Effects of probiotic/synbiotic supplementation on body weight in patients with diabetes: a systematic review and meta-analyses of randomized-controlled trials.

OBJECTIVE: The aim of the present study was to assess the effect of probiotic/synbiotic supplementation on anthropometric measures in adults with diabetes, independent of body weight. METHODS: PubMed, Scopus, Web of Sciences and the Cochrane Library were searched for randomized controlled trials (RCTs) up until December 14, 2022. The effect sizes were pooled using an inverse-variance random-effects model. The methodological quality of studies as well as the quality of evidence was assessed using standard tools. RESULTS: Thirty-two RCTs met the established inclusion criteria. Overall, compared with the respective control groups, probiotic/synbiotic supplementation resulted in a significant reduction in body weight (weighted mean difference [WMD]: -0.50 kg; 95% CI: -0.83, -0.17; I2 = 79.8%, n = 27 studies]), body mass index (WMD: -0.24 kg/m2; 95% CI: -0.39, -0.09; I2 = 85.7%, n = 30 studies), and waist circumference (WMD: -0.90 cm; 95% CI: -1.13, -0.52; I2 = 0%, n = 11 studies). However, hip circumference and waist to hip ratio were not significantly improved. CONCLUSIONS: Our analysis revealed that probiotic/synbiotic supplementation may assist with weight management in patients with diabetes, especially when consumed at higher doses, in younger adults, and in participants with obesity. However, more studies are needed to elucidate the anti-obesity effects of specific strains of probiotics/synbiotics.

Resveratrol may mildly improve renal function in the general adult population: A systematic review and meta-analysis of randomized controlled clinical trials.

Whether renal health biomarkers can benefit from resveratrol supplements is unknown. Thus, we conducted a systematic review and meta-analysis to summarize evidence from randomized controlled trials investigating the effect of resveratrol supplementation on renal health biomarkers. We hypothesized that resveratrol supplementation is associated with improved renal health biomarkers. Four electronic databases, including PubMed, Scopus, and Institute for Scientific Information Web of Science, and Cochrane Central, were searched for relevant articles up to February 2023. The pooled effect sizes were estimated using a random effects model and expressed as weighted mean difference (WMD) and 95% CI. In total, 32 articles were eligible for inclusion in the current meta-analysis. The pooled results indicated that resveratrol significantly decreased blood urea nitrogen (weighted mean difference [WMD]= -0.84 mg/dL; 95% CI, -1.48 to -0.20; P = .01; I2 = 64.4%) and creatinine levels (WMD = -1.90 µmol/L; 95% CI, -3.59 to -0.21; P = .03; I2= 52.1%), and increased glomerular filtration rate (WMD = 7.58 mL/min/1.73 m2; 95% CI, 5.25-9.91; P < .001; I2 = 0%). The favorable change of blood urea nitrogen was significant in studies with short follow-up duration (12 weeks or less), with lower doses of resveratrol (less than 500 mg/d), and those conducted in patients with diabetes. However, higher doses of resveratrol are needed to observe significant reductions in creatinine. No significant change was observed in albumin, total protein, and uric acid concentrations. This meta-analysis provides a low certainty of evidence indicating a mild renal protective effect of resveratrol in adults. Further high-quality evidence in patients with impaired renal function and estimates of mortality risk in these patients is required before resveratrol can be advocated as an adjuvant therapy.

Oral vitamin D supplementation and body weight in children and adolescents: a systematic review and meta-analysis of randomized controlled trials.

This study was designed to ascertain whether oral vitamin D supplementation (oral supplementation and fortified foods) is associated with changes in body weight measures in children and adolescents, using a systematic review and meta-analysis of randomized controlled trials (RCTs). PubMed, Scopus, Cochrane, and Web of Science databases were searched from inception to October 28, 2022. The mean difference and corresponding 95% confidence interval (CI) of interested outcomes were pooled using a random-effects model. Twenty-one RCTs were included in the meta-analysis, and the results showed a significant decrease in body mass index (BMI) following vitamin D supplementation in children and adolescents (n = 9 studies, 1029 participants; weighted mean difference: - 0.43 kg/m2, 95% CI: - 0.79, - 0.08; P = 0.02; I2 = 58.5%). Overall, oral vitamin D supplementation had no significant effect on body weight and other anthropometric indices, including fat mass, lean mass, waist circumference, BMI Z-score, and height. Although results of body weight changed to significant after sensitivity analysis (WMD = 0.39 kg, 95% CI = 0.01, 0.78; P = 0.04; I2 = 0%, P-heterogeneity = 0.71), we also found significant weight gain in healthy pediatric population, and when the dose of vitamin D supplementation was up to 600 IU/day, the certainty of evidence was very low for weight, moderate for height and BMI, and low for the remaining outcomes. CONCLUSION: Our results suggest that vitamin D supplementation may lead to a statistically significant weight gain in children and adolescents, while BMI was reduced. Although no significant change was observed in height, it seems vitamin D supplementation may elicit these changes by increasing skeletal growth; however, this remains to be verified. Further high-quality RCTs, with longer duration and larger sample sizes, are needed to yield more certain evidence in this regard. WHAT IS KNOWN: • Available evidence indicates an inverse association between body weight/fat mass and vitamin D status in children and adolescents; however, findings regarding the effect of vitamin D supplementation on anthropometric measurements in children are controversial. WHAT IS NEW: • Our results showed a significant decrease in BMI following vitamin D supplementation in children. • A significant weight gain also was observed after sensitivity analysis, and in healthy pediatric population, and when the dose of vitamin D supplementation was up to 600 IU/day.

The effect of resveratrol supplementation on biomarkers of liver health: A systematic review and meta-analysis of randomized controlled trials.

This study aimed to evaluate the effect of resveratrol on liver biomarkers in adult participants, using systematic review and meta-analysis of randomized controlled trials. PubMed, Scopus, Web of Science and Cochran Library was searched, up to October 2021. The pooled effects were calculated using a random-effects model and expressed as weighted mean difference and 95% confidence interval. The methodological quality of studies as well as certainty of evidence were assessed by standard tools. Thirty-seven relevant trials were found. Although overall analysis found no significant change, subgroup analysis showed a significant improvement in alanine aminotransferase (ALT; -7.79 U/L) and glutamyl transferase (-6.0 U/L) in patients with liver disorders, and ALT (-2.22 U/L) in younger adults; however, high-dose supplementation (>1,000 mg/day) appeared to increase alkaline phosphatase concentration (+5.07 U/L). ALT also increased in older adults (+2.33 U/L) following resveratrol supplementation. We found resveratrol did not have a significant effect on liver health in the general population. However, resveratrol could be effective in patients with liver disorders. Our findings also suggest that high-dose resveratrol administration and supplementation in older adults should be performed with caution. Further high-quality clinical trials are also needed to firmly establish the clinical efficacy of resveratrol.

Probiotics supplementation and brain-derived neurotrophic factor (BDNF): a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: An emerging body of evidence has demonstrated the beneficial effects of probiotics on various mental health conditions. In this systematic review and meta-analysis, we sought to examine the effects of probiotics supplementation on brain-derived neurotrophic factor (BDNF) in adults. METHODS: PubMed, Scopus, ISI Web of Science, and the Cochrane Library were searched, from database inception to April 2021, for eligible randomized controlled trials (RCTs). We pooled mean differences and standard deviations from RCTs using random-effect models. RESULTS: Overall, meta-analysis of 11 trials (n = 648 participants) showed no significant changes in serum level of BDNF following probiotics. However, subgroup analysis revealed that probiotics increased BDNF levels in individuals suffering from neurological disorders (n = 214 participants; WMD = 3.08 ng/mL, 95% CI: 1.83, 4.34; P = 0.001; I2 = 7.5%; P-heterogeneity 0.34), or depression (n = 268 participants; WMD = 0.77 ng/mL, 95% CI: 0.07, 1.47; P = 0.032; I2 = 88.4%; P-heterogeneity < 0.001). Furthermore, a significant increase in BDNF levels was found in studies that administered the mixture of Lactobacillus and Bifidobacterium genera, and were conducted in Asia . CONCLUSION: Our main findings suggest that probiotics may be effective in elevating BDNF levels in patients with depression and neurological disorders, and a mixed of Lactobacillus and Bifidobacterium appear to show greater efficacy than the single genus supplement. The low quality of evidence reduces clinical advocacy, and indicates that more large-scale, high-quality, RCTs are needed to facilitate reliable conclusions.

The effect of almond intake on cardiometabolic risk factors, inflammatory markers, and liver enzymes: A systematic review and meta-analysis.

Almond intake may be correlated with improvements in several cardiometabolic parameters, but its effects are controversial in the published literature, and it needs to be comprehensively summarized. We conducted a systematic search in several international electronic databases, including MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov until April 2021 to identify randomized controlled trials that examined the effects of almond consumption on cardiometabolic risk factors, inflammatory markers, and liver enzymes. Data were pooled using the random-effects model method and presented as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Twenty-six eligible trials were analyzed (n = 1750 participants). Almond intake significantly decreased diastolic blood pressure, total cholesterol, triglyceride, low-density lipoprotein (LDL), non-high-density lipoprotein (HDL), and very LDL (p < 0.05). The effects of almond intake on systolic blood pressure, fasting blood glucose, insulin, hemoglobin A1c, homeostatic model assessment of insulin resistance, C-peptide, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, C-reactive protein (CRP), hs-CRP (high sensitivity C-reactive protein), interleukin 6, tumor necrosis factor-α, ICAM (Intercellular Adhesion Molecule), VCAM (Vascular Cell Adhesion Molecule), homocysteine, HDL, ox-LDL, ApoA1, ApoB, and lipoprotien-a were not statistically significant (p > .05). The current body of evidence supports the ingestion of almonds for their beneficial lipid-lowering and antihypertensive effects. However, the effects of almonds on antiinflammatory markers, glycemic control, and hepatic enzymes should be further evaluated via performing more extensive randomized trials.

Effect of resveratrol supplementation on hepatic steatosis and cardiovascular indices in overweight subjects with type 2 diabetes: a double-blind, randomized controlled trial.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are prone to develop non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD). We aimed to investigate whether the resveratrol supplementation improves novel hepatic and cardiovascular indices in these patients. METHODS: We conducted a double-blind, randomized controlled trial for 8 weeks. Seventy-six patients with T2DM were randomly assigned to receive 1000 mg/day resveratrol or placebo. Levels of lipid accumulation product (LAP), visceral adiposity index (VAI), Castelli risk index I (CRI-I), CRI-II and atherogenic coefficient (AC) were measured at the beginning and after intervention. RESULTS: A total of 71 participants completed the trial. After adjusting for confounding factors including medications, diabetes duration, energy intake and physical activity, no significant difference was found between the intervention group and the control group in LAP (mean change: - 2.46 ± 23.3 vs. 1.43 ± 14.3; P = 0.43), VAI (mean change: - 0.25 ± 1.1 vs. - 0.02 ± 0.6; P = 0.47), CRI-I (mean change: - 0.25 ± 0.9 vs. - 0.09 ± 0.5; P = 0.79), CRI-II (mean change: - 0.23 ± 0.7 vs. - 0.06 ± 0.6; P = 0.38) and AC (mean change: - 0.25 ± 0.9 vs. - 0.09 ± 0.5; P = 0.79). CONCLUSIONS: Resveratrol supplementation had no effect on hepatic steatosis and cardiovascular indices. Further clinical trials, especially among subjects with dyslipidemia are needed to reach a firm conclusion. In addition, taking all medications should be controlled in future studies. Trial registration The protocol was registered on 29/12/2017 at the Iranian clinical trials website (IRCT20171118037528N1) with URL: https://en.irct.ir/trial/27734 .

The effect of vitamin D supplementation on serum levels of fibroblast growth factor- 23: A systematic review and meta-analysis of randomized controlled trials.

Previous studies of the effect of vtamin D on serum levels of fibroblast growth factor- 23 (FGF-23) have yeilded an inconsistent findings. This systematic review and meta-analysis of randomized controlled trials (RCTs) sought to investigate the effect of vitamin D supplementation on serum levels of FGF-23. PubMed, Scopus, ISI Web of Science, and the Cochrane Library were searched, from database inception to November 2020, for RCTs that evaluated the effects of native or active vitamin D supplementation on serum levels of FGF-23 in adults. Weighted mean difference (WMD) were calculated and random effects meta-analysis was used to estimate the overall effects. Twenty-seven trials were included in the meta-analysis. Supplementation with native vitamin D (23 studies, n = 2247 participants; weighted mean difference [WMD] = 0.5 pg/mL, 95 % CI: -0.52 to 1.51, P = 0.33; I2 = 29.9 %), and active vitamin D (5 studies, n = 342 participants, WMD = 29.45 pg/mL, 95 % CI: -3.9 to 62.81, P = 0.08; I2 = 99.3%) had no significant effects on serum FGF-23 concentration. In subgroup analyses, supplementation with ergocalciferol (3 studies, n = 205 participants; WMD = 18.27 pg/mL, 95 % CI: 5.36-31.17, P = 0.006), and daily dosing regimens (9 studies, n = 1374 participants; WMD = 0.41 pg/mL, 95 % CI: 0.22 to 0.59, P < 0.001) increased serum FGF-23 levels compared to control. Overall, our findings revealed no significan effect of vitamin D supplementation on serum FGF-23 concentration. However, further high quality, large-scale studies are needed to better elucidate this relationship.

Effects of Calcium and Vitamin D Co-supplementation on the Lipid Profile: A Systematic Review and Meta-analysis.

PURPOSE: Calcium and vitamin D co-supplementation is common and widely used, but randomized, controlled trials (RCTs) have yielded inconclusive results concerning its impact on the serum lipid profile. METHODS: A comprehensive literature search of Medline, Web of Science, Scopus, Embase, Cochrane Central Register of Controlled Trials, and clinical trial registry databases was conducted to identify placebo-controlled RCTs that were published through September 2020 and that evaluated the impact of calcium and vitamin D co-supplementation on total cholesterol (TC), triglycerides (TGs), low- and very-low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C). Standardized mean differences (SMDs) were pooled using random-effects meta-analysis models. FINDINGS: Thirteen studies in a total of 2304 participants met the inclusion criteria. Calcium and vitamin D co-supplementation was associated with significant reductions in both TC (SMD, -0.81; 95% CI, -1.35 to -0.27; I2 = 94.6%) and TGs (SMD, -0.50; 95% CI, -0.91 to -0.08; I2 = 91.5%), and with a significant increase in HDL-C (SMD, 1.22; 95% CI, 0.60 to 1.83; I2 = 95.4%). However, calcium and vitamin D co-supplementation were not found to be associated with significantly decreased low-density lipoprotein cholesterol (SMD, -0.39; 95% CI, -0.78 to 0.01; I2 = 90.1%) or very-low-density lipoprotein cholesterol (SMD, -0.01; 95% CI, -0.70 to 0.69; I2 = 82.3%). IMPLICATIONS: The findings from the present systematic review and meta-analysis suggest that calcium and vitamin D co-supplementation has a beneficial effect on TC, TG, and HDL-C. Larger-scale, well-designed RCTs are needed to clarify the effect of calcium and vitamin D co-supplementation on all lipid-profile components.

The effect of vitamin C supplementation on mood status in adults: a systematic review and meta-analysis of randomized controlled clinical trials.

OBJECTIVE: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to clarify the effect of vitamin C supplementation on mood in both depressed and non-depressed populations. METHODS: A systematic search of PubMed, EMBASE, ISI web of science and Scopus databases was conducted, from inception to 1 March 2020. Random-effects meta-analyses were used to estimate the effect size (as Hedge's g) of vitamin C supplementation on depressive symptoms. RESULTS: Finding from 10 trials with 836 participants revealed no significant improvement in mood status in overall analysis (n = 10, Hedge's g = 0.09; 95% confidence interval: -0.15 to 0.33; P = 0.465). However, subgroup analysis showed beneficial effects of vitamin C supplementation in patients who were not prescribed antidepressants (subclinical depressed) (n = 5, Hedge's g: -0.18; 95% CI: -0.35, -0.01, P = 0.041; I2 = 0.00%,). CONCLUSIONS: Although no significant effect on mood status was observed in overall population, this meta-analysis tentatively suggests that vitamin C may produce mood-elevating effects in patients with subclinical depression. Further research is recommended to reach a firm conclusion. PROTOCOL REGISTRATION: The study protocol was registered in the international prospective register of systematic reviews database (http://www.crd.york.ac.uk/PROSPERO, registration no: CRD42018086677).

The effects of resveratrol supplementation on PPARα, p16, p53, p21 gene expressions, and sCD163/sTWEAK ratio in patients with type 2 diabetes mellitus: A double-blind controlled randomized trial.

The present study sought to evaluate the effect of resveratrol supplementation on mRNA expression levels of peroxisome proliferator-activated receptor alpha (PPARα), p53, p21, p16, and serum levels of cluster of differentiation 163 (CD163) to TNF-like weak inducer of apoptosis (TWEAK) ratio in patients with type 2 diabetes. In this double-blind randomized controlled trial, 71 patients were randomly assigned to receive either 1,000 mg of trans-resveratrol or placebo (methyl cellulose) for 8 weeks. Expression levels of genes of interest, and serum levels of sCD163 and sTWEAK were assessed at baseline and at the end of the study. Resveratrol supplementation significantly increased mRNA expression levels of p53 and p21 genes, compared with the placebo group (fold change of p53 = 1.29, p = .04; fold change of p21 = 1.46, p = .006). However, no significant effect on expression levels of PPARα and p16 genes was observed after supplementation. In addition, resveratrol significantly reduced serum levels of sCD163/sTWEAK ratio compared with the placebo group (p = .003). Resveratrol supplementation resulted in significant changes in p53 and p21 genes expression, while serum levels of sCD163/sTWEAK ratio also improved in the resveratrol group, without any significant change in adjusted sCD163 levels. More research is needed to confirm the beneficial effects of resveratrol for patients with diabetes.

The effect of vitamin D supplementation on insulin-like growth factor-1: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: There is equivocality regarding the interaction between vitamin D and insulin-like growth factor-1 (IGF-1). Thus, the aim of this study was to elucidate the effect of vitamin D supplementation on serum levels of IGF-1 by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, Scopus, and ISI Web of Science databases were searched up to May 2019 for RCTs that evaluated the effect of vitamin D supplementation on IGF-1 levels. Mean and standard deviation changes of IGF-1 in each treatment group were considered for analysis and pooled using random-effect model. Risk of bias for included studies was assessed by the Cochrane scale and the NutriGrade approach was applied to evaluate the quality of evidence. RESULTS: Six trials (n = 773 participants) were included in the meta-analysis. Compared with control group, vitamin D supplementation yielded no significant effect on serum level of IGF-1 (weighted mean difference [WMD] =4.66 ng/ml, 95 % CIs: -6.72 to 16.03, P = 0.42, I2 = 74.8, P-heterogeneity = 0.001). Additionally, no meaningful changes were observed in subgroup analyses. CONCLUSION: The evidence from the limited number of published trials does not convincingly show that vitamin D supplementation elicits any clinically relevant effects on IGF-1 levels. More high-quality studies are needed to reach a consensual conclusion in this area.

The effect of resveratrol supplementation on serum levels of asymmetric de-methyl-arginine and paraoxonase 1 activity in patients with type 2 diabetes: A randomized, double-blind controlled trial.

The present study sought to investigate the effect of micronized resveratrol supplementation on serum levels of asymmetric de-methyl-arginine (ADMA) and paraoxonase-1 (PON1) activity in patients with type 2 diabetes (T2D). In this double-blinded randomized trial, 76 patients with T2D were recruited. Participants were randomly assigned to consume 1,000 mg resveratrol or placebo capsules (methylcellulose) per day, for 8 weeks. Serum levels of ADMA and PON1 enzyme activity were measured at the beginning and end of the intervention using the enzyme-linked immunosorbent assay method. In total, 71 participants completed the study. Our results showed that resveratrol significantly decreased serum levels of ADMA (-0.16 ± 0.11, p < .001) and improved PON1 enzyme activity (15.39 ± 13.99, p < .001) compared with placebo, after adjusting for confounding factors (age, sex, and baseline body mass index). Our findings suggest that 8-week resveratrol supplementation may produce beneficial effects on serum levels of ADMA and PON1 enzyme activity in patients with T2DM. However, further research is needed to confirm the veracity of these results.

Zinc Supplementation and Body Weight: A Systematic Review and Dose-Response Meta-analysis of Randomized Controlled Trials.

The aim of this study was to determine the effect of zinc supplementation on anthropometric measures. In this systematic review and dose-response meta-analysis, we searched PubMed, Scopus, ISI Web of Science, and the Cochrane Library from database inception to August 2018 for relevant randomized controlled trials. Mean differences and SDs for each outcome were pooled using a random-effects model. Furthermore, a dose-response analysis for zinc dosage was performed using a fractional polynomial model. Quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Twenty-seven trials (n = 1438 participants) were included in the meta-analysis. There were no significant changes in anthropometric measures after zinc supplementation in the overall analysis. However, subgroup analyses revealed that zinc supplementation increased body weight in individuals undergoing hemodialysis (HD) [3 trials, n = 154 participants; weighted mean difference (WMD) = 1.02 kg; 95% CI: 0.38, 1.65 kg; P = 0.002; I2 = 11.4%] and decreased body weight in subjects who are overweight/obese but otherwise healthy (5 trials, n = 245 participants; WMD = -0.55 kg; 95% CI: -1.06, -0.04 kg; P = 0.03; I2 = 31.5%). Dose-response analyses revealed a significant nonlinear effect of supplementation dosage on BMI (P = 0.001). Our data suggest that zinc supplementation increases body weight in patients undergoing HD and decreases body weight in individuals who are overweight/obese but otherwise healthy, although after normalization for study duration, the association observed in subjects who are overweight/obese disappeared. Although more high-quality studies are needed to reach a definitive conclusion, our study supports the view that zinc may be associated with body weight.

The Effect of Resveratrol Supplementation on Cardio-Metabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized, Double-Blind Controlled Trial.

The aim of the present randomized controlled trial was to evaluate the effect of a micronized resveratrol supplement on glycemic status, lipid profile, and body composition in patients with type 2 diabetes mellitus (T2DM). A total of 71 overweight patients with T2DM (body mass index ranged 25-30) were randomly assigned to receive 1000 mg/day trans-resveratrol or placebo (methyl cellulose) for 8 weeks. Anthropometric indices and biochemical indices including lipid and glycemic profile were measured before and after the intervention. In adjusted model (age, sex, and baseline body mass index), resveratrol decreased fasting blood sugar (-7.97±13.6 mg/dL, p=0.05) and increased high density lipoprotein (3.62±8.75 mg/dL, p=0.01) levels compared with placebo. Moreover, the mean difference in insulin levels reached significance (-0.97±1.91, µIU/mL, p= 0.02). However, no significant differences were observed for anthropometric measures. It was found that 8-week resveratrol supplementation produced useful effects on some cardio-metabolic parameters in patients with T2DM. More studies are needed to confirm these findings.

DHA-enriched fish oil upregulates cyclin-dependent kinase inhibitor 2A (P16INK) expression and downregulates telomerase activity without modulating effects of PPARγ Pro12Ala polymorphism in type 2 diabetic patients: A randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: The present study investigated the effects of docosahexaenoic acid (DHA)-enriched fish oil supplement on telomerase activity, mRNA expression of P16INK, IL-6, and TNF-α considering Pro12Ala polymorphism in the PPARγ gene. METHODS/DESIGN: In this double-blind randomized controlled trial, 72 PPARγ Pro12Ala polymorphism genotyped type 2 diabetic patients aged 30-70 years were randomly assigned to receive 2.4 gr of DHA-enriched fish oil or a placebo for 8 weeks. Genotyping of the Pro12Ala polymorphism in the PPARγ gene was assessed using polymerase chain reaction-restriction length polymorphism (PCR-RFLP), telomerase activity in the peripheral blood mononuclear cell (PBMC) was measured using PCR-ELISA based on the telomeric repeat amplification protocol (TRAP), and changes in the mRNA expression of P16, IL-6, and TNF-α were measured using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In the DHA group, telomerase activity was decreased (p = 0.001) during the intervention. In addition, between-group comparisons showed significant differences in the changes in telomerase activity (p = 0.003) and P16 mRNA expression (p = 0.028) and non-significant differences in TNF-α and IL-6 mRNA expression. The gene*DHA interaction could not affect changes in P16, IL-6, or TNF-α mRNA expression or in telomerase activity in PBMC. DISCUSSION: Short-time DHA-enriched fish oil supplementation caused increased levels of P16 expression and a decline in telomerase activity compared with the control group without modulating the effects of Pro12Ala polymorphism on the PPARγ gene. Because of the positive correlation between P16 activity and cellular senescence, the possibility of senescence stimulation by DHA is proposed.