a negative impact on bone health. This study could be used by healthcare professionals to understand the importance of considering bone health when recommending surgery, especially in those at high-risk of bone loss such as post-menopausal women.
Abstract
INTRODUCTION Roux-en-Y gastric bypass (RYGB) is a well-established treatment for morbid obesity and type 2 diabetes. The effects of RYGB on bone metabolism and bone health are largely unknown. OBJECTIVE Determine the changes in osteoclast function and bone density 1 year after RYGB as compared with a control group undergoing a diabetes support and education program (DSE). DESIGN A prospective cohort study with patients matched for weight and age assigned to RYGB or DSE. SETTING Large academic institution. PATIENTS OR OTHER PARTICIPANTS Patients with type 2 diabetes mellitus and morbid obesity (body mass index greater than 35 kg/m2). INTERVENTION Subjects either received laparoscopic RYBG or DSE, which consisted of nutritional, exercise, and dietary counseling performed by a certified diabetic educator and a nutritionist three times over a year. MAIN OUTCOME MEASURE Osteoclast activity, bone mineral density. RESULTS One year after, intervention subjects undergoing RYGB have a 280% increase in osteoclast activity as compared with a 7.6% increase in the DSE control group (P < 0.001). Furthermore, there was a statistically significant increase in sclerostin levels in subjects undergoing RYGB compared with an increase in the control group. The total bone mineral density was statistically unchanged within 1 year of intervention in both groups. A statistically significant decrease in bone mineral density in the left ribs (decrease of 6.8%, P < 0.05) and lumbar spine (decrease of 4.0%, P < 0.05) was seen 1 year after RYGB. CONCLUSIONS There is a significant increase in osteoclast activity observed 1 year after RYGB; the long-term clinical implications of this increased bone metabolism are unknown.
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Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?
Li, L, Spranger, L, Soll, D, Beer, F, Brachs, M, Spranger, J, Mai, K
Metabolism: clinical and experimental. 2020;113:154401
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Obesity is now recognised as a risk factor for increased severity of Covid-19 infections. ACE-2 is a protein that has many functions but also allows Covid-19 into cells and is particularly evident in body tissues, which store fat. It is therefore possible that Covid-19 will target fat-storing tissues in the body. This 12-month randomised control weight-loss intervention study of 143 obese individuals aimed to determine ACE-2 expression and whether it could be modified by weight loss. The results showed that ACE-2 was only present in fat storing tissue and not muscle tissue. Interestingly individuals with pre-diabetes or diabetes had the lowest levels of ACE-2. Weight loss resulted in reduced ACE-2 in fat storing tissue, which resulted in an improvement in markers for diabetes. It was concluded that reduction of ACE-2 in fat storing tissues as a result of weight loss can improve markers for diabetes and could impact the severity of Covid-19 infection. Healthcare professionals could use this study to understand how weight loss in patients with obesity could decrease their risk of severe Covid-19 infection.
Abstract
BACKGROUND & AIMS Angiotensin converting enzyme (ACE)-2 is a modulator of adipose tissue metabolism. However, human data of adipose ACE-2 is rarely available. Considering that, ACE-2 is believed to be the receptor responsible for cell entry of SARS-CoV-2, a better understanding of its regulation is desirable. We therefore characterized the modulation of subcutaneous adipose ACE-2 mRNA expression during weight loss and the impact of ACE-2 expression on weight loss induced short- and long-term improvements of glucose metabolism. METHODS 143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before and after a standardized 12-week dietary weight reduction program. Afterwards subjects were randomized to a 12-month lifestyle intervention or a control group (Maintain-Adults trial). Insulin sensitivity (IS) was estimated by HOMA-IR (as an estimate of liver IS) and ISIClamp (as an estimate of skeletal muscle IS). ACE-2 mRNA expression (ACE-2AT) was measured in subcutaneous adipose tissue before and after weight loss. RESULTS ACE-2AT was not affected by obesity, but was reduced in insulin resistant subjects. Weight loss resulted in a decline of ACE-2AT (29.0 (20.0-47.9) vs. 21.0 (13.0-31.0); p = 1.6 ∗ 10-7). A smaller reduction of ACE-2 AT (ΔACE-2AT) was associated with a larger improvement of ISIClamp (p = 0.013) during weight reduction over 3 months, but not with the extend of weight loss. The degree of changes in insulin resistance were preserved until month 12 and was also predicted by the weight loss induced degree of ΔACE-2AT (p = 0.011). CONCLUSIONS Our data indicate that subcutaneous adipose ACE-2 expression correlates with insulin sensitivity. Weight loss induced decline of subcutaneous adipose ACE-2 expression might affect short- and long-term improvement of myocellular insulin sensitivity, which might be also relevant in the context of ACE-2 downregulation by SARS-CoV-2. TRIAL REGISTRATION ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.
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Effect of inorganic nitrate on exercise capacity, mitochondria respiration, and vascular function in heart failure with reduced ejection fraction.
Woessner, MN, Neil, C, Saner, NJ, Goodman, CA, McIlvenna, LC, Ortiz de Zevallos, J, Garnham, A, Levinger, I, Allen, JD
Journal of applied physiology (Bethesda, Md. : 1985). 2020;128(5):1355-1364
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Patients with chronic heart failure (CHF) are characterised by reduced aerobic capacity (V ̇O2peak) and early fatigue. Improving V ̇O2peak is an important clinical goal in CHF as it is correlated with reduced mortality rate and increased quality of life. The main aim of this study was to test the hypothesis that chronic oral inorganic nitrate supplementation will improve V ̇O2peak during treadmill exercise in patients with heart failure with reduced ejection fraction (HFrEF). This study is a randomised, placebo-controlled, double-blind, crossover study. Nineteen participants were recruited, and 16 individuals with diagnosed HFrEF completed the study. Participants were randomised to consume either nitrate-rich beetroot juice (210 mL, 16 mmol nitrate) or a nitrate-depleted placebo for 5 days. Results show that in patients with HFrEF, chronic oral inorganic nitrate supplementation had no significant effect on aerobic exercise capacity, vascular function, peripheral and central blood pressures, or muscle respiration. Authors conclude that future studies should characterise the diversity and abundance of the oral microbiome in HFrEF to elucidate approaches that could lead to a potential benefit of oral nitrate supplementation.
Abstract
Chronic underperfusion of the skeletal muscle tissues is a contributor to a decrease in exercise capacity in patients with heart failure with reduced ejection fraction (HFrEF). This underperfusion is due, at least in part, to impaired nitric oxide (NO) bioavailability. Oral inorganic nitrate supplementation increases NO bioavailability and may be used to improve exercise capacity, vascular function, and mitochondrial respiration. Sixteen patients with HFrEF (fifteen men, 63 ± 4 yr, body mass index: 31.8 ± 2.1 kg/m2) participated in a randomized, double-blind, crossover design study. Following consumption of either nitrate-rich beetroot juice (16 mmol nitrate/day) or a nitrate-depleted placebo for 5 days, participants completed separate visits for assessment of exercise capacity, endothelial function, and muscle mitochondrial respiration. Participants then had a 2-wk washout before completion of the same protocol with the other intervention. Statistical significance was set a priori at P < 0.05, and between-treatment differences were analyzed via paired t test analysis. Following nitrate supplementation, both plasma nitrate and nitrite increased (933%, P < 0.001 and 94%, P < 0.05, respectively). No differences were observed for peak oxygen consumption (nitrate: 18.5 ± 1.4 mL·kg-1·min-1, placebo: 19.3 ± 1.4 mL·kg-1·min-1; P = 0.13) or time to exhaustion (nitrate: 1,165 ± 92 s, placebo: 1,207 ± 96 s; P = 0.16) following supplementation. There were no differences between interventions for measures of vascular function, mitochondrial respiratory function, or protein expression (all P > 0.05). Inorganic nitrate supplementation did not improve exercise capacity and skeletal muscle mitochondrial respiratory function in HFrEF. Future studies should explore alternative interventions to improve peripheral muscle tissue function in HFrEF.NEW & NOTEWORTHY This is the largest study to date to examine the effects of inorganic nitrate supplementation in patients with heart failure with reduced ejection fraction (HFrEF) and the first to include measures of vascular function and mitochondrial respiration. Although daily supplementation increased plasma nitrite, our data indicate that supplementation with inorganic nitrate as a standalone treatment is ineffective at improving exercise capacity, vascular function, or mitochondrial respiration in patients with HFrEF.
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Exercise twice-a-day potentiates markers of mitochondrial biogenesis in men.
Andrade-Souza, VA, Ghiarone, T, Sansonio, A, Santos Silva, KA, Tomazini, F, Arcoverde, L, Fyfe, J, Perri, E, Saner, N, Kuang, J, et al
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020;34(1):1602-1619
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Endurance exercise is a powerful stimulus affecting cytoplasmic and nuclear proteins, and genes encoding mitochondrial proteins, with a subsequent increase in mitochondrial biogenesis (ie, the generation of new mitochondrial components leading to increased mitochondrial content and respiratory function). The aim of this study was to investigate whether greater exercise-induced signalling with the “train-low” approach can be attributed to the cumulative effects of performing two exercise sessions in close proximity. This study enrolled eight healthy men whom each completed three experimental trials in a crossover, randomized, and incomplete balanced Latin Square counterbalanced measure design. Results show that the greater exercise-induced nuclear protein abundance and transcription of genes involved in mitochondrial biogenesis with the “train-low” approach might be attributed to performing two exercise sessions in close proximity. Furthermore, the twice-a-day approach was associated with a higher heart rate, ventilation, and oxygen uptake, and a lower plasma glucose concentration, during high-intensity interval exercise than both the once-daily and the control condition. Authors conclude that further studies comparing different “train-low” approached in well-trained athletes are required.
Abstract
Endurance exercise begun with reduced muscle glycogen stores seems to potentiate skeletal muscle protein abundance and gene expression. However, it is unknown whether this greater signaling responses is due to performing two exercise sessions in close proximity-as a first exercise session is necessary to reduce the muscle glycogen stores. In the present study, we manipulated the recovery duration between a first muscle glycogen-depleting exercise and a second exercise session, such that the second exercise session started with reduced muscle glycogen in both approaches but was performed either 2 or 15 hours after the first exercise session (so-called "twice-a-day" and "once-daily" approaches, respectively). We found that exercise twice-a-day increased the nuclear abundance of transcription factor EB (TFEB) and nuclear factor of activated T cells (NFAT) and potentiated the transcription of peroxisome proliferator-activated receptor-ɣ coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor-alpha (PPARα), and peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) genes, in comparison with the once-daily exercise. These results suggest that part of the elevated molecular signaling reported with previous "train-low" approaches might be attributed to performing two exercise sessions in close proximity. The twice-a-day approach might be an effective strategy to induce adaptations related to mitochondrial biogenesis and fat oxidation.
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Additional Effects of Nutritional Antioxidant Supplementation on Peripheral Muscle during Pulmonary Rehabilitation in COPD Patients: A Randomized Controlled Trial.
Gouzi, F, Maury, J, Héraud, N, Molinari, N, Bertet, H, Ayoub, B, Blaquière, M, Bughin, F, De Rigal, P, Poulain, M, et al
Oxidative medicine and cellular longevity. 2019;2019:5496346
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Chronic obstructive pulmonary disease (COPD) is systematically associated with comorbidities. Muscle atrophy and weakness are therefore targets of exercise training interventions in pulmonary rehabilitation (PR). The aim of the study was to test the effects of oral antioxidant supplementation with vitamins and trace elements (i.e. vitamins C and E, zinc and selenium) versus placebo on muscle endurance (primary outcome) and muscle strength, oxidative stress, inflammation, and PR outcomes (secondary outcomes). The study is a randomized double-blind controlled trial during PR. COPD patients (aged between 40 and 78 years) were randomly assigned to the PR antioxidant group or to the PR placebo group. Results indicate that nutritional antioxidant supplementation (vitamins C and E, zinc, and selenium) failed to further improve the patients’ quadriceps endurance. However, results also demonstrate that additional improvements of three secondary outcomes and a trend toward increased muscle type I fiber proportion with supplementation versus placebo during PR. Authors conclude that efficient antioxidant supplementation results in greater improvement in muscle function when compared to placebo in combination with exercise training.
Abstract
BACKGROUND Skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD) is not fully reversed by exercise training. Antioxidants are critical for muscle homeostasis and adaptation to training. However, COPD patients experience antioxidant deficits that worsen after training and might impact their muscle response to training. Nutritional antioxidant supplementation in combination with pulmonary rehabilitation (PR) would further improve muscle function, oxidative stress, and PR outcomes in COPD patients. METHODS Sixty-four COPD patients admitted to inpatient PR were randomized to receive 28 days of oral antioxidant supplementation targeting the previously observed deficits (PR antioxidant group; α-tocopherol: 30 mg/day, ascorbate: 180 mg/day, zinc gluconate: 15 mg/day, selenomethionine: 50 μg/day) or placebo (PR placebo group). PR consisted of 24 sessions of moderate-intensity exercise training. Changes in muscle endurance (primary outcome), oxidative stress, and PR outcomes were assessed. RESULTS Eighty-one percent of the patients (FEV1 = 58.9 ± 20.0%pred) showed at least one nutritional antioxidant deficit. Training improved muscle endurance in the PR placebo group (+37.4 ± 45.1%, p < 0.001), without additional increase in the PR antioxidant group (-6.6 ± 11.3%; p = 0.56). Nevertheless, supplementation increased the α-tocopherol/γ-tocopherol ratio and selenium (+58 ± 20%, p < 0.001, and +16 ± 5%, p < 0.01, respectively), muscle strength (+11 ± 3%, p < 0.001), and serum total proteins (+7 ± 2%, p < 0.001), and it tended to increase the type I fiber proportion (+32 ± 17%, p = 0.07). The prevalence of muscle weakness decreased in the PR antioxidant group only, from 30.0 to 10.7% (p < 0.05). CONCLUSIONS While the primary outcome was not significantly improved, COPD patients demonstrate significant improvements of secondary outcomes (muscle strength and other training-refractory outcomes), suggesting a potential "add-on" effect of the nutritional antioxidant supplementation (vitamins C and E, zinc, and selenium) during PR. This trial is registered with NCT01942889.
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The effect of different sources of fish and camelina sativa oil on immune cell and adipose tissue mRNA expression in subjects with abnormal fasting glucose metabolism: a randomized controlled trial.
de Mello, VD, Dahlman, I, Lankinen, M, Kurl, S, Pitkänen, L, Laaksonen, DE, Schwab, US, Erkkilä, AT
Nutrition & diabetes. 2019;9(1):1
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Dietary fish oils, particularly omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in oily fish, nuts and seeds have long been researched and purported to have both anti-inflammatory and glucose-stabilising effects when consumed orally and it is widely believed that in reducing low-grade inflammation and stabilising blood glucose levels, the risk of suffering from type 2 diabetes, heart disease or a stroke is reduced. Lean fish on the other hand has been far less researched with regards to its protective effects. This study was a randomised controlled study designed to assess and compare the protective effects of fish oils and Camelina Sativa oil (CSO - a seed oil containing alpha-linolenic acid) on inflammatory-related genes in subjects with suggestive pre-diabetes. Subjects were allocated to a randomised group and instructed to consume a given amount of either fatty fish, lean fish, camelina oil, or no fish/oil (control group). The study was carried out on 72 participants over a 12-week period. Although no significant change could be seen on inflammatory gene expression for the group consuming fatty fish, there was a modest decrease in inflammatory gene markers in the group consuming lean fish and a significant decrease in the group consuming CSO. Implications from this study suggest that CSO exerts its protective effect by reducing inflammation, therefore possibly decreasing the risk of strokes and cardiovascular episodes. The authors suggest that consuming a variety of fish, especially lean fish 4 times/ week could also play a protective role in cardiovascular health and type 2 diabetes.
Abstract
BACKGROUND/OBJECTIVES Molecular mechanisms linking fish and vegetable oil intakes to their healthy metabolic effects may involve attenuation of inflammation. Our primary aim was to examine in a randomized controlled setting whether diets enriched in fatty fish (FF), lean fish (LF) or ALA-rich camelina sativa oil (CSO) differ in their effects on the mRNA expression response of selected inflammation-related genes in peripheral blood mononuclear cells (PBMCs) and subcutaneous adipose tissue (SAT) in subjects with impaired fasting glucose. SUBJECTS/METHODS Samples from 72 participants randomized to one of the following 12-week intervention groups, FF (n = 19), LF (n = 19), CSO (n = 17) or a control group (n = 17), were available for the PBMC study. For SAT, 39 samples (n = 8, n = 10, n = 9, n = 12, respectively) were available. The mRNA expression was measured at baseline and 12 weeks by TaqMan® Low Density Array. RESULTS In PBMCs, LF decreased ICAM1 mRNA expression (P < 0.05), which was different (P = 0.06, Bonferroni correction) from the observed increase in the FF group (P < 0.05). Also, compared to the control group, LF decreased ICAM1 mRNA expression (P < 0.05). Moreover, the change in ICAM1 mRNA expression correlated positively with the intake of FF (P < 0.05) and negatively with the intake of LF (P < 0.05), independently of study group. A diet enriched in CSO, a rich source of alpha-linolenic acid (ALA), decreased PBMC IFNG mRNA expression (P < 0.01). The intake of CSO in the CSO group, but not the increase in plasma ALA proportions, correlated inversely with the IFNG mRNA expression in PBMCs (P = 0.08). In SAT, when compared with the control group, the effect of FF on decreasing IL1RN mRNA expression was significant (P < 0.03). CONCLUSION We propose that CSO intake may partly exert its benefits through immuno-inflammatory molecular regulation in PBMCs, while modulation of ICAM1 expression, an endothelial/vascular-related gene, may be more dependent on the type of fish consumed.
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Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance.
Cotte, AK, Aires, V, Fredon, M, Limagne, E, Derangère, V, Thibaudin, M, Humblin, E, Scagliarini, A, de Barros, JP, Hillon, P, et al
Nature communications. 2018;9(1):322
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Lipid droplet (LD) accumulation has been observed in an increasing number of cancer cell lines and is now a well-recognised hallmark of cancer. While the significance of LD accumulation remains unclear, recent studies have suggested it plays a role in tumour cell chemoresistance mechanisms. This study aims to fill in the gaps in the literature regarding LD formation and function under chemotherapy conditions in colorectal cancer cell models. For the first time, this study demonstrates a pertinent mechanism linking LD accumulation and resistance to conventional chemotherapies. The authors found that LD production is driven by the enzyme lysophosphatidylcholine acyltransferase 2 (LPCAT2), and that chemotherapy can trigger LD production, promoting chemoresistance. The authors conclude these findings could be useful for both prognostic factors as well as predictive factors for the patient’s responsiveness to conventional therapies.
Abstract
Lipid droplet (LD) accumulation is a now well-recognised hallmark of cancer. However, the significance of LD accumulation in colorectal cancer (CRC) biology is incompletely understood under chemotherapeutic conditions. Since drug resistance is a major obstacle to treatment success, we sought to determine the contribution of LD accumulation to chemotherapy resistance in CRC. Here we show that LD content of CRC cells positively correlates with the expression of lysophosphatidylcholine acyltransferase 2 (LPCAT2), an LD-localised enzyme supporting phosphatidylcholine synthesis. We also demonstrate that LD accumulation drives cell-death resistance to 5-fluorouracil and oxaliplatin treatments both in vitro and in vivo. Mechanistically, LD accumulation impairs caspase cascade activation and ER stress responses. Notably, droplet accumulation is associated with a reduction in immunogenic cell death and CD8+ T cell infiltration in mouse tumour grafts and metastatic tumours of CRC patients. Collectively our findings highlight LPCAT2-mediated LD accumulation as a druggable mechanism to restore CRC cell sensitivity.
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Hypothesis and data-driven dietary patterns and colorectal Cancer survival: findings from Newfoundland and Labrador colorectal Cancer cohort.
Sharma, I, Roebothan, B, Zhu, Y, Woodrow, J, Parfrey, PS, Mclaughlin, JR, Wang, PP
Nutrition journal. 2018;17(1):55
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Diet and lifestyle play a role in the risk and outcome of chronic diseases including colorectal cancer (CRC). This prospective follow-up study looked at the association between different dietary patterns and the risk of death and cancer recurrence in people with CRC. Over 500 CRC patients diagnosed between 1999 and 2003 were followed-up until 2010. Participants completed a food frequency questionnaire based on their diet a year prior to diagnosis, and this was used to identify several dietary patterns. Diets that were high in processed meats (HR 1.82), meat and dairy products (HR 2.19), and total grains, sugar and soft drinks (HR 1.95) were associated with a higher risk of mortality, cancer recurrence or metastasis. Poor adherence to a Mediterranean-style diet increased the risk of overall mortality (HR 1.62). Prudent vegetable, high sugar pattern, Recommended Food Scores and Dietary Inflammatory Index had no significant association with either mortality or combined mortality, recurrence or metastasis. The authors concluded that the risk of mortality, recurrence and metastasis in patients with colorectal cancer varies with different dietary patterns.
Abstract
BACKGROUND Dietary patterns are commonly used in epidemiological research, yet there have been few studies assessing if and how research results may vary across dietary patterns. This study aimed to estimate the risk of mortality/recurrence/metastasis using different dietary patterns and comparison amongst the patterns. METHODS Dietary patterns were identified by Cluster Analysis (CA), Principal Component Analysis (PCA), Alternate Mediterranean Diet score (altMED), Recommended Food Score (RFS) and Dietary Inflammatory Index (DII) scores using a 169-item food frequency questionnaire. Five hundred thirty-two colorectal cancer patients diagnosed between 1999 and 2003 in Newfoundland were followed-up until 2010. Overall Mortality (OM) and combined Mortality, Recurrence or Metastasis (cMRM) were identified. Comparisons were made with adjusted Cox proportional Hazards Ratios (HRs), correlation coefficients and the distributions of individuals in defined clusters by quartiles of factor and index scores. RESULTS One hundred and seventy cases died from all causes and 29 had a cancer recurrence/metastasis during follow-up. Processed meats as classified by PCA (HR 1.82; 95% confidence interval (CI) 1.07-3.09), clusters characterized by meat and dairy products (HR 2.19; 95% CI 1.03-4.67) and total grains, sugar, soft drinks (HR 1.95; 95% CI 1.13-3.37) were associated with a higher risk of cMRM. Poor adherence to AltMED increased the risk of all-cause OM (HR 1.62; 95% CI 1.04-2.56). Prudent vegetable, high sugar pattern, RFS and DII had no significant association with both OM and cMRM. CONCLUSION Estimation of OM and cMRM varied across dietary patterns which is attributed to the differences in the foundation of each pattern.