***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In 46 elderly ( aged greater than or equal to 60 y ) hypertensive subjects with entry systolic blood pressure ( SBP ) greater than or equal to 160 or diastolic blood pressure ( DBP ) greater than or equal to 90 mm Hg , our specific aim in a r and omized , double-blind , crossover study ( two 8-wk treatment periods separated by a 3-wk washout ) was to compare blood pressure-lowering effects of 9 g fish oil/d [ omega-3 ( n-3 ) fatty acid ] vs 9 g corn oil/d [ omega-6 ( n-6 ) fatty acid ] . After a 4-wk baseline period , 22 subjects were r and omly assigned to receive fish oil and 24 to receive corn oil . For both 8-wk treatments there were no between-group differences in the change in blood pressure . There was a treatment difference for st and ing DBP when baseline values were compared with those after treatment 2 ; DBP decreased by 5.1 mm Hg in the fish-oil group vs 0.72 mm Hg in the corn-oil group ( P = 0.024 ) . Within groups during the first treatment , both fish oil and corn oil lowered all four blood pressure measures ( P less than 0.05 ) ; blood pressures were not further lowered during the second treatment compared with the washout period . There were no significant between-group differences in laboratory safety tests or categorical side effects .  Fish oil lowered triglycerides by 0.47 mmol/L ( P less than 0.001 ) . In elderly subjects , diet plus both omega-3 and omega-6 supplements ( 9 g/d ) safely and effectively lower SBP and DBP Dietary adherence to four different fat-modified diets was examined in 160 subjects by determining the fatty acid composition of serum cholesterol esters ( CEs ) and erythrocyte ( ER ) and platelet ( PT ) membranes in addition to food records . Subjects were r and omly assigned to one of the following diet groups : 1 ) high-sat--35/14:104 ( % of energy from total/saturated : monounsaturated : polyunsaturated fatty acids in the actual diet ) 2 ) AHA ( American Heart Association ) type--32/10:8:8 3 ) monoene-enriched--34/11:11:5 , or 4 ) low-fat--30/12:8:3 for 6 mo . Decreases in the proportions of palmitic acid in CEs were found in the AHA-type and monoene-enriched-diet groups . An increased proportion of linoleic acid in CEs was found in the AHA-type group . The differences in the proportions of palmitic acid in CEs and linoleic and palmitoleic acids in PTs were significant in the AHA-type and monoene-enriched-diet groups compared with the high-sat group . An increase in alpha-linolenic acid in CEs was an indicator of the use of low erucic acid rapeseed oil , which was the main source of monoenes in the monoene-enriched-diet group We tested the specificity of the plasma cholesterol-lowering effect of linoleic acid in a comparison of linoleate-rich and saturated fatty acid-rich foods .  Twelve mildly hypercholesterolemic men and women ate the two diets for three weeks each in a r and om cross-over design , after a two-week baseline period . A linoleic acid-rich supplement was added to the baseline diet so that the saturated and monounsaturated fatty acid content did not change significantly . Despite the consequent increase in total fat intake , the linoleate-rich diet ( 23 per cent energy from polyunsaturated fatty acids ) significantly lowered plasma total and low-density lipoprotein ( LDL ) cholesterol (-8 per cent and -14 per cent respectively ) , while high-density lipoprotein ( HDL ) cholesterol rose 8 per cent . The direction of these changes was similar in all 12 subjects . Compared with a supplement that raised dietary saturated fatty acids to 30 per cent energy , the linoleate acid-rich diet gave lower total cholesterol ( -14 per cent ) , LDL cholesterol ( -18 per cent ) and HDL cholesterol ( -12 per cent ) concentrations . Linoleic acid lowers LDL cholesterol even when saturated fatty acids are not significantly displaced and substantially more when there is such displacement BACKGROUND Replacing SFAs with vegetable PUFAs has cardiometabolic benefits , but the effects on liver fat are unknown . Increased dietary n-6 PUFAs have , however , also been proposed to promote inflammation-a yet unproven theory . OBJECTIVE We investigated the effects of PUFAs on liver fat , systemic inflammation , and metabolic disorders . DESIGN We r and omly assigned 67 abdominally obese subjects ( 15 % had type 2 diabetes ) to a 10-wk isocaloric diet high in vegetable n-6 PUFA ( PUFA diet ) or SFA mainly from butter ( SFA diet ) , without altering the macronutrient intake . Liver fat was assessed by MRI and magnetic resonance proton ( 1H ) spectroscopy ( MRS ) . Proprotein convertase subtilisin/kexin type-9 ( PCSK9 , a hepatic LDL-receptor regulator ) , inflammation , and adipose tissue expression of inflammatory and lipogenic genes were determined . RESULTS A total of 61 subjects completed the study .  Body weight modestly increased but was not different between groups . Liver fat was lower during the PUFA diet than during the SFA diet [ between-group difference in relative change from baseline ; 16 % ( MRI ; P < 0.001 ) , 34 % ( MRS ; P = 0.02 ) ] . PCSK9 ( P = 0.001 ) , TNF receptor-2 ( P < 0.01 ) , and IL-1 receptor antagonist ( P = 0.02 ) concentrations were lower during the PUFA diet , whereas insulin ( P = 0.06 ) tended to be higher during the SFA diet . In compliant subjects ( defined as change in serum linoleic acid ) , insulin , total/HDL-cholesterol ratio , LDL cholesterol , and triglycerides were lower during the PUFA diet than during the SFA diet ( P < 0.05 ) . Adipose tissue gene expression was unchanged . CONCLUSIONS Compared with SFA intake , n-6 PUFAs reduce liver fat and modestly improve metabolic status , without weight loss . A high n-6 PUFA intake does not cause any signs of inflammation or oxidative stress . Downregulation of PCSK9 could be a novel mechanism behind the cholesterol-lowering effects of PUFAs . This trial was registered at clinical trials.gov as NCT01038102 Breast cancer is the most common cancer in women . Controversy exists regarding the role of dietary fat in breast cancer etiology . We investigated the association of dietary polyunsaturated fatty acids ( PUFAs ) and the ratio of n‐6 PUFAs to marine‐derived n‐3 PUFAs with  breast cancer risk in the Shanghai Women 's Health Study , a prospect i ve cohort study including 72,571 cancer‐free participants at baseline .  Dietary fatty acid intake was determined using food frequency question naires . We used Cox proportional hazards analysis to estimate the relative risks ( RRs ) and 95 % confidence intervals ( CIs ) for the association of breast cancer risk with dietary fatty acids consumption . In 583,998 person‐years of follow‐up , we identified 712 breast cancer cases . We found no association of breast cancer risk to dietary intake of linoleic acid , arachidonic acid , α‐linolenic acid or marine‐derived n‐3 PUFA . We found a statistically significant interaction between n‐6 PUFA intake , marine‐derived n‐3 PUFA intake and breast cancer risk ( p = 0.008 ) . Women with lower intake ( the lowest tertile ) of marine‐derived n‐3 PUFA and higher intake ( the highest tertile ) of n‐6 PUFA had an increase risk for breast cancer ( RR = 2.06 ; 95 % CI = 1.27–3.34 ) compared to women with higher intake ( the highest tertile ) of marine‐derived n‐3 PUFAs and lower intake ( the lowest tertile ) of n‐6 PUFAs after adjusting for potential confounders . The relative amounts of n‐6 PUFA to marine‐derived n‐3 PUFAs may be more important for breast cancer risk than individual dietary amounts of these fatty acids Objective : To examine , in free-living adults eating self-selected diets , the effects on plasma cholesterol of substituting saturated fat rich foods with either n-6 polyunsaturated or monounsaturated fat rich foods while at the same time adhering to a total fat intake of 30–33 % of dietary energy . Design : Two r and omised crossover trials . Setting : General community . Subjects : Volunteer sample of healthy free-living nutrition students at the University of Otago . Trial I , n=29 ; and trial II , n=42 . Interventions : In trials I and II participants were asked to follow for 2½ weeks a diet high in saturated fat yet with a total fat content that conformed to nutrition recommendations ( 30–33 % energy ) . During the 2 1/2 week comparison diet , saturated fat rich foods were replaced with foods rich in n-6 polyunsaturated fats ( trial I ) whereas in trial II the replacement foods were rich in monounsaturated fats . Participants were asked to maintain a total fat intake of 30–33 % of energy on all diets . Main outcome measures : Energy and nutrient intakes , plasma triglyceride fatty acids , and plasma cholesterol . Results : When replacing saturated fat with either n-6 polyunsaturated fat or monounsaturated fat , total fat intakes decreased by 2.9 % energy and 5.1 % energy , respectively . Replacing saturated fat with n-6 polyunsaturated fat ( trial I ) lowered plasma total cholesterol by 19 % [ from 4.87 ( 0.88 ) to 3.94 ( 0.92 ) mmol/l , mean ( s.d . ) ] , low density lipoprotein cholesterol by 22 % [ from 2.87 ( 0.75 ) to 2.24 ( 0.67 ) mmol/l ] , and high density lipoprotein cholesterol by 14 % [ from 1.39 ( 0.36 ) to 1.19 ( 0.34 ) mmol/l ] , whereas replacing saturated fat with monounsaturated fat ( trial II ) decreased total cholesterol by 12 % , low density lipoprotein cholesterol by 15 % , and high density lipoprotein cholesterol by 4 % , respectively . The change in the ratio of total to high density lipoprotein cholesterol was similar during trial I and trial II . Conclusions : Young adults are very responsive to dietary-induced changes in plasma cholesterol even when an isocaloric replacement of saturated fat with n-6 polyunsaturated or monounsaturated fat is not achieved . Replacing saturated fat with either n-6 polyunsaturated or monounsaturated fat is equally efficacious at reducing the total to high density lipoprotein cholesterol ratio . Sponsorship : University of Otago , Meadow Lea Ltd . European Journal of Clinical Nutrition ( 2001 ) 55 , BACKGROUND n-3 ( omega-3 ) PUFA has been proposed as having health-promoting effects , primarily in relation to ischemic heart disease ( IHD ) . Whether these benefits can be achieved by both α-linolenic acid ( ALA , 18:3n-3 ) and n-3 long-chain PUFA ( LC-PUFA ) is debatable . OBJECTIVE The objective was to examine the association between ALA intake and risk of IHD  in healthy subjects and to see if this was modified by intake of n-3 LC-PUFA or linoleic acid ( LA , 18:2 n-6 ) . DESIGN This was a prospect i ve cohort study of 3277 healthy Danish women and men free of known IHD . RESULTS Four hundred seventy-one cases of IHD were observed during a median follow-up period of 23.3 y. Higher intake of ALA was not significantly associated with decreased risk of IHD among women or men . Although the HR of IHD was stepwise decreased with increasing ALA intake in men [ 0.84 ( 95 % CI : 0.62 , 1.14 ) in the medium compared with the lowest tertile ( reference ) and 0.83 ( 95 % CI : 0.56 , 1.24 ) in the highest compared with the lowest tertile ] , this change was far from significant ( P-trend : 0.39 ) . No evidence of effect modification by n-3 LC-PUFA or LA was observed . High n-3 LC-PUFA intake , in comparison with low intake , was inversely associated with risk of IHD ; this trend was significant in women ( P = 0.04 ; HR : 0.62 ; 95 % CI : 0.40 , 0.97 ) but not in men ( P = 0.15 ; H 
    Output:
    
In prospect i ve observational studies , dietary LA intake is inversely associated with CHD risk in a dose-response manner .