The Effects of Vitamin D and Marine Omega-3 Fatty Acid Supplementation on Chronic Knee Pain in Older US Adults: Results From a Randomized Trial.
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ABSTRACT: Objective
Knee pain from osteoarthritis is frequent in the adult population. Prior trials have had conflicting results concerning the therapeutic effects of vitamin D on knee pain, and few trials have investigated marine Omega-3 fatty acids (n-3 FA).Methods
In the double-blind, placebo-controlled Vitamin D and Omega-3 Trial (VITAL), 25,871 US adults were randomized in a 2-by-2 factorial design to receive vitamin D or n-3 FA. We identified a subgroup with chronic knee pain prior to randomization and assessed knee pain at baseline and annually during follow-up using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (graded on a 0-100 scale, where 100 indicates worst symptoms). Repeated measures modeling was used to test the effect of randomized treatment on WOMAC pain scores over follow-up after adjustment for age and sex. Analyses were repeated for WOMAC function and stiffness.Results
This study included 1,398 participants who returned at least one knee pain questionnaire. The mean age was 67.7 years, 66% were women, and the mean ± SD WOMAC pain score was 37 ± 19. The mean ± SD follow-up time was 5.3 ± 0.7 years. WOMAC pain did not differ between the active vitamin D group and the vitamin D placebo group or between the active n-3 FA group and the n-3 FA placebo group at any time point during follow-up. Linear time-by-treatment interactions were not significant for either treatment (vitamin D, P = 0.41; n-3 FA, P = 0.77). Vitamin D and n-3 FA supplementation did not significantly affect WOMAC function or stiffness scores over time.Conclusion
Our findings indicate that vitamin D and n-3 FA supplementation for a mean of 5.3 years does not reduce knee pain or improve function or stiffness in a large sample of US adults with chronic knee pain.
SUBMITTER: MacFarlane LA
PROVIDER: S-EPMC7874905 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundObservational studies suggest vitamin D and marine ω-3 fatty acid (n-3 FA) supplements are associated with lower systemic inflammation. However, past trials have been inconsistent.MethodsThe randomized, double-blind, placebo-controlled VITamin D and OmegA-3 TriaL (VITAL) tested vitamin D (2000 IU/day) and/or n-3 FA (1 g/day) supplementation in a 2 × 2 factorial design among women ≥55 and men ≥50 years of age. We assessed changes in interleukin (IL)-6, tumor necrosis factor receptor 2 (TNFR2), and high-sensitivity C-reactive protein (hsCRP) concentrations from baseline to 1 year among participants randomized to vitamin D + n-3 FA (392), vitamin D (392), n-3 FA (392), or placebo only (385). Geometric means and percent changes were compared, adjusting for baseline factors.ResultsBaseline characteristics were well balanced. In the active arms, 25-OH vitamin D rose 39% and n-3 FA rose 55% vs minimal change in placebo arms. Neither supplement reduced biomarkers at 1 year. Vitamin D resulted in 8.2% higher IL-6 (95% CI, 1.5%-15.3%; adjusted P = 0.02), but TNFR2 and hsCRP did not. Among 784 receiving vitamin D, hsCRP increased 35.7% (7.8%-70.9%) in those with low (<20 ng/mL) but not with higher baseline serum 25(OH) vitamin D [0.45% (-8.9% to 10.8%); P interaction = 0.02]. Among 777 randomized to n-3 FA, hsCRP declined [-10.5% (-20.4% to 0.8%)] in those with baseline low (<1.5 servings/week), but not with higher fish intake [6.4% (95% CI, -7.11% to 21.8%); P interaction = 0.06].ConclusionsIn this large sample from a population-based randomized controlled trial, neither vitamin D nor n-3 FA supplementation over 1 year decreased these biomarkers of inflammation.Clinicaltrialsgov identifierNCT01169259; NCT01351805.
| S-EPMC6883134 | biostudies-literature
Project description:ObjectiveTo investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk.DesignVitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design.SettingNationwide in the United States.Participants25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment.InterventionsVitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence.Main outcome measuresThe primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others.Results25 871 participants were enrolled and followed for a median of 5.3 years. 18 046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease.ConclusionsVitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo).Study registrationClinicalTrials.gov NCT01351805 and NCT01169259.
| S-EPMC8791065 | biostudies-literature
Project description:OBJECTIVES:Osteoarthritis (OA) is associated with inflammation, chronic pain, functional limitations, and psychosocial distress. High omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are associated with lower levels of inflammatory mediators, anti-nociception, and adaptive cognitive/emotional functioning. High omega-6 (n-6) PUFAs are associated with inflammation, nociception, and psychological distress. While findings related to n-3 supplementation in knee OA are mixed, consideration of the n-6:n-3 ratio and additional outcome measures may provide improved understanding of the potential relevance of these fatty acids in OA. On the basis of recommended and typical ranges of the n-6:n-3 ratio, we hypothesized that in adults with knee pain, those with a high n-6:n-3 ratio would have greater pain/functional limitations, experimental pain sensitivity, and psychosocial distress compared with those with a low n-6:n-3 ratio. MATERIALS AND METHODS:A cross-sectional investigation of clinical and experimental pain and physical and psychosocial functioning was completed in 167 adults ages 45 to 85 meeting knee OA screening criteria. Blood samples were collected and the plasma n-6:n-3 PUFA ratio determined. Quartile splits were computed and low (n=42) and high (n=41) ratio groups were compared. RESULTS:The high ratio group reported greater pain and functional limitations, (all Ps<0.04), mechanical temporal summation (hand and knee, P<0.05), and perceived stress (P=0.008) but not depressive symptoms. DISCUSSION:In adults with knee pain, a high n-6:n-3 ratio is associated with greater clinical pain/functional limitations, experimental pain sensitivity, and psychosocial distress compared with a low ratio group. Findings support consideration of the n-6:n-3 PUFA ratio and additional clinical endpoints in future research efforts.
| S-EPMC5701880 | biostudies-literature
Project description:ImportanceThe benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear.ObjectiveTo test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults.Design, setting, and participantsDouble-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017.InterventionsParticipants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270).Main outcomes and measuresThe 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P < .01 was required for statistical significance.ResultsAmong 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both -0.8 (99% CI, -2.1 to 0.5) mm Hg, with P < .13 and P < .11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was -0.5 (99% CI, -1.2 to 0.2) mm Hg; P = .06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups.Conclusions and relevanceAmong adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes.Trial registrationClinicalTrials.gov Identifier: NCT01745263.
| S-EPMC7656284 | biostudies-literature
Project description:ImportanceAtrial fibrillation (AF) is the most common heart rhythm disturbance, continues to increase in incidence, and results in significant morbidity and mortality. The marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D have been reported to have both benefits and risks with respect to incident AF, but large-scale, long-term randomized trial data are lacking.ObjectiveTo test the effects of long-term administration of marine omega-3 fatty acids and vitamin D on incident AF.Design, setting, and participantsAn ancillary study of a 2 × 2 factorial randomized clinical trial involving 25 119 women and men aged 50 years or older without prior cardiovascular disease, cancer, or AF. Participants were recruited directly by mail between November 2011 and March 2014 from all 50 US states and were followed up until December 31, 2017.InterventionsParticipants were randomized to receive EPA-DHA (460 mg/d of EPA and 380 mg/d of DHA) and vitamin D3 (2000 IU/d) (n = 6272 analyzed); EPA-DHA and placebo (n = 6270 analyzed); vitamin D3 and placebo (n = 6281 analyzed); or 2 placebos (n = 6296 analyzed).Main outcomes and measuresThe primary outcome was incident AF confirmed by medical record review.ResultsAmong the 25 119 participants who were randomized and included in the analysis (mean age, 66.7 years; 50.8% women), 24 127 (96.1%) completed the trial. Over a median 5.3 years of treatment and follow-up, the primary end point of incident AF occurred in 900 participants (3.6% of study population). For the EPA-DHA vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.24; P = .19). For the vitamin D3 vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.25; P = .19). There was no evidence for interaction between the 2 study agents (P = .39).Conclusions and relevanceAmong adults aged 50 years or older, treatment with EPA-DHA or vitamin D3, compared with placebo, resulted in no significant difference in the risk of incident AF over a median follow-up of more than 5 years. The findings do not support the use of either agent for the primary prevention of incident AF.Trial registrationClinicalTrials.gov Identifiers: NCT02178410; NCT01169259.
| S-EPMC7967086 | biostudies-literature
Project description:BackgroundOmega-3 (n-3) PUFAs are recognized for triglyceride-lowering effects in people with dyslipidemia, but it remains unclear if n-3-PUFA intake influences lipoprotein profiles in older adults without hypertriglyceridemia.ObjectivesThe objective was to determine the effect of n-3-PUFA supplementation on plasma lipoprotein subfractions in healthy older men and women in the absence of cardiovascular disease (CVD) or hypertriglyceridemia. This was a secondary analysis and considered exploratory.MethodsThirty young (20-35 y old) and 54 older (65-85 y old) men and women were enrolled in the study. Fasting plasma samples were collected. After baseline sample collection, 44 older adults were randomly assigned to receive either n-3-PUFA ethyl esters (3.9 g/d) or placebo (corn oil) for 6 mo. Pre- and postintervention plasma samples were used for quantitative lipoprotein subclass analysis using high-resolution proton NMR spectroscopy.ResultsThe number of large, least-dense LDL particles decreased 17%-18% with n-3 PUFAs compared with placebo (<1% change; P < 0.01). The number of small, dense LDL particles increased 26%-44% with n-3 PUFAs compared with placebo (∼11% decrease; P < 0.01). The cholesterol content of large HDL particles increased by 32% with n-3 PUFAs and by 2% in placebo (P < 0.01). The cholesterol content of small HDL particles decreased by 23% with n-3 PUFAs and by 2% in placebo (P < 0.01).ConclusionsDespite increasing abundance of small, dense LDL particles that are associated with CVD risk, n-3 PUFAs reduced total triglycerides, maintained HDL, reduced systolic blood pressure, and shifted the HDL particle distribution toward a favorable cardioprotective profile in healthy older adults without dyslipidemia. This study suggests potential benefits of n-3-PUFA supplementation to lipoprotein profiles in healthy older adults without dyslipidemia, which should be considered when weighing the potential health benefits against the cost and ecological impact of widespread use of n-3-PUFA supplements.This trial was registered at clinicaltrials.gov as NCT03350906.
| S-EPMC9258601 | biostudies-literature
Project description:Vitamin D deficiency is common among older adults and has been linked to muscle weakness. Vitamin D supplementation has been proposed as a strategy to improve muscle function in older adults. The aim of this study was to investigate the effect of calcifediol (25-hydroxycholecalciferol) on whole genome gene expression in skeletal muscle of vitamin D deficient frail older adults. A double-blind placebo controlled trial was conducted in vitamin D deficient frail older adults (aged above 65), characterized by blood 25-hydroxycholecalciferol concentrations between 20 and 50 nmol/L. Subjects were randomized across the placebo group (n=12) and the calcifediol group (n=10, 10 µg per day). Muscle biopsies were obtained before and after six months of calcifediol or placebo supplementation and subjected to whole genome gene expression profiling using Affymetrix HuGene 2.1ST arrays. Expression of the vitamin D receptor gene was virtually undetectable in human skeletal muscle biopsies. Calcifediol supplementation led to a significant increase in blood 25-hydroxycholecalciferol levels compared to the placebo group. No difference between treatment groups was observed on strength outcomes. The whole transcriptome effects of calcifediol and placebo were very weak. Correcting for multiple testing using false discovery rate did not yield any differentially expressed genes using any sensible cut-offs. P-values were uniformly distributed across all genes, suggesting that low p-values are likely to be false positives. Partial least squares-discriminant analysis and principle component analysis was unable to separate treatment groups. Calcifediol supplementation did not affect the skeletal muscle transcriptome in frail older adults. Our findings indicate that vitamin D supplementation has no effects on skeletal muscle gene expression, suggesting that skeletal muscle may not be a direct target of vitamin D in older adults.
2019-06-10 | GSE123993 | GEO
Project description:Loss of muscle mass with aging is a major public health concern. Omega-3 (n-3) fatty acids stimulate protein anabolism in animals and might therefore be useful for the treatment of sarcopenia. However, the effect of omega-3 fatty acids on human protein metabolism is unknown.The objective of this study was to evaluate the effect of omega-3 fatty acid supplementation on the rate of muscle protein synthesis in older adults.Sixteen healthy, older adults were randomly assigned to receive either omega-3 fatty acids or corn oil for 8 wk. The rate of muscle protein synthesis and the phosphorylation of key elements of the anabolic signaling pathway were evaluated before and after supplementation during basal, postabsorptive conditions and during a hyperaminoacidemic-hyperinsulinemic clamp.Corn oil supplementation had no effect on the muscle protein synthesis rate and the extent of anabolic signaling element phosphorylation in muscle. Omega-3 fatty acid supplementation had no effect on the basal rate of muscle protein synthesis (mean ± SEM: 0.051 ± 0.005%/h compared with 0.053 ± 0.008%/h before and after supplementation, respectively; P = 0.80) but augmented the hyperaminoacidemia-hyperinsulinemia-induced increase in the rate of muscle protein synthesis (from 0.009 ± 0.005%/h above basal values to 0.031 ± 0.003%/h above basal values; P < 0.01), which was accompanied by greater increases in muscle mTOR(Ser2448) (P = 0.08) and p70s6k(Thr389) (P < 0.01) phosphorylation.Omega-3 fatty acids stimulate muscle protein synthesis in older adults and may be useful for the prevention and treatment of sarcopenia. This trial was registered at clinical trials.gov as NCT00794079.
| S-EPMC3021432 | biostudies-literature
Project description:Intervention 1: Intervention 1: a 50000 IU vitamin D tablet (Zahravi, Iran), weekly+ 2 omega-3 fatty acid capsules (each capsule containing 330 mg omega-3 fatty acid) (Minami Nutrition, Belgium), daily, for 8 weeks. Intervention 2: Intervention group 2: a 50000 IU vitamin D tablet (Zahravi, Iran), weekly+ 2 omega-3 fatty acid placebo (Zahravi, Iran), daily, for 8 weeks. Intervention 3: Intervention group 3: two omega-3 fatty acid capsules (each capsule containing 330 mg omega-3 fatty acid) (Minami Nutrition, Belgium), daily+ a vitamin D placebo (Zahravi, Iran), weekly, for 8 weeks. Intervention 4: Control group: a vitamin D placebo (Zahravi, Iran), weekly+ 2 omega-3 fatty acid placebo (Zahravi, Iran), daily, for 8 weeks.
Primary outcome(s): Serum level of TNF-a. Timepoint: Before and 8 weeks after intervention. Method of measurement: Serum TNF-a levels will be assessed by ELISA and Bender Med kit (Bender Med, Germany).
Study Design: Randomization: Randomized, Blinding: Double blinded, Placebo: Used, Assignment: Factorial, Purpose: Treatment, Randomization description: For randomized allocation performing, permuted block randomization will be used by quadrilateral blocks. According to the sample size of 80 subjects, 20 blocks will be generated using the online site (www.sealedenvelope.com). In order to allocation concealment in the randomized process, unique codes will be used on the drug boxes that is generated by the software. Participants will enter based on the sequence produced into study and the drug packets with code registered will allocate to the individual. Therefore, before participants selection, they will be unaware of the type of intervention that will receive, as well as a random sequence produced during the study will be immune from prediction, Blinding description: For blinding, a person who is not involved in study protocol created the randomization list assigning participants to the vit
| 2475288 | ecrin-mdr-crc
Project description:Study questionIs self-reported use of omega-3 fatty acid supplements associated with fecundability, the probability of natural conception, in a given menstrual cycle?Summary answerProspectively recorded omega-3 supplement use was associated with an increased probability of conceiving.What is known alreadyIn infertile women, omega-3 fatty acid intake has been associated with increased probability of pregnancy following IVF. In natural fertility, studies are conflicting, and no study of natural fertility has evaluated omega-3 fatty acid supplementation and fecundity.Study design, size, durationSecondary data analysis of 900 women contributing 2510 cycles in Time to Conceive (TTC), a prospective, time to pregnancy cohort study from 2008 to December 2015.Participants/materials, setting, methodsWomen aged 30-44 years, trying to conceive <3 months, without history of infertility were followed using standardized pregnancy testing. While attempting to conceive, women daily recorded menstrual cycle events and supplement and medication intake using the Cerner Multum Drug Database. Supplements and vitamins containing omega-3 were identified. Omega-3 use, defined as use in at least 20% of days in a given menstrual cycle, in each pregnancy attempt cycle was determined. A discrete-time Cox proportional hazards model was used to calculate the fecundability ratio.Main results and the role of chanceWomen taking omega-3 supplementation were more likely to be younger, thinner, nulligravid, white and to take vitamin D, prenatal and multivitamins compared to women not taking omega-3s. After adjusting for age, obesity, race, previous pregnancy, vitamin D and prenatal and multivitamin use, women taking omega-3 supplements had 1.51 (95% CI 1.12, 2.04) times the probability of conceiving compared to women not taking omega-3s.Limitations, reasons for cautionOur study was not a randomized controlled trial. The women who used omega-3 supplements may represent a more health-conscious population. We sought to address this by adjusting for multiple factors in our model. Additionally, the omega-3 fatty acid supplements that TTC participants used included multiple types and brands with varying dosages of omega-3 fatty acids. Women reported the type of supplement they were taking but not the concentration of omega-3s in that supplement. It is therefore not possible to compare dosing or a dose-response relationship in our study.Wider implications of the findingsOmega-3 supplementation may present a feasible and inexpensive modifiable factor to improve fertility. Randomized controlled trials are needed to further investigate the benefits of omega-3 supplementation for women trying to conceive naturally.Study funding/competing interestsThis study was supported by the Division of Reproductive Endocrinology and Infertility at the University of North Carolina at Chapel Hill, the NIH/NICHD (R21 HD060229-01 and R01 HD067683-01), and in part by the Intramural Research Program of the National Institute of Environmental Health Sciences (Z01ES103333). The authors declare that there is no conflict of interest.Trial registration numberN/A.
| S-EPMC9308390 | biostudies-literature