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Olive pomace oil can improve blood lipid profile: a randomized, blind, crossover, controlled clinical trial in healthy and at-risk volunteers.
González-Rámila, S, Sarriá, B, Seguido, MA, García-Cordero, J, Mateos, R, Bravo, L
European journal of nutrition. 2023;62(2):589-603
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Morbidity and mortality from cardiovascular diseases (CVD) are increasing. It is known that a healthy diet and physical exercise can modulate the risk of CVD. In this regard, the Mediterranean Diet (MD) is considered a model of healthy eating and olive oil is an essential component of this diet, as its primary fat source. The aims of this study were to assess the possible beneficial role of consuming olive pomace oil (OPO) as the main source of fat in the diet on serum lipid concentrations (primary outcome) and other biomarkers of cardiovascular health such as blood pressure, endothelial function and inflammation (secondary outcomes) in at-risk (hypercholesterolaemic) subjects. This study was a randomised, blind, crossover, controlled clinical trial in free-living subjects. Participants, men and women aged 18–55 years, were randomly assigned to one of the two groups; normocholesterolaemic or hypercholesterolaemic group. Results showed that consumption of OPO for four weeks resulted in an improved blood lipid profile, decreasing low-density lipoprotein cholesterol, Apo B and low-density lipoprotein/ high-density lipoprotein ratio both in healthy and at-risk volunteers, in contrast to the opposite effect observed with high-oleic acid sunflower oil (HOSO), with no significant changes in other CVD risk factors. Furthermore, no changes were observed in relation to blood pressure, and biomarkers linked to inflammation and endothelial function. Authors conclude that OPO could have hypolipidemic actions in healthy consumers and in subjects with high blood cholesterol, contributing to cardiovascular disease prevention.
Abstract
PURPOSE This study aimed to assess the effect of dietary consumption of olive pomace oil (OPO) on blood lipids (primary outcome) and other cardiovascular disease (CVD) risk factors (blood pressure, inflammation and endothelial function as secondary outcomes). METHODS A randomized, controlled, blind, crossover intervention was carried out in healthy and at-risk (hypercholesterolemic) subjects. Participants consumed daily 45 g of OPO or high-oleic acid sunflower oil (HOSO) as control oil during 4 weeks. RESULTS OPO significantly reduced low-density lipoprotein cholesterol (LDL-C; P = 0.003) and apolipoprotein B (Apo B; P = 0.022) serum concentrations, and LDL/HDL ratio (P = 0.027) in healthy and at-risk volunteers. These effects were not observed with HOSO. Blood pressure, peripheral artery tonometry (PAT), endothelial function and inflammation biomarkers were not affected. CONCLUSIONS Regular consumption of OPO in the diet could have hypolipidemic actions in subjects at cardiovascular risk as well as in healthy consumers, contributing to CVD prevention. CLINICAL TRIAL REGISTRY NCT04997122, August 8, 2021, retrospectively registered.
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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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Effect of Flaxseed (Linum usitatissimum L.) Supplementation on Vascular Endothelial Cell Morphology and Function in Patients with Dyslipidaemia-A Preliminary Observation.
Kanikowska, D, Malińska, A, Mickiewicz, A, Zawada, A, Rutkowski, R, Pawlaczyk, K, Sato, M, Bręborowicz, A, Witowski, J, Korybalska, K
Nutrients. 2022;14(14)
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Flaxseed appears to be a valuable source of polyunsaturated fatty acids, phytosterols and fibre, which lower lipids and have anti-atherogenic activity. The aim of this study was to determine the effects of 10 weeks of supplementation with the flaxseed (28g/day) on endothelial cells function, serum lipids and proinflammatory mediators in patients with mild and severe dyslipidaemia. This study is a prospective study of two groups of patients. The first group (n=14) was composed of lean (n=6), and obese (n=8) outpatients receiving therapy of lipoprotein apheresis (once every two weeks) for severe hyperlipidaemia. The second group was composed of 11 obese outpatients with dyslipidaemia receiving a diet at home. In both groups, flaxseed was given blindly. Results show that patients diagnosed with dyslipidaemia who took 28g daily of flaxseed showed a significant reduction in serum lipids but exhibited a slight beneficial effect on endothelial cells. However, it only shows that flaxseed might have the potential ability to improve endothelial function but, in obese patients, it does not have the potency to reverse endothelial ultrastructural changes observed in electron microscopy. Authors conclude that flaxseed supplementation produced consistent lipid-lowering effects and can modulate VEGF (endothelial cell marker) concentration depending on the severity of dyslipidaemia.
Abstract
CONTEXT Flaxseed has a characteristic fatty acids composition and unique phytonutrient profile that may have health-promoting properties. OBJECTIVE This study aimed to determine the effects of 10 weeks of supplementation with the flaxseed (28 g/day) on endothelial cells (EC) function, serum lipids and proinflammatory mediators in patients with mild and severe dyslipidaemia. MATERIALS AND METHODS Eleven lean patients with severe dyslipidaemia treated with apheresis (group 1; 10 weeks treated in four phases: (i) ordinary diet, (ii) ordinary diet + flaxseed, (iii) ordinary diet (wash out), (iv) ordinary diet + placebo) and eleven obese patients with mild dyslipidaemia-not treated with apheresis (group 2; 10 weeks treated in two phases: (i) ordinary diet, (ii) low fat diet + flaxseed). Flaxseed was given blindly. Serum was collected at the end of each phase of the study. ECs were exposed in vitro to the medium supplemented with pooled serum taken from patients from both groups to detect their morphological changes using light and electron microscopy. ECs proliferation was also measured at the end of each study phase. RESULTS Serum vascular endothelial growth factor was decreased after flaxseed supplementation but only in group 1. ECs proliferation was increased after flaxseed supplementation only in obese patients. ECs exposed to medium supplemented with obese patients' serum revealed the following cellular abnormalities: accumulation of lipid droplets, changes of rough endoplasmic reticulum and mitochondria, and flaxseed did not reverse observed changes. At the same time, flaxseed supplementation decreases total cholesterol in both tested groups, low-density lipoprotein cholesterol in group 1 and triglycerides in group 2. CONCLUSIONS Our findings support the potential role of flaxseed in treating dyslipidaemia but indicate only a slight impact on endothelial cell function.
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Diverging metabolic effects of 2 energy-restricted diets differing in nutrient quality: a 12-week randomized controlled trial in subjects with abdominal obesity.
Schutte, S, Esser, D, Siebelink, E, Michielsen, CJR, Daanje, M, Matualatupauw, JC, Boshuizen, HC, Mensink, M, Afman, LA
The American journal of clinical nutrition. 2022;116(1):132-150
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Energy restriction (ER) diets are considered an effective strategy for managing obesity and preventing or reducing the risk of associated comorbidities. However, there are very few previous studies comparing the quality of energy restriction diets and their effect on maximising the health benefits. Therefore, this 12-week, parallel-designed, randomised controlled trial compared the effects of a 25% high-quality ER diet with a 25% low-quality ER diet and a habitual diet on cardiometabolic risk factors of 110 participants with abdominal obesity. Both ER diets were nutritionally balanced. The high-quality ER diet had added Monounsaturated fatty acids (MUFAs), Omega-3 Polyunsaturated fatty acids (n-3 PUFAs), fibre, and plant protein and had less fructose in it. The low-quality ER diet contained Saturated fatty acids (SFAs) and monosaccharides such as fructose. At the end of the 12-week trial, participants on the 25% high-quality diet showed more promising results in weight loss, reduction in cholesterol and triglycerides, and adipose tissue gene expression of energy metabolism pathways compared to the 25% low-quality ER diet. Insulin-sensitive participants with abdominal obesity on a 25% high-quality diet lost more weight compared to the rest of the participants. Further robust studies are required to evaluate the findings due to the limitations of this study. However, healthcare professionals can use the results of this study to understand the beneficial effects of an ER diet when it is enriched with specific nutrients.
Abstract
BACKGROUND Despite the established relation between energy restriction (ER) and metabolic health, the most beneficial nutrient composition of a weight-loss diet is still a subject of debate. OBJECTIVES The aim of the study was to examine the additional effects of nutrient quality on top of ER. METHODS A parallel-designed, 12-week 25% ER dietary intervention study was conducted (clinicaltrials.gov: NCT02194504). Participants aged 40-70 years with abdominal obesity were randomized over 3 groups: a 25% ER high-nutrient-quality diet (n = 40); a 25% ER low-nutrient-quality diet (n = 40); or a habitual diet (n = 30). Both ER diets were nutritionally adequate, and the high-nutrient-quality ER diet was enriched in MUFAs, n-3 PUFAs, fiber, and plant protein and reduced in fructose. Before and after the intervention, intrahepatic lipids, body fat distribution, fasting and postprandial responses to a mixed-meal shake challenge test of cardiometabolic risk factors, lipoproteins, vascular measurements, and adipose tissue transcriptome were assessed. RESULTS The high-nutrient-quality ER diet (-8.4 ± 3.2) induced 2.1 kg more weight loss (P = 0.007) than the low-nutrient-quality ER diet (-6.3 ± 3.9), reduced fasting serum total cholesterol (P = 0.014) and plasma triglycerides (P < 0.001), promoted an antiatherogenic lipoprotein profile, and induced a more pronounced decrease in adipose tissue gene expression of energy metabolism pathways than the low-quality ER diet. Explorative analyses showed that the difference in weight loss between the two ER diets was specifically present in insulin-sensitive subjects (HOMA-IR ≤ 2.5), in whom the high-nutrient-quality diet induced 3.9 kg more weight loss than the low-nutrient-quality diet. CONCLUSIONS A high-nutrient-quality 25% ER diet is more beneficial for cardiometabolic health than a low-nutrient-quality 25% ER diet. Overweight, insulin-sensitive subjects may benefit more from a high- than a low-nutrient-quality ER diet with respect to weight loss, due to potential attenuation of glucose-induced lipid synthesis in adipose tissue.
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Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial.
Holm Nielsen, S, Sardar, S, Siebuhr, AS, Schlemmer, A, Schmidt, EB, Bay-Jensen, AC, Karsdal, MA, Christensen, JH, Kristensen, S
Rheumatology international. 2021;41(6):1065-1077
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Psoriatic arthritis is a chronic inflammatory condition that causes joint pain and swelling along with red, flaky, and scaly skin. Inflammation affects the extracellular matrix, which comprises proteins and molecules that support cartilage, bone, and soft tissues in joints. A high level of collagen fragments is released into the bloodstream as a result. Fish oils and fish are good sources of n-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid and docosahexaenoic acid. Inflammation and joint pain have been shown to be reduced by n-3 PUFA in previous studies. This randomised, double-blinded, placebo-controlled study randomly assigned 142 patients with psoriatic arthritis to receive 3g n-3 PUFA (50% EPA and 50% DHA) or 3g of olive oil as the control for 24 weeks. Taking N-3 PUFA supplementation did not affect extracellular matrix turnover in psoriatic arthritis patients. This may be due to the anti-inflammatory properties of olive oil, which was used as a control, and to the short duration of the study. The benefits of using n-3 PUFA as a therapeutic strategy in patients with psoriatic arthritis need to be evaluated in larger, robust long-term studies. Furthermore, the clinical efficacy of n-3 PUFA cannot be distinguished since 75% of the patients took anti-rheumatic drugs. A study like this can provide healthcare professionals with insights into the potential benefits of n-3 PUFAs, which may aid them in making therapeutic decisions.
Abstract
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013-Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1.
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A Randomized, Double-blind, Placebo-controlled Clinical Study to Investigate the efficacy of Herring Roe Oil for treatment of Psoriasis.
Tveit, KS, Brokstad, KA, Berge, RK, Sæbø, PC, Hallaråker, H, Brekke, S, Meland, N, Bjørndal, B
Acta dermato-venereologica. 2020;100(10):adv00154
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Psoriasis can be divided into mild, moderate or severe psoriasis based on the extent of body surface area covered by psoriasis, and into mild and moderate to severe based on Psoriasis Area Severity Index (PASI). The aim of this study was to investigate the efficacy of capsulated herring roe oil (HRO) in psoriasis patients with PASI <10. This study is a randomised, double-blind, placebo-controlled clinical study. Sixty-four patients with stable, plaque psoriasis were recruited and randomised to one of the two arms: HRO (n=32) or control group (n=32). Results demonstrate improvement of the mean PASI score in the HRO group compared to the control group at 26 weeks. The effect was statistically significant in the intention-to-treat population and in a post-hoc analysis the effect was larger for patients with PASI over 5.5 at baseline. Beneficial effects of treatment on PASI were not observed at the earlier visits (weeks 6, 12 and 18). Authors conclude that HRO supplementation is a safe systemic treatment option in patients with psoriasis with PASI<10.
Abstract
The effect of omega-3 polyunsaturated fatty acid supplements in patients with psoriasis vulgaris has previously been investigated, but interventions varied in source, composition, dose, administration route and duration of treatment. The observed beneficial effects in patients with psoriasis vulgaris using herring roe oil as a dietary supplement prompted this investigation. This randomised, double-blind and placebo-controlled study was designed and performed to explore the efficacy and safety of herring roe oil supplementation in 64 patients with plaque psoriasis (ClinicalTrials.gov: NCT03359577). The primary end-point was comparing the change in mean Psoriasis Area Severity Index (PASI) scores in the herring roe oil treatment group and the placebo group from baseline to week 26. In the intention-to-treat population, a statistically significant improvement in the mean PASI score was observed with herring roe oil compared to placebo at 26 weeks. In the recruited patient group, the measured improvement was greatest in patients with a PASI score from 5.5-9.9 at baseline.
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Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans.
Stekovic, S, Hofer, SJ, Tripolt, N, Aon, MA, Royer, P, Pein, L, Stadler, JT, Pendl, T, Prietl, B, Url, J, et al
Cell metabolism. 2019;30(3):462-476.e6
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Intermittent fasting and calorie restriction are believed to reduce cardiometabolic risk factors and increase longevity. Fasting alternate days (ADF) involves fasting for 36 hours and eating ad libitum for 12 hours. Thirty healthy participants were randomly assigned to a long-term ADF intervention group for ≥6 months against sixty participants in the control group. After completing the cross-sectional study arm, sixty healthy participants in the control group were randomly assigned to either a four-week short-term ADF intervention group or a control group with an ad libitum diet. Study participants adhered well to the fasting regimen. Both short-term and long-term ADF intervention groups showed a significant reduction in calorie intake, improvements in anthropometric and cardiovascular parameters including reduced BMI, substantial reduction in trunk fat, lower heart rate, increased serum β-hydroxybutyrate which is cardioprotective and anti-ageing, reduced circulating triiodothyronine (fT3) levels which indicate longevity. Short-term ADF reduced systolic and diastolic pressure, mean arterial pressure, pulse pressure, and pulse wave velocity. Long-term ADF intervention reduced circulating total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides, the age-related biomarker sICAM-1 for disease and inflammation, and improved lipid and amino acid metabolites. ADF did not affect insulin sensitivity. Although red blood cells and iron levels were altered, ADF interventions were not associated with iron deficiency. Healthcare professionals can use the results of this study to understand the cardioprotective and anti-ageing properties of ADF. However, further long-term robust studies are required to evaluate the effect of long-term ADF on bone health.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Short duration (<4 weeks) alternate day fasting may be an effective way to implement caloric restriction, improve body composition and reduce cardiovascular disease risk in healthy non-overweight adults.
- >6 months alternate fasting does not appear to be associated with reduced bone mass, bone mineral density of the lumbar spine region, white blood cell counts, ferritin and transferrin when compared to healthy controls.
- Both short term and long term alternate day fasting may reduce triiodothyronine in healthy adults. Low levels of fT3 without thyroid gland dysfunction has been associated with longevity in humans.
- Alternate day fasting should be performed alongside a trained clinician to reduce the risk of adverse effects due to critical medical conditions.
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
Animal models have consistently demonstrated the healthspan and lifespan benefits of caloric restriction. However, chronic caloric restriction in humans has proven difficult to maintain.
Intermittent fasting may serve as a more manageable alternative to continuous caloric restriction. This randomised controlled trial and cross sectional analysis aimed to investigate the effects of alternate day fasting (ADF) on heart rate, blood pressure, cholesterol levels, CVD risk, body composition, and the metabolome and proteome of healthy, non-overweight adults (cohort median age between 48 and 52 years).
Methods
Prior to the enrollment of the study a cross sectional analysis was conducted on healthy adults engaged in long term (>6 months) alternate day fasting (n=30) and a control group (n=60).
The 60 participants from the cross sectional analysis control group were then randomised to either a 4 week ADF group or a control group. In both the >6 months and 4 weeks of ADF groups, participants were instructed to eat every second-day ad libitum, but to completely exclude solid and liquid foods and caloric beverages on fasting days.
Results
The cross sectional analysis identified that the alternate day fasting group:
- Consumed fewer calories vs the control group (−28.56%, p=0.0002).
- Had lower levels of circulating total cholesterol (p=0.004), LDL (p=0.011), VLDL (p=0.009), triglycerides (p=0.010) and a lower heart rate (p=0.040) vs the control group.
- Lower levels of soluble intercellular adhesion molecule-1 (sICAM-1) (p value 0.048), an age-associated inflammatory marker.
- Reduced circulating triiodothyronine (p<0.001) compared to the control group.
- In the metabolome, 54 out of 113 detected significantly modified metabolites (p value < 0.05) were at least 20% higher after 36 h of fasting, of which the majority (>95%) were lipids or free fatty acids, including polyunsaturated free fatty acids (PUFAs), α-tocopherol, and a type of vitamin E. 49 metabolites were at least 20% lower, consisting mainly (44.9%) of amino acids or related metabolites. Low levels of circulating amino acids have been found to increase lifespan in model organisms. The authors concluded that the elevation in fatty acids may be due to increased lipolysis from adipose tissue while the reduction in amino acids may be the result of increased gluconeogenesis.
- 13 out of 2,089 significantly (p value < 0.05) modulated protein hits within the PBMC proteome showed an increase of ≥15%, while the remaining proteins were downregulated after 36 h of fasting. Gene set enrichment analysis (GSEA) performed on the PBMC proteome unveiled changes in pathways related to lipid metabolism, pathways related to energy metabolism and stress response.
Following the 4 week intervention the alternate day fasting group demonstrated:
- Reduced caloric intake from baseline vs. the control group (−37.40% vs. −8.22%, p=0.0012).
- Greater reductions in body weight (−3.5kg vs −0.2kg, p<0.0001), BMI (−1.23kg/m2 vs −0.02kg/m2, p<0.0001) and improvements in their fat to lean mass ratio (−6.3% ± 5.0 percentage points, p value < 0.0001).
- Reduced systolic (−4.5mmHg, p=0.006) and diastolic (−2.5mmHg, p=0.03) blood pressure, heart rate (-4.5 b/min, p=0.0019), arterial (−3mmHg, p=0.0087) and pulse pressure (−2.5mmHg, p=0.0088) as well as pulse wave velocity (−1.538%, p=0.0362). Pulse wave velocity measures the rate at which pressure moves down the vessel wall and is a measure of arterial stiffness.
- Reduced circulating triiodothyronine (p<0.001) from baseline values.
Clinical practice applications:
The cross sectional analysis did not identify any differences in the long-term (>6 months) alternate day fasting group and control group in bone mass, bone mineral density of the lumbar spine region, white blood cell counts, ferritin and transferrin when compared to healthy controls. RBC counts and iron metabolism markers in the blood plasma (hematocrit, haemoglobin, iron, and transferrin saturation), were lower in the >6 months of ADF group but stayed within the reference range.
The randomised controlled trial demonstrated that alternate day fasting may be an effective intervention to reduce caloric intake, improve body composition and reduce cardiovascular disease risk in healthy non-overweight adults within 4 weeks.
Compliance rate was high with only 1 drop out in the alternate day fasting group of the randomised controlled trial.
Both the 4 week intervention and long-term (>6 month) analysis identified a reduction in triiodothyronine amongst the ADF groups. Low levels of triiodothyronine in absence of thyroid gland dysfunction has been associated with longevity in humans.
Considerations for future research:
- Future larger studies in non-healthy and/or overweight/obese populations would be useful to determine safety and efficacy of alternate day fasting within that population group.
- Further studies comparing alternate day fasting with continuous caloric restriction would be useful to identify which intervention is most beneficial for body composition and cardioprotection.
- Subgroup analysis of diet composition and diet quality may help to identify the most appropriate/inappropriate diet to compliment alternate day fasting.
- Longer duration randomised controlled trials are needed to identify any health risks or deficiencies which may develop with long term caloric restriction and alternate day fasting.
Abstract
Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.
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Mixed Nut Consumption May Improve Cardiovascular Disease Risk Factors in Overweight and Obese Adults.
Abbaspour, N, Roberts, T, Hooshmand, S, Kern, M, Hong, MY
Nutrients. 2019;11(7)
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A large portion of heart disease cases are preventable through lifestyle and dietary modifications. The aim of this study was to assess the effect of daily intake of 42.5 g of mixed nuts on cardiovascular disease (CVD) risk factors in overweight and obese adults. This study is an 8-week randomized, parallel-arm, controlled trial with two isocaloric treatment groups of mixed-nuts and pretzels. A total of 54 participants (22 females and 32 males) were recruited. Results indicate that supplementation of 42.5 g/day of mixed nuts for 8 weeks decreases body weight, insulin, blood glucose, and lactate dehydrogenase [enzyme] levels compared with consumption of an isocaloric amount of pretzels. Additionally, consumption of pretzels increased low-density lipoprotein cholesterol and triglyceride levels while decreasing high-density lipoprotein cholesterol. Authors conclude that the incorporation of mixed nuts into a usual diet improves some risk factors for CVD.
Abstract
Emerging research indicates that nuts are a source of health-promoting compounds demonstrating cardioprotective benefits. However, most studies have assessed the effect of single nuts rather than a nut mixture. The objective of this study was, therefore, to examine the effect of mixed-nut consumption on cardiovascular disease (CVD) risk factors in overweight and obese adults. In a randomized, parallel-arm, controlled trial, 48 participants consumed isocaloric (250 kcal) amounts of pretzels or mixed-nuts. Body weight (BW) (p = 0.024), BMI (p = 0.043), and insulin levels (p = 0.032) were significantly lower in the nut group compared to the pretzel group. Mixed-nut consumption also significantly reduced glucose (p = 0.04) and insulin (p = 0.032) levels after 4 and 8 weeks compared to baseline, respectively. Lactate dehydrogenase of the nut group was significantly lower than the pretzel group (p = 0.002). No significant differences were detected between groups for triglycerides, LDL-C, and HDL-C. However, pretzel consumption increased triglycerides (p = 0.048) from 4 weeks to 8 weeks. Moreover, LDL-C increased (p = 0.038) while HDL-C transiently decreased (p = 0.044) from baseline to 4 weeks. No significant lipid changes were detected within the nut group. Our results suggest that supplementing the diet with mixed-nuts could improve CVD risk factors by improving BW and glucose regulation in comparison to a common carbohydrate-rich snack without promoting the negative effects on lipids detected with pretzels.
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A Mediterranean Diet with Fresh, Lean Pork Improves Processing Speed and Mood: Cognitive Findings from the MedPork Randomised Controlled Trial.
Wade, AT, Davis, CR, Dyer, KA, Hodgson, JM, Woodman, RJ, Keage, HAD, Murphy, KJ
Nutrients. 2019;11(7)
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Dementia is characterised by severe cognitive impairment and reduced quality of life. Observational studies have demonstrated that populations following a traditional Mediterranean diet experience less cognitive decline and a lowered risk of dementia. The aim of this study was to examine a Mediterranean diet modified to include 2–3 fresh servings of pork each week across measures of cognitive function and well-being. The study is a 24-week parallel randomised controlled crossover design to compare a Mediterranean diet with 2-3 weekly servings of fresh, lean pork (MedPork) and a low-fat control diet (LF). It recruited adults aged 45–80 years due to their increased risk of developing cardiovascular disease. Results indicate that compared with the LF control diet, the MedPork intervention led to higher performance in the cognitive domain of processing speed and higher scores for the SF-36 subscale emotional role functioning. No significant differences were observed for other domains of cognitive function, nor for additional measures of psychological well-being. Authors conclude that the MedPork intervention can improve processing speed and mood in a population at risk of cardiovascular disease and therefore dementia.
Abstract
BACKGROUND The Mediterranean diet may be capable of improving cognitive function. However, the red meat restrictions of the diet could impact long-term adherence in Western populations. The current study therefore examined the cognitive effects of a Mediterranean diet with additional red meat. METHODS A 24-week parallel crossover design compared a Mediterranean diet with 2-3 weekly servings of fresh, lean pork (MedPork) and a low-fat (LF) control diet. Thirty-five participants aged between 45 and 80 years and at risk of cardiovascular disease followed each intervention for 8 weeks, separated by an 8-week washout period. Cognitive function was assessed using the Cambridge Neuropsychological Test Automated Battery. Psychological well-being was measured through the SF-36 Health Survey and mood was measured using the Profile of Mood States (POMS). RESULTS During the MedPork intervention, participants consumed an average of 3 weekly servings of fresh pork. Compared to LF, the MedPork intervention led to higher processing speed performance (p = 0.01) and emotional role functioning (p = 0.03). No other significant differences were observed between diets. CONCLUSION Our findings indicate that a Mediterranean diet inclusive of fresh, lean pork can be adhered to by an older non-Mediterranean population while leading to positive cognitive outcomes.
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Untargeted metabolomic on urine samples after α-lipoic acid and/or eicosapentaenoic acid supplementation in healthy overweight/obese women.
Romo-Hualde, A, Huerta, AE, González-Navarro, CJ, Ramos-López, O, Moreno-Aliaga, MJ, Martínez, JA
Lipids in health and disease. 2018;17(1):103
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Eicosapentaenoic acid (EPA - an omega-3 fatty acid) and alpha-lipoic acid (an antioxidant) have both been investigated for their beneficial impacts on weight loss and heart health. The aim of this double-blind randomised placebo-controlled intervention lasting 8 weeks was to assess the effect of dietary supplementation with EPA and alpha-lipoic acid, separately or in combination, and together with a calorie restricted diet, on breakdown products (metabolites) present in the urine. The study recruited a group of 70 healthy overweight/obese sedentary females. Results indicate a higher reduction in body mass index and fat mass in those groups supplemented with alpha-lipoic acid. EPA supplementation had no effect on urinary breakdown products. Authors conclude that alpha-lipoic acid administration has beneficial effects on body weight reduction, mainly through its antioxidant properties.
Abstract
BACKGROUND Eicosapentaenoic acid (EPA) and α-lipoic acid (α-LA) have been investigated for their beneficial effects on obesity and cardiovascular risk factors. In the current research, the goal was to evaluate metabolomic changes following the dietary supplementation of these two lipids, alone or combined in healthy overweight/obese sedentary women following an energy-restricted diet. For this purpose, an untargeted metabolomics approach was conducted on urine samples using liquid chromatography coupled with time of flight mass spectrometry (HPLC-TOF-MS). METHODS This is a short-term double blind placebo-controlled study with a parallel nutritional design that lasted 10 weeks. Participants were assigned to one of the 4 experimental groups [Control, EPA (1.3 g/d), α-LA (0.3 g/d) and EPA+α-LA (1.3 g/d + 0.3 g/d)]. All intervention groups followed an energy-restricted diet of 30% less than total energy expenditure. Clinically relevant biochemical measurements were analyzed. Urine samples (24 h) were collected at baseline and after 10 weeks. Untargeted metabolomic analysis on urine samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were performed for the pattern recognition and characteristic metabolites identification. RESULTS Urine samples were scattered in the PCA scores plots in response to the supplementation with α-LA. Totally, 28 putative discriminant metabolites in positive ionization, and 6 in negative ionization were identified among groups clearly differentiated according to the α-LA administration. Remarkably is the presence of an ascorbate intermediate metabolite (one of the isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate) in the groups supplemented with α-LA. This fact might be associated with antioxidant properties of both α-LA and ascorbic acid. Correlations between phenotypical parameters and putative metabolites of provided additional information on whether there is a direct or inverse relationship between them. Especially interesting are the negative correlation between ascorbate intermediate metabolite and asymmetric dimethylarginine (ADMA) and the positive one between superoxide dismutase (SOD) and α-LA supplementation. CONCLUSIONS This metabolomic approach supports that the beneficial effects of α-LA administration on body weight reduction may be partly explained by the antioxidant properties of this organosulfur carboxylic acid mediated by isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate. TRIAL REGISTRATION Clinicaltrials.gov NCT01138774 .