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Potential Modulation of Inflammation and Physical Function by Combined Probiotics, Omega-3 Supplementation and Vitamin D Supplementation in Overweight/Obese Patients with Chronic Low-Grade Inflammation: A Randomized, Placebo-Controlled Trial.

ABSTRACT: Obesity is characterized by low-grade inflammation and increased gut permeability. Here, we aim to evaluate the effect of a nutritional supplement on these parameters in subjects with overweight and obesity. A double-blinded, randomized clinical trial was conducted in 76 adults with overweight or obesity (BMI 28 to 40) and low-grade inflammation (high-sensitivity C-reactive protein (hs-CRP) between 2 and 10 mg/L). The intervention consisted of a daily intake of a multi-strain probiotic of Lactobacillus and Bifidobacterium, 640 mg of omega-3 fatty acids (n-3 FAs), and 200 IU of vitamin D (n = 37) or placebo (n = 39), administered for 8 weeks. hs-CRP levels did not change post-intervention, other than an unexpected slight increase observed in the treatment group. Interleukin (IL)-6 levels decreased in the treatment group (p = 0.018). The plasma fatty acid (FA) levels of the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio and n-6/n-3 ratio (p < 0.001) decreased, and physical function and mobility improved in the treatment group (p = 0.006). The results suggest that hs-CRP may not be the most useful inflammatory marker, but probiotics, n-3 FAs, and vitamin D, as non-pharmaceutical supplements, may exert modest effects on inflammation, plasma FA levels, and physical function in patients with overweight and obesity and associated low-grade inflammation.

SUBMITTER: Kopp L

PROVIDER: S-EPMC10217964 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Potential Modulation of Inflammation and Physical Function by Combined Probiotics, Omega-3 Supplementation and Vitamin D Supplementation in Overweight/Obese Patients with Chronic Low-Grade Inflammation: A Randomized, Placebo-Controlled Trial.

Kopp Lena L Schweinlin Anna A Tingö Lina L Hutchinson Ashley N AN Feit Viktoria V Jähnichen Tabea T Lehnert Katja K Vetter Walter W Rings Andreas A Jensen Morten G MG Brummer Robert J RJ Bischoff Stephan C SC

International journal of molecular sciences 20230510 10

Obesity is characterized by low-grade inflammation and increased gut permeability. Here, we aim to evaluate the effect of a nutritional supplement on these parameters in subjects with overweight and obesity. A double-blinded, randomized clinical trial was conducted in 76 adults with overweight or obesity (BMI 28 to 40) and low-grade inflammation (high-sensitivity C-reactive protein (hs-CRP) between 2 and 10 mg/L). The intervention consisted of a daily intake of a multi-strain probiotic of <i>Lac ...[more]

PMID: 37239916

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Project description:BackgroundThe placentas of obese women accumulate lipids that may alter fetal lipid exposure. The long-chain omega-3 fatty acids (n–3 FAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) alter FA metabolism in hepatocytes, although their effect on the placenta is poorly understood.ObjectiveWe aimed to investigate whether n–3 supplementation during pregnancy affects lipid metabolism in the placentas of overweight and obese women at term.DesignA secondary analysis of a double-blind randomized controlled trial was conducted in healthy overweight and obese pregnant women who were randomly assigned to DHA plus EPA (2 g/d) or placebo twice a day from early pregnancy to term. Placental FA uptake, esterification, and oxidation pathways were studied by measuring the expression of key genes in the placental tissue of women supplemented with placebo and n–3 and in vitro in isolated trophoblast cells in response to DHA and EPA treatment.ResultsTotal lipid content was significantly lower in the placentas of overweight and obese women supplemented with n–3 FAs than in those supplemented with placebo (14.14 ± 1.03 compared with 19.63 ± 1.45 mg lipid/g tissue; P < 0.05). The messenger RNA expression of placental FA synthase (FAS) and diacylglycerol O-acyltransferase 1 (DGAT1) was negatively correlated with maternal plasma enrichment in DHA and EPA (P < 0.05). The expression of placental peroxisome proliferator–activated receptor γ (r = −0.39, P = 0.04) and its target genes DGAT1 (r = −0.37, P = 0.02) and PLIN2 (r = −0.38, P = 0.04) significantly decreased, with an increasing maternal n–3:n–6 ratio (representing the n–3 status) near the end of pregnancy. The expression of genes that regulate FA oxidation or uptake was not changed. Birth weight and length were significantly higher in the offspring of n–3-supplemented women than in those in the placebo group (P < 0.05), but no differences in the ponderal index were observed. Supplementation of n–3 significantly decreased FA esterification in isolated trophoblasts without affecting FA oxidation.ConclusionSupplementing overweight and obese women with n–3 FAs during pregnancy inhibited the ability of the placenta to esterify and store lipids. This trial was registered at clinicaltrials.gov as NCT00957476.

Project description:BackgroundA critical need exists to better understand the physiological sequel of vitamin D supplementation in obese individuals and African Americans. The aim was to comprehensively evaluate dose- and time-responses of a panel of vitamin D biomarkers to vitamin D supplements in this population.MethodsWe conducted a 16-week randomized, double-blinded, and placebo-controlled clinical trial. Seventy overweight/obese African Americans (age 13-45 years, 84 % females) with 25-hydroxyvitamin D [25(OH)D] concentrations ≤20 ng/mL were randomly assigned to receive a supervised monthly oral vitamin D3 of 18,000 IU (~600 IU/day, n = 17), 60,000 IU (~2000 IU/day, n = 18), 120,000 IU (~4000 IU/day, n = 18), or placebo (n = 17).ResultsThere were significant dose- and time-responses of circulating 25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)2D], and intact parathyroid hormone (iPTH), but not fibroblast growth factor-23 (FGF-23), phosphorus and urine calcium to the vitamin D supplements. The mean 25(OH)D concentrations in the 2000 IU and 4000 IU groups reached ≥30 ng/mL as early as 8-weeks and remained at similar level at 16-weeks. The increase of 25(OH)D was significantly higher in the 4000 IU group than all the other groups at 8-weeks. The increase of 1,25(OH)2D was significantly higher in the 2000 IU and 4000 IU groups than the placebo at 8-weeks. Only the 4000 IU compared to the placebo significantly reduced iPTH at 8- and 16-weeks.ConclusionsOur RCT, for the first time, comprehensively evaluated time- and dose- responses of vitamin D supplementation in overweight/obese African Americans with suboptimal vitamin D status. Circulating 25(OH)D, 1,25(OH)2D, and iPTH, but not FGF-23, phosphorus and urine calcium, respond to vitamin D supplementation in a time- and dose-response manner. By monthly dosing, 2000 IU appears to be sufficient in achieving a 25(OH)D level of 30 ng/mL in this population. However, importantly, 4000 IU, rather than 2000 IU, seems to suppress iPTH. If replicated, these data might be informative in optimizing vitamin D status and providing individualized dosing recommendation in overweight/obese African Americans.Trial registrationClinicalTrials.gov number: NCT01583621, Registered on April 3, 2012.

Project description:BackgroundAbout 30% of women entering pregnancy in the US are obese. We have previously reported mitochondrial dysregulation and increased inflammation in the placentae of obese women. Vitamin D (VitD) is a major player in calcium uptake and was shown to modulate mitochondrial respiration and the immune/inflammation system. Studies show decreased VitD levels in obese individuals; however, the effect of maternal obesity on VitD metabolism and its association with placental function remains understudied.MethodsMaternal and cord blood plasma and placental samples were collected upon C-section from normal-weight (NW, body mass index [BMI]<25) and obese (OB, BMI>30) women with uncomplicated pregnancies at term. We measured 25(OH)D3 (calcidiol) levels in maternal and cord blood plasma using ELISA. We assessed the expression of CYP27B1, an activator of calcidiol, and Vitamin D receptor (VDR) in placentae from NW and OB, and women with gestational diabetes and preeclampsia. In addition, we examined the effects of VitD supplementation on mitochondrial function and inflammation in trophoblasts from NW and OB, using the Seahorse Bioanalyzer and Western blot, respectively.ResultsVitamin D levels in blood from OB but not NW women and in cord blood from babies born to NW and OB women showed a significant inverse correlation with maternal pre-pregnancy BMI (r=-0.50, p<0.1 and r=-0.55, p=0.004 respectively). Cord plasma VitD levels showed a positive correlation with placental efficiency, i.e., the ratio between fetal and placental weight, as well as with maternal blood VitD levels (r=0.69 and 0.83 respectively, p<0.00). While we found no changes in CYP27B1 in OB vs. NW women, VDR expression were decreased by 50% (p<0.03) independent of fetal sex. No changes in VDR expression relative to BMI-matched controls were observed in the placentae of women with gestational diabetes or preeclampsia. Cytotrophoblasts isolated from placentae of OB women showed a dose-dependent increase in VDR expression after 24-hour treatment with calcitriol (10 nM and 100 nM), an active form of VitD. Trophoblasts isolated from OB women and treated with calcitriol improved mitochondrial respiration (p<0.05). We also found a two-fold increase in expression of the NLRP3 inflammasome and the pro-inflammatory cytokine IL-18 in trophoblasts isolated from placentae of OB women (p<0.05), with IL-18 expression being reversed by calcitriol treatment (100 nM).ConclusionsWe show that VitD deficiency is at least partially responsible for mitochondrial dysfunction and increased inflammation in the placentae of obese women. Vitamin D supplementation could be beneficial in improving placental dysfunction seen in obese women.

Project description:PurposeVitamin D supplementation may have non-skeletal health benefits and enhance exercise responsiveness, particularly in those with low vitamin D levels. We determined whether, compared with placebo, vitamin D supplementation taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight and obese older adults with vitamin D deficiency.MethodsFifty overweight or obese older adults (mean ± SD age: 60 ± 6 years; BMI 30.6 ± 5.7 kg/m2) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) were recruited. Participants were randomly allocated to receive either vitamin D3 (4000 IU/day) or matching placebo for 24 weeks. Between weeks 12 and 24, all participants completed multi-modal exercise three days per week while continuing with vitamin D/placebo. Mean changes in physical function (primary outcome: gait speed), body composition and biochemical parameters at weeks 12 and 24 were compared between groups.ResultsVitamin D supplementation, with or without exercise, had no effect on gait speed. From baseline to week 12, vitamin D supplementation increased serum 25(OH)D levels (placebo: 2.5 ± 14.7 nmol/L; treatment: 43.4 ± 18.4 nmol/L; P < 0.001) and reduced stair climb times (placebo: 0.3 ± 1.0 s; treatment: - 0.2 ± 1.0 s; P = 0.046). From 12 to 24 weeks, vitamin D supplementation combined with exercise decreased waist circumference (placebo: 1.3 ± 7.3 cm; treatment: - 3.0 ± 6.1 cm; P = 0.02) and waist-to-hip ratio (placebo: 0.01 ± 0.05; treatment: - 0.03 ± 0.05; P = 0.01) relative to placebo. Vitamin D supplementation, with or without exercise, had no effect on other physical function, body composition or metabolic health outcomes.ConclusionVitamin D supplementation had no effect on most physical function, body composition or metabolic health parameters when taken alone, or during exercise, in overweight or obese older adults with vitamin D deficiency. Vitamin D-related improvements in stair climb times and waist circumference suggest that future trials should explore the effects of vitamin D on muscle power, and its effects on body composition when combined with exercise, in populations with moderate or severe vitamin D deficiency.

Project description:BackgroundObese children are vulnerable to vitamin D deficiency and impaired cardiovascular health; vitamin D replenishment might improve their cardiovascular health.ObjectivesThe aims were to determine, in vitamin D-deficient overweight and obese children, whether supplementation with vitamin D3 1000 or 2000 IU/d is more effective than 600 IU/d in improving arterial endothelial function, arterial stiffness, central and systemic blood pressure (BP), insulin sensitivity (1/fasting insulin concentration), fasting glucose concentration, and lipid profile and to explore whether downregulation of adipocytokines and markers of systemic inflammation underlies vitamin D effects.MethodsWe conducted a randomized, double-masked, controlled clinical trial in 225 10- to 18-y-old eligible children. Change in endothelial function at 6 mo was the primary outcome.ResultsDose-response increases in serum 25-hydroxyvitamin D concentrations were significant and tolerated without developing hypercalcemia. Changes at 3 and 6 mo in endothelial function, arterial stiffness, systemic-systolic BP, lipids, and inflammatory markers did not differ between children receiving 1000 or 2000 IU vitamin D and children receiving 600 IU. Some secondary outcomes differed between groups. Compared with the 600-IU group, central-systolic, central-diastolic, and systemic-diastolic BP was lower at 6 mo in the 1000-IU group [-2.66 (95% CI: -5.27, -0.046), -3.57 (-5.97, -1.17), and -3.28 (-5.55, -1.00) mm Hg, respectively]; insulin sensitivity increased at 3 and 6 mo and fasting glucose concentration declined at 6 mo (-2.67; 95% CI: -4.88, -0.46 mg/dL) in the 2000-IU group.ConclusionsCorrection of vitamin D deficiency in overweight and obese children by vitamin D3 supplementation with 1000 or 2000 IU/d versus 600 IU/d did not affect measures of arterial endothelial function or stiffness, systemic inflammation, or lipid profile, but resulted in reductions in BP and fasting glucose concentration and in improvements in insulin sensitivity. Optimization of children's vitamin D status may improve their cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01797302.

Dataset Information

Potential Modulation of Inflammation and Physical Function by Combined Probiotics, Omega-3 Supplementation and Vitamin D Supplementation in Overweight/Obese Patients with Chronic Low-Grade Inflammation: A Randomized, Placebo-Controlled Trial.

Publications

Potential Modulation of Inflammation and Physical Function by Combined Probiotics, Omega-3 Supplementation and Vitamin D Supplementation in Overweight/Obese Patients with Chronic Low-Grade Inflammation: A Randomized, Placebo-Controlled Trial.

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