Fatty acid profile of plasma NEFA does not reflect adipose tissue fatty acid profile. Is Antioxidant and n–3 Supplementation Able to Improve Functional Status in Poststroke Patients? Results from the Nutristroke Trial The older people, omega-3, and cognitive health (EPOCH) trial design and methodology: A randomised, double-blind, controlled trial investigating the effect of long-chain omega-3 fatty acids on cognitive ageing and wellbeing in cognitively healthy older adults Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease: the omega-3 Alzheimer's disease study. Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial. Financial impact of sarcopenia on hospitalization costs Fish oil-derived n-3 PUFA therapy increases muscle mass and function in healthy older adults. Treatment of diabetic neuropathy with gamma-linolenic acid. The gamma-Linolenic Acid Multicenter Trial Group. The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish1234 The SU.FOL.OM3 Study: a secondary prevention trial testing the impact of supplementation with folate and B-vitamins and/or Omega-3 PUFA on fatal and non fatal cardiovascular events, design, methods and participants characteristics The effect of n-3 fatty acids on bone biomarkers in Iranian postmenopausal osteoporotic women: a randomized clinical trial Fish oil supplemented for 9 months does not improve glycaemic control or insulin sensitivity in subjects with impaired glucose regulation: a parallel randomised controlled trial. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial Long-term aerobic exercise and omega-3 supplementation modulate osteoporosis through inflammatory mechanisms in post-menopausal women: a randomized, repeated measures study Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women. Influence of a Mediterranean Dietary Pattern on Body Fat Distribution: Results of the PREDIMED–Canarias Intervention Randomized Trial Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation on Bone Turnover in Older Women. A Mediterranean diet enriched with olive oil is associated with higher serum total osteocalcin levels in elderly men at high cardiovascular risk. Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis Does consumption of polyunsaturated fatty acids influence on neurorehabilitation in traumatic spinal cord-injured individuals? a double-blinded clinical trial Double-blind Randomized Placebo-controlled Clinical Trial of Omega 3 Fatty Acids for the Treatment of Diabetic Patients With Nonalcoholic Steatohepatitis Efficacy of cod liver oil as an adjunct to non-steroidal anti-inflammatory drug treatment in the management of osteoarthritis in general practice. Treatment for 6 months with fish oil-derived n-3 polyunsaturated fatty acids has neutral effects on glycemic control but improves dyslipidemia in type 2 diabetic patients with abdominal obesity: a randomized, double-blind, placebo-controlled trial Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis Fish oil in knee osteoarthritis: a randomised clinical trial of low dose versus high dose Dietary intake and status of n-3 polyunsaturated fatty acids in a population of fish-eating and non-fish-eating meat-eaters, vegetarians, and vegans and the product-precursor ratio [corrected] of α-linolenic acid to long-chain n-3 polyunsaturated fatty acids: results from the EPIC-Norfolk cohort. Supplementation with omega-3 fish oil has no effect on bone mineral density in adults with knee osteoarthritis: a 2-year randomized controlled trial Efficacy and tolerability of calcium, vitamin D and a plant-based omega-3 oil for osteopenia: a pilot RCT. The impact of supplemental N-3 long chain polyunsaturated fatty acids and dietary antioxidants on physical performance in postmenopausal women Lack of effect of supplementation with essential fatty acids on bone mineral density in healthy pre- and postmenopausal women: two randomized controlled trials of Efacal v. calcium alone. Creation of a database to assess effects of omega-3, omega-6 and total polyunsaturated fats on health: methodology for a set of systematic reviews Retraction and Republication: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N Engl J Med 2013;368:1279-90.
Adipose tissue ( AT ) fatty acid ( FA ) composition partly reflects habitual dietary intake . Circulating NEFA are mobilised from AT and might act as a minimally invasive surrogate marker of AT FA profile . Agreement between twenty-eight FA in AT and plasma NEFA was assessed using concordance coefficients in 204 male and female participants in a 12-month intervention using supplements to increase the intake of EPA and DHA . Concordance coefficients generally showed very poor agreement between AT FA and plasma NEFA at baseline SFA : 0·07 ; MUFA : 0·03 ; n-6 PUFA : 0·28 ; n-3 PUFA : 0·01 ) . Participants were r and omly divided into training ( 70 % ) and validation ( 30 % ) data sets , and models to predict AT and dietary FA were fitted using data from the training set , and their predictive ability was assessed using data from the validation set . AT n-6 PUFA and SFA were predicted from plasma NEFA with moderate accuracy ( mean absolute percentage error n-6 PUFA : 11 % and SFA : 8 % ) , but predicted values were unable to distinguish between low , medium and high FA values , with only 25 % of n-6 PUFA and 33 % of SFA predicted values correctly assigned to the appropriate tertile group . Despite an association between AT and plasma NEFA EPA ( P=0·001 ) and DHA ( P=0·01 ) at baseline , there was no association after the intervention . To conclude , plasma NEFA are not a suitable surrogate for AT FA Background : To test whether supplementary antioxidants and n–3 fatty acids , alone or in combination , could improve functional status in stroke survivors . Methods : We performed a r and omized , double-blind , placebo-controlled clinical trial in 72 stroke patients ( 47 males ; age 65.3 ± 12.9 years ) admitted to a rehabilitation hospital for sequelae of first-ever ischemic stroke , and divided them into 4 subgroups . Group 1 patients received daily oral antioxidants , group 2 received n–3 polyunsaturated fatty acids , group 3 both supplements , and group 4 placebo , all for 12 months . No difference at baseline was observed among groups in neurological severity or in disability . All measures were repeated after 6 and 12 months of treatment . All major clinical events were recorded . Results : At baseline , 25 % of the patients had a low plasma vitamin status , and 48.5 % was at risk of undernutrition . At the 1-year follow-up , we observed a trend for lower mortality ( p = 0.060 ) in subgroups treated with n–3 fatty acids , but without significant differences in rehabilitation result status among groups . Conclusions : Malnutrition is widely observed in patients admitted to a rehabilitative hospital for stroke rehabilitation , and dietary supplementation , even if not able to improve rehabilitation results , is likely to reduce mortality at the 1-year follow-up Background Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids ( n-3 LC PUFAs ) and better cognitive outcomes in older adults . To date , only two r and omised , controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy population s. Of these trials only one found a benefit , in the subgroup carrying the ApoE-ε4 allele . The benefits of n-3 LC PUFA supplementation on cognitive function in older normal population s thus still remain unclear . The main objective of the current study was to provide a comprehensive assessment of the potential of n-3 LC PUFAs to slow cognitive decline in normal elderly people , and included ApoE-ε4 allele carriage as a potential moderating factor . The detailed methodology of the trial is reported herein . Methods The study was a parallel , 18-month , r and omised , double-blind , placebo-controlled intervention with assessment at baseline and repeated 6-monthly . Participants ( N = 391 , 53.7 % female ) aged 65 - 90 years , English-speaking and with normal cognitive function , were recruited from metropolitan Adelaide , South Australia . Participants in the intervention arm received capsules containing fish-oil at a daily dosage of 1720 mg of docosahexaenoic acid and 600 mg of eicosapentaenoic acid while the placebo arm received the equivalent amount of olive oil in their capsules . The primary outcome is rate of change in cognitive performance , as measured by latent variables for the cognitive constructs ( encompassing Reasoning , Working Memory , Short-term Memory , Retrieval Fluency , Inhibition , Simple and Choice-Reaction Time , Perceptual Speed , Odd-man-out Reaction Time , Speed of Memory Scanning , and Psychomotor Speed ) and assessed by latent growth curve modeling . Secondary outcomes are change in the Mini-mental State Examination , functional capacity and well-being ( including health status , depression , mood , and self-report cognitive functioning ) , blood pressure , and biomarkers of n-3 LC PUFA status , glucose , lipid metabolism , inflammation , oxidative stress , and DNA damage . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : OBJECTIVES To study the effects of omega (Omega)-3 fatty acid ( FA ) supplements on weight and appetite in patients with mild to moderate Alzheimer 's disease ( AD ) in relation to inflammatory biomarkers and apolipoprotein E epsilon4 ( APOEepsilon4 ) . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Specialist memory clinics in the Stockholm catchment area . PARTICIPANTS Two hundred four patients ( aged 73+/-9 , 52 % women ) with mild to moderate AD . INTERVENTION Patients with AD received 1.7 g of docosahexaenoic acid ( DHA ) and 0.6 g of eicosapentaenoic acid ( EPA ) ( Omega-3/Omega-3 group ; n=89 , aged 73+/-9 , 57 % women ) or placebo 0.6 g of linoleic acid per day ( placebo/Omega-3 group ; n=85 , aged 73+/-9 , 46 % women ) for 6 months . After 6 months , all patients received DHA and EPA for another 6 months . MEASUREMENTS Anthropometry , biochemical nutritional and inflammatory markers , and appetite assessed by caregiver . RESULTS Mean weight and body mass index ( kg/m(2 ) ) at baseline were 70.0+/-11.8 kg and 24.3+/-3.0 kg/m(2 ) , respectively . At 6- and 12-month follow-up , weight had increased 0.7+/-2.5 kg ( P=.02 ) and 1.4+/-2.9 kg ( P<.001 ) in the Omega-3/Omega-3 group . In the placebo group , weight was unchanged at 6 months but had increased ( P=.01 ) at 12 months follow-up after Omega-3 supplementation was initiated . Appetite improved in the Omega-3/Omega-3 group over the treatment period ( P=.01 ) . In logistic regression analyses , not carrying the APOEepsilon4 allele and high plasma DHA concentrations were independently related to weight gain in the combined group of patients at 6 months follow-up . CONCLUSION A DHA-enriched Omega-3 FA supplement may positively affect weight and appetite in patients with mild to moderate AD . Not carrying the APOEepsilon4 allele and high DHA were independently associated with weight gain Depressive symptoms may increase the risk of progressing from mild cognitive impairment ( MCI ) to dementia . Consumption of n-3 PUFA may alleviate both cognitive decline and depression . The aim of the present study was to investigate the benefits of supplementing a diet with n-3 PUFA , DHA and EPA , for depressive symptoms , quality of life ( QOL ) and cognition in elderly people with MCI . We conducted a 6-month double-blind , r and omised controlled trial . A total of fifty people aged > 65 years with MCI were allocated to receive a supplement rich in EPA ( 1·67 g EPA + 0·16 g DHA/d ; n 17 ) , DHA ( 1·55 g DHA + 0·40 g EPA/d ; n 18 ) or the n-6 PUFA linoleic acid ( LA ; 2·2 g/d ; n 15 ) . Treatment allocation was by minimisation based on age , sex and depressive symptoms ( Geriatric Depression Scale , GDS ) . Physiological and cognitive assessment s , question naires and fatty acid composition of erythrocytes were obtained at baseline and 6 months ( completers : n 40 ; EPA n 13 , DHA n 16 , LA n 11 ) . Compared with the LA group , GDS scores improved in the EPA ( P=0·04 ) and DHA ( P=0·01 ) groups and verbal fluency ( Initial Letter Fluency ) in the DHA group ( P=0·04 ) . Improved GDS scores were correlated with increased DHA plus EPA ( r 0·39 , P=0·02 ) . Improved self-reported physical health was associated with increased DHA . There were no treatment effects on other cognitive or QOL parameters . Increased intakes of DHA and EPA benefited mental health in older people with MCI . Increasing n-3 PUFA intakes may reduce depressive symptoms and the risk of progressing to dementia . This needs to be investigated in larger , depressed sample s with MCI Background / Objectives : This study aims to increase knowledge regarding the association of sarcopenia with hospitalization costs among a wide-ranging sample of adult hospitalized patients .Subjects/ Methods : A prospect i ve study was conducted among hospitalized adult patients . Sarcopenia was identified according to the European Working Group on Sarcopenia in Older People , as low muscle mass , assessed by bioelectrical impedance analysis and low muscle function evaluated by h and grip strength .  Hospitalization cost was calculated for each patient based on discharge diagnosis-related group codes and determined on the basis of a relative weight value . Costs were defined as the percentage of deviation from the cost of a patient with a relative weight equal to one . Multivariable linear regression models were performed to identify the factors independently associated with hospitalization costs . Results : A total of 656 hospitalized patients aged ⩾18 years ( 24.2 % sarcopenic ) composed the study sample . Sarcopenia increased hospitalization costs by [ euro ] 1240 ( 95 % confidence interval ( CI ) : [ euro ] 596–1887 ) for patients aged < 65 years and [ euro ] 721 ( 95 % CI : [ euro ] 13–1429 ) for patients aged ⩾65 years . Sarcopenic overweight was related to an increase in hospitalization costs of [ euro ] 884 ( 95 % CI : [ euro ] 295–1476 ) . Conclusions : Sarcopenia is independently related to hospitalization costs . This condition is estimated to increase hospitalization costs by 58.5 % for patients aged < 65 years and 34 % for patients aged ⩾65 years BACKGROUND Age-associated declines in muscle mass and function are major risk factors for an impaired ability to carry out activities of daily living , falls , prolonged recovery time after hospitalization , and mortality in older adults . New strategies that can slow the age-related loss of muscle mass and function are needed to help older adults maintain adequate performance status to reduce these risks and maintain independence . OBJECTIVE We evaluated the efficacy of fish oil-derived n-3 ( ω-3 ) PUFA therapy to slow the age-associated loss of muscle mass and function . DESIGN Sixty healthy 60 - 85-y-old men and women were r and omly assigned to receive n-3 PUFA ( n = 40 ) or corn oil ( n = 20 ) therapy for 6 mo . Thigh muscle volume , h and grip strength , one-repetition maximum ( 1-RM ) lower- and upper-body strength , and average power during isokinetic leg exercises were evaluated before and after treatment . RESULTS Forty-four subjects completed the study [ 29 subjects ( 73 % ) in the n-3 PUFA group ; 15 subjects ( 75 % ) in the control group ] . Compared with the control group , 6 mo of n-3 PUFA therapy increased thigh muscle volume ( 3.6 % ; 95 % CI : 0.2 % , 7.0 % ) , h and grip strength ( 2.3 kg ; 95 % CI : 0.8 , 3.7 kg ) , and 1-RM muscle strength ( 4.0 % ; 95 % CI : 0.8 % , 7.3 % ) ( all P < 0.05 ) and tended to increase average isokinetic power ( 5.6 % ; 95 % CI : -0.6 % , 11.7 % ; P = 0.075 ) . CONCLUSION Fish oil-derived n-3 PUFA therapy slows the normal decline in muscle mass and function in older adults and should be considered a therapeutic approach for preventing sarcopenia and maintaining physical independence in older adults . This study was registered at clinical trials.gov as NCT01308957 OBJECTIVE To compare the effects of placebo and GLA on the course of mild diabetic neuropathy over 1 yr . RESEARCH DESIGN AND METHODS We entered 111 patients with mild diabetic neuropathy from seven centers into a r and omized , double-blind , placebo-controlled parallel study of GLA at a dose of 480 mg/day .  MNCV , SNAP , CMAP , hot and cold thresholds , sensation , tendon reflexes , and muscle strength were assessed by st and ard tests in upper and lower limbs . RESULTS For all 16 parameters , the change over 1 yr in response to GLA was more favorable than the change with placebo , and for 13 parameters , the difference was statistically significant . Sex , age , and type of diabetes did not influence the result , but treatment was more effective in relatively well-controlled than in poorly-controlled diabetic patients . CONCLUSIONS GLA had a beneficial effect on the course of diabetic neuropathy Phytoestrogens are increasingly incorporated into the diet of menopausal women . However , there are limited data on the efficacy of flaxseed on the consequences of estrogen deficiency in menopausal women . The purpose of the study was to assess the effects of flaxseed incorporation into the diet of healthy menopausal women . One hundred and ninety-nine menopausal women were r and omly assigned to consume 40 g flaxseed/d ( n = 101 ) or wheat germ placebo ( n = 98 ) for 12 months . At baseline and at month 12 , serum levels of lipids , bone mineral density ( BMD ) , and menopausal symptoms were evaluated . Statistical analysis was performed under the intention to treat principle . Flaxseed reduced serum total ( -0.20 + /- 0.51 mmol/liter ; P = 0.012 ) and high-density lipoprotein ( -0.08 + /- 0.24 mmol/liter ; P = 0.031 ) cholesterol concentrations compared with wheat germ placebo .  BMD did not differ significantly between the two arms . Both flaxseed and wheat germ reduced ( P < 0.0001 ) the severity scores of menopausal symptoms , but no statistical difference was found between the two arms . Our findings suggest that 1-yr incorporation of flaxseed into the diet produced a favorable , but not clinical ly significant , effect on blood cholesterol and caused no significant change in BMD or symptoms in healthy menopausal women BACKGROUND No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline . We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention ( physical activity , cognitive training , and nutritional advice ) , alone or in combination , compared with placebo , on cognitive decline . METHODS The Multidomain Alzheimer Preventive Trial was a 3-year , multicentre , r and omised , placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco . Participants were non-demented , aged 70 years or older , and community-dwelling , and had either relayed a spontaneous memory complaint to their physician , limitations in one instrumental activity of daily living , or slow gait speed . They were r and omly assigned ( 1:1:1:1 ) to either the multidomain intervention ( 43 group sessions integrating cognitive training , physical activity , and nutrition , and three preventive consultations ) plus omega 3 polyunsaturated fatty acids ( ie , two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid ) , the multidomain intervention plus placebo , omega 3 polyunsaturated fatty acids alone , or placebo alone . A computer-generated r and omisation procedure was used to stratify patients by centre . All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment , but were unblinded to the multidomain intervention component . Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment . The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests ( free and total recall of the Free and Cued Selective Reminding test , ten Mini-Mental State Examination orientation items , Digit Symbol Substitution Test , and Category Naming Test ) in the modified intention-to-treat population . The trial was registered with Clinical Trials.gov ( NCT00672685 ) . FINDINGS 1680 participants were enrolled and r and omly allocated between May 30 , 2008 , and Feb 24 , 2011 . In the modified intention-to-treat population ( n=1525 ) , there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group . Between-group differences compared with placebo were 0·093 ( 95 % CI 0·001 to 0·184 ; adjusted p=0·142 ) for the combined intervention group , 0·079 ( -0·012 to 0·170 ; 0·179 ) for the multidomain intervention plus placebo group , and 0·011 ( -0·081 to 0·103 ; 0·812 ) for the omega 3 polyunsaturated fatty acids group . 146 ( 36 % ) participants in the multidomain plus polyunsaturated fatty acids group , 142 ( 34 % ) in the multidomain plus placebo group , 134 ( 33 % ) in the polyunsaturated fatty acids group , and 133 ( 32 % ) in the placebo group had at least one serious emerging adverse event . Four treatment-related deaths were recorded ( two in the multidomain plus placebo group and two in the placebo group ) . The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events . INTERPRETATION The multidomain intervention and polyunsaturated fatty acids , either alone or in combination , had no significant effects on cognitive decline over 3 years in elderly people with memory complaints . An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined , particularly in real-world setting s. FUNDING French Ministry of Health , Pierre Fabre Research Institute , Gerontopole , Exhonit Therapeutics , Avid Radiopharmaceuticals Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background : Estimation of the intake of oily fish at a population level is difficult . The measurement of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) in biological sample s may provide a useful biomarker of intake . Objective : We identified the most appropriate biomarkers for the assessment of habitual oily fish intake and changes in intake by elucidating the dose- and time-dependent response of EPA and DHA incorporation into various biological sample s that represent roles in fatty acid transport , function , and storage . Design : This was a double-blind , r and omized , controlled intervention trial in 204 men and women that lasted 12 mo .  EPA and DHA capsules were provided in a manner to reflect sporadic consumption of oily fish ( ie , 1 , 2 , or 4 times/wk ) .  EPA and DHA  were assessed at 9 time points over 12 mo in 9 sample types ( red blood cells , mononuclear cells , platelets , buccal cells , adipose tissue , plasma phosphatidylcholine , triglycerides , cholesteryl esters , and nonesterified fatty acids ) . Results : A dose response ( P < 0.05 ) was observed for EPA and DHA in all pools except for red blood cell EPA ( P = 0.057 ) . EPA and DHA measures in plasma phosphatidylcholine and platelets were best for the discrimination between different intakes ( P < 0.0001 ) . The rate of incorporation varied between sample types , with the time to maximal incorporation ranging from days ( plasma phosphatidylcholine ) to months ( mononuclear cells ) to > 12 mo ( adipose tissue ) . Conclusions : Plasma phosphatidylcholine EPA plus DHA was identified as the most suitable biomarker of acute changes in  EPA and DHA intake , and platelet and mononuclear cell EPA plus DHA were the most suitable biomarkers of habitual intake . This trial was registered at Current Controlled Trials ( www.controlled-trials.com ) as IS RCT N48398526 Background During the last decades , many basic and clinical research have pointed to the role of B vitamins ( folate , vitamins B6 and B12 ) and n-3 fatty acids as nutritional factors that might have a protective effect on the development of cardiovascular diseases ( CVD ) . Methods / design The SU.FOL.OM3 ( SUpplementation with FOlate , vitamin B6 and B12 and /or OMega-3 fatty acids ) trial is a r and omized double-blind , placebo-controlled , secondary -prevention trial design ed to test the efficacy of 5-methyl tetra-hydro-folates ( 5-MTHF ) supplementation , in combination with vitamin B6 and B12 and /or n-3 fatty acids , at nutritional doses , on fatal and non fatal ischemic CVD in a 2 × 2 factorial design . A total of 2501 patients aged between 45 and 80 years who had a past history , in the previous year , of myocardial infa rct ion ( n = 1151 ) or instable angina pectoris ( n = 711 ) or an ischemic stroke ( n = 639 ) were included . Subjects have to be supplemented and followed up for five years . Daily supplementation comprised nutritional doses of 5-MTHF ( 560 μg ) , vitamin B6 ( 3 mg ) and B12 ( 20 μg ) and /or n-3 fatty acids ( 600 mg with an EPA : DHA ratio of 2:1 ) . A factorial design 2 × 2 has been applied to investigate the separate effects of the B-vitamins , and the n-3 fatty acids , as well as their interaction as compared to the placebo . The primary endpoint is a combination of myocardial infa rct ion , ischemic stroke and cardiovascular death . Secondary endpoints are events of the composite endpoint taken separately , total mortality , and other cardiovascular events such as acute coronary syndromes , coronary revascularization , cardiac failure , arrhythmia ... Conclusion Baseline socio-demographic and medical characteristics of participants are totally comparable in the four r and omized groups . Trial registration Current Controlled Trials IS RCT Recently , n-3 fatty acids are in the center of attention for their potent anti-inflammatory effects . Osteoporosis as a chronic senile disease is associated with inflammation , and the role of inflammatory mediators has been demonstrated in recent years . The beneficial effects of n-3 fatty acids on bone were proven in many animal studies , while to date , no conclusive data is available in human . The aim of this study was to evaluate the impact of n-3 fatty acids on bone biomarkers in osteoporotic postmenopausal women . Twenty-five osteoporotic postmenopausal women were recruited in the study and r and omized in treatment and control groups . The patients received 900 mg n-3 fatty acid capsules or placebo per day for 6 months . Serum levels of osteocalcin , bone alkaline phosphatase ( BALP ) , calcium , vitamin D , and parathormone and urine concentration of pyridinoline ( Pyd ) were measured at baseline , second month , and sixth month in both groups . In the treatment group , compared with baseline , at the second month , osteocalcin increased slightly ; thereafter , it showed decrement trend until the end of the study . In the control group , it decreased all over the study . None of these changes was significant . BALP showed nonsignificant decrease from baseline over the time in both groups . Urine level of Pyd decreased significantly ( P < 0.05 ) in the treatment group , while no significant change was seen in the control group . Serum calcium and vitamin D increased in both groups ; however , changes were not significant . No significant changes were seen in calcium clearance and parathormone . In conclusion , n-3 fatty acids can decrease bone resorption ; however , it could not affect bone formation significantly after 6 months treatment . Further investigations are recommended The effects of fish oil ( FO ) supplementation on glycaemic control are unclear , and positive effects may occur only when the phospholipid content of tissue membranes exceeds 14 % as n-3 PUFA . Subjects ( n 36 , thirty-three completed ) were paired based on metabolic parameters and allocated into a parallel double-blind r and omised trial with one of each pair offered daily either 6 g of FO ( 3·9 g n-3 PUFA ) or 6 g of maize oil ( MO ) for 9 months . Hyperinsulinaemic-euglycaemic-euaminoacidaemic ( HIEGEAA ) clamps ( with [ 6,6 2H2 glucose ] ) were performed at the start and end of the intervention . Endogenous glucose production ( EGP ) and whole-body protein turnover ( WBPT ) were each measured after an overnight fast . The primary outcome involved the effect of oil type on insulin sensitivity related to glycaemic control . The secondary outcome involved the effect of oil type on WBPT . Subjects on  FO ( n 16 ) had increased erythrocyte n-3 PUFA concentrations > 14 % , whereas subjects on MO ( n 17 ) had unaltered n-3 PUFA concentrations at 9 % . Type of oil had no effect on fasting EGP , insulin sensitivity or total glucose disposal during the HIEGEAA clamp . In contrast , under insulin-stimulated conditions , total protein disposal ( P=0·007 ) and endogenous WBPT ( P=0·001 ) were both increased with FO . In an associated pilot study ( n 4 , three completed ) , although n-3 PUFA in erythrocyte membranes increased to > 14 % with the FO supplement , the enrichment in muscle membranes remained lower ( 8 % ; P<0·001 ) . In conclusion , long-term supplementation with FO , at amounts near the safety limits set by regulatory authorities in Europe and the USA , did not alter glycaemic control but did have an impact on WBPT Objective To investigate whether dietary supplementation with B vitamins or omega 3 fatty acids , or both , could prevent major cardiovascular events in patients with a history of ischaemic heart disease or stroke . Design Double blind , r and omised , placebo controlled trial ; factorial design . Setting Recruitment throughout France via a network of 417 cardiologists , neurologists , and other physicians . Participants 2501 patients with a history of myocardial infa rct ion , unstable angina , or ischaemic stroke . Intervention Daily dietary supplement containing 5-methyltetrahydrofolate ( 560 μg ) , vitamin B-6 ( 3 mg ) , and vitamin B-12 ( 20 μg ) or placebo ; and containing omega 3 fatty acids ( 600 mg of eicosapentanoic acid and docosahexaenoic acid at a ratio of 2:1 ) or placebo . Median duration of supplementation was 4.7 years . Main outcome measures Major cardiovascular events , defined as a composite of non-fatal myocardial infa rct ion , stroke , or death from cardiovascular disease . Results Allocation to B vitamins lowered plasma homocysteine concentrations by 19 % compared with placebo , but had no significant effects on major vascular events ( 75 v 82 patients , hazard ratio , 0.90 ( 95 % confidence interval 0.66 to 1.23 , P=0.50 ) ) . Allocation to omega 3 fatty acids  increased plasma concentrations of omega 3 fatty acids by 37 % compared with placebo , but also had no significant effect on major vascular events ( 81 v 76 patients , hazard ratio 1.08 ( 0.79 to 1.47 , P=0.64 ) ) . Conclusion This study does not support the routine use of dietary supplements containing B vitamins or omega 3 fatty acids for prevention of cardiovascular disease in people with a history of ischaemic heart disease or ischaemic stroke , at least when supplementation is introduced after the acute phase of the initial event . Trial registration Current Controlled Trials IS RCT N41926726 Background Evidence indicates that dietary fats and physical activity influence bone health . The purpose of this study was to examine the effects of long-term aerobic exercise and omega-3 ( N-3 ) supplementation on serum inflammatory markers , bone mineral density ( BMD ) , and bone biomarkers in post-menopausal women . Methods Seventy-nine healthy sedentary post-menopausal women aged 58 - 78 years participated in this study . Subjects were r and omized to one of 4 groups : exercise + supplement ( E+S , n = 21 ) , exercise ( E , n = 20 ) , supplement ( S , n = 20 ) , and control ( Con , n = 18 ) groups . The subjects in the E+S and E groups performed aerobic exercise training ( walking and jogging ) up to 65 % of HRmax , three times a week for 24 weeks . Subjects in the E+S and S groups consumed 1000 mg/d N-3 for 24 weeks . The lumbar spine ( L2-L4 ) and femoral neck BMD , serum tumor necrosis factor ( TNF ) α , interleukin ( IL ) 6 , prostagl and in ( PG ) E2 , estrogen , osteocalcin , 1 , 25-dihydroxyvitamin D3 ( 1 , 25 Vit D ) , C-telopeptide ( CTX ) , parathyroid hormone ( PTH ) and calcitonin ( CT ) were measured at baseline , the end of week 12 and 24 . Results Serum estrogen , osteocalcin , 1 , 25 Vit D , CT , L2-L4 and femoral neck BMD measures increased ( P < 0.05 ) and the serum CTX , PTH , TNF-α , IL-6 , and PGE2 decreased ( P < 0.05 ) in E + S group after the 24 wk intervention but not in the E or S intervention groups . L2-L4 and femoral neck BMD , estrogen , osteocalcin , and CT were negatively ( P < 0.05 ) correlated with TNF-α and PGE2 . PTH and CT were correlated positively and negatively with IL-6 , respectively ( P < 0.05 ) . Conclusions The present study demonstrates that long-term aerobic exercise training plus N-3 supplementation have a synergistic effect in attenuating inflammation and augmenting BMD in post-menopausal osteoporosis The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues ; however , nutritional determinants of insulin-like growth factor I ( IGF-I ) and its binding proteins in healthy individuals are not well defined . Three test diets-high-fat diet ( 40 % energy as fat ) , low-fat diet ( LF ; 20 % energy as fat ) , and a diet with low fat and high omega-3 fatty acid ( LFn3 ; 23 % energy as fat)--were tested in a r and omized crossover design ed controlled feeding trial in healthy postmenopausal women .  Plasma IGF-I , IGF binding protein-3 ( IGFBP-3 ) , insulin , glucose , and ratio of IGF-I/IGFBP-3 concentrations were measured in response to diets . Insulin sensitivity was calculated using the homeostatic model assessment of insulin resistance We hypothesized that IGF-I , insulin , and glucose concentrations would decrease and IGFBP-3 concentration would increase in response to the low-fat diets . Eight weeks of the LFn3 diet increased circulating IGF-I ( P < .001 ) and IGFBP-3 ( P = .01 ) and the LF diet increased IGFBP-3 ( P = .04 ) , result ing in trends toward an increased IGF-I/IGFBP-3 ratio with the LFn3 diet and a decreased IGF-I/IGFBP-3 ratio with the LF diet ( P = .13 for both comparisons ) . No statistically significant differences were detected between treatments at baseline or 8 weeks for IGF-1 , IGFBP-3 , or the ratio of IGF-1/IGFBP-3 . Insulin , glucose , and the homeostatic model assessment of insulin resistance were not altered by the interventions . Low-fat diet with high n-3 fatty acids may increase circulating IGF-I concentrations without adversely affecting insulin sensitivity in healthy individuals Objective : To assess the influence of a Mediterranean dietary pattern ( MeDiet ) on anthropometric and body composition parameters in one of the centers of the PREDIMED r and omized dietary trial . Subjects/ Setting s : 351 Canarian free-living subjects aged 55 to 80 years , with type 2 diabetes or ≥3 cardiovascular risk factors . Intervention : Participants were r and omly assigned to one of 3 different dietary interventions : MeDiet + extra-virgin olive oil ( EVOO ) , MeDiet + nuts ( walnuts , almonds , and hazelnuts ) , or a control low-fat diet . Total energy intake was ad libitum . Outcome measures : Measures included changes in anthropometric measures ( weight , body mass index [ BMI ] and waist circumference [ WC ] ) , body fat distribution , energy , and nutrient intake after 1 year . Body composition ( percentage of total body fat [ % TBF ] , total fat mass [ TFM ] , free fat mass [ FFM ] , percentage of truncal fat [ % TrF ] , truncal fat mass [ TrFM ] ) and total body water ( TBW ) were estimated by octapolar electrical impedance analysis . Statistical analyses : Paired t tests were conducted to assess within-group changes . Analyses of variance ( ANOVAs ) were used to assess the effect of the dietary intervention on the percentage change in anthropometric variables , body composition , and dietary intake profile . All pairwise comparisons that were statistically significant in ANOVA were subsequently adjusted using the Benjamini-Hochberg test , which penalizes for multiple comparisons . Results : After 1 year of intervention , significant within-group reductions in all anthropometric variables were observed for the MeDiet + EVOO and the control group . The MeDiet + nuts group exhibited a significant reduction in WC and TBW . The control group showed a significant increase in % TBF and a reduction in TBW . The control group showed a significant increase in the percentage of total body fat and a reduction in TBW . However , we did not find any between-group significant difference in anthropometric or body composition changes . Conclusions : Mediterranean diets enriched with EVOO or specific mixed nuts ( walnuts , almonds , hazelnuts ) that contain approximately 40 % total fat can be alternative options to low-fat diets for weight maintenance regimes in older overweight or obese adults Animal and human studies indicate that omega (n)-3 polyunsaturated fatty acids ( PUFA ) can influence bone health . We conducted a r and omized , double-blind , placebo-controlled trial of the effects of n-3 long chain ( LC ) PUFA supplementation ( N-3 LCPUFA ) on red blood cell ( RBC ) fatty acid levels and bone turnover markers in older postmenopausal women . One hundred and twenty-six postmenopausal women ( mean age 75±7 years ) were treated with n-3 LCPUFA ( 1.2 g eicosapentaenoic acid [EPA]/docosahexaenoic acid [DHA]/day , n=85 ) or placebo ( olive oil , n=41 ) for 6 months . All women received 315 mg calcium citrate and 1000 IU  cholecalciferol . RBC DHA ( weight % ) increased in the n-3 LCPUFA group , compared to no change in the placebo group ( P<0.001 ) . The ratio of DHA+EPA : arachidonic acid ( AA ) increased by 42 % in the n-3 LCPUFA group and by 5 % in the placebo group ( P<0.001 ) . Bone-specific alkaline phosphatase and osteocalcin decreased in the n-3 LCPUFA group ( P<0.05 ) with no between-group difference . Short-term n-3 LCPUFA supplementation increased RBC concentrations of DHA and n-3:n-6 ratios . Bone turnover decreased with n-3 LCPUF , but not statistically compared to placebo . The results point to the need for investigations with greater dosages of n-3 LCPUFA for a longer duration to underst and the contribution to bone metabolism in postmenopausal women BACKGROUND The intake of olive oil has been related to the prevention of osteoporosis in experimental and in in vitro models . Very few prospect i ve studies have evaluated the effects of olive oil intake on circulating osteocalcin ( OC ) in humans . OBJECTIVE The objective of the study was to examine the longitudinal effects of a low-fat control diet ( n=34 ) , a Mediterranean diet enriched with nuts ( MedDiet+nuts , n=51 ) , or a Mediterranean diet enriched with virgin olive oil ( MedDiet+VOO , n=42 ) on circulating forms of OC and bone formation markers in elderly men at high cardiovascular risk . DESIGN Longitudinal associations between baseline and follow-up ( 2 yr ) measurements of total OC , undercarboxylated osteocalcin , C-telopeptide of type I collagen , and procollagen I N-terminal propeptide ( P1NP ) concentrations were examined in 127 elderly men r and omized to three healthy dietary interventions . RESULTS Baseline characteristics ( age , body mass index , waist circumference , lipid profile , fasting insulin levels , and bone formation and resorption markers ) were similar in all intervention groups . The total osteocalcin concentration increased robustly in the MedDiet+VOO group ( P=0.007 ) in parallel to increased P1NP levels ( P=0.01 ) and homeostasis model assessment -β-cell function ( P=0.01 ) but not in subjects on the MedDiet+nuts ( P=0.32 ) or after the control diet ( P=0.74 ) . Interestingly , the consumption of olives was associated positively with both baseline total osteocalcin ( r=0.23 , P=0.02 ) and the 2-yr osteocalcin concentrations ( r=0.21 , P=0.04 ) in the total cohort . CONCLUSIONS Consumption of a Mediterranean diet enriched with virgin olive oil for 2 years is associated with increased serum osteocalcin and P1NP concentrations , suggesting protective effects on bone There is no licensed treatment for non-alcoholic fatty liver disease ( NAFLD ) , a condition that increases risk of chronic liver disease , type 2 diabetes and cardiovascular disease . We tested whether 15 - 18 months treatment with docosahexaenoic acid ( DHA ) plus eicosapentaenoic acid ( EPA ) ( Omacor/Lovaza ) ( 4 g/day ) decreased liver fat and improved two histologically-vali date d liver fibrosis biomarker scores ( primary outcomes ) . Patients with NAFLD were r and omised in a double blind placebo-controlled trial [ DHA+EPA(n=51 ) , placebo(n=52 ) ] . We quantified liver fat percentage ( % ) by magnetic resonance spectroscopy in three liver zones . We measured liver fibrosis using two vali date d scores . We tested adherence to the intervention ( Omacor group ) and contamination ( with DHA and EPA ) ( placebo group ) by measuring erythrocyte percentage DHA and EPA enrichment ( gas chromatography ) . We undertook multivariable linear regression to test effects of : a ) DHA+EPA treatment ( ITT analyses ) and b ) erythrocyte DHA and EPA enrichment ( secondary analysis ) . Median ( IQR ) baseline and end of study liver fat% were 21.7 ( 19.3 ) and 19.7 ( 18.0 ) ( placebo ) , and 23.0 ( 36.2 ) and 16.3 ( 22.0 ) , ( DHA+EPA ) . In the fully adjusted regression model there was a trend towards improvement in liver fat%  with DHA+EPA treatment ( β=-3.64 ( 95%CI -8.0,0.8 ) ; p=0.1 ) but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group . Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat% ( for each 1 % enrichment , β=-1.70 ( 95%CI -2.9,-0.5 ) ; p=0.007 ) . No improvement in the fibrosis scores occurred . Conclusion . Erythrocyte DHA enrichment with DHA+EPA treatment is linearly associated with decreased liver fat% . Substantial decreases in liver fat% can be achieved with high percentage erythrocyte DHA enrichment in NAFLD . ( Hepatology 2014 ; ) Recent animal work suggests that gamma-linolenic acid ( GLA ) and eicosapentaenoic acid ( EPA ) enhance calcium absorption , reduce excretion and increase calcium deposition in bone . A pilot study was set up to test the interactions between calcium and GLA+EPA in humans . Sixty-five women ( mean age 79.5 ) , taking a background diet low in calcium , were r and omly assigned to GLA+EPA or coconut oil placebo capsules ; in addition , all received 600 mg/day calcium as the carbonate . Markers of bone formation/degradation and bone mineral density ( BMD ) were measured at baseline , 6 , 12 and 18 months . Twenty-one patients were continued on treatment for a second period of 18 months , after which BMD ( 36 months ) was measured . At 18 months , osteocalcin and deoxypyridinoline levels fell significantly in both groups , indicating a decrease in bone turnover , whereas bone specific alkaline phosphatase rose indicating beneficial effects of calcium given to all the patients . Lumbar and femoral BMD , in contrast , showed different effects in the two groups . Over the first 18 months , lumbar spine density remained the same in the treatment group , but decreased 3.2 % in the placebo group . Femoral bone density increased 1.3 % in the treatment group , but decreased 2.1 % in the placebo group . During the second period of 18 months with all patients now on active treatment , lumbar spine density increased 3.1 % in patients who remained on active treatment , and 2.3 % in patients who switched from placebo to active treatment ; femoral BMD in the latter group showed an increase of 4.7 % . This pilot controlled study suggests that GLA and EPA have beneficial effects on bone in this group of elderly patients , and that they are safe to administer for prolonged periods of time Study design : A double-blinded r and omized clinical trial . Objectives : The anti-inflammatory and neuroprotective effect of omega-3 fatty acids have been shown so far , but still its influence on clinical measures in spinal cord-injured human models were not known . We tried to investigate changes in disability and dependency scores in chronic traumatic spinal cord-injured patients after 14 months of ω-3 fatty-acid consumption . Methods : Main inclusion criteria were : traumatic spinal cord injury ( SCI ) and post injury duration longer than 1 year .  Disability and dependency was assessed using UK Functional Independence Measure and Functional Assessment Measure ( FIM+FAM ) scale . MorDHA capsules ( 435 mg of docosahexaenoic acid and 65 mg of eicosapentaenoic acid ) were administered in treatment group , whereas control group received placebo capsules for 14 months . UK FIM+FAM scale were estimated before intervention and at the end of the trial . Results : Fifty-four patients in treatment group and 50 patients in placebo group completed the trial . Highest scores were detected in cognitive domain in both groups before and after intervention . Most dependency was observed in locomotion subscale and secondly in sphincter control . Scores of none of these components were changed by ω-3 fatty-acid consumption . Conclusion : Although omega-3 fatty acids have been shown to have neuroprotective effect in acute phase of SCI , it seems that they have no significant influence in chronic inflammatory state of SCI . The positive effect of ω-3 fatty acid in chronic neurorecovery process , if exists , is weaker to exert any significant improvement in UK FIM+FAM scores in spinal cord-injured individuals Background : Nonalcoholic steatohepatitis ( NASH ) is common and severe in patients with diabetes mellitus . Although , there are no effective treatments for NASH in diabetic patients , preliminary reports suggest that polyunsaturated fatty acids ( PUFA ) may be beneficial in these patients . Aim : A prospect i ve , r and omized , double-blind placebo-controlled study ( NCT 00323414 ) was performed in NASH patients with diabetes . Clinical trials.gov ( NCT 00323414 ) . Subjects and Methods : A total of 37 patients ( 50.6±9.8 y ) with well-controlled diabetes ( HbA1C<8.5 % ) were r and omized to receive either PUFA containing eicosapentaenoic acid ( 2160 mg ) and docosahexaenoic acid ( 1440 mg ) daily or an isocaloric , identical placebo containing corn oil for 48 weeks under CONSORT guidelines . Clinical , demographics , biochemical laboratory tests , body composition using DEXA , and liver biopsy were performed at r and omization and at the end of treatment . Liver biopsy was scored by the NASH CRN criteria . An intention-to-treat analysis was performed . Results : At inclusion , sex , age , body weight , biochemical tests , glucose control , and liver histology were similar in the 2 treatment groups . There was no change in liver enzymes , body weight , or body composition during the study in either group . At the end of the treatment , hepatic steatosis and the activity score improved ( P<0.05 ) and lobular inflammation worsened ( P<0.001 ) with placebo but was unchanged with PUFA . At the end of the treatment , insulin resistance ( serum glucose and HOMA ) worsened with PUFA but not placebo . Conclusions : PUFA provided no benefit over placebo in NASH patients with diabetes . The effects of PUFA on histology and insulin resistance were inferior to placebo . These data provide no support for PUFA supplements in NASH A double blind , placebo controlled trial was carried out to assess the efficacy of cod liver oil as an adjunct treatment to non-steroidal anti-inflammatory drugs ( NSAIDs ) in the management of  osteoarthritis  in general practice . Eighty six patients were given 10 ml of either cod liver oil or olive oil placebo daily as a supplement to their regular NSAID treatment for 24 weeks . Patients were assessed by their general practitioner at four week intervals for joint pain/inflammation , overall interference with activities , and unwanted effects of treatment . Patients recorded on visual analogue scales their daily pain and the extent to which arthritis interfered with everyday activities . There was no significant benefit for the patients taking cod liver oil compared with those taking placebo Purpose This study aim ed to determine the effects of fish oil-derived n-3 PUFA on glycemic control and lipid profiles in type 2 diabetic patients with abdominal obesity . Methods In a r and omized , double-blind , placebo-controlled trial , 100 type 2 diabetic patients with abdominal obesity were r and omized into two groups including 4 g/day of fish oil ( 2.4 g n-3 PUFA ) or placebo ( corn oil ) for 6 months . Serum fatty acid , body composition , as well as markers of glucose regulation and lipid parameters were measured before and after intervention . Results Thirty-five men and 64 women aged 65.4 ± 5.3 years completed the intervention . Although body composition was unchanged , serum EPA and DHA were higher in the fish oil group than those in the placebo group ( P < 0.001 and P < 0.001 , respectively ) . Serum triglyceride ( TG ) decreased ( P = 0.007 ) , whereas high-density lipoprotein cholesterol ( HDL-C ) increased ( P = 0.006 ) in the fish oil group compared with the placebo group after 6 months . Serum total cholesterol , low-density lipoprotein cholesterol ( LDL-C ) , the ratio of LDL-C to HDL-C , and glycemic control ( measured by serum glucose , glycated hemoglobin , insulin , and homeostasis model assessment –insulin resistance ) were not significantly different between the two groups after 6 months . Conclusions This study showed that 6 months of fish oil supplement had no statistically significant effects on glycemic control , but improved TG and HDL-C in type 2 diabetic patients with abdominal obesity . Trial registration Chictr.org ChiCTR-TRC-14005084 Introduction A total of 177 patients with moderate-to-severe hip or knee osteoarthritis ( OA ) were tested over a period of 26 weeks in a two-center , two-armed , r and omized , double-blind , comparison study . The aim was to see if a combination of glucosamine sulfate ( 1500 mg/day ) and the omega-3 polyunsaturated fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) ( group A ) , showed equivalence ( noninferiority ) or superiority as opposed to glucosamine sulfate alone ( group B ) . Methods The primary therapy evaluation was performed using the Western Ontario and McMaster Universities Arthrosis index ( WOMAC ) score . At the end of the study , a reduction in the pain score of ≥20 % was required ( primary target criterion ) and the quantitative difference in the WOMAC subscores pain , stiffness , and function were analyzed ( secondary target criteria ) . Results and Conclusion When a minimal pain reduction of ≥20 % was chosen , there was no statistically significant difference in the number of responders between the two groups ( 92.2 % group A , 94.3 % group B ) . A higher responder criterion ( ≥80 % reduction in the WOMAC pain score ) was chosen . Therefore , the frequency of responders showed a therapeutic and statistical superiority for the combination product of glucosamine sulfate and the omega-3 polyunsaturated fatty acids in patients who complied with the study protocol ( group A 44 % , group B 32 % ; P=0.044 ) . OA symptoms ( morning stiffness , pain in hips and knees ) were reduced at the end of the study : by 48.5%–55.6 % in group A and by 41.7%–55.3 % in group B. The reduction was greater in group A than in group B. There was a tendency toward superiority shown in the secondary target criteria and concurrent variables . In the global safety evaluation , both products have been demonstrated to be very safe in long-term treatment over 26 weeks . To our knowledge , this is the first clinical trial in which glucosamine was given in combination with omega-3 fatty acids to patients with OA Objectives To determine whether high-dose fish oil is superior to low-dose supplementation for symptomatic and structural outcomes in knee osteoarthritis ( OA ) . Methods A r and omised , double-blind , multicentre trial enrolled 202 patients with knee OA and regular knee pain . They were r and omised 1:1 to high-dose fish oil ( 4.5 g omega-3 fatty acids ) 15 mL/day or ( 2 ) low-dose fish oil ( blend of fish oil and sunola oil ; ratio of 1:9 , 0.45 g omega-3 fatty acids ) 15 mL/day . The primary endpoints were Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) pain score at 3 , 6 , 12 and 24 months , and change in cartilage volume at 24 months . Secondary outcomes included WOMAC function , quality of life , analgesic and non-steroidal anti-inflammatory drug use and bone marrow lesion score . Results Although there was improvement in both groups , the low-dose fish oil group had greater improvement in WOMAC pain and function scores at 2 years compared with the high-dose group , whereas between-group differences at 1 year did not reach statistical significance . There was no difference between the two groups in cartilage volume loss at 2 years . For other secondary endpoints , there was no difference between the two groups at 2 years . Conclusions In people with symptomatic knee OA , there was no additional benefit of a high-dose fish oil compared with low-dose fish oil . The combination comparator oil appeared to have better efficacy in reducing pain at 2 years , suggesting that this requires further investigation . Trial registration number Australian New Zeal and Clinical Trials Registry ( ACTRN 12607000415404 ) BACKGROUND Intakes of n-3 ( omega-3 ) polyunsaturated fatty acids ( PUFAs ) are important for health . Because fish is the major source of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , non-fish-eaters may have suboptimal n-3 PUFA status , although the importance of the conversion of plant-derived α-linolenic acid ( ALA ) to EPA and DHA is debated . OBJECTIVE The objective was to determine intakes , food sources , and status of n-3 PUFAs  according to dietary habit ( fish-eaters and non-fish-eating meat-eaters , vegetarians , or vegans ) and estimated conversion between dietary ALA and circulating long-chain n-3 PUFAs . DESIGN This study included 14,422 men and women aged 39 - 78 y from the EPIC ( European Prospect i ve Investigation into Cancer and Nutrition)-Norfolk cohort with 7-d diary data and a sub study in 4902 individuals with plasma phospholipid fatty acid measures .  Intakes and status of n-3 PUFAs were measured , and the product-precursor ratio [ corrected ] of ALA to circulating n-3 PUFAs was calculated . RESULTS Most of the dietary intake of  EPA and DHA was supplied by fish ; however , meat was the major source in meat-eaters , and spreading fats , soups , and sauces were the major sources in vegetarians . Total n-3 PUFA intakes in non-fish-eaters were 57 - 80 % of those in fish-eaters , but status differences were considerably smaller [ corrected ] . The estimated product-precursor ratio [ corrected ] was greater in women than in men and greater in non-fish-eaters than in fish-eaters . CONCLUSIONS Substantial differences in intakes and in sources of n-3 PUFAs existed between the dietary-habit groups , but the differences in status were smaller than expected , possibly because the product-precursor ratio [ corrected ] was greater in non-fish-eaters than in fish-eaters , potentially indicating increased estimated conversion of ALA . If intervention studies were to confirm these findings , it could have implication s for fish requirements Summary This study aim ed to determine the effect of fish oil on bone mineral density ( BMD ) . There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD . This r and omized controlled trial did not demonstrate any efficacy of omega-3 fatty acids on  bone loss in adults . Introduction The purpose of this study is to investigate whether supplementation with high dose omega-3 fish oil could have an impact on BMD . Methods In a multicentre , double-blind r and omized controlled trial ( RCT ) ( ACTRN 12607000415404 ) , 202 Australian participants aged ≥40 with knee osteoarthritis ( mean age , 61.0 ± 10.0 years ; 49 % female ) were r and omized to receive either high dose ( 4.5 g eicosapentaenoic acid and docosahexaenoic acid daily ) or low dose ( 0.45 g/day ) omega-3 fish oil for 2 years . BMD was assessed at baseline and 2 years by dual energy X-ray absorptiometry . Results In subjects with baseline and 2-year assessment s , mean st and ardized BMD at baseline for low or high dose group was 1198 ± 198 and 1157 ± 169 mg/cm2 , respectively , for the lumbar spine and was 1035 ± 165 and 1017 ± 174 mg/cm2 , respectively , for the femoral neck . There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD in the complete case regression analyses ( lumbar spine 3.7 , 95 % confidence interval ( CI ) −7.9 to 15.3 mg/cm2 and femoral neck −5.5 , 95 % CI −14.9 to 3.9 mg/cm2 ) . The findings did not change with additional adjustments of age , gender , study centre and uses of bone-related drugs during the study period as well as using the intention-to-treat analysis or limiting to older participants ( ≥55 years at the baseline ) ( all P ≥ 0.25 ) . Mild adverse events such as headache and gastrointestinal intolerance were common but did not occur more frequently in either group . There were no serious adverse events related to the intervention . Conclusion A 2-year supplementation with high-dose omega-3 fish oil did not alter bone loss among men and women with knee osteoarthritis OBJECTIVES Our pilot study tested the efficacy , acceptability and tolerability of DHA supplementation in addition to calcium and vitamin D in individuals with osteopenia . STUDY DESIGN 40 participants were r and omised to either algal oil containing 400 mg docosahexanoic acid ( DHA ) daily or placebo . All participants received 1200 mg calcium carbonate with vitamin D(3 ) 1000 IU daily . MAIN OUTCOME MEASURES Bone mineral density ( BMD ) was measured at baseline and 12 months . Bone turnover was assessed with serum c-terminal telopeptides ( CTx ) at baseline and 12 months . Tolerability and acceptability were assessed using a vali date d question naire . RESULTS Mean CTx was suppressed after 12 months for all participants ( p=0.04 ) with no difference in effect size between DHA and control groups ( p=0.53 ) . Changes in CTx at 12 months were significantly correlated with changes in BMD at the lumbar spine ( p=0.01 ) and total proximal femur ( TPF ) ( p=0.03 ) . There was a non-significant trend towards rising BMD at 12 months . Participants rated the supplements as tolerable and acceptable , with few adverse events . CONCLUSIONS The combination of oral calcium , vitamin D(3 ) and DHA was safe , tolerable and acceptable when used for 12 months by osteopenic individuals in this pilot study . The combination had a positive effect on bone health as indicated by serum CTx , with no effect demonstrated from the addition of DHA 400 mg . Changes in BMD at the lumbar spine and TPF were significantly correlated with changes in CTx , which may be useful in monitoring bone health and response to treatment Objectives Identify relationships and evaluate effects of long chain polyunsaturated fatty acids ( LCPUFA ) on frailty and physical performance . Design : R and omized , double blind pilot study . Setting University General Clinical Research Center . Participants 126 postmenopausal women . Intervention2 fish oil ( 1.2 g eicosapentaenoic acid [ EPA ] and docosahexaenoic acid [ DHA ] ) or 2 placebo ( olive oil ) capsules per day for 6 months . All participants received calcium and vitamin D supplements . Measurements Fatty acid levels , frailty assessment , h and grip strength , 8 foot walk , body composition , medical history and co-morbidities , nutrient intake , and inflammatory biomarkers taken at baseline and 6 months . Results At baseline , those with greater red blood cell ( RBC ) DHA and DHA/arachidonic acid ( AA ) presented with less frailty ( r=−0.242 , p=0.007 and r=−0.254 , p=0.004 , respectively ) . Fish oil supplementation result ed in higher RBC DHA and lower AA compared to baseline and placebo ( p<0.001 ) and an improvement in walking speed  compared to placebo ( 3.0±16 vs. −3.5±14 , p=0.038 ) . A linear regression model included age , antioxidant intake ( selenium and vitamin C ) , osteoarthritis , frailty phenotype , and tumor necrosis factor alpha ( TNFα ) . The model explained 13.6 % of the variance in the change in walking speed . Change in DHA/AA ( p=0.01 ) and TNFα ( p=0.039 ) , and selenium intake ( p=0.031 ) had the greatest contribution to change in walking speed . Conclusion Physical performance , measured by change in walking speed , was significantly affected by fish oil supplementation . Dietary intake of antioxidants ( selenium and vitamin C ) and changes in TNFα also contributed to change in walking speed suggesting LCPUFA may interact with antioxidants and inflammatory response to impact physical performance R and omized controlled trials of the effects of the dietary supplement Efacal ( Scotia Pharmaceuticals Plc , Guildford , Surrey , UK ) v. Ca only on total body bone mineral density ( BMD ) and markers of bone turnover were conducted in healthy pre- and postmenopausal women separately . Total daily dose for 12 months for the Efacal groups was : Ca 1.0 g , evening primrose oil 4.0 g and marine fish oil 440 mg ; and for the control groups was : Ca 1.0 g. Reported compliance was better than 90 % in both age groups . For the forty-three premenopausal women ( age range 25 - 40 years ) , initial mean total body BMD values were similar for Efacal and control groups and both groups showed highly significant mean increases of about 1 % ; however , there were no significant between-group differences for the changes in BMD or markers of bone turnover . For the forty-two postmenopausal women ( age range 50 - 65 years ) , initial mean total body BMD values were again well-matched across treatment groups . Both Efacal and control groups showed highly significant decreases in total body BMD of about 1 % , but again there were no significant between-group differences in total body BMD or markers of bone turnover . Possible confounding variables such as initial total body BMD were explored but had no effect on the outcome in either age group . Nail quality improved in both age groups and in both Efacal and control groups . Again , there was no significant difference between treatment groups . No evidence was found to support a beneficial effect of Efacal on BMD in these women Objective To create a data base of long-term r and omised controlled trials ( RCTs ) comparing higher with lower omega-3 , omega-6 or total polyunsaturated fatty acid ( PUFA ) , regardless of reported outcomes , and to develop methods to assess effects of increasing omega-6 , alpha-linolenic acid ( ALA ) , long-chain omega-3 ( LCn3 ) and total PUFA on health outcomes . Design Systematic review search , methodology and meta-analyses . Data sources Medline , Embase , CENTRAL , WHO International Clinical Trials Registry Platform , Clinical trials.gov and trials in relevant systematic review s. Eligibility criteria RCTs of ≥24 weeks ' duration assessing effects of increasing ALA , LCn3 , omega-6 or total PUFAs , regardless of outcomes reported . Data synthesis Methods included r and om-effects meta-analyses and sensitivity analyses . Funnel plots were examined , and subgrouping assessed effects of intervention type , replacement , baseline diabetes risk and use of diabetic medications , trial duration and dose . Quality of evidence was assessed using Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) . Results Electronic search es generated 37 810 hits , de-duplicated to 19 772 titles and abstract s. We assessed 2155 full-text papers , conference abstract s and trials registry entries independently in duplicate . Included studies were grouped into 363 RCTs comparing higher with lower omega-3 , omega-6 and /or total PUFA intake of at least 6 months ’ duration —the Data base . Of these 363 included RCTs , 216 RCTs were included in at least one of our review s of health outcomes , data extracted and risk of bias assessed in duplicate . Ninety five RCTs were included in the Data base but not included in our current review s. Of these 311 completed trials , 27 altered ALA intake , 221 altered LCn3 intake and 16 trials altered omega-3 intake without specifying whether ALA or LCn3 . Forty one trials altered omega-6 and 59 total PUFA.The remaining 52 trials are ongoing though 13 ( 25 % ) appear to be outst and ing , or constitute missing data . Conclusions This extensive data base of trials is available to allow assessment of further health outcomes To the Editor : Because of irregularities in the r and omization procedures , we wish to retract the following article : Primary Prevention of Cardiovascular Disease with a Mediterranean Diet . N Engl J Med 2013;368:1279 - 90 . DOI : 10.1056/NEJMoa1200303.1 We have reanalyzed the data and have published a new report : Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts . N Engl J Med . DOI : 10.1056/NEJMoa1800389.2 . .
We conducted a systematic review and meta- analysis to assess the effects of increasing dietary omega-3 , omega-6 and mixed polyunsaturated fatty acids ( PUFA ) on  musculoskeletal health , functional status , sarcopenia and risk of fractures .