Substituting Walnuts for Monounsaturated Fat Improves the Serum Lipid Profile of Hypercholesterolemic Men and Women Effects of supplementing n-3 fatty acid enriched eggs and walnuts on cardiovascular disease risk markers in healthy free-living lacto-ovo-vegetarians: a randomized, crossover, free-living intervention study Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers. Walnut Consumption Is Associated with Lower Risk of Type 2 Diabetes in Women12 Walnut Consumption in Hyperlipidemic Patients Effects of walnut consumption as part of a low-fat, low-cholesterol diet on serum cardiovascular risk factors. A diet rich in walnuts favourably influences plasma fatty acid profile in moderately hyperlipidaemic subjects Effects of a Mediterranean-Style Diet on Cardiovascular Risk Factors Walnuts and fatty fish influence different serum lipid fractions in normal to mildly hyperlipidemic individuals: a randomized controlled study. Impact of polyunsaturated vegetable oils on adiponectin levels, glycaemia and blood lipids in individuals with type 2 diabetes: a randomised, double-blind intervention study. A Walnut Diet Improves Endothelial Function in Hypercholesterolemic Subjects: A Randomized Crossover Trial Including walnuts in a low-fat/modified-fat diet improves HDL cholesterol-to-total cholesterol ratios in patients with type 2 diabetes. Effects of walnuts on serum lipid levels and blood pressure in normal men. A macadamia nut-rich diet reduces total and LDL-cholesterol in mildly hypercholesterolemic men and women. Chronic and acute effects of walnuts on antioxidant capacity and nutritional status in humans: a randomized, cross-over pilot study Nut Consumption and Risk of Cardiovascular Disease. Effect of pistachio consumption on plasma lipoprotein subclasses in pre-diabetic subjects. Effect of moderate walnut consumption on lipid profile, arterial stiffness, and platelet activation in humans Walnut Consumption Alters the Gastrointestinal Microbiota, Microbially Derived Secondary Bile Acids, and Health Markers in Healthy Adults: A Randomized Controlled Trial Olive oil and walnut breakfasts reduce the postprandial inflammatory response in mononuclear cells compared with a butter breakfast in healthy men. Walnut-enriched diet increases the association of LDL from hypercholesterolemic men with human HepG2 cells. Benefits of foods supplemented with vegetable oils rich in α-linolenic, stearidonic or docosahexaenoic acid in hypertriglyceridemic subjects: a double-blind, randomized, controlled trail A Walnut-Enriched Diet Affects Gut Microbiome in Healthy Caucasian Subjects: A Randomized, Controlled Trial
Lifestyle modification is the cornerstone of population -based strategies for prevention of coronary heart disease and is the first line of therapy in patients with hypercholesterolemia . Diets low in saturated fatty acids and cholesterol have long been recommended to decrease low-density lipoprotein ( LDL ) cholesterol levels and reduce cardiovascular risk ( 1 ) . Ample evidence suggests that polyunsaturated fatty acids and monounsaturated fatty acids have a similar cholesterol-lowering effect when substituted for saturated fatty acids ( 2 - 4 ) . However , most studies of fatty acids and blood lipids have been done with fats and oils , rarely with whole fatty foods . Because people usually buy and consume whole food products , it is desirable to know the effects of specific foods on risk factors for coronary heart disease . Recent reports suggest that the regular consumption of nuts might reduce cardiovascular risk ( 5 ) . Walnuts are particularly rich in polyunsaturated fatty acids ( 6 ) , and epidemiologic evidence suggests that frequent walnut consumption protects against coronary heart disease ( 7 ) . In a controlled feeding trial by Sabat and colleagues ( 8) , a diet in which walnuts represented 55 % of the energy from fat reduced blood cholesterol levels in normal young men when compared with a st and ard low-fat diet . However , the results can not easily be extrapolated to the population at risk for coronary heart disease because women , older age groups , and hypercholesterolemic persons were not studied ( 8) . In addition , because meals were served at a metabolic kitchen , the study did not address the question of whether free-living persons would incorporate substantial quantities of walnuts into their diets . Because oxidized LDL plays a key role in atherogenesis ( 9 ) and oxidative damage involves peroxidation of polyunsaturated fatty acids in LDL lipids ( 10 ) , there is concern that walnut intake may promote LDL oxidation . Therefore , we design ed a dietary intervention study in free-living adult men and women with polygenic hypercholesterolemia to compare the effects of a walnut-rich diet with those of a cholesterol-lowering Mediterranean diet on serum lipid levels , lipoprotein levels , and LDL resistance to oxidation . Methods Patients Adult men and women with polygenic hypercholesterolemia attending the Lipid Clinic of the Hospital Clnic of Barcelona were eligible if they had serum LDL cholesterol concentrations greater than 3.36 mmol/L ( 130 mg/dL ) and triglyceride concentrations less than 2.82 mmol/L ( 250 mg/dL ) ; no evidence of alcohol , tobacco , or drug abuse ; absence of diabetes mellitus and liver , kidney , thyroid , or other endocrine diseases , as assessed by medical history , a complete physical examination , and laboratory tests ; no intake in the previous 8 weeks of medications known to affect lipid metabolism , including hypolipidemic agents and estrogen compounds in women ; infrequent consumption of nuts and no known history of allergy to them ; and no use of multivitamin or vitamin E supplements  . Because the target population had common ( polygenic ) hypercholesterolemia , we excluded persons whose elevated blood cholesterol levels had a strong genetic basis ( such as heterozygous familial hypercholesterolemia or familial combined hyperlipidemia ) , as established by st and ard criteria . On admission to the Lipid Clinic , all patients were advised to follow a  Mediterranean-type hypolipidemic diet ( 11 ) . For a crossover design , statistical power calculations indicated that to detect mean differences of 0.39 mmol/L ( 15 mg/dL ) , 34 patients would need to complete the two treatment periods ( statistic , 0.05 ; power>0.8 ) . From a computerized register of clinical records , 75 hypercholesterolemic patients ( 35 women and 40 men ) who initially met the eligibility criteria were selected for screening and were asked to participate in the study . They were offered free walnuts but no monetary compensation . Study Design A crossover design was used . Patients were r and omly assigned to the two diet sequences by using a computer-generated r and om-number table , with stratification by sex . Because patients followed each diet for 6 weeks and lipoprotein changes due to dietary intervention stabilize in less than 4 weeks ( 12 ) , we did not incorporate a washout period between diets . In their crossover feeding study with walnuts , Sabat and colleagues ( 8) did not observe a carryover effect . In the week before the trial began , patients received expert dietary counseling individually and in a group class . Twice during the pretrial week and on weeks 5 and 6 of each one of the two dietary periods , patients came to the clinic for a medical visit , an interview with the dietitian , anthropometric measurements , and blood extraction . The main outcomes of the study were changes in serum levels of total and LDL cholesterol from the control diet period to the walnut diet period . Secondary outcomes were changes in other lipid variables and oxidizability of LDL particles . The study protocol was approved by the institutional review board of the Hospital Clnic of Barcelona , and all patients gave informed consent . Diets The experimental diets were individually prescribed and were based on estimated energy requirements . Because participants ate on their own , detailed dietary information was provided to them and , if appropriate , to their partners .  Diets were calculated in increments of 200 kcal to cover the range from 1600 to 2200 kcal . The control diet was Mediterranean and was composed of natural foodstuffs . Red meat and eggs were limited , vegetable products and fish were emphasized , olive oil was indicated for culinary use , and no nuts were allowed . The walnut diet was similar to the control diet , but walnuts partially replaced olive oil and other fatty foods . Prepackaged daily allowances of raw , shelled walnuts were provided daily in amounts varying from 41 g to 56 g ( the equivalent of 8 to 11 walnuts ) , according to the participants ' total energy intake . Walnuts were consumed as snacks or with meals in desserts or salads . In the walnut diet , walnuts contributed approximately 18 % of the total energy and 35 % of the total fat . To improve compliance , each family unit was given 1000-g packs of walnuts at the beginning of the walnut diet period .  Adherence to the study diets was carefully monitored . Unannounced 24-hour diet recalls were performed weekly by telephone during the two dietary periods , for a total of 12 recalls per patient . This method allows reliable estimations of food intake ( 13 ) . The nutrient composition of the diets was calculated with Food Processor Plus software , version 5.0 ( ESHA Research , Salem , Oregon ) , which was adapted to nutrient data bases of specific Mediterranean foods when appropriate . We defined noncompliance as at least 20 % deviation from dietary instructions regarding walnut or nutrient intake . Compliance during the walnut diet was also assessed at each clinic visit by a count of the empty walnut packages . The fatty acid content of LDL lipids was analyzed as a biological measure of adherence to the prescribed diets . Laboratory Measurements Blood sample s were obtained after an overnight fast , and serum and EDTA plasma were collected and processed immediately . Serum lipid and apolipoprotein levels were determined as described elsewhere ( 11 ) . In brief , serum cholesterol and triglyceride levels were measured by using enzymatic reagents ( Trinder , Bayer Diagnostics , Tarrytown , New York ) adapted to a Cobas Mira automated analyzer ( Hoffmann-LaRoche , Basel , Switzerl and ) . High-density lipoprotein ( HDL ) cholesterol was quantified after precipitation with phosphotungstic acid and magnesium chloride . Levels of apolipoprotein A-I and apolipoprotein B were determined by an immunoturbidimetric method ( Unimate 3 , Roche Diagnostic Systems , Basel , Switzerl and ) . Measurements of the cholesterol content of very-low-density lipoprotein particles and LDL particles were based on preparative ultracentrifugation ( 11 ) . Lipoprotein(a ) levels were measured by using an immunoturbidimetric method ( Lipoprotein[a ] SPQ II Test Kit , DiaSorin , Stillwater , Minnesota ) . To obtain the LDL fraction for fatty acid and oxidizability studies , lipoproteins were fractionated by sequential centrifugation adjusting with NaBr to separate very-low-density lipoprotein particles ( d=1.006 g/mL ) and to obtain LDL particles ( d=1.063 g/mL ) , as described elsewhere ( 14 ) . Low-density lipoprotein fatty acids were measured by capillary gas chromatography in the cholesteryl ester , phospholipid , and triglyceride lipid fractions ( 14 ) . Low-density lipoprotein susceptibility to oxidation was determined by measuring the -tocopherol content of LDL particles and conjugated diene kinetics after incubation of 50 g of LDL protein with 5 mol of copper sulfate at 37 C ( 15 , 16 ) . Statistical Analysis The two measurements obtained at baseline and at the end of each dietary period were averaged . Means and SDs are presented for each measurement . With methods described by Fleiss ( 17 ) , two-tailed t-tests were used to compare changes in outcome variables in response to dietary treatment and diet period and carryover effects for the two-period crossover design . Differences between the walnut and control diets were also tested by analysis of covariance using general linear models ; baseline values or sex were used as covariates . Analyses were performed by using SAS software ( SAS , Inc. , Cary , North Carolina ) ( 18 ) . Role of the Funding Sources The California Walnut Commission provided funding and walnuts . Research grants were also obtained from national and local nonprofit agencies . The funding sources were not involved in the design of the study and had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . None of the authors has any financial interest in the nut food industry . Results Patient Characteristics Of the 75 eligible patients , 20 left the study before r and omization for Background Plant and marine n-3 fatty acids ( FA ) may favorably modify select markers of cardiovascular disease risk . Whether supplementing the habitual diet of lacto-ovo-vegetarians ( LOV ) with walnuts ( containing α-linolenic acid , ALA ) and n-3 FA enriched eggs ( containing primarily docosahexaenoic acid , DHA and ALA ) would have equivalent effects on CVD risk factors is explored in this study . Methods In this study , 20 healthy free-living LOVs following their habitual diet were r and omly assigned in a crossover design to receive one of three supplements : n-3 FA enriched egg ( 6/week ) , walnuts ( 28.4 g , 6/week ) or a st and ard egg , 6/week ( control ) for 8 weeks each with 4-wk washout between treatments . Erythrocyte membrane fatty acids , serum lipids and inflammatory markers were measured at the end of each treatment . Results Dietary compliance was observed by an expected increase in erythrocyte membrane ALA following the walnut treatment and in DHA following the n-3 FA enriched egg treatment . Walnut treatment lowered serum triacylglycerol , total cholesterol and Apo B ( p < 0.05 ) compared to the st and ard egg but not the n-3 FA enriched egg treatment . However , walnut treatment significantly reduced total : HDL cholesterol ratio compared to both egg treatments . There were no differences between treatments for any of the inflammatory markers . Conclusions For LOV , a direct source of DHA such as n-3 FA enriched eggs seems necessary to increase membrane levels of DHA . However for producing an overall favorable blood lipid profile , daily consumption of a h and ful of walnuts rich in ALA may be a preferred option for lacto-ovo vegetarian BACKGROUND AND AIMS Virgin olive oil ( VOO ) and nuts are basic components of the Mediterranean diet , a heart-healthy dietary pattern . Nuts have well known cholesterol lowering effects , while evidence is unclear for VOO . We design ed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40 % of the fat in the background diet with VOO , walnuts or almonds . METHODS AND RESULTS After a 4 week run-in period with a healthy diet , eligible c and i date s were r and omized into three diet sequences in a crossover design , with a common background diet enriched with VOO , walnuts or almonds , lasting 4 weeks each . Outcomes were changes of serum lipids and oxidation and inflammation markers , measured by st and ard methods . Plasma fatty acids were determined by gas chromatography to assess compliance . In 18 participants completing the study ( 9 women , mean age 56 y , BMI 25.7 kg/m(2 ) ) , LDL-cholesterol was reduced from baseline by 7.3 % , 10.8 % and 13.4 % after the VOO , walnut and almond diets , respectively ( P = 0.001 , Friedman test ) . Total cholesterol and LDL/HDL ratios decreased in parallel . LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets . No changes of other lipid fractions , oxidation analytes or inflammatory biomarkers were observed . Plasma fatty acid changes after each diet sequence supported good compliance . CONCLUSION The results confirm the cholesterol lowering properties of nut-enriched diets . They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content , which clearly deserves further study Walnuts are rich in polyunsaturated fatty acids and have been shown to improve various cardiometabolic risk factors . We aim ed to investigate the association between walnut intake and incident type 2 diabetes  in 2 large cohort studies : the Nurses ’ Health Study ( NHS ) and NHS II . We prospect ively followed 58,063 women aged 52–77 y in NHS ( 1998–2008 ) and 79,893 women aged 35–52 y in NHS II ( 1999–2009 ) without diabetes , cardiovascular disease , or cancer at baseline .  Consumption of walnuts and other nuts was assessed every 4 y using vali date d food frequency question naires .  Self-reported type 2 diabetes was confirmed by a vali date d supplemental question naire . We documented a total of 5930 incident type 2 diabetes cases during 10 y of follow-up . In the multivariable-adjusted Cox proportional hazards model without body mass index ( BMI ) , walnut consumption was associated with a lower risk of type 2 diabetes , and the HRs ( 95 % CIs ) for participants consuming 1–3 servings/mo ( 1 serving = 28 g ) , 1 serving/wk , and ≥2 servings/wk of walnuts were 0.93 ( 0.88–0.99 ) , 0.81 ( 0.70–0.94 ) , and 0.67 ( 0.54–0.82 ) compared with women who never/rarely consumed walnuts ( P-trend < 0.001 ) . Further adjustment for up date d BMI slightly attenuated the association and the HRs ( 95 % CIs ) were 0.96 ( 0.90–1.02 ) , 0.87 ( 0.75–1.01 ) , and 0.76 ( 0.62–0.94 ) , respectively ( P-trend = 0.002 ) . The consumption of total nuts ( P-trend < 0.001 ) and other tree nuts ( P-trend = 0.03 ) was also inversely associated with risk of type 2 diabetes , and the associations were largely explained by BMI . Our results suggest that higher walnut consumption is associated with a significantly lower risk of type 2 diabetes in women Walnut ( Juglans regia L. ) is described as an anticancer , tonic , blood purifier , and detoxifier agent . It is said that nuts have favorable fatty acids and nutrients . This study was performed to determine the lipid-lowering properties of walnut in a population in Shiraz , Southern Iran . In a r and omized case-control study , 52 volunteers were divided into 2 groups : Group A consumed walnuts , 20 grams per day for 8 weeks and the control group ( group B ) consumed no walnuts .  Triglycerides , total high-density lipoprotein ( HDL ) , and low-density lipoprotein ( LDL ) levels were checked for each subject prior to , after 4 weeks , and at 8 weeks after the beginning of the study . In group A , the mean plasma TG level dropped by 17.1 % from the baseline and HDL cholesterol also increased significantly by 9 % . It was shown that frequent consumption of nuts in the daily diet was associated with a potentially decreased risk of coronary artery disease by decreasing the level of triglyceride and increasing the level of HDL Serum components , such as lipoproteins , coagulation factors ( factor VII , tissue plasminogen activator ( tPA ) , plasminogen activator inhibitor-1 ( PAI-1 ) , fibrinogen ) , and homocysteine have been associated with cardiovascular disease . Dietary intervention with a low-fat , low-cholesterol diet has favorably influenced cardiovascular disease and certain food , specifically the consumption of nuts , has been associated with reduced cardiovascular risks . The effects of walnuts , as part of a low-fat , low-cholesterol diet , on serum cardiovascular risk factors were determined . Sixty-seven ( 67 ) out patients with borderline high total cholesterol following a low-fat , low-cholesterol diet for six weeks before being r and omly assigned to continue the diet or have 64 grams/day of walnuts in conjunction with the diet . After six weeks , the patients ' diets were switched . Therefore , all patients consumed 64 grams/day of walnuts for six weeks during part of the trial as part of a low-fat , low cholesterol diet .  Serum lipids demonstrated a significant reduction in triacyglycerols and favorable trend with decreases in total cholesterol , low-density lipoprotein ( LDL ) cholesterol , and a slight increase in high-density lipoprotein ( HDL ) cholesterol . No statistical effects on homocysteine or the coagulation factors were observed . However , there was a slight favorable trend for tPA and PAI-1 . This study demonstrated that walnuts , when consumed as part of a low fat , low-cholesterol diet , have a beneficial effect on serum cardiovascular risk factors . However , these changes may not explain all of the beneficial effects that walnut consumption has on cardiovascular disease Objective : To compare two low fat diets one rich in walnuts on parameters of lipid metabolism in a group of hyperlipidaemic subjects . Design : A r and omised cross over study . Setting : Department of Human Nutrition , University of Otago , Dunedin , New Zeal and Subjects : Twenty one men with mean ( s.d ) levels of total and LDL cholesterol of 6.58 ( 0.60 ) and 4.63 ( 0.58 ) respectively . Interventions : For two periods of four weeks subjects were asked to consume two low fat diets ( fat 30 % total energy ) , one containing , on average , 78 g/d walnuts . Walnuts obtained through Lincoln University and the Walnut Growers Group ( South Canterbury ) . Results : Participants reported a higher total fat intake on the walnut diet ( 38 % compared with 30 % on the low fat diet P<0.01 ) The most consistent change in fatty acid profile of triacylglycerol , phospholipid and cholesterol ester on the walnut diet was a significant ( P<0.01 ) increase in linoleic acid . Triacylglycerol linolenate also increased significantly ( P<0.01 ) . Total and LDL cholesterol were lower on both experimental diets than at baseline , 0.25 mmol/l and 0.36 mmol/l respectively on the walnut diet and 0.13 mmol/l and 0.20 mmol/l respectively on the low fat diet . High density lipoprotein cholesterol was higher on both the walnut and low fat diets when compared to baseline ( 0.15 mmol/l and 0.12 mmol/l , respectively ) . When comparing the walnut and low fat diets only apo B was significantly lower ( P<0.05 ) on the walnut diet . Conclusions : Despite an unintended increase in the total fat intake on the walnut diet , fatty acid profile of the major lipid fractions showed changes which might be expected to reduce risk of cardiovascular disease . The reduction of apolipoprotein B suggests a reduction in lipoprotein mediated risk , the relatively low myristic acid content of both diets perhaps explaining the absence of more extensive differences in lipoprotein levels on the two diets . Sponsorship : Nutrition Department University of Otago , New Zeal and Context Some experts attribute a low incidence of heart disease in Mediterranean countries to dietary habits . Contribution In this multicenter , 3-group trial , investigators r and omly assigned 772 adults at high risk for cardiovascular disease to a low-fat diet or to a Mediterranean diet supplemented with either virgin olive oil ( 1 L per week ) or nuts ( 30 g per day ) . After 3 months , the Mediterranean diet groups had lower mean plasma glucose level , systolic blood pressure , and total cholesterolhigh-density lipoprotein cholesterol ratio than the low-fat diet group . Caution s The Mediterranean diet groups received more nutritional education than the low-fat diet group . Implication s Mediterranean diets supplemented with olive oil or nuts may improve cardiovascular risk factors . The Editors Cardiovascular disease is the main cause of death in industrialized countries , but incidence rates have marked geographic differences . The low incidence of coronary heart disease ( CHD ) in Mediterranean countries has been partly ascribed to dietary habits ( 1 - 3 ) . Recent findings from large European cohort studies ( 4 - 6 ) suggest that a high degree of adherence to the Mediterranean diet is associated with a reduction in mortality . In small clinical studies , the Mediterranean diet or some of its components have reduced blood pressure ( 7 ) and have improved lipid profiles ( 8 , 9 ) and endothelial function ( 10 ) . Moreover , a recent cross-sectional study ( 11 ) and a 2-year feeding trial ( 12 ) have shown that adherence to the Mediterranean diet is associated with reduced markers of vascular inflammation . These beneficial effects on surrogate markers of cardiovascular risk add biological plausibility to the epidemiologic evidence that supports a protective effect of the Mediterranean diet . Olive oil , a rich source of monounsaturated fatty acids , is a main component of the Mediterranean diet . Virgin olive oil retains all the lipophilic components of the fruit , -tocopherol , and phenolic compounds with strong antioxidant and anti-inflammatory properties ( 13 , 14 ) . Tree nuts , which are also typical in the Mediterranean diet , have a favorable fatty acid profile and are a rich source of nutrients and other bioactive compounds that may beneficially influence the risk for CHD , such as fiber , phytosterols , folic acid , and antioxidants ( 15 ) . Frequent nut intake has been associated with decreased CHD rates in prospect i ve studies ( 15 ) . Walnuts differ from all other nuts through their high content of polyunsaturated fatty acids , particularly -linolenic acid , a plant n-3 fatty acid ( 16 ) , which may confer additional antiatherogenic properties ( 17 ) . Therefore , we design ed a large-scale feeding trial in high-risk participants to assess the effects of 2 Mediterranean diets , one supplemented with virgin olive oil and the other supplemented with mixed nuts , compared with a low-fat diet on cardiovascular outcomes . We report the results of a 3-month intervention on intermediate markers of cardiovascular risk in the first 772 participants who were recruited into the trial . Supplement . Original Version ( PDF ) Methods Study Design The Prevencin con Dieta Mediterrnea ( PREDIMED ) Study is a large , parallel-group , multicenter , r and omized , controlled , 4-year clinical trial that aims to assess the effects of the Mediterranean diet on the primary prevention of cardiovascular disease ( www.predimed.org ) . An estimated 9000 high-risk participants ( > 5000 participants are already recruited ) will be assigned to 3 interventions : Mediterranean diet with virgin olive oil , Mediterranean diet with mixed nuts , or low-fat diet . The main outcome is an aggregate of cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke ) . The anticipated completion date of the trial is December 2010 . We design ed our present study to assess the 3-month effects of the dietary interventions on surrogate markers of cardiovascular risk in participants entering the study during the first 6 months of recruitment . The institutional review boards of the 10 participating centers approved the study protocol . Participants and Recruitment From October 2003 to March 2004 , we selected 930 potential participants in primary care centers affiliated with 10 teaching hospitals across Spain . Eligible participants were community-dwelling men , 55 to 80 years of age , and women , 60 to 80 years of age , who fulfilled at least 1 of 2 criteria : type 2 diabetes or 3 or more CHD risk factors ( current smoking , hypertension [ blood pressure > 140/90 mm Hg or treatment with antihypertensive drugs ] , low-density lipoprotein [ LDL ] cholesterol level 4.14 mmol/L [ 160 mg/dL ] [ or treatment with hypolipidemic drugs ] , high-density lipoprotein [ HDL ] cholesterol level 1.04 mmol/L [ 40 mg/dL ] , body mass index [ BMI ] 25 kg/m2 , or a family history of premature CHD ) . Exclusion criteria were history of cardiovascular disease , any severe chronic illness , drug or alcohol addiction , history of allergy or intolerance to olive oil or nuts , or low predicted likelihood of changing dietary habits according to the stages-of-change model ( 18 ) . The primary care physicians based participants ' eligibility on review of clinical records and a screening visit . They obtained a list of c and i date s from computer-based records of patients who attended each participating center and review ed their clinical records to exclude those who did not meet eligibility criteria . They then invited suitable c and i date s by telephone to attend a screening visit . The visit included an interview with administration of a 26-item question naire to inquire about medical conditions and risk factors related to eligibility . Of the eligible c and i date s who met entry requirements , 95 % agreed to participate and provided informed consent . R and omization and Intervention After the screening visit , each center r and omly assigned eligible participants to 1 of 3 diet groups by using a computer-generated r and om-number sequence . The coordinating center constructed the r and omization table , and participants were r and omly assigned into blocks of 50 participants balanced by center , sex , and age group ( < 70 years and 70 years ) . We concealed allocation into the intervention groups by using closed envelopes with correlative numbers by prespecified subgroups of sex and age . The baseline examination included the administration of a 14-item question naire , an extension of a previously vali date d question naire ( 19 ) , that assessed the degree of adherence to the traditional Mediterranean diet . We assigned values of 0 or 1 to each item ( Appendix Table 1 ) . We also administered a 137-item vali date d food frequency question naire ( 20 ) ; the vali date d Spanish version ( 21 ) of the Minnesota Leisure Time Physical Activity Question naire ; and a 47-item question naire about education , lifestyle , history of illnesses , and medication use . We performed anthropometric and blood pressure measurements and obtained sample s of fasting blood and spot urine . We repeated all examinations at 3 months . The same dietitian delivered the interventions to the 3 r and omized groups in each center . On the basis of the assessment of individual Mediterranean diet scores , the dietitian gave personalized dietary advice during a 30-minute session to each participant , with recommendations on the desired frequency of intake of specific foods . We advised participants who were allocated to the low-fat diet to reduce intake of all types of fat , and we gave them a leaflet with written recommendations according to the American Heart Association guidelines ( 22 ) . For total fat intake , these recommendations were opposite to those given to participants in the 2 Mediterranean diet groups , who received instructions intended to increase the 14-item Mediterranean diet score , including increased consumption of vegetable fats and oils . We did not suggest any energy restriction . While the participants who were allocated to the low-fat diet did not receive further intervention , those assigned the 2 Mediterranean diet groups had access to more intense intervention in 2 ways . First , they were given a free provision of typical Mediterranean fatty foods ( olive oil or nuts ) . Depending on group assignment , participants were given either free virgin olive oil ( 15 L [ 1 L/wk ] for 3 months ) or free sachets of walnuts , hazelnuts , and almonds ( 1350 g of walnuts [ 15 g/d ] , 675 g of hazelnuts [ 7.5 g/d ] , and 675 g of almonds [ 7.5 g/d ] for 3 months ) . To improve adherence and account for family needs , participants in the corresponding Mediterranean diet groups were given excess olive oil or additional 1000-g packets of nuts . We analyzed the nutrient composition of the olive oil and nuts used in the study by st and ard methods in a reference laboratory ( Appendix Table 2 ) ) . Second , 1 week after inclusion , the dietitian delivered a 1-hour group session with up to 20 participants , with separate sessions for each Mediterranean diet group . Each group session consisted of informative talks and provision of written material s with elaborate descriptions of typical Mediterranean foods and seasonal shopping lists , meal plans , and cooking recipes . Throughout the study , all participants had free and continuous access to their center dietitian for advice and consultation . Measurements Trained personnel measured weight and height by using calibrated scales and a wall-mounted stadiometer , respectively ; waist circumference midway between the lowest rib and the iliac crest by using an anthropometric tape ; and blood pressure in triplicate with a vali date d semiautomatic oscillometer ( Omron HEM-705CP , Hoofddorp , the Netherl and s ) . We calculated energy and nutrient intake from Spanish food composition tables ( 23 ) . At the 3-month visit and when consulted by participants , dietitians assessed any adverse effects from the interventions by administering a checklist of symptoms and gave advice on how to remedy them . The checklist included mouth symptoms ; bloating , fullness , or indigestion ; altered bowel BACKGROUND Increased consumption of n-3 ( omega-3 ) fatty acids decreases the incidence of coronary heart disease ( CHD ) . OBJECTIVE The objective was to determine whether walnuts ( plant n-3 fatty acid ) and fatty fish ( marine n-3 fatty acid ) have similar effects on serum lipid markers at intakes recommended for primary prevention of CHD . DESIGN In a r and omized crossover feeding trial , 25 normal to mildly hyperlipidemic adults consumed 3 isoenergetic diets ( approximately 30 % total fat and < 10 % saturated fat ) for 4 wk each : a control diet ( no nuts or fish ) , a walnut diet ( 42.5 g walnuts/10.1 mJ ) , or a fish diet ( 113 g salmon , twice/wk ) . Fasting blood was drawn at baseline and at the end of each diet period and analyzed for serum lipids . RESULTS Serum total cholesterol and LDL cholesterol concentrations in adults who followed the walnut diet ( 4.87 + /- 0.18 and 2.77 + /- 0.15 mmol/L , respectively ) were lower than in those who followed the control diet ( 5.14 + /- 0.18 and 3.06 + /- 0.15 mmol/L , respectively ) and those who followed the fish diet ( 5.33 + /- 0.18 and 3.2 + /- 0.15 mmol/L , respectively ; P < 0.0001 ) . The fish diet result ed in decreased serum triglyceride and increased HDL-cholesterol concentrations ( 1.0 + /- 0.11 and 1.23 + /- 0.05 mmol/L , respectively ) compared with the control diet ( 1.12 + /- 0.11 and 1.19 + /- 0.05 mmol/L , respectively ) and the walnut diet ( 1.11 + /- 0.11 mmol/L , P < 0.05 , and 1.18 + /- 0.05 mmol/L , P < 0.001 , respectively ) . The ratios of total cholesterol : HDL cholesterol , LDL cholesterol : HDL cholesterol , and apolipoprotein B : apolipoprotein A-I were lower ( P < 0.05 ) in those who followed the walnut diet compared with those who followed the control and fish diets . CONCLUSION Including walnuts and fatty fish in a healthy diet lowered serum cholesterol and triglyceride concentrations , respectively , which affects CHD risk favorably BACKGROUND Low adiponectin levels are discussed as risk factor for cardiovascular events . This is of special importance in individuals with type 2 diabetes ( T2DM ) because they are at higher risk for cardiovascular diseases . The present study aim ed to investigate the effect of two plant oils rich in polyunsaturated fatty acids ( PUFA ) , with different content of omega-3 fatty acids , on adiponectin levels , glucose and lipid metabolism in T2DM individuals treated either with insulin or oral anti-diabetics ( OAD ) . METHODS Ninety-two subjects with T2DM [ 34 treated with insulin ( T2DM-Ins ) and 58 treated with OAD ( T2DM-OAD ) ] participated in this r and omised , double-blind , parallel intervention study . Individuals received either 9 g of nut oil ( n-3:n-6 ratio : 1.3 : 6.1 ) or mixed oil ( n-3:n-6 ratio : 0.6 : 5.7 ) per day for 10 weeks . The fatty acid profile , tocopherol , adiponectin levels and parameters regarding glucose and lipid metabolism were assessed at baseline , during and after the intervention . RESULTS Compliance was confirmed by significant increases in γ-tocopherol and PUFA in both oil groups . An increase in adiponectin levels in T2DM-Ins participants ( + 6.84 % in nut oil and + 4.47 % in mixed oil group after 10 weeks compared to baseline ) was observed , albeit not significantly different from T2DM-OAD individuals ( P = 0.051 ) . Lipid and glucose metabolism were not affected by the intervention . CONCLUSIONS The present study provides evidence that a small and easy change in dietary behaviour towards better fat quality moderately increases adiponectin levels in T2DM-Ins subjects , independently of the administered plant oil Background —Epidemiological studies suggest that nut intake decreases coronary artery disease ( CAD ) risk . Nuts have a cholesterol-lowering effect that partly explains this benefit . Endothelial dysfunction is associated with CAD and its risk factors and is reversed by antioxidants and marine n-3 fatty acids . Walnuts are a rich source of both antioxidants and & agr;-linolenic acid , a plant n-3 fatty acid . Methods and Results —To test the hypothesis that walnut intake will reverse endothelial dysfunction , we r and omized in a crossover design 21 hypercholesterolemic men and women to a cholesterol-lowering Mediterranean diet and a diet of similar energy and fat content  in which walnuts replaced ≈32 % of the energy from monounsaturated fat . Participants followed each diet for 4 weeks . After each intervention , we obtained fasting blood and performed ultrasound measurements of brachial artery vasomotor function . Eighteen subjects completing the protocol had suitable ultrasound studies . Compared with the Mediterranean diet , the walnut diet improved endothelium-dependent vasodilation and reduced levels of vascular cell adhesion molecule-1 ( P < 0.05 for both ) . Endothelium-independent vasodilation and levels of intercellular adhesion molecule-1 , C-reactive protein , homocysteine , and oxidation biomarkers were similar after each diet . The walnut diet significantly reduced total cholesterol ( −4.4±7.4 % ) and LDL cholesterol ( −6.4±10.0 % ) ( P < 0.05 for both ) . Cholesterol reductions correlated with increases of both dietary & agr;-linolenic acid and LDL & ggr;-tocopherol content , and changes of endothelium-dependent vasodilation correlated with those of cholesterol-to-HDL ratios ( P < 0.05 for all ) . Conclusions —Substituting walnuts for monounsaturated fat in a Mediterranean diet improves endothelium-dependent vasodilation in hypercholesterolemic subjects . This finding might explain the cardioprotective effect of nut intake beyond cholesterol lowering OBJECTIVE The aim of this study was to examine the effect of a moderate-fat diet inclusive of walnuts on blood lipid profiles in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS This was a parallel r and omized controlled trial comparing three dietary advice groups each with 30 % energy as fat : low fat , modified low fat , and modified low fat inclusive of 30 g of walnuts per day .  Fifty-eight men and women , mean age 59.3 + /- 8.1 years , started the trial . Dietary advice was given at baseline with monthly follow-up and fortnightly phone calls for support .  Body weight , percent body fat , blood lipids , HbA1c , total antioxidant capacity , and erythrocyte fatty acid levels were measured at 0 , 3 , and 6 months . Data were assessed by repeated- measures ANOVA with an intention-to-treat model . RESULTS The walnut group achieved a significantly greater increase in HDL cholesterol-to-total cholesterol ratio ( P=0.049 ) and HDL ( P=0.046 ) than the two other treatment groups . A 10 % reduction in LDL cholesterol was also achieved in the walnut group , reflecting a significant effect by group ( P=0.032 ) and time ( P=0.036 ) . There were no significant differences between groups for changes in body weight , percent body fat , total antioxidant capacity , or HbA1c levels . The higher dietary polyunsaturated fat-to-saturated fat ratio and intakes of omega-3 fatty acids in the walnut group were confirmed by erythrocyte biomarkers of dietary intake . CONCLUSIONS Structured " whole of diet " advice that included 30 g of walnuts/day delivering substantial amounts of polyunsaturated fatty acid improved the lipid profile of patients with type 2 diabetes BACKGROUND In a recent six-year follow-up study , we found that frequent consumption of nuts was associated with a reduced risk of ischemic heart disease .  To explore possible explanations for this finding , we studied the effects of nut consumption on serum lipids and blood pressure . METHODS We r and omly placed 18 healthy men on two mixed natural diets  , each diet to be followed for four weeks . Both diets conformed to the National Cholesterol Education Program Step 1 diet and contained identical foods and macronutrients , except that 20 percent of the calories of one diet ( the walnut diet ) were derived from walnuts ( offset by lesser amounts of fatty foods , meat , and visible fat [ oils , margarine , and butter ] ) . RESULTS With the reference diet , the mean ( + /- SD ) serum values for total , low-density lipoprotein ( LDL ) , and high-density lipoprotein ( HDL ) cholesterol were , respectively , 182 + /- 23 , 112 + /- 16 , and 47 + /- 11 mg per deciliter ( 4.71 + /- 0.59 , 2.90 + /- 0.41 , and 1.22 + /- 0.28 mmol per liter ) . With the walnut diet , the mean total cholesterol level was 22.4 mg per deciliter ( 0.58 mmol per liter ) lower than the mean level with the reference diet ( 95 percent confidence interval , 28 to 17 mg per deciliter [ 0.72 to 0.44 mmol per liter ] ) ; the LDL and HDL cholesterol levels were , respectively , 18.2 mg per deciliter ( 0.47 mmol per liter ) ( P < 0.001 ) and 2.3 mg per deciliter ( 0.06 mmol per liter ) ( P = 0.01 ) lower . These lower values represented reductions of 12.4 , 16.3 , and 4.9 percent in the levels of total , LDL , and HDL cholesterol , respectively . The ratio of LDL cholesterol to HDL cholesterol was also lowered ( P < 0.001 ) by the walnut diet .  Mean blood-pressure values did not change during either dietary period . CONCLUSIONS Incorporating moderate quantities of walnuts into the recommended cholesterol-lowering diet while maintaining the intake of total dietary fat and calories decreases serum levels of total cholesterol and favorably modifies the lipoprotein profile in normal men . The long-term effects of walnut consumption and the extension of this finding to other population groups deserve further study Epidemiologic studies and clinical trials have demonstrated that the unique fatty acid profile of nuts beneficially affects serum lipids/lipoproteins , reducing cardiovascular disease ( CVD ) risk .  Nuts are low in SFA and high in PUFA and monounsaturated fatty acids ( MUFA ) . Macadamia nuts are a rich source of MUFA . A r and omized , crossover , controlled feeding study ( 5-wk diet periods ) compared a Macadamia nut-rich diet [ 42.5 g ( 1.5 ounces)/8.79 MJ ( 2100 kcal ) ] [ MAC ; 33 % total fat ( 7 % SFA , 18 % MUFA , 5 % PUFA ) ] vs. an average American diet [ AAD ; 33 % total fat ( 13 % SFA , 11 % MUFA , 5 % PUFA ) ] on the lipid/lipoprotein profile of mildly hypercholesterolemic ( n = 25 ; 15 female , 10 male ) subjects .  Serum concentrations of total cholesterol ( TC ) and LDL cholesterol ( LDL-C ) following the MAC ( 4.94 + /- 0.17 mmol/L , 3.14 + /- 0.14 mmol/L ) were lower than the AAD ( 5.45 + /- 0.17 mmol/L , 3.44 + /- 0.14 mmol/L ; P < 0.05 ) . The serum non-HDL cholesterol ( HDL-C ) concentration and the ratios of TC : HDL-C and LDL-C : HDL-C were reduced following consumption of the MAC diet ( 3.83 + /- 0.17 , 4.60 + /- 0.24 , and 2.91 + /- 0.17 , respectively ) compared with the AAD ( 4.26 + /- 0.17 , 4.89 + /- 0.24 , and 3.09 + /- 0.18 , respectively ; P < 0.05 ) . There was no change in serum triglyceride concentration . Thus , macadamia nuts can be included in a heart-healthy dietary pattern that reduces lipid/lipoprotein CVD risk factors . Nuts as an isocaloric substitute for high SFA foods increase the proportion of unsaturated fatty acids and decrease SFA , thereby lowering CVD risk Background Compared with other common plant foods , walnuts ( Juglans regia ) are consistently ranked among the highest in antioxidant capacity . In vitro , walnut polyphenols inhibit plasma and LDL oxidation , while in animal models they lower biomarkers of oxidative stress and raise antioxidant capacity . A limited number of human feeding trials indicate that walnuts improve some measures of antioxidant status , but not others . Methods A 19 wk , r and omized crossover trial was conducted in 21 generally healthy men and postmenopausal women ≥50 y to study the dose-response effects of walnut intake on biomarkers of antioxidant activity , oxidative stress , and nutrient status . Subjects were r and omized to receive either 21 or 42 g raw walnuts/d during each 6 wk intervention phase with a 6 wk washout between phases . Subjects were instructed to consume their usual diet , but refrain from eating any other tree nuts , seeds , peanuts , or ellagitannin-rich foods during the entire study , and other polyphenol-rich foods for 2 d prior to each study visit . Results Compared to baseline levels , red blood cell ( RBC ) linoleic acid and plasma pyridoxal phosphate ( PLP ) were significantly higher after 6 wk with 42 g/d walnuts ( P < 0.05 for both ) . Overall , changes in plasma total thiols , and other antioxidant biomarkers , were not significant with either walnut dose . However , when compared to fasting levels , plasma total thiols were elevated within 1 h of walnut consumption with both doses during the baseline and end visits for each intervention phase ( P < 0.05 for all ) . Despite the observed increase in RBC linoleic and linolenic acids associated with walnut consumption , this substrate for lipid peroxidation only minimally affected malondialdehyde ( MDA ) and antioxidant capacity . The proportional changes in MDA and Oxygen Radical Absorbance Capacity ( ORAC ) were consistent with a dose-response effect , although no significant within- or between-group differences were observed for these measures . Conclusions Walnut consumption did not significantly change the plasma antioxidant capacity of healthy , well-nourished older adults in this pilot study . However , improvements in linoleic acid and pyridoxal phosphate were observed with chronic consumption , while total plasma thiols were enhanced acutely . Future studies investigating the antioxidant effects of walnuts in humans are warranted , but should include either a larger sample size or a controlled feeding intervention . Trial Registration Clinical Trials.gov : BACKGROUND The associations between specific types of nuts , specifically peanuts and walnuts , and cardiovascular disease remain unclear . OBJECTIVES The authors sought to analyze the associations between the intake of total and specific types of nuts and cardiovascular disease , coronary heart disease , and stroke risk . METHODS The authors included 76,364 women from the Nurses ' Health Study ( 1980 to 2012 ) , 92,946 women from the Nurses ' Health Study II ( 1991 to 2013 ) , and 41,526 men from the Health Professionals Follow-Up Study ( 1986 to 2012 ) who were free of cancer , heart disease , and stroke at baseline .  Nut consumption was assessed using food frequency question naires at baseline and was up date d every 4 years . RESULTS During 5,063,439 person-years of follow-up , the authors documented 14,136 incident cardiovascular disease cases , including 8,390 coronary heart disease cases and 5,910 stroke cases . Total nut consumption was inversely associated with total cardiovascular disease and coronary heart disease after adjustment for cardiovascular risk factors . The pooled multivariable hazard ratios for cardiovascular disease and coronary heart disease among participants who consumed 1 serving of nuts ( 28 g ) 5 or more times per week , compared with the reference category ( never or almost never ) , were 0.86 ( 95 % confidence interval : 0.79 to 0.93 ; p for trend = 0.0002 ) and 0.80 ( 95 % confidence interval : 0.72 to 0.89 ; p for trend < 0.001 ) , respectively . Consumption of peanuts and tree nuts ( 2 or more times/week ) and walnuts ( 1 or more times/week ) was associated with a 13 % to 19 % lower risk of total cardiovascular disease and 15 % to 23 % lower risk of coronary heart disease . CONCLUSIONS In 3 large prospect i ve cohort studies , higher consumption of total and specific types of nuts was inversely associated with total cardiovascular disease and coronary heart disease BACKGROUND AND AIMS Nuts have been demonstrated to improve several cardiovascular risk factors and the lipid profile in diabetic and pre-diabetic subjects . However , analysis of conventional serum lipid profiles does not completely explain the atherogenic risk associated with pre-diabetes . We therefore investigated whether chronic consumption of pistachio modifies the lipoprotein subclasses to a healthier profile in pre-diabetic subjects . METHODS AND RESULTS R and omized cross-over clinical trial in 54 subjects with pre-diabetes . Subjects consumed a pistachio-supplemented diet ( PD , 50 % carbohydrates , 33 % fat , including 57 g/d of pistachios daily ) and a control diet ( CD , 55 % carbohydrates , 30 % fat ) for 4 months each , separated by a 2-week wash-out . Diets were isocaloric and matched for protein , fiber and saturated fatty acids . Nuclear magnetic resonance ( NMR ) was performed to determine changes in plasma lipoprotein subclasses . Small low-density lipoprotein particles ( sLDL-P ) significantly decreased after pistachio consumption compared to the nut-free diet ( P = 0.023 ) . The non-high-density lipoprotein particles ( non-HDL-P i.e. VLDL-P plus LDL-P ) significantly decreased under the PD compared to CD ( P = 0.041 ) . The percentage of sHDL-P increased by 2.23 % after the PD compared with a reduction of 0.08 % after the CD ( P = 0.014 ) . Consequently , the overall size of HDL-P significantly decreased in the PD ( P = 0.007 ) . CONCLUSION Chronic pistachio consumption could modify the lipoprotein particle size and subclass concentrations independently of changes in total plasma lipid profile , which may help to explain the decreased risk of cardiovascular disease and mortality associated with those individuals who frequently consumed nuts . REGISTRATION NUMBER This study is registered at www . clinical trials.gov as NCT01441921 Background / Objectives : A large intake of walnuts may improve lipid profile and endothelial function . The effect of moderate walnut consumption is not known . We investigated whether a moderate intake of walnuts would affect lipid profile , arterial stiffness and platelet activation in healthy volunteers . Subjects/ Methods : A total of 30 healthy males were recruited into a single-blind r and omized controlled crossover trial of 4 weeks of dietary walnut supplementation ( 15 g/day ) and 4 weeks of control ( no walnuts ) . Arterial stiffness was assessed using pulse waveform analysis to determine the augmentation index and augmented pressure . Platelet activation was determined using flow cytometry to measure circulating platelet – monocyte aggregates . Results : There were no differences in lipid profile after 4 weeks of walnut supplementation compared with control . Dietary intake of α-linolenic acid was increased during the walnut diet ( 2.1±0.4 g/day versus 0.7±0.4 g/day , P<0.0001 ) . There were no differences in augmentation index or augmented pressure  during walnut supplementation . Walnut supplementation did not affect platelet – monocyte aggregation . Conclusions : Dietary intervention with a moderate intake of walnuts does not affect lipid profile , arterial stiffness or platelet activation in man . Our results suggest that the potentially beneficial cardiac effects of walnuts may not be apparent at lower and more practical levels of consumption Abstract Background Epidemiologic data suggest that diets rich in nuts have beneficial health effects , including reducing total and cause-specific mortality from cancer and heart disease . Although there is accumulating pre clinical evidence that walnuts beneficially affect the gastrointestinal microbiota and gut and metabolic health , these relations have not been investigated in humans . Objective We aim ed to assess the impact of walnut consumption on the human gastrointestinal microbiota and metabolic markers of health . Methods A controlled-feeding , r and omized crossover study was undertaken in healthy men and women [ n = 18 ; mean age = 53.1 y ; body mass index ( kg/m2 ) : 28.8 ] . Study participants received isocaloric diets containing 0 or 42 g walnuts/d for two 3-wk periods , with a 1-wk washout between diet periods .  Fecal and blood sample s were collected at baseline and at the end of each period to assess secondary outcomes of the study , including effects of walnut consumption on fecal microbiota and bile acids and metabolic markers of health . Results Compared with after the control period , walnut consumption result ed in a 49–160 % higher relative abundance of Faecalibacterium , Clostridium , Dialister , and Roseburia and 16–38 % lower relative abundances of Ruminococcus , Dorea , Oscillospira , and Bifidobacterium ( P < 0.05 ) . Fecal secondary bile acids , deoxycholic acid and lithocholic acid , were 25 % and 45 % lower , respectively , after the walnut treatment compared with the control treatment ( P < 0.05 ) . Serum LDL cholesterol and the noncholesterol sterol campesterol concentrations were 7 % and 6 % lower , respectively , after walnut consumption compared with after the control treatment ( P < 0.01 ) . Conclusion Walnut consumption affected the composition and function of the human gastrointestinal microbiota , increasing the relative abundances of Firmicutes species in butyrate-producing Clostridium clusters XIVa and IV , including Faecalibacterium and Roseburia , and reducing microbially derived , proinflammatory secondary bile acids and LDL cholesterol . These results suggest that the gastrointestinal microbiota may contribute to the underlying mechanisms of the beneficial health effects of walnut consumption . This trial was registered at www . clinical trials.gov as NCT01832909 BACKGROUND Inflammation is crucial in all stages of atherosclerosis , and few studies have investigated the effect of dietary fat on markers of inflammation related to this disease during the postpr and ial period . OBJECTIVE To evaluate the chronic effects of dietary fat on the postpr and ial expression of proinflammatory genes in peripheral blood mononuclear cells ( P BMC s ) in healthy subjects . DESIGN 20 healthy men followed three different diets for 4 weeks each , according to a r and omized crossover design : Western diet : 15 % protein , 47 % carbohydrates ( CHO ) , 38 % fat ( 22 % saturated fatty acid ( SFA ) ) ; Mediterranean diet : 15 % protein , 47 % CHO , 38 % fat ( 24 % monounsaturated fatty acid ( MUFA ) ) ; CHO-rich and n-3 diet : 15 % protein , 55 % CHO , < 30 % fat ( 8 % polyunsaturated fatty acid ( PUFA ) ) . After 12-h fast , volunteers were given a breakfast with a fat composition similar to that consumed in each of the diets-butter breakfast : 35 % SFA ; olive oil breakfast : 36 % MUFA ; walnut breakfast : 16 % PUFA , 4 % alpha-linolenic acid ( LNA ) . RESULTS The butter breakfast induced a higher increase in tumor necrosis factor (TNF)-alpha messenger RNA ( mRNA ) expression than the olive oil or walnut breakfasts ( P=0.014 ) in P BMC s. Moreover , we found a higher postpr and ial response in the mRNA of interleukin (IL)-6 with the intake of butter and olive oil breakfasts than with the walnut breakfast ( P=0.025 ) in these cells . However , the effects of the three fatty breakfasts on the plasma concentrations of these proinflammatory parameters showed no significant differences ( P = N.S. ) . CONCLUSION Consumption of a butter-enriched meal elicits greater postpr and ial expression of proinflammatory cytokine mRNA in P BMC s , compared to the olive oil and walnut breakfasts In a r and omized , cross-over feeding trial involving 10 men with polygenic hypercholesterolemia , a control , Mediterranean-type cholesterol-lowering diet , and a diet of similar composition in which walnuts replaced approximately 35 % of energy from unsaturated fat , were given for 6 weeks each . Compared with the control diet , the walnut diet reduced serum total and LDL cholesterol by 4.2 % ( P = 0.176 ) , and 6.0 % ( P = 0.087 ) , respectively . No changes were observed in HDL cholesterol , triglycerides , and apolipoprotein A-I levels or in the relative proportion of protein , triglycerides , phospholipids , and cholesteryl esters in LDL particles . The apolipoprotein B level declined in parallel with LDL cholesterol ( 6.0 % reduction ) . Whole LDL , particularly the triglyceride fraction , was enriched in polyunsaturated fatty acids from walnuts ( linoleic and alpha-linolenic acids ) . In comparison with LDL obtained during the control diet , LDL obtained during the walnut diet showed a 50 % increase in association rates to the LDL receptor in human hepatoma HepG2 cells . LDL uptake by HepG2 cells was correlated with alpha-linolenic acid content of the triglyceride plus cholesteryl ester fractions of LDL particles ( r(2 ) = 0.42 , P < 0.05 ) . Changes in the quantity and quality of LDL lipid fatty acids after a walnut-enriched diet facilitate receptor-mediated LDL clearance and may contribute to the cholesterol-lowering effect of walnut consumption Abstract Purpose The aim of the study was to investigate the influence of foods enriched with vegetable oils varying in their n-3 polyunsaturated fatty acids profile on  cardiovascular risk factors for hypertriglyceridemic subjects . Methods Fifty-nine hypertriglyceridemic subjects ( triglycerides ≥ 1.5 mmol/L ) were included in the r and omized , double-blind , placebo-controlled , crossover study . The placebo group received sunflower oil [ linoleic acid ( LA ) group ; 10 g LA/day ] . The intervention groups received linseed oil [ α-linolenic acid ( ALA ) group ; 7 g ALA/day ] , echium oil [ stearidonic acid ( SDA ) group ; 2 g SDA/day ] or microalgae oil [ docosahexaenoic acid ( DHA ) group ; 2 g DHA/day ] over 10 weeks . Blood sample s were collected at baseline and at the end of each period . Results Total cholesterol ( TC ) and low-density-lipoprotein cholesterol decreased significantly in the LA and ALA groups ( LA : P ≤ 0.01 , ALA : P ≤ 0.05 ) . No changes in blood lipids were observed in the SDA group . Significant increases in TC and high-density-lipoprotein cholesterol occurred in the DHA group ( P ≤ 0.05 ) . In the ALA and SDA groups , the content of eicosapentaenoic acid in erythrocyte lipids increased significantly ( P ≤ 0.05 ) after 10 weeks ( ALA group : 38 ± 37 % , SDA group : 73 ± 59 % ) . Conclusion Foods enriched with different vegetable oils rich in ALA or SDA are able to increase the n-3 long-chain polyunsaturated fatty acids content in erythrocyte lipids ; echium oil is more potent in comparison with linseed oil . Blood lipids were beneficially modified through the consumption of food products enriched with sunflower , linseed and microalgae oils , whereas echium oil did not affect blood lipids . Clinical Trials.gov : NCT01437930 Regular walnut consumption is associated with  better health . We have previously shown that eight weeks of walnut consumption ( 43 g/day ) significantly improves  lipids in healthy subjects . In the same study , gut microbiome was evaluated . We included 194 healthy subjects ( 134 females , 63 ± 7 years , BMI 25.1 ± 4.0 kg/m2 ) in a r and omized , controlled , prospect i ve , cross-over study . Following a nut-free run-in period , subjects were r and omized to two diet phases ( eight weeks each ) ; 96 subjects first followed a walnut-enriched diet ( 43 g/day ) and then switched to a nut-free diet , while 98 subjects followed the diets in reverse order . While consuming the walnut-enriched diet , subjects were advised to either reduce fat or carbohydrates or both to account for the additional calories . Fecal sample s were collected from 135 subjects at the end of the walnut-diet and the control-diet period for microbiome analyses . The 16S rRNA gene sequencing data was clustered with a 97 % similarity into Operational Taxonomic Units ( OTUs ) . UniFrac distances were used to determine diversity between groups . Differential abundance was evaluated using the Kruskal – Wallis rank sum test . All analyses were performed using Rhea . Generalized UniFrac distance shows that walnut consumption significantly affects microbiome composition and diversity . Multidimensional scaling ( metric and non-metric ) indicates dissimilarities of approximately 5 % between walnut and control ( p = 0.02 ) . The abundance of Ruminococcaceae and Bifidobacteria increased significantly ( p < 0.02 ) while Clostridium sp. cluster XIVa species ( Blautia ; Anaerostipes ) decreased significantly ( p < 0.05 ) during walnut consumption . The effect of walnut consumption on the microbiome only marginally depended on whether subjects replaced fat , carbohydrates or both while on walnuts . Daily intake of 43 g walnuts over eight weeks significantly affects the gut microbiome by enhancing probiotic- and butyric acid-producing species in healthy individuals . Further evaluation is required to establish whether these changes are preserved during longer walnut consumption and how these are linked to the observed changes in lipid metabolism
Overall , high-walnut-enriched diets significantly decreased total and LDL cholesterol for the duration of the short-term trials .
BACKGROUND Consumption of nuts has been associated with a decreased risk of  cardiovascular disease events  and death .
Walnuts in particular have a unique profile : they are rich in polyunsaturated fatty acids , which may improve blood lipids and other cardiovascular disease risk factors .
OBJECTIVES We aim ed to conduct a literature review and a meta- analysis to combine the results from several trials and to estimate the effect of walnuts on blood lipids .