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Evaluating adherence, tolerability and safety of oral calcium citrate in elderly osteopenic subjects: a real-life non-interventional, prospective, multicenter study.
Rondanelli, M, Minisola, S, Barale, M, Barbaro, D, Mansueto, F, Battaglia, S, Bonaccorsi, G, Caliri, S, Cavioni, A, Colangelo, L, et al
Aging clinical and experimental research. 2024;36(1):38
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The occurrence of fractures and osteoporosis are significant concerns in elderly adults, as ageing remains one of the primary risk factors for these conditions. While the incidence of fracture and risk may vary, the incidence of fragility fractures significantly increases with advancing age, particularly after the age of 50 years. This study's aim was to evaluate the adherence, tolerability, and safety of calcium citrate administration in an "outpatient" population in routine clinical practice. This study was a non-interventional, prospective, multicentre study. Two-hundred and sixty-eight individuals (comprised 245 females (91.4%) and 23 males (8.6%)) were enrolled. Results showed a high rate of adherence to calcium citrate supplementation over a one-year period in osteopenic elderly subjects. Additionally, the incidence of adverse reactions was low (3.9%), further emphasizing the tolerability of calcium citrate. Authors concluded that future studies designed to assess the long-term impact of calcium citrate supplementation on hard endpoints, such as bone density, fractures/falls, quality of life measures and adherence are needed.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The occurrence of fractures and osteoporosis are significant concerns in older adults, as ageing remains one of the primary risk factors for this condition.
- Calcium supplementation, usually with vitamin D, is a recommended complement to other specific pharmacological treatments of osteoporosis.
- This non-interventional, prospective multicentre study suggests a 91% adherence to calcium citrate supplementation over one year in elderly osteopenic patients with generally good (80%) tolerability and 4% reporting gastrointestinal adverse effects.
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
A non-interventional, prospective multicentre study was conducted to evaluate the adherence, safety, and tolerability of calcium citrate supplementation in elderly osteopenic subjects.
Method:
A total of 231 Caucasian female (91%) and male (8%) participants with a median age of 70 received 500mg of calcium citrate supplementation daily for one year. Adherence was assessed based on tolerability, compliance, and persistence. Safety evaluations included monitoring of adverse reactions (ARs), physical examinations, and clinical laboratory evaluations.
Results
A total of 222 out of 231 participants (96%) completed the study. Nine subjects did not return for assessments or complete their diaries.
The primary and secondary findings of this study were as follows:
- An average adherence of 91% of oral calcium citrate supplementation was observed which was higher than the reported reference rate of 57% (p = 0.0179).
- Subjects with adherence <80% experienced a higher frequency of adverse events compared to those with adherence >80% (32/77; 42% vs 16/145%, (p = 0.0001).
- Gastrointestinal ARs were the most commonly reported, with constipation comprising 50% of all reported ARs.
- Reductions in systolic (130.7 ± 16.9 mmHg to 127.9 ± 14.5 mmHg) (p = 0.0102) and diastolic blood pressure 79.5 ± 8.7 mmHg to 77.4 ± 8.6 mmHg (baseline to V2) (p = 0.0116) were observed from baseline to the second visit.
- Positive changes were also noted in nutritional status (p = 0.0116), circulatory system disorders (p = 0.0001), and muscles/skeleton disorders (p = 0.0067) from baseline to post-baseline visit.
Conclusion:
This study revealed a 91% adherence to calcium citrate supplementation over one year in older adults with osteopenia, Additionally, the 4% incidents of ARs reported were related to gastrointestinal disorders.
Clinical practice applications:
- The prevalence of osteoporosis rises as individuals age, with approximately 10% of women at 60 years, 20% at 70 years, and 40% at 80 years.
- Calcium supplementation, usually with vitamin D, is a recommended complement to other specific pharmacological treatments of osteoporosis.
- The safety of calcium supplements remains controversial regarding an increased risk of cardiovascular events. Therefore, it is essential to investigate the safety profile of calcium in these populations.
- This study reported adherence, tolerability, and safety of calcium citrate supplementation in osteopenic elderly patients with 4% of patients reporting gastrointestinal adverse effects.
Considerations for future research:
- This study was conducted on 91% Caucasian females and 8% males with a mean age of 70 years therefore, there is a need to include more male and Asian participants from various age groups in further research.
- Future studies are needed to assess the long-term impact of calcium citrate supplementation on bone density, fractures, and quality of life.
Abstract
BACKGROUND Osteoporosis is a common concern in the elderly that leads to fragile bones. Calcium supplementation plays a crucial role in improving bone health, reducing fracture risk, and supporting overall skeletal strength in this vulnerable population. However, there is conflicting evidence on the safety of calcium supplements in elderly individuals. AIM: The aim of this study was to evaluate the adherence, safety and tolerability of calcium citrate supplementation in elderly osteopenic subjects. METHODS In this non-interventional, prospective, multicenter study, subjects received daily 500 mg calcium citrate supplementation for up to one year. Adherence was calculated based on compliance and persistence. Safety was assessed through adverse reactions (ARs), deaths, and clinical laboratory evaluations. RESULTS A total of 268 Caucasian subjects (91.4% female, mean age 70 ± 4.5 years) participated in the study. Mean adherence to treatment was 76.6 ± 29.5% and half of subjects had an adherence of 91% and ~ 33% of participants achieved complete (100%) adherence. ARs were reported by nine (3.9%) subjects, primarily gastrointestinal disorders, with no serious ARs. The frequency of all adverse events (including ARs) was significantly higher in subjects with adherence of < 80% (41.6%; 32/77) vs. those with adherence ≥ 80% (11%; 16/145, p < 0.0001). Both systolic and diastolic blood pressure decreased from baseline to follow-up visit (change of -2.8 ± 13.9 mmHg, p = 0.0102 and -2.1 ± 10.4 mmHg, p = 0.0116, respectively). CONCLUSION This study demonstrated favorable adherence to calcium citrate supplementation in elderly osteopenic subjects. The occurrence of ARs, though generally mild, were associated with lower adherence to calcium supplementation.
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Impact of probiotics on muscle mass, muscle strength and lean mass: a systematic review and meta-analysis of randomized controlled trials.
Prokopidis, K, Giannos, P, Kirwan, R, Ispoglou, T, Galli, F, Witard, OC, Triantafyllidis, KK, Kechagias, KS, Morwani-Mangnani, J, Ticinesi, A, et al
Journal of cachexia, sarcopenia and muscle. 2023;14(1):30-44
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Sarcopenia is a progressive skeletal muscle disorder involving accelerated loss of muscle mass, strength and function. It generally occurs in older age groups but can also be seen in younger people. Multiple factors contribute to the development of the condition. Besides nutritional management strategies, probiotics have recently caught the interest of researchers. As probiotics promote metabolic building activity, aid digestion and absorption and reduce muscle breakdown by favourably managing inflammation, they present great potential for the management of sarcopenia. This systematic review and meta-analysis explored the impact of probiotic supplementation on muscle mass, total lean mass and muscle strength in human adults. The review included 24 studies, with probiotics mainly from the Bifidobacteria or Lactobacilli family. The analysis concluded that probiotic supplementation improved muscle mass in comparison to placebos. It also significantly increased overall muscle strength in 6 randomized controlled trials, which was most obvious in age groups of 50 and above. However, no changes were seen concerning total lean mass. It appeared that longer studies, of >12 weeks or more, showed better outcomes in this review. Furthermore, Bifidobacteria species seemed to exhibit more favourable effects, and the authors also noted the beneficial results were more significant in Asian populations. Further research is needed to understand more about the underlying mechanism, best probiotics strains and the specifics of different demographic groups. This article yields a concise overview of sarcopenia, the nutritional aspects of the disease and how probiotics may be beneficial in disease management, strengthened with data from the review.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This was a well-conducted meta-analysis based on its methodological approach that demonstrated that Lactobacillus and Bifidobacterium probiotic supplementation may contribute to improved muscle mass in younger adults and improved muscle strength in older adults.
- Bifidobacterium probiotic supplementation was associated with enhanced muscle mass in younger adults, a potential focus for those considering probiotic supplements.
- The duration of probiotic therapy matters, with longer-term (12 weeks or more) supplementation showing improvements in muscle mass and strength..
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This systematic review and meta-analysis evaluated the effect of probiotics on muscle mass, total lean mass and muscle strength in both young and older adults.
Methods
- The search encompassed PubMed, Scopus, Web of Science, and Cochrane Library databases, from inception up to June 2022; studies included spanned a period from 2013 to June 2022.
- The study adhered to Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines and included the Risk-of-Bias tool to assess study quality.
- The study focused on changes in muscle mass, total lean mass, and muscle strength.
- Inclusion criteria: randomised controlled trials (RCTs) with adult participants (>18 years); interventions involving any probiotics, and a control group receiving either no treatment or a placebo.
Results
- 24 RCTs were included (709 participants), with studies conducted in Europe, USA, and Asia. Intervention durations: ranged from 3 weeks to 12 months.
- Participants included overweight, untrained healthy and resistance-trained individuals, and those with specific conditions like metabolic syndrome and frailty.
- Body composition assessments were conducted using bioelectrical impedance (BIA) and/or dual-energy X-ray absorptiometry (DXA).
- Probiotic strains employed in the included studies varied, with Lactobacillus the most common, followed by Bifidobacterium; some combined both. 5 of 24 studies also used additional strains.
- Dosages: ranged from 2 × 10^9 to 11.2 × 10^10 colony-forming units (CFU).
- 4 out of 24 studies used fermented food products like cheese and noodles as sources of probiotics.
- 22 RCTs measured muscle mass and total lean mass; 6 RCTs measured global muscle strength.
- Probiotic supplementation (≥12 weeks) moderately increased muscle mass, with a standardised mean difference (SMD) of 0.42. This significant effect (95% CI: 0.10–0.74, P=0.009) was observed only in younger Asian adults (<50 years) after Bifidobacterium supplementation, based on a meta-analysis of 10 studies.
- Probiotic supplementation (≥12 weeks) significantly increased global muscle strength in older adults (>50 years; SMD: 0.69, 95% CI: 0.33–1.06, P = 0.0002).
- Probiotic supplementation showed no significant impact on lean mass (SMD: -0.03, 95% CI: 0.19 – 0.13, P = 0.69).
Conclusion
Probiotic supplementation, especially Lactobacillus and Bifidobacterium may have a positive impact on muscle mass and global strength
Clinical practice applications:
- Consumption of probiotics, mainly Lactobacillus and Bifidobacterium may contribute to improved muscle strength in older individuals (>50y).
- Consumption of Bifidobacterium strains was associated with improved muscle mass in younger individuals (<50y) in Asian countries, in a low number of studies (k=2).
- Bifidobacterium breve B-3 was associated with an improvement in muscle mass in older overweight individuals, although a causal relationship was not established.
- Probiotics may enhance muscle mass or strength by enhancing protein digestion and amino acid absorption for muscle synthesis and function.
- Considering an individual’s goals, a practitioner could consider probiotic supplementation as a complementary intervention when aiming to enhance muscle mass or strength .
Considerations for future research:
- Future research could focus on pinpointing which specific probiotic strains are most effective for muscle strength or muscle mass to tailor more precise interventions.
- Most studies did not exceed 12 weeks, highlighting the need for long-term research on probiotics sustained muscle impact.
- Future research could investigate the effects of probiotics across diverse demographic groups including different ages, sexes, and ethnic backgrounds to understand the impact in different populations.
- Delving deeper into the mechanisms by which probiotics influence muscle health could lead to targeted probiotic therapies that address specific physiological pathways.
- Finally, future research could explore how probiotics can be combined with other interventions, such as exercise or nutritional modifications, to synergistically improve muscle health and function.
Abstract
Probiotics have shown potential to counteract sarcopenia, although the extent to which they can influence domains of sarcopenia such as muscle mass and strength in humans is unclear. The aim of this systematic review and meta-analysis was to explore the impact of probiotic supplementation on muscle mass, total lean mass and muscle strength in human adults. A literature search of randomized controlled trials (RCTs) was conducted through PubMed, Scopus, Web of Science and Cochrane Library from inception until June 2022. Eligible RCTs compared the effect of probiotic supplementation versus placebo on muscle and total lean mass and global muscle strength (composite score of all muscle strength outcomes) in adults (>18 years). To evaluate the differences between groups, a meta-analysis was conducted using the random effects inverse-variance model by utilizing standardized mean differences. Twenty-four studies were included in the systematic review and meta-analysis exploring the effects of probiotics on muscle mass, total lean mass and global muscle strength. Our main analysis (k = 10) revealed that muscle mass was improved following probiotics compared with placebo (SMD: 0.42, 95% CI: 0.10-0.74, I2 = 57%, P = 0.009), although no changes were revealed in relation to total lean mass (k = 12; SMD: -0.03, 95% CI: -0.19 - 0.13, I2 = 0%, P = 0.69). Interestingly, a significant increase in global muscle strength was also observed among six RCTs (SMD: 0.69, 95% CI: 0.33-1.06, I2 = 64%, P = 0.0002). Probiotic supplementation enhances both muscle mass and global muscle strength; however, no beneficial effects were observed in total lean mass. Investigating the physiological mechanisms underpinning different ageing groups and elucidating appropriate probiotic strains for optimal gains in muscle mass and strength are warranted.
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Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.
Xia, J, Yu, J, Xu, H, Zhou, Y, Li, H, Yin, S, Xu, D, Wang, Y, Xia, H, Liao, W, et al
Pharmacological research. 2023;188:106647
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Type 2 diabetes mellitus (T2DM), characterised by sustained hyperglycaemia and insulin resistance, remains a severe driver of chronic metabolic diseases such as cardiovascular diseases. The aim of this study was to investigate and compare the efficacy of vitamin and mineral supplements in the management of glycaemic control and lipid metabolism for type 2 diabetic patients to inform clinical practice. This study is a systematic review and meta-analysis of one hundred and seventy articles with a total of 4223 adults with T2DM. Participants were randomised to either the placebo/no treatment group (n= 6345) or to the treatment group (n= 7878). Results show that: - chromium was the most effective micronutrient for decreasing fasting blood glucose and insulin resistance. - vitamin K was the top-ranked micronutrient in reducing haemoglobin A1C and fasting insulin levels. - vanadium was the top-ranked micronutrient in total cholesterol reductions. - niacin was ranked as the most effective in triglycerides reductions and increasing high-density lipoprotein cholesterol levels. - vitamin E was the top-ranked micronutrient in low-density lipoprotein cholesterol reductions. Authors conclude that micronutrient supplements especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more effective in the management of T2DM compared with other micronutrients.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Clinicians could consider the adjunctive effect of micronutrients supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements in a nutrition protocol to manage T2DM and slow or prevent its complications.
- The study authors state that the vitamin and mineral supplements under review had a statistically significant improvement, however they did not reach the study threshold for clinical significance. Therefore they advise caution in utilising micronutrient supplements in the management of glucose and lipid metabolism for T2DM.
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:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
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Effects of Omega-3 Fatty Acids Supplementation on Serum Lipid Profile and Blood Pressure in Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Liu, YX, Yu, JH, Sun, JH, Ma, WQ, Wang, JJ, Sun, GJ
Foods (Basel, Switzerland). 2023;12(4)
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Metabolic syndrome (MetS) is a group of disorders that cause disturbed metabolism, including abdominal obesity, insulin resistance, hypertension, and dyslipidaemia. People with MetS may have a higher risk of coronary heart disease and stroke than those without MetS. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have cardioprotective, anti-inflammatory, and triglyceride-lowering properties, so they may help treat obesity and improve metabolic syndrome. The aim of this study was to explore the effects of n-3 PUFAs on lipid profile and blood pressure in patients with MetS. This study is a meta-analysis of eight studies. One of the studies was a crossover trial, whereas the remaining seven studies were parallel-controlled trials. The mean age of the participants was 45.54 years old. Results show that following supplementation with n-3 PUFAs in patients with metabolic syndrome: - there weren’t significant changes in serum total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. - there was a significant reduction in serum triglycerides and blood pressure. Authors conclude that n-3 PUFA supplementation may serve as a potential dietary supplement for improving lipids and blood pressure in patients with metabolic syndrome.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Omega 3 PUFA may be beneficial for patients with metabolic syndrome by improving serum lipid profile and blood pressure.
- Omega-3 rich foods include fatty fish, walnuts, flaxseeds and chia seeds.
- While Omega-3 PUFA may be beneficial, they should be considered as part of a comprehensive approach to managing metabolic syndrome that include physical activity and a balanced diet.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
This journal article presents a systematic review and meta-analysis of randomised controlled trials (RCTs) investigating the effects of omega-3 fatty acid supplementation on serum lipid profile and blood pressure in patients with metabolic syndrome. Metabolic syndrome is a cluster of conditions that increase the risk of cardiovascular disease and type 2 diabetes.
Methods
This meta-analysis included 8 RCTs with 387 participants with metabolic syndrome. Participants in the intervention group took omega-3 fatty acid supplements and the outcomes included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), systolic blood pressure (SBP), and diastolic blood pressure (DBP).
Results
- Based on a meta-analysis of data from the included trials, supplementation with omega 3- PUFAs led to no reduction in serum LDL-c level among patients with metabolic syndrome (Standardised Mean Difference (SMD) = 0.18; 95% CI: −0.18 ~ 0.53, I2 = 55%); did not increase serum high-density lipoprotein cholesterol levels (SMD = 0.02; 95% CI: −0.21 ~ 0.25, I2 = 0%); and had no reduction in serum total cholesterol level (SMD = −0.02; 95% CI: −0.22~0.18, I2 = 24%).
- On the other hand, in patients with metabolic syndrome, supplementation with omega 3- PUFAs may decrease serum triglyceride levels (SMD = −0.39; 95% CI: −0.59 ~ −0.18, I2 = 17.2%); systolic blood pressure (SMD = −0.54; 95% CI: −0.86 ~ −0.22, I2 = 48.6%); and diastolic blood pressure (SMD = −0.56; 95% CI: −0.79~ −0.33, I2 = 14.0%).
- Sensitivity analyses indicated that the pooled estimates wererobust for all outcomes.
- The following mechanisms may explain how PUFAs may reduce the risk of metabolic syndrome. First, adequate intake of omega 3 PUFAs may reduce triglyceride and LDL synthesis in the liver. In addition, they may lower blood pressure by reducing angiotensin-converting enzyme levels in the aorta. Finally, PUFAs can increase insulin sensitivity and prevent hyperglycaemia.
Limitations
This study presents some limitations: The literature search may have some omissions. The conclusions may be hindered by the risk of bias of the trials included. No bias test was performed due to the limited number of studies.
Clinical practice applications:
- Improved serum lipid profile: The findings from the paper indicate that omega-3 fatty acid supplementation can have a positive impact on the serum lipid profile in patients with metabolic syndrome.
- Blood pressure management: omega-3 fatty acid supplementation may help reduce blood pressure in patients with metabolic syndrome.
- Nutritional therapists can use this information to consider omega-3 supplementation as part of nutritional therapy
- Complementary approach: Nutritional therapists can utilise the findings as supportive evidence for a holistic approach to managing metabolic syndrome. By incorporating omega-3 fatty acids into personalized nutrition plans, therapists may be able to offer additional dietary or supplemental interventions for individuals with metabolic syndrome, aiming to lower triglyceride levels and manage blood pressure, alongside other lifestyle modifications.
- Patient education: Nutritional therapists can educate their patients with metabolic syndrome about the benefits of omega-3 fatty acids on lipid profile and blood pressure. By explaining the findings from the systematic review and meta-analysis, therapists can empower patients to make informed choices regarding their dietary habits and supplement use, promoting self-management and improved long-term outcomes.
Considerations for future research:
- Future research could focus on determining the optimum dosage of Omega-3 PUFAs for improving lipid profile and BP.
- More investigation is needed to analyse the long term effect of the supplements. The longest RCT was 90 days.
- Comparative studies comparing the effects of omega-3 fatty acids supplementation with other interventions commonly used in metabolic syndrome management, such as pharmacological approaches or diet, would provide a comprehensive understanding of their relative effectiveness.
- Future research could explore potential variations in the effects of omega-3 fatty acids supplementation based on different patient characteristics, such as age, gender, baseline lipid profile, and blood pressure levels.
- Conducting mechanistic studies could shed light on the underlying pathways through which omega-3 fatty acids exert their effects on serum lipid profile and blood pressure.
Abstract
The purpose of this study was to explore the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation on serum lipid profile and blood pressure in patients with metabolic syndrome. We searched PubMed, Web of Science, Embase, and the Cochrane library from database inception to 30 April 2022. This meta-analysis included eight trials with 387 participants. We found that supplementation of n-3 PUFAs has no significant reduction in TC level (SMD = -0.02; 95% CI: -0.22 ~ 0.18, I2 = 23.7%) and LDL-c level in serum (SMD = 0.18; 95% CI: -0.18 ~ 0.53, I2 = 54.9%) of patients with metabolic syndrome. Moreover, we found no significant increase in serum high-density lipoprotein cholesterol level (SMD = 0.02; 95% CI: -0.21 ~ 0.25, I2 = 0%) in patients with metabolic syndrome after consuming n-3 PUFAs. In addition, we found that n-3 PUFAs can significantly decrease serum triglyceride levels (SMD= -0.39; 95% CI: -0.59 ~ -0.18, I2 = 17.2%), systolic blood pressure (SMD = -0.54; 95% CI: -0.86 ~ -0.22, I2 = 48.6%), and diastolic blood pressure (SMD = -0.56; 95% CI: -0.79 ~ 0.33, I2 = 14.0%) in patients with metabolic syndrome. The results from the sensitivity analysis confirmed that our results were robust. These findings suggest that n-3 PUFA supplementation may serve as a potential dietary supplement for improving lipids and blood pressure in metabolic syndrome. Given the quality of the included studies, further studies are still needed to verify our findings.
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Distribution of energy intake across the day and weight loss: A systematic review and meta-analysis.
Young, IE, Poobalan, A, Steinbeck, K, O'Connor, HT, Parker, HM
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2023;24(3):e13537
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Obesity increases an individual's risk of metabolic disease, such as diabetes and cardiovascular disease, musculoskeletal disorders such as osteoarthritis, and some cancers. “Chrononutrition” relates to the timing of meals and distribution of total energy intake across the day. Evidence is building chrononutrition as a potential target in both weight loss and metabolic disease interventions. The aim of this study was to examine the impact of earlier versus later distribution of total daily energy intake on weight loss, and to evaluate the potential for utilizing altered energy distribution as a tool in weight loss interventions. This study is a systematic review and meta-analysis of nine clinical studies. Total number of participants was 485 (earlier distributed total energy intakes: n = 244, later distributed total energy intakes; n = 241). Results show that energy intakes with a focus on earlier distribution resulted in significantly greater weight loss when compared with similarly energy-restricted diets with individuals consuming a larger proportion of their total energy intake later in the day and into the evening. Authors conclude that earlier energy intakes may be a promising tool to be used in conjunction with other weight loss strategies such as energy restriction to enhance weight loss. However, further research is required to elucidate the additional positive impacts that earlier distributed total energy intakes may have on weight and metabolic health.
Expert Review
Conflicts of interest:
None
Take Home Message:
Implementing a dietary strategy where a higher proportion of energy is consumed earlier in the day may offer additional benefits to an energy restricted diet for weight loss, blood glucose, improve markers of insulin resistance, increase satiety and improve hunger management. Based on the findings, earlier distribution of energy intake may serve as an effective component of a weight loss protocol.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Chrononutrition refers to the timing and distribution of total daily energy intake across the day. It has been proposed that consuming a greater proportion of total daily energy intake earlier in the day as opposed to the evening may be beneficial for weight loss and metabolic health.
Aims
This systematic review and meta-analysis aimed to assess the impact of earlier versus later distribution of total daily energy intake on weight loss.
Results
A total of 9 randomised controlled trials involving 485 participants were included in this analysis. The study durations ranged from 5-16 weeks. All of the studies included in this analysis applied energy-restricted diets to both intervention arms. The mean percentages of energy intake in 8 of the 9 studies per meal were:
- Earlier distributed intakes: breakfast: 34% ± 16%, lunch: 38% ± 7%, dinner: 20% ± 6%.
- Later distributed intakes: breakfast: 19% ± 6%, lunch: 30% ± 10%, dinner; 40% ± 11%.
One of the studies advised percentage of energy intakes as either:
- Earlier: 70% for breakfast, morning tea and lunch and 30% for afternoon tea and dinner
- Late: 55% for breakfast, morning tea and lunch and 45% for afternoon tea and dinner.
The earlier distributed energy intake groups demonstrated significantly greater weight loss when compared with later distributed energy intake groups ( Mean Difference (MD) −1.23 kg; 95% CI −2.40, −0.06, p = 0.04;
I2 = 98%).
The earlier energy intake groups also displayed lower fasting and bedtime glucose levels (fasting: −0.83 vs. −0.27 mmol/L, p = 0.001; before sleep: −1.70 vs. −0.28 mmol/L, p = 0.009).
A random-effects model demonstrated that the earlier intake groups displayed greater reductions in LDL (MD: −0.11 mmol/L; 95% CI −0.14, −0.07, p < 0.01), fasting glucose (MD: 0.15 mmol/L, 95% CI −0.23, −0.06, p < 0.001) and HOMA-IR (MD: −0.38; 95% CI −0.64, −0.11, p = 0.005).
One study reported that earlier distribution energy intake also led to a greater reduction in medications following the intervention for type 2 diabetics (31% vs. 0%, P=0.002).
Two of the studies assessed both appetite and hunger and identified that earlier distribution of energy led to improvements in their urge to eat, preoccupation with food and cravings for sweets and fats.
Clinical practice applications:
Earlier distribution of energy intake may be beneficial for:
- Weight loss
- Improve fasting insulin, HOMA-IR, fasting glucose and HbA1c
- Reducing LDL
- Improving satiety and hunger management
- Supporting the reduction of medications for individuals with type 2 diabetes
- Improving regularity of sleep and waking times
Considerations for future research:
As the included studies only ranged from 5-16 weeks, longer duration studies would be useful to identify the effect of earlier distribution of energy intake on body weight, metabolic health and appetite over a longer period of time. There was a high degree of heterogeneity between the studies and a lack of uniformity in the distributions of energy intake across the day. Further studies with more uniformity of energy distribution would be needed to identify the optimal distribution of energy across the day to improve body weight and metabolic health.
Abstract
Consuming a greater proportion of total energy intake earlier in the day rather than in the evening is proposed to positively influence weight loss and health, potentially due to greater synchronization of human body circadian rhythms. This systematic review provides an update on existing evidence regarding earlier distributed eating patterns in weight loss interventions. Using a robust search strategy in five electronic databases, nine randomized controlled trials investigating the impact of energy intake distribution on weight loss were identified. Following critical appraisal, a random-effects meta-analyses found that, in the context of an energy-reduced diet, distributing energy intake with a focus on earlier intake resulted in significantly greater weight loss (-1.23 kg; 95% CI 2.40, -0.06, p = 0.04). Improvements in HOMA-IR, fasting glucose, and LDL cholesterol were also seen. The current study provides a timely update on the evidence linking distribution of total daily energy intake and health, showing that a focus on earlier intakes can result in greater short-term weight loss compared with later intakes. Future studies are needed to elucidate the impact that earlier intakes may have on weight management and metabolic health.
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6.
The Effect of Regular Consumption of Reformulated Breads on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Schadow, AM, Revheim, I, Spielau, U, Dierkes, J, Schwingshackl, L, Frank, J, Hodgson, JM, Moreira-Rosário, A, Seal, CJ, Buyken, AE, et al
Advances in nutrition (Bethesda, Md.). 2023;14(1):30-43
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The metabolic effect of bread depends on several qualitative aspects ranging from the type of grain, the amount of carbohydrates, levels of other nutrients, as well as the chemical structure and processing. The aim of this study was to assess the certainty of the evidence and to investigate the overall effect of regular consumption of reformulated breads on glycaemic control in the following groups: a) healthy adults; b) those at risk of developing cardiometabolic disease (e.g., having hypertension, hyperglycaemia, hypercholesterolemia and/or overweight/obesity); and c) those with manifest type 2 diabetes mellitus (T2DM). This study is a systematic review and meta-analysis of 22 studies and 23 distinct study populations. All studies were randomised controlled trials, 12 of which had a crossover design and 10 had a parallel design. In total, 1037 participants were included. These provided 669 and 595 data points for intervention and control comparisons, respectively. Results show a beneficial effect of reformulated bread variants on fasting blood glucose concentrations. This benefit may be more pronounced among people with manifest T2DM (low certainty of evidence). Authors conclude that bread quality is relevant for metabolic health among adults and that future studies should address its relevance among people at risk of T2DM.
Expert Review
Conflicts of interest:
None
Take Home Message:
This study’s findings suggest the effect of reformulated breads high in dietary fibre, whole grains, and/or functional ingredients may be more beneficial than regular breads on fasting blood glucose concentrations in adults, primarily among those with T2DM. Reformulated breads however, did not lower fasting insulin concentrations, HOMA-IR and HbA1C when compared to regular bread.
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:
Overview
This study evaluated the effect of regular consumption of “reformulated breads” on glycemic control among healthy adults, adults at cardiometabolic risk or with manifest T2DM in 22 RCTs with 1037 participants. Compared with “regular” or comparator bread, consumption of reformulated intervention breads yielded lower fasting blood glucose concentrations only among people with T2DM (low certainty of evidence), yet no differences in fasting insulin, HOMA-IR, HbA1c, or postprandial glucose response were identified.
[*’reformulated bread’ as defined by the World Health Organisation of altering the processing or composition of a food to improve its nutritional profile, and contained whole-grains and dietary fibre]
Results
Sub group analysis revealed that the effect of reformulated breads high in dietary fibre, whole grains, and/or functional ingredients on lowering fasting blood glucose was confined to participants with T2DM, with no significant effect among participants without T2DM (0.68 mmol/L; 95% CI: 1.11, 0.36; I2 1⁄4 57% and 0.04 mmol/L; 95% CI: 0.13, 0.05; I2 1⁄4 25%, respectively; P < 0.001).
Subgroup analyses by continent revealed a more pronounced effect on fasting blood glucose concentrations in studies conducted in Asia and the Middle East compared with studies conducted in Europe, North America, and Oceania (MD: 0.84 mmol/L; 95% CI: 1.35, 0.33; I2 1⁄4 52% and MD: 0.04 mmol/L; 95% CI: 0.10, 0.03; I2 1⁄4 0%, respectively; P < 0.001)
Additional subgroup analyses found that the type of control bread, but not the type of intervention bread, affected the pooled effect estimate of fasting blood glucose concentration (P 1⁄4 0.03), with the largest difference reported in studies not describing the control bread used.
Limitations
Publication bias was considered negligible for the studies included in this meta-analysis, and the risk of bias assessment revealed that most of the studies had some concerns of risk of bias. One author is a member of the International Carbohydrate Quality Consortium and another is a member of the GRADE working group.
Strengths
This systematic review and meta-analysis include the focus on high-quality intervention studies (i.e., RCTs using either crossover or parallel design) and the inclusion of longer-term studies (>2 wk) to address the effectiveness of regular bread replacement for glycemic control in everyday life.
Clinical practice applications:
- This data suggests that bread quality is relevant for metabolic health among adults at risk of T2DM. In particular, reformulated breads were found to have a more beneficial impact than regular breads on fasting blood glucose concentrations in adults with TsDM. However, consumption of the reformulated bread (enriched with dietary fiber, whole grains, or functional ingredients) did not lower fasting insulin concentrations compared with the control breads (MD: 1.59 pmol/L; 95% CI: 5.78, 2.59; moderate certainty of evidence)
- Consumption of the reformulated bread did not lower HOMA-IR compared with the control breads (MD: 0.09; 95% CI: 0.35, 0.22; moderate certainty of evidence)
- Consumption of the reformulated bread did not lower HbA1c concentrations compared with the control bread (0.14; 95% CI: 0.39, 0.10; P 1⁄4 0.195; very low certainty of evidence).
Considerations for future research:
- Longer intervention periods may be required to determine the beneficial effects on the HbA1c concentrations and to elicit changes in markers of insulin resistance
- Future studies should use the 2022 WHO standardised HbA1c diagnostic reference criterion for diabetes mellitus
- Improvements in specific outcomes may also be linked to defined groups within populations such as persons with manifest T2DM.
- The type of reformulation of the bread may be an important factor but differ considerably around the world
Abstract
Bread is a major source of grain-derived carbohydrates worldwide. High intakes of refined grains, low in dietary fiber and high in glycemic index, are linked with increased risk for type 2 diabetes mellitus (T2DM) and other chronic diseases. Hence, improvements in the composition of bread could influence population health. This systematic review evaluated the effect of regular consumption of reformulated breads on glycemic control among healthy adults, adults at cardiometabolic risk or with manifest T2DM. A literature search was performed using MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials. Eligible studies employed a bread intervention (≥2 wk) in adults (healthy, at cardiometabolic risk or manifest T2DM) and reported glycemic outcomes (fasting blood glucose, fasting insulin, HOMA-IR, HbA1c, and postprandial glucose responses). Data were pooled using generic inverse variance with random-effects model and presented as mean difference (MD) or standardized MD between treatments with 95% CIs. Twenty-two studies met the inclusion criteria (n = 1037 participants). Compared with "regular" or comparator bread, consumption of reformulated intervention breads yielded lower fasting blood glucose concentrations (MD: -0.21 mmol/L; 95% CI: -0.38, -0.03; I2 = 88%, moderate certainty of evidence), yet no differences in fasting insulin (MD: -1.59 pmol/L; 95% CI: -5.78, 2.59; I2 = 38%, moderate certainty of evidence), HOMA-IR (MD: -0.09; 95% CI: -0.35, 0.23; I2 = 60%, moderate certainty of evidence), HbA1c (MD: -0.14; 95% CI: -0.39, 0.10; I2 = 56%, very low certainty of evidence), or postprandial glucose response (SMD: -0.46; 95% CI: -1.28, 0.36; I2 = 74%, low certainty of evidence). Subgroup analyses revealed a beneficial effect for fasting blood glucose only among people with T2DM (low certainty of evidence). Our findings suggest a beneficial effect of reformulated breads high in dietary fiber, whole grains, and/or functional ingredients on fasting blood glucose concentrations in adults, primarily among those with T2DM. This trial was registered at PROSPERO as CRD42020205458.
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7.
Inflammatory and insulinemic dietary patterns and risk of endometrial cancer among US women.
Romanos-Nanclares, A, Tabung, FK, Sinnott, JA, Trabert, B, De Vivo, I, Playdon, MC, Eliassen, AH
Journal of the National Cancer Institute. 2023;115(3):311-321
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Expert Review
Conflicts of interest:
None
Take Home Message:
- Endometrial cancer is increasing in many populations, and evidence links this to rising obesity and increasing age.
- Dietary factors that increase systemic inflammation and raise blood insulin levels appear associated with the development of EC in the population of women studied.
- Women with obesity are at increased risk of developing EC, compared with women in the normal weight range, and the dietary inflammatory and insulinemic potential may contribute to this association
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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X
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:
This cohort study examined the incidence of endometrial cancer (EC) in women recruited to two large prospective studies in the USA. The Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHS-II) recruited female nurses from 1984 to 2016 and 1991 to 2017 respectively. These large studies have produced significant epidemiological data, reporting associations between lifestyle factors and health outcomes across many health conditions including cancer. The two studies had combined recruitment of 237950 women and a follow up rate of 90%. This analysis applied two novel dietary indices developed and validated using cohorts within the NHS and NHS-II studies and a parallel study in male health professionals, the Health Professionals Follow-Up Study (HPFS).
Methods
Data collection:
- Researchers collected medical histories and lifestyle information using self-administered questionnaires at intervals during the study.
- In this subset analysis, 133756 women with an intact uterus were studied, which represented 2823221 person years of follow up.
- Physical activity, smoking status, medication use including contraceptive use and hormone replacement therapy were recorded. Diabetes diagnosis and anthropometric data were collected.
- Dietary intakes were assessed using a semi-quantitative food frequency questionnaire (FFQ) of 116 foods items in NHS, increased to 130 food items NHS-II. The FFQ had previously been validated using 24-hour dietary recall and multi-week dietary records.
Analysis of dietary impact:
- The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory potential (EDIP) index were developed and validated using stepwise regression models (reported in detail elsewhere). Intakes of 39 predetermined food items within the FFQ were compared with biomarkers from three cohorts of matched cases, nested within the NHS and NHS-II studies and the HPFS, which studied male health professionals.
- Biomarkers for inflammation used to develop EDIP were plasma concentrations of IL-6, C-reactive protein (CRP), TNF-α receptor 2 (TNFαR2), and adiponectin. Validation of the EDIP identified eighteen foods of which 9 were considered anti-inflammatory and 9 proinflammatory.
- Plasma C-peptide was the biomarker for insulinemic impact for EDIH, validated to scores for intake of eighteen food groups; thirteen positively associated with C-peptide and five inversely associated.
- These indices therefore score dietary pattern, however, notably, there were some curious findings for individual foods identified as pro-inflammatory (tomatoes) and anti-inflammatory (pizza), which were noted in the publication reporting development of the EDIP.
Findings
- There were 1565 diagnoses of endometrial cancer, of which 1462 Type 1 EC were considered, discounting rare or uncertain EC subtypes.
- Associations between EDIH and EDIP scores by quintile and endometrial cancer were calculated and identified increased incidence of EC with more inflammatory and insulinemic dietary patterns. For dietary inflammatory potential assessed using EDIP, comparing highest to lowest quintile, HR = 1.46, (95% CI = 1.24 to 1.73; Ptrend < .001). For dietary insulinemic potential, comparing highest to lowest quintile, hazard ratio (HRQ5vsQ1) = 1.58, 95% CI = 1.34 to 1.87; Ptrend < .001).
- Multivariate analysis indicated a substantial effect of the combined scores on EC risk.
- However, adjusting these scores for BMI attenuated the effect, with HR close to 1 after adjustment (EDIP HR = 1.03, 95% CI = 0.87 to 1.22; EDIH HR = 1.01, 95% CI = 0.85 to 1.21). Body mass index was assessed to explain 60.4% of the association of endometrial cancer with dietary inflammatory potential as expressed as EDIP and 71.8% of inflammatory potential as expressed as EDIH. These data suggest therefore that adiposity and obesity are strongly influential in these effects.
Clinical practice applications:
- Endometrial cancer is increasing in incidence in industrialised countries, predicted to overtake colorectal cancer as the leading type of cancer in women in the USA by 2030.
- There is clear evidence for a link with obesity and with unopposed oestrogen. This study demonstrates the impact of dietary intake on EC risk and highlights a role for appropriate nutritional guidance to support women who may be at risk of developing EC.
- Since the association with inflammatory and insulinemic foods appears strongly influenced by obesity, measures to address body composition are important.
Considerations for future research:
- Apparent anomalies in the inflammatory potential scores reman unexplained, although overall dietary pattern is more important to consider than intakes of individual food items.
- This study did not report biomarkers of insulin resistance and BMI was the only anthropometric data reported. Analysis of risk associated with body composition and adiposity would be useful. For example, waist to height ratio is considered a useful anthropometric indicator
- Further exploration of the role of dietary insulinemic impact on insulin resistance could include measurement of HbA1c in this patient group.
- As exposure to excess unopposed oestrogen is also implicated in EC, assessment of oestrogen metabolism and adiposity would also add to the understanding of this condition.
Abstract
BACKGROUND Although unopposed estrogen exposure is considered a major driver of endometrial carcinogenesis, chronic inflammation and insulin resistance and hyperinsulinemia are also major endometrial cancer risk factors. However, it is unclear whether diets with inflammatory or insulinemic potential are associated with risk of endometrial cancer. METHODS We followed 48 330 women from the Nurses' Health Study (1984-2016) and 85 426 women from the Nurses' Health Study II (1989-2017). Using food frequency questionnaires, we calculated repeated measures of empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores, which characterize the potential of the whole diet to modulate circulating biomarkers of inflammation or C-peptide, respectively. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for type I endometrial cancer risk. RESULTS We documented 1462 type I endometrial cancer cases over 2 823 221 person-years of follow-up. In the pooled multivariable-adjusted analyses, women in the highest compared with lowest quintiles were at higher risk of type I endometrial cancer (EDIP HRQ5vsQ1 = 1.46, 95% CI = 1.24 to 1.73; Ptrend < .001; EDIH HRQ5vsQ1 = 1.58, 95% CI = 1.34 to 1.87; Ptrend < .001). Additional adjustment for body mass index attenuated the associations (EDIP HR = 1.03, 95% CI = 0.87 to 1.22; EDIH HR = 1.01, 95% CI = 0.85 to 1.21), and mediation analyses showed that body mass index may explain 60.4% (95% CI = 37.4% to 79.6%; P < .001) and 71.8% (95% CI = 41.0% to 90.4%; P < .001) of the association of endometrial cancer with EDIP and EDIH, respectively. CONCLUSIONS In this large cohort study, higher dietary inflammatory and insulinemic potential were each associated with increased endometrial cancer incidence, and this association may be almost entirely mediated by adiposity.
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8.
Effects of exercise training programmes on fasting gastrointestinal appetite hormones in adults with overweight and obesity: A systematic review and meta-analysis.
Almesbehi, T, Harris, L, McGarty, A, Alqallaf, S, Westrop, S, Edwards, CA, Dorling, JL, Malkova, D
Appetite. 2023;182:106424
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Plain language summary
Appetite is controlled by several hormones including those of the gastrointestinal (GI) system. There has been controversy over whether exercise can affect these hormones resulting in altered food intake and this systematic review and meta-analysis aimed to address this. The results showed that 9 studies have been performed aimed at the effect of 16 different exercise interventions on appetite hormones of the GI system. Exercise had no effect on total ghrelin, acetylated ghrelin and peptide YY, however body mass index and body mass were significantly reduced in individuals with obesity or who are overweight. It was concluded that any increased appetite or energy intake during exercise interventions is unlikely related to GI appetite hormones. This study could be used by healthcare professionals to understand that although exercise may not affect food intake it can still aid weight loss in individuals who are overweight or obese.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This systematic review and meta-analysis found that exercise training programmes in individuals living with overweight and obesity have no impact on fasting concentrations of total and acylated ghrelin, PYY, GLP-1 and CCK.
- This finding suggests that any increase in appetite and energy intake typical of exercise training, would be related to different factors and not from changes in fasting concentrations of gastrointestinal appetite hormones.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Overweight and obesity prevalence is increasing globally. Exercise is advocated as an effective preventive and treatment for obesity. However, exercise may affect appetite regulation, and understanding how this functions in people with overweight and obesity is of interest. Notably, the evidence regarding the effects of exercise training on gastrointestinal hormones such as ghrelin, has not been extensively synthesised.
Aim
- The aim of this systematic review and meta-analysis was therefore to synthesise the literature describing the effect of exercise programmes of >4 weeks’ duration from randomised controlled trials (RCT) on the fasting and gastrointestinal appetite hormones of adults living with overweight and obesity.
- The review followed PRISMA reporting guidelines and standard systematic review and meta analysis methodology.
Results
- After screening 13,204 records, nine studies with a total of 707 participants (259 men and 448 women) were identified that fit the pre-defined inclusion criteria and were included in the review.
- Overall, after exercise interventions in comparison to control, there was a reduction in body mass (effect size (d)= −0.22, 95% CI −0.42 to −0.03, p = 0.03; 7 studies) and BMI (d= −0.31, 95% CI −0.50 to −0.12, p = 0.001; 8 studies).
- Exercise had no impact on total fasting ghrelin (d = 1.06; 95% CI -0.38 to 2.5; p=0.15; 4 interventions) or fasting acylated ghrelin concentration (d = 0.08; 95% CI -0.31 to 0.47; p=0.68; 7 interventions).
- Fasting anorexigenic peptide YY did not differ between exercise and control (d = −0.16, 95% CI: −0.62 to 0.31, P = 0.51; 7 interventions).
- Two studies assessed the effects of exercise training on GLP-1 and meta-analyses were not possible. In one study, fasting GLP-1 was higher in the intervention group (p=0.04) though the other study found no difference (P>0.05). Only one study looked at fasting plasma cholecystokinin (CCK), which found no change between exercise and control interventions (p>0.5).
- When looking at the correlation between body mass and appetite hormone changes, weight loss (p<0.05) and BMI reduction (p<0.05) occurring with exercise was positively associated with an increase in total plasma ghrelin (p<0.05); increased ghrelin was associated to reductions in body weight and BMI (both p<0.0001). Further, one study reported a positive correlation of body mass loss and BMI reduction with a reduction in acylated ghrelin (p=0.003 and 0.009, respectively) and negatively with an increase in plasma PYY concentration (p=0.003 and 0.03, respectively).
Clinical practice applications:
This systematic review suggested that any compensatory increase in energy intake due to exercise training is unlikely to be related to fasting gastrointestinal appetite hormone changes. Therefore, nutritional therapists should bear this in mind when consulting with clients and find personalised lifestyle strategies to help people manage their caloric consumption in relation to exercise training.
Considerations for future research:
- The relation between changes in body mass or BMI and fasting appetite hormones could not be fully explored due to the small number of studies included in this review. Moreover, the results of this review should be interpreted with caution because most studies were underpowered with a high risk of bias, and there was considerable heterogeneity within some meta-analyses. The effect of exercise training on gastrointestinal satiety hormones including ghrelin, PYY, and CCK therefore require further investigation in individuals living with overweight and obesity, in order to reach more substantial conclusions.
- Exercise enhances the coupling between energy intake and energy expenditure after food consumption, where controlled studies are needed to test how postprandial concentrations of gastrointestinal hormones are influenced by exercise training in individuals with overweight and obesity.
Abstract
A systematic review and meta-analysis was performed to determine the effect of exercise training on fasting gastrointestinal appetite hormones in adults living with overweight and obesity. For eligibility, only randomised controlled trials (duration ≥ four weeks) examining the effect of exercise training interventions were considered. This review was registered in the International Prospective Register of Systematic Reviews (CRD42020218976). The searches were performed on five databases: MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus. The initial search identified 13204 records. Nine studies, which include sixteen exercise interventions, met the criteria for inclusion. Meta-analysis was calculated as the standardised mean difference (Cohen's d). Exercise training had no effect on fasting concentrations of total ghrelin (d: 1.06, 95% CI -0.38 to 2.50, P = 0.15), acylated ghrelin (d: 0.08, 95% CI: -0.31 to 0.47, P = 0.68) and peptide YY (PYY) (d = -0.16, 95% CI: -0.62 to 0.31, P = 0.51) compared to the control group. Analysis of body mass index (BMI) (d: -0.31, 95% CI: -0.50 to -0.12, P < 0.01) and body mass (d: -0.22, 95% CI: -0.42 to -0.03, P = 0.03) found a significant reduction after exercise compared to controls. Overall, exercise interventions did not modify fasting concentrations of total ghrelin, acylated ghrelin, and PYY in individuals with overweight or obesity, although they reduced body mass and BMI. Thus, any upregulation of appetite and energy intake in individuals with overweight and obesity participating in exercise programmes is unlikely to be related to fasting concentrations of gastrointestinal appetite hormones.
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9.
Influence of water-based exercise on energy intake, appetite, and appetite-related hormones in adults: A systematic review and meta-analysis.
Grigg, MJ, Thake, CD, Allgrove, JE, King, JA, Thackray, AE, Stensel, DJ, Owen, A, Broom, DR
Appetite. 2023;180:106375
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Plain language summary
Exercise is an effective way to improve mental and physical health and can influence weight management due to the energy expenditure. Energy balance is influenced by day-to-day variations in energy intake and expenditure. The aim of this study was to address whether water-based exercise influences energy intake, appetite, and appetite related hormones differently to land based exercise in adults. This study is a systematic review and meta-analysis of nine studies which include randomised crossover ( 7 trials), semi-random (1 trial) (water-trial was required prior to iso-energetically matched water trial) and independent group (1 trial) (used in the 12-week study) designs. Results show that post-exercise energy intake is higher after water-based exercise versus a resting control. However, there wasn’t any difference in energy intake when water-based exercise was compared with land-based exercise. Furthermore, when different water temperatures were analysed, post-exercise energy intake was higher in cold water versus neutral water. Additionally, cycling and swimming did not alter fasting plasma concentrations of appetite regulating hormones (ghrelin and leptin), insulin or total peptide YY [gut hormone] but contributed to body mass loss. Authors conclude that if body mass management is a person’s primary focus, it is important to be mindful of the tendency to eat more in the subsequent hours after water-based exercise, as energy intake may be increased when compared to a no exercise control.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The only type of exercise reporting an increase in energy intake was in water-based activities, where the temperature was between 18-20• C. However, this was only when explored in comparison to a resting control. No difference was reported in energy intake when water-based exercise was compared with land-based exercise.
- Any form of exercise, whether land or water-based should be considered where appropriate to reduce the risks of sedentary behaviour.
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:
Exercise is effective for weight-management alongside other physical and mental health benefits. Changes in appetite-regulating hormones may affect energy balance, e.g. some exercise may suppress appetite, known as exercise-induced anorexia. This review evaluated differences in energy intake, appetite and appetite-related hormones in land-based versus water-based exercise.
Methods:
The meta-analysis followed PRISMA guidelines and was registered on PROSPERO. Literature searching resulted in eight studies published between 1991 and 2021, which met the inclusion criteria (water v control), 5 studies (water v land) and 2 studies (water at different temperatures). Risk of Bias was assessed using Cochrane’s Risk of Bias for randomised trials.
Results:
Data were analysed in RevMan 5.4.1 using fixed effects, generic inverse variance method on energy intake. High heterogeneity prevented analysis on appetite and appetite-related hormones. Standard deviation was inputted based on estimated values for missing data. Heterogeneity was calculated using the I2 index. Sensitivity analyses were conducted. Statistical significance was set at p<0.05 and analyses based on two-tailed Z tests.
All participants had a healthy BMI, were aged 19-39 and ranged from well-trained to non-exercisers. A single bout of water-based exercise increased ad-libitum energy intake compared to a non-exercise control (mean difference [95% CI]: 330 [118, 542] kJ, P = 0.002) but no difference was identified between water and land-based exercise (78 [-176, 334] kJ, P = 0.55). Cold water exercise (18–20 •C) increased energy intake more than neutral water (27–33 •C) temperature (719 [222, 1215] kJ; P < 0.005). One 12-week study reported cycling and swimming did not alter fasting plasma concentrations of total ghrelin, insulin, leptin or total PYY but contributed to body mass loss 87.3 (5.2) to 85.9 (5.0) kg and 88.9 (4.9) to 86.4 (4.5) kg (P < 0.05) respectively.
Conclusion:
Despite limitations, this review may provide preliminary evidence on energy intake and appetite for water-based activities. If weight management is a primary focus, then water temperature needs to be considered, particularly if sub 20•C .
Clinical practice applications:
Although this study suggests cold water exercise may cause an increase in energy intake, 95% confidence intervals for individual studies are very large so results should be interpreted cautiously. Those preferring exercise in cold water, should be encouraged, providing they are mindful of the tendency to eat more post-exercise.
It is not possible to draw any robust conclusions about the ratings of hunger in response to different types of exercise due to limited data. However, according to the review, five studies demonstrated that hunger was suppressed more than control prior at the start of water-based exercise, and during and immediately after exercise.
Considerations for future research:
Most participants were of healthy weight and physically active, however since appetite signals may be dysregulated in obesity, including all weight categories and different activity levels may generate a more comprehensive overview.
Further research recommendations include:
- Measuring the effects of water- based activities on appetite, appetite related hormones and energy intake at different time points following exercise in order to provide recommendations for effective weight management strategies and in a range of different temperatures.
- Using a ‘no exercise’ water immersion control. Evidence suggests that immersion in cold water alone may increase energy expenditure
- Evaluating the effect of a water-based activity, such as swimming performed in a ‘fasted’ and ‘non-fasted’ state to investigate the impact on appetite, appetite related hormones and energy intake.
Abstract
Single bouts of land-based exercise suppress appetite and do not typically alter energy intake in the short-term, whereas it has been suggested that water-based exercise may evoke orexigenic effects. The primary aim was to systematically review the available literature investigating the influence of water-based exercise on energy intake in adults (PROSPERO ID number CRD42022314349). PubMed, Medline, Sport-Discus, Academic Search Complete, CINAHL and Public Health Database were searched for peer-reviewed articles published in English from 1900 to May 2022. Included studies implemented a water-based exercise intervention versus a control or comparator. Risk of bias was assessed using the revised Cochrane 'Risk of bias tool for randomised trials' (RoB 2.0). We identified eight acute (same day) exercise studies which met the inclusion criteria. Meta-analysis was performed using a fixed effects generic inverse variance method on energy intake (8 studies (water versus control), 5 studies (water versus land) and 2 studies (water at two different temperatures)). Appetite and appetite-related hormones are also examined but high heterogeneity did not allow a meta-analysis of these outcome measures. We identified one chronic exercise training study which met the inclusion criteria with findings discussed narratively. Meta-analysis revealed that a single bout of exercise in water increased ad-libitum energy intake compared to a non-exercise control (mean difference [95% CI]: 330 [118, 542] kJ, P = 0.002). No difference in ad libitum energy intake was identified between water and land-based exercise (78 [-176, 334] kJ, P = 0.55). Exercising in cold water (18-20 °C) increased energy intake to a greater extent than neutral water (27-33 °C) temperature (719 [222, 1215] kJ; P < 0.005). The one eligible 12-week study did not assess whether water-based exercise influenced energy intake but did find that cycling and swimming did not alter fasting plasma concentrations of total ghrelin, insulin, leptin or total PYY but contributed to body mass loss 87.3 (5.2) to 85.9 (5.0) kg and 88.9 (4.9) to 86.4 (4.5) kg (P < 0.05) respectively. To conclude, if body mass management is a person's primary focus, they should be mindful of the tendency to eat more in the hours after a water-based exercise session, particularly when the water temperature is cold (18-20 °C).
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10.
Effects of acute sleep loss on leptin, ghrelin, and adiponectin in adults with healthy weight and obesity: A laboratory study.
van Egmond, LT, Meth, EMS, Engström, J, Ilemosoglou, M, Keller, JA, Vogel, H, Benedict, C
Obesity (Silver Spring, Md.). 2023;31(3):635-641
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Plain language summary
A lack of sleep may be a risk factor for weight gain. Leptin is an adipocyte-derived hormone that activates satiety networks within the brain. Ghrelin, as opposed to leptin, is mainly produced by the stomach and it acts as a hunger hormone, signalling fuel status to the central nervous system. Some studies have found either no alterations or higher leptin and lower ghrelin blood levels following experimental sleep deprivation. The aim of this study was to investigate whether blood concentrations of leptin, ghrelin, and adiponectin are affected by acute total sleep deprivation in a sex- and weight-specific manner. This study is a laboratory study based on blood samples from 44 participants, mainly university students. Results show that: - acute total sleep deprivation is linked to lower serum levels of the adipokine leptin and higher blood levels of ghrelin. - following sleep deprivation, serum adiponectin levels were elevated. - the drop in serum leptin was larger in women after total sleep deprivation; however, there wasn’t a significant association between biological sex and experimental condition. - the increase in blood levels of adiponectin was slightly more pronounced among women, whereas there weren’t any differences in the effects of sleep loss on plasma ghrelin. Authors conclude that acute total sleep deprivation shifts the endocrine balance from the satiety hormone leptin toward the hunger-promoting hormone ghrelin. However, further investigation in larger samples focusing on their findings linked to sex- and weight-specific differences in leptin, ghrelin, and adiponectin are needed.
Expert Review
Conflicts of interest:
None
Take Home Message:
Sleep deprivation may shift the balance of appetite controlling hormones causing an increase in hunger and decreased satiety and therefore resulting in increased food intake. These changes may be more pronounced in biological females.
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
Sleep deprivation may contribute to weight gain and obesity through its effect on the hormonal pathways promoting hunger and satiety. Research has also linked chronic sleep loss with an increase in the brain reward response to food, thus driving an increase in daily food intake. Leptin and ghrelin are hormones involved in the control of food intake. Some research has associated alterations in these hormones following sleep loss, whilst others have not.
This study aimed to investigate whether biological sex and weight status affect fasting serum levels of leptin, ghrelin and adiponectin following chronic sleep deprivation in a supervised laboratory setting.
Methods
This randomised crossover design study included n=44 mixed sex participants with a mean age of 24.9 years. A total of 19 of the participants were classed as obese, with the remaining n= 25 participants were considered normal weight. Participants completed 2 nights in experimental sessions under continuously supervised conditions in a laboratory. One night was spent awake and the other asleep. Fasting blood samples were taken the morning after each session to measure levels of leptin, ghrelin and adiponectin.
Results
Serum levels of leptin after one night’s sleep loss were around 7% lower than those measured after sleep (17.3 = +/-2.6 vs 18.6 +/- 2.8 ng/mL, p = 0.037). Adjustments using sex-stratified analysis showed significantly lower levels of serum leptin in women (25.8 +/_4.3 vs 28.1 +/_ 4.7 ng/mL, p = 0.030) but not for men (10.1 +/_ 2.4 vs 10.6 +/_ 2.3 ng/mL, p = 0.458). However, when comparing individual participant differences between sleep and wake sessions, the results were not significant. Additionally, no significant differences were found between normal weight and obese participants.
Higher levels of ghrelin were found following sleep deprivation in both sexes and weight sub-groups (839.4 +/-77.5 vs 741.4+/-63.2 pg/mL, p= 0.003). Adiponectin was also found to be elevated in all participants regardless of biological sex or weight status (7.5 +/- 0.6 vs 6.8 +/- 0.6ug/mL, p= 0.003). However, ghrelin was observed to increase slightly more in participants with obesity, whereas elevations in adiponectin were slightly greater in those of normal weight.
Conclusion
In this study, sleep loss was associated with lowered levels of leptin and higher levels of ghrelin. Analysis between biological sexes indicated that there may be a greater decrease in leptin in females. Serum levels of adiponectin were also found to be elevated after sleep deprivation for both sexes with a slightly larger increase in women. These changes may result in increased hunger and food intake and decreased satiety. No significant differences were found between normal weight and obese participants.
Notes: The authors reported no conflicts of interest.
Clinical practice applications:
Sleep deprivation may lead to lower levels of leptin in both sexes with a greater decrease for females. Ghrelin and adiponectin levels may be increased in both men and women after sleep loss with a slightly larger increase in adiponectin for women. This could lead to an increase in appetite, food consumption and therefore weight gain, particularly in women.
Considerations for future research:
- Larger studies are needed to investigate sex and weight status related differences in serum levels of ghrelin, leptin and adiponectin.
- It may be beneficial for blood samples to be taken at different points during the day to allow for fluctuations in hormone levels.
- Food intake should be measured to monitor any increases in food intake.
Abstract
OBJECTIVE This study investigated whether blood concentrations of leptin, ghrelin, and adiponectin are affected by acute total sleep deprivation in a sex- and weight-specific manner. METHODS A total of 44 participants (mean age 24.9 years; 20 women; 19 with obesity) participated in a crossover design, including one night of sleep deprivation and one night of sleep in the laboratory. After each night, fasting blood was collected. RESULTS After sleep deprivation, fasting levels of leptin were lower (mean [SE], vs. sleep: 17.3 [2.6] vs. 18.6 [2.8] ng/mL), whereas those of ghrelin and adiponectin were higher (839.4 [77.5] vs. 741.4 [63.2] pg/mL and 7.5 [0.6] vs. 6.8 [0.6] μg/mL, respectively; all p < 0.05). The changes in leptin and adiponectin following sleep loss were more pronounced among women. Furthermore, the ghrelin increase was stronger among those with obesity after sleep loss. Finally, the sleep loss-induced increase in adiponectin was more marked among normal-weight participants. CONCLUSIONS Acute sleep deprivation reduces blood concentrations of the satiety hormone leptin. With increased blood concentrations of ghrelin and adiponectin, such endocrine changes may facilitate weight gain if persisting over extended periods of sleep loss. The observed sex- and weight-specific differences in leptin, ghrelin, and adiponectin call for further investigation.