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The effect of weight loss following 18 months of lifestyle intervention on brain age assessed with resting-state functional connectivity.
Levakov, G, Kaplan, A, Yaskolka Meir, A, Rinott, E, Tsaban, G, Zelicha, H, Blüher, M, Ceglarek, U, Stumvoll, M, Shelef, I, et al
eLife. 2023;12
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Obesity is linked to premature brain ageing and subsequent development of diseases such as dementia and Alzheimer’s disease. Weight loss through lifestyle modifications may be able to attenuate brain ageing. This sub-study of 102 individuals from a randomised control trial known as the Dietary Intervention Randomised Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS), aimed to determine the effect of 18 months lifestyle modifications and weight loss on brain age. The results showed that a decrease in BMI attenuated brain ageing and that 1% body weight loss reduced brain ageing by 8.9 months. Reduced brain age was also associated with decreased waist circumference and fat mass. Interestingly, reduced consumption of processed foods was also associated with reduced brain age. It was concluded that weight loss can be of benefit to brain health. This study could be used by healthcare professionals to understand that people with obesity are at a higher risk of brain related diseases, and that weight loss may be an effective way to prevent their development.
Abstract
BACKGROUND Obesity negatively impacts multiple bodily systems, including the central nervous system. Retrospective studies that estimated chronological age from neuroimaging have found accelerated brain aging in obesity, but it is unclear how this estimation would be affected by weight loss following a lifestyle intervention. METHODS In a sub-study of 102 participants of the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS) trial, we tested the effect of weight loss following 18 months of lifestyle intervention on predicted brain age based on magnetic resonance imaging (MRI)-assessed resting-state functional connectivity (RSFC). We further examined how dynamics in multiple health factors, including anthropometric measurements, blood biomarkers, and fat deposition, can account for changes in brain age. RESULTS To establish our method, we first demonstrated that our model could successfully predict chronological age from RSFC in three cohorts (n=291;358;102). We then found that among the DIRECT-PLUS participants, 1% of body weight loss resulted in an 8.9 months' attenuation of brain age. Attenuation of brain age was significantly associated with improved liver biomarkers, decreased liver fat, and visceral and deep subcutaneous adipose tissues after 18 months of intervention. Finally, we showed that lower consumption of processed food, sweets and beverages were associated with attenuated brain age. CONCLUSIONS Successful weight loss following lifestyle intervention might have a beneficial effect on the trajectory of brain aging. FUNDING The German Research Foundation (DFG), German Research Foundation - project number 209933838 - SFB 1052; B11, Israel Ministry of Health grant 87472511 (to I Shai); Israel Ministry of Science and Technology grant 3-13604 (to I Shai); and the California Walnuts Commission 09933838 SFB 105 (to I Shai). Obesity is linked with the brain aging faster than would normally be expected. Researchers are able to capture this process by calculating a person’s ‘brain age’ – how old their brain appears on detailed scans, regardless of chronological age. This approach also helps to monitor how certain factors, such as lifestyle, can influence brain aging over relatively short time scales. It is not clear whether lifestyle interventions that promote weight loss can help to slow obesity-driven brain aging. To answer this question, Levakov et al. studied 102 individuals who met the criteria for obesity and took part in a lifestyle intervention aimed to improve diet and physical activity levels over 18 months. The participants received a brain scan at the beginning and the end of the program; additional tests and measurements were also conducted at these times to capture other biological processes impacted by obesity, such as liver health. Levakov et al. used the brain scans taken at the start and end of the study to examine the impact of the lifestyle intervention on the aging trajectory. The results revealed that a reduction in body weight of 1% led to the participants’ brain age being nearly 9 months younger than the expected brain age after 18 months. This attenuated aging was associated with changes in other biological measures, such as decreased liver fat and liver enzymes. Increases in liver fat and production of specific liver enzymes were previously shown to negatively impact brain health in Alzheimer’s disease. Finally, examining more closely the food consumption reports completed by participants showed that reduced consumption of processed food, sweets and beverages were linked to attenuated brain aging. The findings show that lifestyle interventions which promote weight loss can have a beneficial impact on the aging trajectory of the brain observed with obesity. The next steps will include determining whether slowing down obesity-driven brain aging results in better clinical outcomes for patients. In addition, the work by Levakov et al. demonstrates a potential strategy to evaluate the success of lifestyle changes on brain health. With global rates of obesity rising, identifying interventions that have a positive impact on brain health could have important clinical, educational and social impacts.
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The effects of time-restricted eating and weight loss on bone metabolism and health: a 6-month randomized controlled trial.
Papageorgiou, M, Biver, E, Mareschal, J, Phillips, NE, Hemmer, A, Biolley, E, Schwab, N, Manoogian, ENC, Gonzalez Rodriguez, E, Aeberli, D, et al
Obesity (Silver Spring, Md.). 2023;31 Suppl 1:85-95
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Intermittent fasting (IF) involves an alternation of abstinence and consumption of food and caloric beverages over a cycle of hours to days. Time-restricted feeding (in animals) or eating (TRE in humans) is a form of IF that entails restricting eating within a window of 4 to 12 hours per 24-hour cycle and prolonging the time spent in the fasted state to realign eating-fasting patterns with circadian rhythms. The aim of this study was to explore the impact of a 6-month randomised controlled trial of TRE versus standard dietary advice (SDA, active control arm) on bone metabolism and health in a population with at least one component of the metabolic syndrome. This study is a secondary analysis of an open-label 6-month randomised controlled trial in which participants who ate within a time interval > 14 hours per 24-hour cycle (n=54) were randomised to TRE or SDA (active control) with a 1:1 allocation ratio. A total of 42 participants (76% women) with available bone turnover markers and/or bone mass measurements were included in this study. Results show that there weren’t any detrimental effects on bone health outcomes i.e. bone metabolism or bone loss after 6 months of TRE. Additionally, weight loss following a period of TRE might be associated with small bone-sparing effects compared with SDA. Authors conclude that future studies of longer duration (>6 months) assessing multiple bone phenotypes are required in order to confirm the study’s findings and explore the effects of various TRE regimens particularly among individuals at risk for bone fragility such as postmenopausal women and the elderly.
Abstract
OBJECTIVE This study explored the impact of time-restricted eating (TRE) versus standard dietary advice (SDA) on bone health. METHODS Adults with ≥1 component of metabolic syndrome were randomized to TRE (ad libitum eating within 12 hours) or SDA (food pyramid brochure). Bone turnover markers and bone mineral content/density by dual energy x-ray absorptiometry were assessed at baseline and 6-month follow-up. Statistical analyses were performed in the total population and by weight loss response. RESULTS In the total population (n = 42, 76% women, median age 47 years [IQR: 31-52]), there were no between-group differences (TRE vs. SDA) in any bone parameter. Among weight loss responders (≥0.6 kg weight loss), the bone resorption marker β-carboxyterminal telopeptide of type I collagen tended to decrease after TRE but increase after SDA (between-group differences p = 0.041), whereas changes in the bone formation marker procollagen type I N-propeptide did not differ between groups. Total body bone mineral content decreased after SDA (p = 0.028) but remained unchanged after TRE (p = 0.31) in weight loss responders (between-group differences p = 0.028). Among nonresponders (<0.6 kg weight loss), there were no between-group differences in bone outcomes. CONCLUSIONS TRE had no detrimental impact on bone health, whereas, when weight loss occurred, it was associated with some bone-sparing effects compared with SDA.
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Evidence of lifestyle interventions in a pregnant population with chronic hypertension and/or pre-existing diabetes: A systematic review and narrative synthesis.
Goddard, L, Patel, R, Astbury, NM, Tucker, K, McManus, RJ
Pregnancy hypertension. 2023;31:60-72
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Chronic hypertension complicates ≤5 % of pregnancies, and those entering pregnancy with a pre-existing diagnosis of diabetes has a global prevalence of between 0.5 % and 2.6 %. The aim of this study was to collate the evidence around lifestyle interventions during pregnancy for women with chronic hypertension and/or pre-existing diabetes (type 1 and type 2). This study is a systematic review and meta-analysis of nine randomised controlled trials. Results show lack of clarity and data on the effect of lifestyle interventions in pregnant women with chronic hypertension and/or pre-existing diabetes, thereby exposing key gaps in the literature. Authors conclude that there is a shortage of primary interventional studies examining the effect of lifestyle interventions in high-risk pregnant populations who enter pregnancy with chronic conditions.
Abstract
BACKGROUND Pregnant people with chronic hypertension, pre-existing diabetes or both are at high risk of developing cardiovascular disease. Lifestyle interventions play an important role in disease management in non-pregnant populations. AIM: To review the existing evidence of randomised controlled trials (RCTs) that examine lifestyle interventions in pregnant people with chronic hypertension and/or pre-existing diabetes. METHODS A systematic review and narrative synthesis was conducted. Five electronic databases were searched from inception to April 2021 for RCTs evaluating antenatal lifestyle interventions in people with chronic hypertension and/or pre-existing diabetes with outcomes to include weight or blood pressure change. RESULTS Nine randomised controlled trials including 7438 pregnant women were eligible. Eight studies were mixed pregnant populations that included women with chronic hypertension and/or pre-existing diabetes. One study included only pregnant women with pre-existing diabetes. Intervention characteristics and procedures varied and targeted diet, physical activity and/or gestational weight. All studies reported weight and one study reported blood pressure change. Outcome data were frequently unavailable for the subset of women of interest, including subgroup data on important pregnancy and birth complications. Eligibility criteria were often ambiguous and baseline data on chronic hypertension was often omitted. CONCLUSION A lack of primary interventional trials examining the effect of lifestyle interventions on weight and blood pressure outcomes in pregnant populations with chronic hypertension and/or pre-existing diabetes was evident. Lifestyle modification has the potential to alter disease progression. Future trials should address the ambiguity and frequent exclusion of these important populations.
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Macronutrient composition and its effect on body composition changes during weight loss therapy in patients with non-alcoholic fatty liver disease: Secondary analysis of a randomized controlled trial.
Lindqvist, C, Holmer, M, Hagström, H, Petersson, S, Tillander, V, Brismar, TB, Stål, P
Nutrition (Burbank, Los Angeles County, Calif.). 2023;110:111982
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Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and it is closely linked to overweight and obesity. Weight loss leads to an amelioration of NAFLD, which preferably should lead to loss of fat mass while maintaining lean body mass. The aim of this study was to examine if different diet compositions during weight loss therapy were associated with different reductions in abdominal fat mass compared with standard weight loss advice given by a physician. This study was a secondary analysis of data collected in an open-label, randomised controlled trial. The trial examined the effect of two popular weight loss diets, calorie-restricted intermittent fasting (5:2) and a calorie-restricted low-carbohydrate high-fat (LCHF) diet, compared with standard of care (SOC) on reduction in liver fat in 74 persons with NAFLD. Results show that a dietitian-led nutrition counselling treatment with an LCHF or 5:2 diet reduced weight to a higher extent than physician-supported SOC during a 12-wk treatment. Improvements in most of the variables related to body composition parameters and metabolic function were found, independent of dietary composition. Furthermore, during weight loss, visceral fat was mobilized to a greater extent than subcutaneous fat. Authors conclude that further studies are needed with a focus on the effect of diet composition on body composition changes during weight loss.
Abstract
OBJECTIVES Dietary composition may affect body composition during weight loss therapy. We tested the hypothesis of whether dietary macronutrient composition influences the reduction of total abdominal adipose tissue, subcutaneous adipose tissue (SAT), or visceral adipose tissue (VAT) during weight loss. METHODS Dietary macronutrient composition and body composition were analyzed as a secondary outcome of a randomized controlled trial of 62 participants with non-alcoholic fatty liver disease. Patients were randomly assigned to a calorie-restricted intermittent fasting (5:2), calorie-restricted low-carbohydrate high-fat (LCHF), or healthy lifestyle advice (standard-of-care) diet in a 12-wk intervention phase. Dietary intake was assessed by self-reported 3-d food diaries and by characterization of total plasma fatty acid profile. Percentage of energy intake (E%) from different macronutrients was calculated. Body composition was assessed by magnetic resonance imaging and anthropometric measurements. RESULTS The macronutrient composition differed significantly between the 5:2 (fat 36 E% and carbohydrates 43 E%) and the LCHF (fat 69 E% and carbohydrates 9 E%) groups (P < 0.001). Weight loss was similar in the 5:2 and LCHF groups (-7.2 [SD = 3.4] kg versus 8.0 [SD = 4.8] kg; P = 0.44) and significantly larger than for standard of care (-2.5 kg [SD = 2.3]; P < 0.001). The volume of total abdominal fat, adjusted for height, decreased on average by 4.7% (standard of care), 14.3% (5:2), and 17.7% (LCHF), with no significant differences between the 5:2 and LHCF groups (P = 0.32). VAT and SAT, adjusted for height, decreased on average by 17.1% and 12.7% for 5:2, respectively, and by 21.2% and 17.9% for LCHF, with no significant group differences (VAT [P = 0.16] and SAT [P = 0.10]). VAT was mobilized to a greater extent than SAT in all diets. CONCLUSIONS The 5:2 and LCHF diets had similar effects on changes in intraabdominal fat mass and anthropometrics during weight loss. This might indicate that overall weight loss is more important than diet composition to achieve changes in total abdominal adipose tissue, VAT, or SAT. The results of the present study suggest that there is a need for further studies on the effect of diet composition on body composition changes during weight loss therapy.
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Is Extra Virgin Olive Oil the Critical Ingredient Driving the Health Benefits of a Mediterranean Diet? A Narrative Review.
Flynn, MM, Tierney, A, Itsiopoulos, C
Nutrients. 2023;15(13)
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Cardiovascular diseases (CVDs) are the largest contributor to deaths globally, followed by cancers, chronic respiratory diseases and diabetes. It is estimated that 90% of deaths from CVD can be prevented with modifiable risk factors such as diet. The Mediterranean diet, which is rich in extra virgin olive oil (EVOO), is important in the prevention of chronic diseases. There is however very little focus on differentiating healthy fats such as EVOO from other fats and oils in dietary guidelines. This review of 34 studies aims to compare the effect of diets that include EVOO on cardiometabolic risk factors for heart disease, metabolic syndrome, and type 2 diabetes. It looks at the effects on blood pressure (SBP), low- and high-density lipoprotein cholesterol, (HDP-c and LDD-c) fasting blood glucose (FBG) and body weight. It also assesses from published studies the minimum daily amount of EVOO and the shortest time needed to see improvements in the risk factors. There is evidence to support EVOO in improving SBP in patients with high blood pressure, with studies suggesting that specific phenols in the oil may be important compared with a refined olive oil. Compared with other dietary fats or low-fat diets, EVOO can decrease LDL-c and increase HDL-c. Diets including daily EVOO are effective for weight loss. The effect of EVOO on FBG compared with other diets is not yet clear. The authors state that EVOO would be a far superior choice compared with other dietary fats, low-fat diets, or refined olive oil. The daily use of EVOO starting at approximately two tablespoons a day will improve a range of risk factors in as few as three weeks.
Abstract
Most chronic diseases are preventable with a healthy diet, although there is debate about the optimal dietary approach. Increasingly more countries are focusing on food-based guidelines rather than the traditional nutrient-based approach. Although there is good agreement on plant foods, controversy remains about the types and amounts of fats and oils. This narrative review aims to systematically summarize and evaluate the latest evidence on the protective effects of extra virgin olive oil (EVOO) on disease risk factors. A systematic search of the relevant literature using PubMed, Cochrane Library, and Embase databases was conducted for the years 2000 through December 2022. A narrative synthesis was then undertaken. Of 281 retrieved articles, 34 articles fulfilled our inclusion criteria and were included. Compared with other dietary fats and low-fat diets, EVOO is superior in the management of clinical biomarkers including lowering blood pressure and LDL-c, increasing protective HDL-c, improving glycemic control, and weight management. The protective effects of EVOO are likely due to its polyphenol content rather than the monounsaturated fat content. It is therefore important to promote the regular use of EVOO in the context of healthy dietary patterns such as the Mediterranean diet for maximal health benefit.
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Time-restricted eating and exercise training improve HbA1c and body composition in women with overweight/obesity: A randomized controlled trial.
Haganes, KL, Silva, CP, Eyjólfsdóttir, SK, Steen, S, Grindberg, M, Lydersen, S, Hawley, JA, Moholdt, T
Cell metabolism. 2022;34(10):1457-1471.e4
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A healthy diet and regular physical activity are primary lifestyle strategies for the prevention and treatment of obesity and its associated conditions. However, poor adherence rates to these strategies limit their effectiveness. Time-restricted eating (TRE) is a popular dietary strategy that emphasises the timing of meals in alignment with diurnal circadian rhythms, permitting ad libitum energy intake during a restricted eating window (8–10 h between the first and last energy intake of the day). The aim of this study was to investigate the isolated and combined effects of TRE and high-intensity interval training (HIIT) on glycaemic control and cardiometabolic health outcomes in women with overweight/obesity. This study is a 7-week randomised controlled trial with four parallel groups: TRE (energy intake limited to a %10-h eating window every day), HIIT (three supervised treadmill exercise sessions per week), a combination (TREHIIT), and a control group (CON, no intervention). Participants (n=131) were randomly assigned to one of the four groups. . Results show that 7 weeks of TRE, HIIT, or a combination failed to improve glycaemic control in reproductive-aged women with overweight/obesity. However, the combination of TRE and HIIT significantly reduced glycated haemoglobin levels compared with CON and induced greater losses in body weight, fat mass, and visceral fat area compared with either intervention alone. Isolated TRE resulted in lower nocturnal glucose concentrations compared with CON. Authors conclude that combining TRE with HIIT can rapidly induce several health benefits and decrease metabolic disease risk in women with overweight/obesity. In fact, the high rates of compliance and adherence shown in their findings, highlight the potential of these diet-exercise (TRE and HIIT) protocols to be implemented in clinical practice for treatment and primary prevention of overweight/ obesity.
Abstract
Diet modification and exercise training are primary lifestyle strategies for obesity management, but poor adherence rates limit their effectiveness. Time-restricted eating (TRE) and high-intensity interval training (HIIT) improve cardiometabolic health in at-risk individuals, but whether these two interventions combined induce superior improvements in glycemic control than each individual intervention is not known. In this four-armed randomized controlled trial (ClinicalTrials.gov NCT04019860), we determined the isolated and combined effects of 7 weeks of TRE (≤10-h daily eating window, with ad libitum energy intake) and HIIT (three exercise sessions per week), compared with a non-intervention control group, on glycemic control and secondary cardiometabolic outcomes in 131 women (36.2 ± 6.2 years) with overweight/obesity. There were no statistically significant effects after isolated TRE, HIIT, or a combination (TREHIIT) on glucose area under the curve during an oral glucose tolerance test (the primary outcome) compared with the control group (TRE, -26.3 mmol/L; 95% confidence interval [CI], -82.3 to 29.7, p = 0.36; HIIT, -53.8 mmol/L; 95% CI, -109.2 to 1.6, p = 0.057; TREHIIT, -41.3 mmol/L; 95% CI, -96.4 to 13.8, p = 0.14). However, TREHIIT improved HbA1c and induced superior reductions in total and visceral fat mass compared with TRE and HIIT alone. High participant adherence rates suggest that TRE, HIIT, and a combination thereof may be realistic diet-exercise strategies for improving markers of metabolic health in women at risk of cardiometabolic disease.
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Effects of the 5:2 intermittent fasting diet on non-alcoholic fatty liver disease: A randomized controlled trial.
Kord Varkaneh, H, Salehi Sahlabadi, A, Găman, MA, Rajabnia, M, Sedanur Macit-Çelebi, M, Santos, HO, Hekmatdoost, A
Frontiers in nutrition. 2022;9:948655
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Non-alcoholic fatty liver disease (NAFLD) is associated with modifiable risk factors such as obesity, diabetes and metabolic syndrome. The 5:2 diet is an intermittent fasting regimen in which you fast for two days and eat liberally for five days per week. Time-restricted eating or intermittent fasting is a great way to limit energy intake and manage metabolic markers, making fasting diets like the 5:2 a viable option for the treatment of NAFLD. In this study, fifty patients with NAFLD were randomly assigned to either the intermittent fasting (5:2) or the control group. In the 5:2 group, the intervention resulted in a modest reduction in calorie intake. Participants on the 5:2 diet showed significant improvements in biomarkers of NAFLD, inflammatory markers, and body composition after 12 weeks of intervention. An evaluation of the effectiveness of a 5:2 diet on improving lipid profiles and diabetes requires further robust research. This study provides healthcare professionals insight into the benefits of implementing intermittent fasting as a cost-effective and safe therapeutic method.
Abstract
Background and aims: Dietary regimens are crucial in the management of non-alcoholic fatty liver disease (NAFLD). The effects of intermittent fasting (IF) have gained attention in this regard, but further research is warranted. Thus, we aimed to ascertain the overall effects of the 5:2 IF diet (5 days a week of normal food intake and 2 consecutive fasting days) in patients with NAFLD compared to a control group (usual diet). Methods and results: A 12-week randomized controlled trial was performed to evaluate the effects of the 5:2 IF diet on anthropometric indices, body composition, liver indices, serum lipids, glucose metabolism, and inflammatory markers in patients with NAFLD. The IF group (n = 21) decreased body weight (86.65 ± 12.57-82.94 ± 11.60 kg), body mass index (30.42 ± 2.27-29.13 ± 1.95 kg/m2), waist circumference (103.52 ± 6.42-100.52 ± 5.64 cm), fat mass (26.64 ± 5.43-23.85 ± 5.85 kg), fibrosis (6.97 ± 1.94-5.58 ± 1.07 kPa), steatosis scores/CAP (313.09 ± 25.45-289.95 ± 22.36 dB/m), alanine aminotransferase (41.42 ± 20.98-28.38 ± 15.21 U/L), aspartate aminotransferase (34.19 ± 10.88-25.95 ± 7.26 U/L), triglycerides (171.23 ± 39.88-128.04 ± 34.88 mg/dl), high-sensitivity C-reactive protein (2.95 ± 0.62 -2.40 ± 0.64 mg/L), and cytokeratin-18 (1.32 ± 0.06-1.19 ± 0.05 ng/ml) values compared to the baseline and the end of the control group (n = 23)-p ≤ 0.05 were considered as significant. However, the intervention did not change the levels of high-density lipoprotein cholesterol, total cholesterol, low-density lipoprotein cholesterol, fasting blood sugar, insulin, HOMA-IR, and total antioxidant capacity. Conclusion: Adhering to the 5:2 IF diet can reduce weight loss and related parameters (fat mass and anthropometric indicators of obesity), as well as hepatic steatosis, liver enzymes, triglycerides, and inflammatory biomarkers in patients with NAFLD.
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Efficacy and safety of oral alpha-lipoic acid supplementation for type 2 diabetes management: a systematic review and dose-response meta-analysis of randomized trials.
Jibril, AT, Jayedi, A, Shab-Bidar, S
Endocrine connections. 2022;11(10)
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Many studies have shown that type 2 diabetes is associated with increased formation of free radicals and decreased antioxidant potential, leading to oxidative damage of cell components. Increased formation of free radicals and decreased antioxidant potential, coupled with lipid abnormalities, are substantial risk factors for developing complications, especially microvascular ones. The aim of this study was to investigate the effect of oral supplementation of alpha-lipoic acid (ALA) on cardiometabolic risk factors in patients with type 2 diabetes. This study is a systematic review and dose–response meta-analysis of 16 randomised controlled trials with a total of 1035 patients with type 2 diabetes. Results show that: - each 500 mg/day oral ALA supplementation reduced haemoglobin A1c and body weight but did not affect low-density lipoprotein cholesterol concentration. - ALA supplementation reduced c-reactive protein, fasting plasma glucose, serum triglycerides, and diastolic blood pressure but it had no affect on serum total cholesterol and high-density lipoprotein cholesterol concentrations and systolic blood pressure. Authors conclude that their findings do not support ALA supplementation in clinical practice for patients with type 2 diabetes.
Abstract
OBJECTIVE To examine the dose-dependent influence of oral alpha-lipoic acid (ALA) supplementation on cardiometabolic risk factors in patients with type 2 diabetes (T2D). DESIGN We followed the instructions outlined in the Cochrane Handbook for Systematic Reviews of Interventions and the Grading of Recommendations, Assessment, Development, and Evaluation Handbook to conduct our systematic review. The protocol of the study was registered in PROSPERO (CRD42021260587). METHOD We searched PubMed, Scopus, and Web of Science to May 2021 for trials of oral ALA supplementation in adults with T2D. The primary outcomes were HbA1c, weight loss, and LDL cholesterol (LDL-C). Secondary outcomes included fasting plasma glucose (FPG), triglyceride (TG), C-reactive protein (CRP), and blood pressure. We conducted a random-effects dose-response meta-analysis to calculate the mean difference (MD) and 95% CI for each 500 mg/day oral ALA supplementation. We performed a nonlinear dose-response meta-analysis using a restricted cubic spline. RESULTS We included 16 trials with 1035 patients. Each 500 mg/day increase in oral ALA supplementation significantly reduced HbA1c, body weight, CRP, FPG, and TG. Dose-response meta-analyses indicated a linear decrement in body weight at ALA supplementation of more than 600 mg/day (MD600 mg/day: -0.30 kg, 95% CI: -0.04, -0.57). A relatively J-shaped effect was seen for HbA1c (MD: -0.32%, 95% CI: -0.45, -0.18). Levels of FPG and LDL-C decreased up to 600 mg/day ALA intake. The point estimates were below minimal clinically important difference thresholds for all outcomes. CONCLUSION Despite significant improvements, the effects of oral ALA supplementation on cardiometabolic risk factors in patients with T2D were not clinically important.
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The Effect of Omega-3 Enriched Oral Nutrition Supplement on Nutritional Indices and Quality of Life in Gastrointestinal Cancer Patients: A Randomized Clinical Trial.
Sim, E, Kim, JM, Lee, SM, Chung, MJ, Song, SY, Kim, ES, Chun, HJ, Sung, MK
Asian Pacific journal of cancer prevention : APJCP. 2022;23(2):485-494
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Cancer cachexia is a multifactorial condition that reveals impairments in energy and protein balance leading to weight loss through the loss of skeletal muscle and body fat. Nutritional status of cancer patients affects therapeutic efficacy, and the disease survival is influenced by the degree of anorexia. The aim of this study was to evaluate the efficacy of omega-3 fatty acids fortified nutrition supplement intervention on nutritional status, quality of life (QOL) and pro-inflammatory cytokine concentrations of cancer patients. This study was a randomised controlled study. Participants (n = 58) included in the study were patients who were in stages between II to IV receiving one or more cancer therapies without taking any nutritional supplements. Both control and experimental groups received regular nutrition counselling and education, while only the experimental group was asked to take oral nutrition supplements (ONS) twice a day (400 ml, 400 kcal). Results show that ONS intervention: - alleviated symptoms of gastrointestinal symptoms including nausea, vomiting and constipation; - exerted improvements in many of QOL indices; and - did not improve (statistically significant) biochemical markers of nutritional status and concentration level of pro-inflammatory cytokines. Authors conclude that nutritional supplements can improve some of the QOL components which need evidence-based explanation in mechanistic aspects.
Abstract
OBJECTIVE Gastrointestinal (GI) cancer patients often experience severe malnutrition during cancer therapies due to gastrointestinal dysfunctions including poor digestion and absorption as well as tumor-associated anorexia. In this study, we performed a randomized clinical trial to determine the efficacy of oral nutrition supplement (ONS) enriched with omega-3 fatty acids on nutritional status, quality of life (QOL), and pro-inflammatory indices. METHODS Patients diagnosed with GI cancers were recruited and screened for eligibility. A total of 58 patients were randomly allocated to either the control group (n=27) or the experimental group (n=31). The intervention group received 200 ml ONS twice a day while the control group received routine care. Anthropometrics, Patient-Generated Subjective Global Assessment (PG-SGA) score, QOL score and nutrient intake data were collected at baseline, week 4 and week 8. Blood was drawn for biochemical assessments. Nine patients from each group dropped out of the study Forty patients (18 control patients and 22 intervention patients) completed the study. RESULTS This study showed that ONS intervention improved PG-SGA scores in the intervention group (p<0.01). Scores of physical functioning score and role functioning were declined only in the control group and the difference between week 8 and baseline for role functioning was significant (p<0.001). Fatigue score was steadily decreased in the experiment group, and the differences between week 8 and baseline was significant between two groups (p<0.02). However, no statistically significant improvement in biochemical markers of nutritional status and pro-inflammatory cytokine concentrations were found. These results suggests that ONS intervention for 8 weeks improves PG-SGA scores and QOL scores in patients undergoing cancer therapy.
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A Double-Blind, Placebo-Controlled Randomized Phase IIa Study: Evaluating the Effect of Curcumin for Treatment of Cancer Anorexia-Cachexia Syndrome in Solid Cancer Patients.
Chaiworramukkul, A, Seetalarom, K, Saichamchan, S, Prasongsook, N
Asian Pacific journal of cancer prevention : APJCP. 2022;23(7):2333-2340
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Cancer anorexia–cachexia syndrome (CACS) is usually found in advanced cancer patients. CACS is a multifactorial process which comprises skeletal muscle and adipose tissue loss which may be compounded by anorexia and a dysregulated metabolic state. The hypothesis of this study was that curcumin will increase body compositions and body weight in patients with solid malignancy and CACS when compared to placebo after adjusting by age, gender, primary site of cancer, stage of cancer, performance status, and supplementary nutrition support. This study was a double-blind, placebo-controlled randomised phase lla study. A total of 46 patients were enrolled, of whom 33 underwent 1:1 block of four randomisations. Seventeen patients were randomly assigned to receive curcumin at dose of 800 mg twice daily orally and sixteen patients were randomly assigned to received placebo. Results show that curcumin supplementation: (1) did not statistically significantly improve body compositions and body weight when compared to placebo; (2) may cause clinical benefit in term of hand grip muscle strength and slow progress of CACS by decreasing in basal metabolic rate and preventing the decline in serum albumin; and (3) administered orally for two months at a dose of up to 2 grams daily appeared safe and no serious adverse events were reported. Authors conclude that curcumin inhibited process of CACS via reduction of basal metabolic rate and slowed down the progression of hand-grip muscle strength loss. Furthermore, nuclear factor kappa B [regulator of gene expression] levels merit further exploration as potentially suitable predictive biomarker for CACS treatment with curcumin.
Abstract
OBJECTIVE We aim to investigate the effect of curcumin on preventing cancer anorexia-cachexia syndrome (CACS) via through mechanism of inhibition on NF-kB signal pathway. Outcome measurement for primary end point was improvement of body tissue composition, and the secondary end points were body weight and body mass index, hand grip muscle strengthening, and safety. METHODS This is randomized, double-blind, placebo-controlled phase ll a study, 33 patients with CACS in solid malignancy were enrolled and randomized in 1:1 to receive oral curcumin (at a dose of 800 mg twice daily) or placebo for 8 weeks. RESULTS All parameters of body compositions were not statistically significant different between two groups, which were consist body fat mass [-1.25(SEM 0.87) vs. +0.63(SEM 0.55); p=0.119], skeletal muscle mass [-0.35(SEM 0.60) vs.+0.33(SEM 0.42); p=0.408] and percent body fat [-0.47(SEM 0.95) vs. -0.29(SEM 0.82); p=0.893] including with basal metabolic rate [-13.47(SEM 21.94) vs. +15.30(13.76); p=0.336]. The average of weight loss was also not statistically significant different between two groups. [-1.4 kg(SEM 0.89) in curcumin vs-1.12 kg(SEM 0.73), p=0.810]. Notably, patient with curcumin had less reduction of hand-grip muscle strength on both hands [Rt. handed: -2.47 in curcumin vs. -5.36 in placebo; p=0.318] [Lt. handed: -1.98 vs. -5.43; p=0.317], and basal metabolic rate than placebo group. Most adverse events were grade 1 on both groups similarly. CONCLUSION Curcumin was not shown to be superior to placebo with regard to increasing the body composition in cancer patients with CACS. However, curcumin might show some clinical benefits, including slow progression of hand-grip muscle strength loss, and basal metabolic rate. Further investigations should be explored.