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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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Lipids activate skeletal muscle mitochondrial fission and quality control networks to induce insulin resistance in humans.
Axelrod, CL, Fealy, CE, Erickson, ML, Davuluri, G, Fujioka, H, Dantas, WS, Huang, E, Pergola, K, Mey, JT, King, WT, et al
Metabolism: clinical and experimental. 2021;121:154803
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Insulin resistance is a key pathophysiological mechanism in the development and progression of type 2 diabetes. Abnormalities in lipid metabolism and ectopic lipid accumulation are known to directly contribute to the onset of insulin resistance. Authors hypothesised that lipid infusion would increase dynamin related protein 1 [a type of protein]-mediated mitochondrial fission in skeletal muscle independent of function and content, consequently reducing peripheral insulin sensitivity. The study included sedentary but otherwise healthy adults who were prospectively randomized to receive either lipid or saline infusion to isolate the direct contribution of fatty acids to skeletal muscle mitochondrial dynamics. Results show that mitochondrial fission and quality control networks are activated in response to lipid infusion which occurs independent of changes in mitochondrial content or capacity and contributes to the onset of insulin resistance in healthy humans. Authors conclude that treatments that limit lipid-induced activation of mitochondrial fission and/or quality control processes may have therapeutic value in the treatment of insulin resistance.
Abstract
BACKGROUND AND AIMS A diminution in skeletal muscle mitochondrial function due to ectopic lipid accumulation and excess nutrient intake is thought to contribute to insulin resistance and the development of type 2 diabetes. However, the functional integrity of mitochondria in insulin-resistant skeletal muscle remains highly controversial. METHODS 19 healthy adults (age:28.4 ± 1.7 years; BMI:22.7 ± 0.3 kg/m2) received an overnight intravenous infusion of lipid (20% Intralipid) or saline followed by a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity using a randomized crossover design. Skeletal muscle biopsies were obtained after the overnight lipid infusion to evaluate activation of mitochondrial dynamics proteins, ex-vivo mitochondrial membrane potential, ex-vivo oxidative phosphorylation and electron transfer capacity, and mitochondrial ultrastructure. RESULTS Overnight lipid infusion increased dynamin related protein 1 (DRP1) phosphorylation at serine 616 and PTEN-induced kinase 1 (PINK1) expression (P = 0.003 and P = 0.008, respectively) in skeletal muscle while reducing mitochondrial membrane potential (P = 0.042). The lipid infusion also increased mitochondrial-associated lipid droplet formation (P = 0.011), the number of dilated cristae, and the presence of autophagic vesicles without altering mitochondrial number or respiratory capacity. Additionally, lipid infusion suppressed peripheral glucose disposal (P = 0.004) and hepatic insulin sensitivity (P = 0.014). CONCLUSIONS These findings indicate that activation of mitochondrial fission and quality control occur early in the onset of insulin resistance in human skeletal muscle. Targeting mitochondrial dynamics and quality control represents a promising new pharmacological approach for treating insulin resistance and type 2 diabetes. CLINICAL TRIAL REGISTRATION NCT02697201, ClinicalTrials.gov.
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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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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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The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage.
Williamson, J, Hughes, CM, Cobley, JN, Davison, GW
Redox biology. 2020;36:101673
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Mitochondria have an established role in the life cycle of a cell, contributing to cellular networks aligned to metabolism, biosynthetic pathways, and apoptotic cell death. Exercise increases the univalent reduction of ground state molecular dioxygen to superoxide in skeletal muscle. The aim of this study was to determine whether (1) a bout of high-intensity intermittent exercise (HIIE) damaged mitochondrial (mt)DNA; and (2) Mitoquinone (MitoQ) [orally available mitochondrial-targeted coenzyme Q10] could prevent mtDNA damage. This study is a double-blind, randomized, placebo-controlled design. Twenty-four (n = 24) healthy, recreationally active males volunteered to take part in the study. The participants were allocated to two groups: MitoQ (n = 12) and placebo (n = 12), and subsequently took part in a two-phased supplementation trial. Results showed that: - exercise increased DNA damage in nucleus and mitochondria. In fact, HIIE damages mtDNA both systemically in lymphocytes and locally in muscle tissue, occurring in parallel with nuclear DNA damage. - chronic MitoQ supplementation offers a prophylactic effect. - MitoQ decreases exercise-induced DNA damage. Authors conclude that the notion that a protective effect of a mitochondria-targeted antioxidant is only unmasked by exercise, reinforces the value of interrogating multiple physiological states when appraising the efficacy of an antioxidant.
Abstract
High-intensity exercise damages mitochondrial DNA (mtDNA) in skeletal muscle. Whether MitoQ - a redox active mitochondrial targeted quinone - can reduce exercise-induced mtDNA damage is unknown. In a double-blind, randomized, placebo-controlled design, twenty-four healthy male participants consisting of two groups (placebo; n = 12, MitoQ; n = 12) performed an exercise trial of 4 x 4-min bouts at 90-95% of heart rate max. Participants completed an acute (20 mg MitoQ or placebo 1-h pre-exercise) and chronic (21 days of supplementation) phase. Blood and skeletal muscle were sampled immediately pre- and post-exercise and analysed for nuclear and mtDNA damage, lipid hydroperoxides, lipid soluble antioxidants, and the ascorbyl free radical. Exercise significantly increased nuclear and mtDNA damage across lymphocytes and muscle (P < 0.05), which was accompanied with changes in lipid hydroperoxides, ascorbyl free radical, and α-tocopherol (P < 0.05). Acute MitoQ treatment failed to impact any biomarker likely due to insufficient initial bioavailability. However, chronic MitoQ treatment attenuated nuclear (P < 0.05) and mtDNA damage in lymphocytes and muscle tissue (P < 0.05). Our work is the first to show a protective effect of chronic MitoQ supplementation on the mitochondrial and nuclear genomes in lymphocytes and human muscle tissue following exercise, which is important for genome stability.
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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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A Pilot Study To Investigate the Immune-Modulatory Effects of Fasting in Steroid-Naive Mild Asthmatics.
Han, K, Nguyen, A, Traba, J, Yao, X, Kaler, M, Huffstutler, RD, Levine, SJ, Sack, MN
Journal of immunology (Baltimore, Md. : 1950). 2018;201(5):1382-1388
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Previous studies have shown that caloric restriction and fasting may modulate immune function and have positive effects in asthmatics. The aim of this pilot study was to evaluate the effects of fasting on specific inflammatory markers that might mediate such benefits. 18 mild asthmatics, 5 of whom were not on steroid inhalers, fasted for 24 hours. Lung function and immune parameters were evaluated at baseline and 2.5 hours after the first meal following the fast. There were significant differences between subjects who were and were not on steroid inhalers. Whilst one day of fasting did not affect lung function, a number of inflammatory parameters were improved by fasting in those not taking steroid inhalers, but not in those who were taking steroids. The authors conclude that caloric restriction might be considered as a strategy to improve systemic and pulmonary inflammation in asthma.
Abstract
A fasting mimetic diet blunts inflammation, and intermittent fasting has shown ameliorative effects in obese asthmatics. To examine whether canonical inflammatory pathways linked with asthma are modulated by fasting, we designed a pilot study in mild asthmatic subjects to assess the effect of fasting on the NLRP3 inflammasome, Th2 cell activation, and airway epithelial cell cytokine production. Subjects with documented reversible airway obstruction and stable mild asthma were recruited into this study in which pulmonary function testing (PFT) and PBMCextraction was performed 24 h after fasting, with repeated PFT testing and blood draw 2.5 h after refeeding. PFTs were not changed by a prolonged fast. However, steroid-naive mild asthmatics showed fasting-dependent blunting of the NLRP3 inflammasome. Furthermore, PBMCs from these fasted asthmatics cocultured with human epithelial cells resulted in blunting of house dust mite-induced epithelial cell cytokine production and reduced CD4+ T cell Th2 activation compared with refed samples. This pilot study shows that prolonged fasting blunts the NLRP3 inflammasome and Th2 cell activation in steroid-naive asthmatics as well as diminishes airway epithelial cell cytokine production. This identifies a potential role for nutrient level-dependent regulation of inflammation in asthma. Our findings support the evaluation of this concept in a larger study as well as the potential development of caloric restriction interventions for the treatment of asthma.