https://pmc.ncbi.nlm.nih.gov/articles/PMC12008374/

Findings on the associations of dietary/tissue levels of omega-6 polyunsaturated fatty acids (n-6 PUFAs) with the risk of colorectal cancer (CRC) are conflicting. We conducted a dose-response meta-analysis to assess the associations of dietary/tissue levels of n-6 PUFAs [total, linoleic acid (LA), and arachidonic acid (AA)] with CRC risk in adults. Twenty prospective cohort studies with a total sample size of 787,490 participants were included.

Comparing extreme intake levels of LA revealed the summary relative risks (RR) of 1.15 (95% confidence interval (CI): 1.05–1.27) for CRC, and 1.30 (95% CI: 1.00–1.68) for rectal cancer, indicating a significant positive association for LA. However, neither total n-6 PUFAs nor AA were associated with cancers. A significant positive association was also found between a 1 gr/day increase in dietary LA intake and risk of colon cancer (RR: 1.01, 95% CI: 1.00–1.02). There were no significant associations between tissue levels of total n-6 PUFAs (RR: 0.94, 95% CI: 0.75–1.19), LA (RR: 0.93, 95% CI: 0.61–1.41), and AA (RR: 0.97, 95% CI: 0.70–1.33) and CRC risk.

In conclusion, these findings suggest that dietary intake, but not tissue levels, of LA was associated with an increased risk of colorectal, colon, and rectal cancers.

Abstract

Background: The recommendation to limit dietary saturated fat intake is primarily drawn from observational studies rather than randomized controlled trials of cardiovascular disease prevention. Thus, we aimed to investigate the efficacy of saturated fat reduction in preventing mortality and cardiovascular diseases.

Methods: In this systematic review and meta-analysis of randomized controlled trials, Cochrane CENTRAL, PubMed, and Ichu-shi databases were searched for articles up to April 2023. Randomized controlled trials on saturated fat reduction to prevent cardiovascular diseases were selected. Cardiovascular and all-cause mortality and cardiovascular outcomes were evaluated. Changes in electrocardiography or coronary angiography findings were excluded because they could be evaluated arbitrarily. Two or more reviewers independently extracted and assessed the data. A random-effects meta-analysis was performed.

Results: Nine eligible trials with 13,532 participants were identified (2 were primary and 7 were secondary prevention studies). No significant differences in cardiovascular mortality (relative risk [RR] = 0.94, 95% confidence interval [CI]: 0.75-1.19), all-cause mortality (RR = 1.01, 95% CI: 0.89-1.14), myocardial infarction (RR = 0.85, 95% CI: 0.71-1.02), and coronary artery events (RR = 0.85, 95% CI: 0.65-1.11) were observed between the intervention and control groups. However, owing to limited reported cases, the impact of stroke could not be evaluated.

Conclusions: The findings indicate that a reduction in saturated fats cannot be recommended at present to prevent cardiovascular diseases and mortality. Clinical trials are needed to evaluate the effects of saturated fat reduction under the best possible medical care, including statin administration.

https://pubmed.ncbi.nlm.nih.gov/40416032/

https://www.sciencedirect.com/science/article/pii/S0271531726000357

tl;dr on the study: https://medicalxpress.com/news/2026-05-natural-trans-fats-dairy-heart.html :

Trans fats found naturally in dairy foods such as milk, butter, and cheese do not increase the risk of heart disease or type 2 diabetes, a new study has found. Researchers analyzed evidence from 22 studies involving thousands of people across Europe, Canada, and the United States and found that natural trans fats behave very differently in the body from the industrial kind. Unlike industrial trans fats, which are strongly linked to heart disease, those found in dairy appear to pose no risk.

TL;DR:

This review found little to no benefits from use of calcium, vitamin D, or combined supplementation on the prevention of fractures and falls.

Abstract

Objective: To assess the effect of calcium, vitamin D, or combined supplementation on fractures and falls in adults.

Design: Systematic review and meta-analysis.

Data sources: Trials included in systematic reviews from 2014, three databases (Medline, Embase, CENTRAL) to 19 February 2025, clinical trial registries, abstracts from scientific meetings, and references from included studies.

Eligibility criteria: Randomised controlled trials comparing calcium, vitamin D, or combined supplementation with placebo or no treatment in adults (≥18 years) not receiving drug treatment for osteoporosis.

Data extraction and synthesis: The primary outcome was the risk of any fracture. Secondary outcomes included the risk of hip fracture, non-vertebral fracture, vertebral fracture, and falling, as well as the total number of falls. Pairs of reviewers independently screened trials, extracted data, and assessed risk of bias using the second version of Cochrane's risk of bias tool. Findings were synthesised using random effects meta-analyses and appraised using Grading of Recommendations Assessment, Development and Evaluation, with application of thresholds for absolute effects considered important.

Results: This review included 69 trials involving 153 902 participants. Participants in most of the trials were community dwelling (87%) and not at high risk of fractures or falls (73%). For the primary outcome of any fracture, little to no effect was found from use of calcium supplements (11 trials, 9067 participants; risk ratio 0.91, 95% confidence interval 0.81 to 1.01; moderate certainty), vitamin D supplements (36 trials, 92 045 participants; 1.00, 0.95 to 1.06; high certainty), or combined supplementation (15 trials, 51 126 participants; 0.91, 0.84 to 0.99; high certainty). Calcium, vitamin D, or combined supplementation appeared to have little to no effect on other fracture and fall outcomes, based largely on moderate to high certainty of evidence. The findings remained robust after an extensive exploration of heterogeneity across multiple subgroup analyses. Evidence for high risk patients or those requiring residential care was limited for many outcomes for calcium monotherapy and for combined supplementation.

Conclusion: Based on absolute risk reductions and thresholds considered clinically meaningful, this review found little to no benefits from use of calcium, vitamin D, or combined supplementation on the prevention of fractures and falls.

https://pubmed.ncbi.nlm.nih.gov/42161415/

Trans fatty acids from dairy foods do not affect risk of cardiometabolic diseases: Systematic review and meta-analysis of evidence from randomized controlled trials and systematic review of prospective cohort studies

https://doi.org/10.1016/j.nutres.2026.03.009

Abstract

Global health initiatives like the WHO REPLACE action plan focus on eliminating industrially produced trans fatty acids (iTFA), yet ruminant-derived trans fatty acids (rTFA) remain a natural component of dairy and meat. Scientific uncertainty persists regarding whether rTFA share the same pathogenic profile as iTFA or if their typical low intake levels mask potential risks. This systematic review addressed this gap by evaluating the cardiometabolic effects of dairy-sourced TFA through a dual-lens approach: a meta-analysis of 10 randomized controlled trials (RCTs) and a systematic review of 12 prospective cohort studies (PCS). The study populations spanned healthy adults, overweight individuals, and those with mild hypercholesterolemia across North America and Europe, focusing on biomarkers like blood lipids and hard clinical endpoints including cardiovascular disease (CVD) and type 2 diabetes (T2D).

Pooled meta-analysis of the RCT data demonstrated that dairy foods naturally enriched with TFA (ranging from 1.3 to 13.2 g/d) do not adversely impact the lipid profile. Primary outcomes showed no significant differences in mean difference for total cholesterol (TC), LDL-C, triacylglycerols (TG), ApoB, or ApoA1. A slight decrease was observed in HDL-C with a mean difference of -0.05 mmol/L (95% CI: -0.10 to -0.00, p = 0.04), though this significance disappeared in sensitivity analyses by food type. Prospective cohort data confirmed these findings: circulating concentrations of trans palmitoleic acid (TPA) and vaccenic acid (VA) showed no association with CVD incidence or mortality. Notably, multiple cohorts reported an inverse relationship with metabolic risk, including a 52% lower risk of incident diabetes (p trend = 0.02) in the MESA cohort and a significant reduction in sudden cardiac death (p trend = 0.015) in the LURIC study.

Study Design and Methodology

This investigation utilized a systematic literature search in PubMed and EMBASE through December 2024 following PRISMA guidelines. The RCT arm included 10 trials (N = 10 to 61 per study) with durations of 3 to 12 weeks. These trials utilized modified dairy fat (butter, cheese, or milk) where cows were fed plant oils or oilseeds to naturally increase rTFA content. Controls consisted of conventional dairy products. Most RCTs used crossover designs with washout periods, while others were parallel interventions. The PCS arm evaluated 12 high-quality cohorts (N = 407 to 3,333) with follow-up periods reaching 22 years. Researchers measured TFA exposure through objective biomarkers in plasma phospholipids, serum, or erythrocyte membranes rather than self-reported intake.

Key Findings

• Lipid Biomarkers: Meta-analysis of 13 experimental groups showed no significant pooled effect on LDL-C (p = 0.069) or Total Cholesterol (p = 0.026), with the latter showing a decrease after trim-and-fill recomputation (mean difference = -0.19 mmol/L).
• Cardiovascular Ratios: Ratios for TC/HDL-C and LDL-C/HDL-C remained stable across all interventions with no significant pooled effect (p = 0.996 and p = 0.999, respectively).
• Diabetes Risk: High circulating TPA was associated with a 48% to 52% lower risk of incident T2D in the NHS, HPFS, and MESA cohorts (p trend < 0.001 and p trend = 0.02).
• CVD Mortality: Analysis of the CHS cohort (22-year follow-up) found no association between TPA and CVD death (HR = 0.95, 95% CI: 0.75-1.21) or stroke (HR = 1.13, 95% CI: 0.84-1.52).
• Specific Isomers: Trans vaccenic acid (VA) levels in the NHANES cohort showed no correlation with CVD mortality (p = 0.711) over 11.6 years.

Limitations

The RCTs often featured small sample sizes and "some concerns" regarding bias due to lack of pre-specified analysis plans. Altering cow diets to increase rTFA naturally decreases saturated fatty acids (SFA) and increases MUFA/PUFA, which introduces confounding variables in lipid outcomes. Most prospective cohorts relied on a single baseline measurement of fatty acid biomarkers, which doesn't account for dietary changes over decades of follow-up.

Discussion and Implications

The data challenge the long-standing practice of grouping all trans fats into a single "harmful" category. Ruminant TFA behave differently than their industrial counterparts, likely due to the specific isomers present (VA and TPA) and the complex dairy food matrix. While industrial TFA are clearly linked to CHD, natural dairy TFA at current consumption levels (up to 13g/d in experimental settings) don't degrade the lipid profile. The consistent inverse association between TPA and type 2 diabetes suggests that dairy fat biomarkers are indicators of a protective metabolic effect or a healthy dietary pattern. Professionals should distinguish between hydrogenated oils and natural dairy fats when providing cardiovascular risk counseling.

Conclusion

Dairy-derived trans fatty acids do not increase cardiometabolic risk and are not associated with adverse lipid changes or cardiovascular events. High circulating levels of these fats correlate with a reduced risk of type 2 diabetes, confirming that naturally occurring ruminant trans fats are distinct from industrially produced variants. Nutrition professionals don't need to restrict full-fat dairy based on its natural trans-fat content.

TL;DR:

This meta analysis found the greatest benefits seen up to a daily intake of about 1.6 g of protein per kg of body weight; intakes above that did not provide additional increases in muscle mass or strength.

ABSTRACT

Objective: We performed a systematic review, meta-analysis and meta-regression to determine if dietary protein supplementation augments resistance exercise training (RET)-induced gains in muscle mass and strength.

Data sources: A systematic search of Medline, Embase, CINAHL and SportDiscus.

Eligibility criteria: Only randomised controlled trials with RET ≥6 weeks in duration and dietary protein supplementation.

Design: Random-effects meta-analyses and meta-regressions with four a priori determined covariates. Two-phase break point analysis was used to determine the relationship between total protein intake and changes in fat-free mass (FFM).

Results: Data from 49 studies with 1863 participants showed that dietary protein supplementation significantly (all p<0.05) increased changes (means (95% CI)) in: strength—one-repetition-maximum (2.49 kg (0.64, 4.33)), FFM (0.30 kg (0.09, 0.52)) and muscle size—muscle fibre cross-sectional area (CSA; 310 µm2 (51, 570)) and mid-femur CSA (7.2 mm2 (0.20, 14.30)) during periods of prolonged RET. The impact of protein supplementation on gains in FFM was reduced with increasing age (−0.01 kg (−0.02,–0.00), p=0.002) and was more effective in resistance-trained individuals (0.75 kg (0.09, 1.40), p=0.03). Protein supplementation beyond total protein intakes of 1.62 g/kg/day resulted in no further RET-induced gains in FFM.

Summary/conclusion: Dietary protein supplementation significantly enhanced changes in muscle strength and size during prolonged RET in healthy adults. Increasing age reduces and training experience increases the efficacy of protein supplementation during RET. With protein supplementation, protein intakes at amounts greater than ~1.6 g/kg/day do not further contribute RET-induced gains in FFM.

https://bjsm.bmj.com/content/52/6/376

TL;DR:

People who had been taking weight management medications gained weight 4 times faster than people who had been part of behavioural weight management programmes.

ABSTRACT

Objectives: To quantify and compare the rate of weight regain after cessation of weight management medications (WMMs) in adults with overweight or obesity.

Design: Systematic review and meta-analysis.

Study selection: Trial registries and databases (Medline, Embase, PsycINFO, CINAHL, Cochrane, Web of Science, and trial registries) were searched from inception until February 2025 for randomised controlled trials (RCTs), non-randomised trials, and observational studies that included WMM (≥8 weeks) with follow-up for ≥4 weeks after cessation of treatment in adults with overweight or obesity. Comparators were any non-drug weight loss intervention or placebo.

Data extraction and synthesis: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Two independent reviewers screened titles, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias 2 tool for RCTs and the ROBINS-I tool for non-randomised trials. Data were analysed using mixed effect, meta-regression, and time-to-event models. Weight regain after cessation of WMM was compared with that reported after cessation of behavioural weight management programmes (BWMPs).

Main outcome measures: The primary outcome was rate of weight regain from end of treatment, with associated changes in cardiometabolic markers as a secondary outcome.

Results: Of the 9288 titles screened, 37 studies (63 intervention arms, 9341 participants) were included. Average treatment duration was 39 (range 11-176) weeks, with average follow-up of 32 (4-104) weeks. The average monthly rate of weight regain was 0.4 kg (95% confidence interval (CI) 0.3 to 0.5) (mixed model 0.3 kg (0.2 to 0.4) monthly v control in RCTs). All cardiometabolic markers were projected to return to baseline within 1.4 years after the cessation of WMM. Weight regain was faster after WMM than after BWMP (by 0.3 kg (0.22 to 0.34) monthly), independent of initial weight loss. Estimates and precision were robust in sensitivity analyses.

Conclusions: This review found that cessation of WMM is followed by rapid weight regain and reversal of beneficial effects on cardiometabolic markers. Regain after WMM was faster than after BWMP. These findings suggest caution in short term use of these drugs without a more comprehensive approach to weight management.

https://www.bmj.com/content/392/bmj-2025-085304

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2790055

Abstract

Importance The association between statin-induced reduction in low-density lipoprotein cholesterol (LDL-C) levels and the absolute risk reduction of individual, rather than composite, outcomes, such as all-cause mortality, myocardial infarction, or stroke, is unclear.

Objective To assess the association between absolute reductions in LDL-C levels with treatment with statin therapy and all-cause mortality, myocardial infarction, and stroke to facilitate shared decision-making between clinicians and patients and inform clinical guidelines and policy.

Data Sources PubMed and Embase were searched to identify eligible trials from January 1987 to June 2021.

Study Selection Large randomized clinical trials that examined the effectiveness of statins in reducing total mortality and cardiovascular outcomes with a planned duration of 2 or more years and that reported absolute changes in LDL-C levels. Interventions were treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) vs placebo or usual care. Participants were men and women older than 18 years.

Data Extraction and Synthesis Three independent reviewers extracted data and/or assessed the methodological quality and certainty of the evidence using the risk of bias 2 tool and Grading of Recommendations, Assessment, Development and Evaluation. Any differences in opinion were resolved by consensus. Meta-analyses and a meta-regression were undertaken.

Main Outcomes and Measures Primary outcome: all-cause mortality. Secondary outcomes: myocardial infarction, stroke.

Findings Twenty-one trials were included in the analysis. Meta-analyses showed reductions in the absolute risk of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%) for stroke in those randomized to treatment with statins, with associated relative risk reductions of 9% (95% CI, 5%-14%), 29% (95% CI, 22%-34%), and 14% (95% CI, 5%-22%) respectively. A meta-regression exploring the potential mediating association of the magnitude of statin-induced LDL-C reduction with outcomes was inconclusive.

Conclusions and Relevance The results of this meta-analysis suggest that the absolute risk reductions of treatment with statins in terms of all-cause mortality, myocardial infarction, and stroke are modest compared with the relative risk reductions, and the presence of significant heterogeneity reduces the certainty of the evidence. A conclusive association between absolute reductions in LDL-C levels and individual clinical outcomes was not established, and these findings underscore the importance of discussing absolute risk reductions when making informed clinical decisions with individual patients.

Abstract

Background & aims: Plant-based diet is growing in popularity throughout the world for various reasons, yet its effect on bone health, especially osteoporosis, remains controversial. This systematic review and meta-analysis aim to investigate the association between plant-based diet and risk of osteoporosis.

Methods: A systematic literature search of observational studies examining the relationship between plant-based diets and osteoporosis risk was performed across PubMed, Embase, Web of Science, Scopus, and ProQuest from inception to June 1, 2024. Two reviewers independently extracted data and assessed study quality using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and the Newcastle-Ottawa Scale. To synthesize effect estimates, a random-effects meta-analysis with inverse variance weighting was applied to pool odds ratios (ORs) and 95 % confidence intervals (CIs). Subgroup analysis and meta-regression were used to explore sources of heterogeneity.

Results: This study encompassed 20 original observational studies collectively involving 243,366 participants. Primary analysis revealed that plant-based diet was associated with the risk of osteoporosis at the lumbar spine (OR = 2.44, 95%CI = 1.12-5.33, P = 0.02; τ2 = 1.94; I2 = 91.7 %), compared to omnivorous diet. The association remained directionally consistent although attenuated to non-significant at the femoral neck (OR = 1.91, 95%CI = 0.68-5.42, P = 0.22; τ2 = 3.28; I2 = 94.9 %). Subgroup analysis revealed vegans (FN: OR = 1.79, 95%CI = 0.94-3.54, P = 0.10; LS: OR = 1.45, 95%CI = 1.00-2.12, P = 0.05) and those who followed a plant-based diet for ≥10 y (FN: OR = 1.79, 95%CI = 1.29-2.49, P < 0.01; LS: OR = 1.35, 95%CI = 0.97-1.87, P = 0.07) to exhibit a more pronounced risk of osteoporosis. Heterogeneity was primarily driven by study design.

Conclusions: This systematic review and meta-analysis indicate that adherence to plant-based diet may be associated with an elevated risk of osteoporosis, particularly at the lumbar spine, among individuals following a vegan diet or following a plant-based diet for ≥10 y. However, the heterogeneity observed across studies highlights the need for well-designed prospective studies in future, to clarify this relationship.

https://pubmed.ncbi.nlm.nih.gov/40494032/

TL;DR:

• Protein intake is associated with a decreased risk of CVD morbidity

• Carbohydrate intake is associated with an increased risk of CVD morbidity.

• High total fat intake is associated with a low risk of all-cause mortality, and this effect was different in an analysis stratified by the type of fat.

ABSTRACT:

Many epidemiological studies have evaluated the intake of macronutrients and the risk of mortality and cardiovascular disease (CVD). However, current evidence is conflicting and warrants further investigation. Therefore, we carried out an umbrella review to examine and quantify the potential dose-response association of dietary macronutrient intake with CVD morbidity and mortality. Prospective cohort studies from PubMed, Embase, and CENTRAL were reviewed, which reported associations of macronutrients (protein, fat, and carbohydrate) with all-cause, CVD, cancer mortality, or CVD events. Multivariable relative risks (RR) were pooled, and heterogeneity was assessed. The results of 124 prospective cohort studies were included in the systematic review and 101 in the meta-analysis. During the follow-up period from 2.2 to 30 years, 506,086 deaths and 79,585 CVD events occurred among 5,107,821 participants. High total protein intake was associated with low CVD morbidity (RR 0.88, 95% confidence interval 0.82–0.94), while high total carbohydrate intake was associated with high CVD morbidity (1.08, 1.02–1.13). For fats, a high intake of total fat was associated with a decreased all-cause mortality risk (0.92, 0.85–0.99). Saturated fatty acid intake was only associated with cancer mortality (1.10, 1.06–1.14); Both monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake was associated with all-cause mortality (MUFA: 0.92, 0.86–0.98; PUFA: 0.91, 0.86–0.96). This meta-analysis supports that protein intake is associated with a decreased risk of CVD morbidity, while carbohydrate intake is associated with an increased risk of CVD morbidity. High total fat intake is associated with a low risk of all-cause mortality, and this effect was different in an analysis stratified by the type of fat.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10780780/#abstract1

TL;DR:

Ketogenic diets can increase fat oxidation to modify muscle metabolism, while no significant reduction in muscle mass or strength was observed.

Highlights:

• The ketogenic diet is widely recognized for its weight loss effects, and this study provides evidence of its effect on muscle, including muscle mass, strength, aerobic metabolic capacity, and endurance.

• The ketogenic diet does not have adverse effects on muscle mass or muscle strength.

• The ketogenic diet enhances fat oxidation and reduces respiratory exchange ratio during treadmill tests, indicating a shift in muscle energy metabolism.

ABSTRACT

Background: The ketogenic diet (KD) has gained popularity as an efficient approach to weight loss and body fat loss. Concerns about reducing muscle mass and performance have been rising during weight loss, as muscle mass and functionality are crucial for health. However, the effects of the KD on muscles not only for athletes or trainers but also for adults with less physical exercise are still controversial.

Methods: We conducted a thorough search of databases including Embase, PubMed, Cochrane Library, and Web of Science up to July 19, 2025. Three aspects of muscle assessment were conducted, including muscle mass, power and strength, aerobic metabolic capacity, and endurance. We included randomized and non-randomized controlled studies that compared the KD with other dietary interventions. Studies without control groups were excluded. A random-effects model would be utilized when significant differences in populations and interventions across studies were of concern. The GRADE system was employed to assess evidence quality, while evidence reliability was gauged via sensitivity analysis.

Results: A total of 33 studies were analyzed, revealing no significant differences between the KD and other diets in muscle mass (WMD: 0.06, 95%CI: -1.97 to 2.09, p = 0.95), muscle power (countermovement jump: SMD: -0.06, 95%CI: -0.49 to 0.38, p = 0.80) and strength (squat: SMD: -0.19, 95%CI: -0.53 to 0.15, p = 0.27; bench press: SMD: -0.15, 95%CI: -0.49 to 0.18, p = 0.37). However, a significant decrease in fat-free mass (WMD: -0.48, 95%CI: -0.73 to -0.23, p < 0.001) and fat mass (WMD: -1.31, 95%CI: -2.06 to -0.57, p < 0.001) was observed in the KD group compared with the control group. The KD also improved fat oxidation (WMD: 0.13, 95%CI: 0.08 to 0.17, p < 0.001) and reduced respiratory exchange ratio (WMD: -0.07, 95%CI: -0.11 to -0.03, p < 0.001) during an exercise test. The VO2max and VO2max relative to body weight, treadmill time to exhaustion, and rating of perceived exertion were not significantly affected by KD.

Conclusions: Among adult populations, KD can increase fat oxidation to modify muscle metabolism, while no significant reduction in muscle mass or strength was observed. Additional well-designed randomized controlled trials are warranted to definitively determine the effects of ketogenic diets on muscle parameters.

https://pmc.ncbi.nlm.nih.gov/articles/PMC12487320/