human
***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: BACKGROUND Atherosclerosis is a chronic inflammatory disease . We previously reported that a diet high in alpha-linolenic acid ( ALA ) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects . OBJECTIVE The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells ( P BMC s ) from subjects fed the experimental diets . DESIGN A r and omized , controlled , 3-diet , 3-period crossover study design was used . Hypercholesterolemic subjects ( n = 23 ) were assigned to 3 experimental diets : a diet high in ALA ( ALA diet ; 6.5 % of energy ) , a diet high in linoleic acid ( LA diet ; 12.6 % of energy ) , and an average American diet ( AAD ) for 6 wk . Serum interleukin (IL)-6 , IL-1beta , and tumor necrosis factor-alpha ( TNF-alpha ) concentrations and the production of IL-6 , IL-1beta , and TNF-alpha by P BMC s were measured . RESULTS IL-6 , IL-1beta , and TNF-alpha production by P BMC s and serum TNF-alpha concentrations were lower ( P < 0.05 and P < 0.08 , respectively ) with the ALA diet than with the LA diet or AAD .  P BMC production of TNF-alpha was inversely correlated with ALA ( r = -0.402 , P = 0.07 ) and with eicosapentaenoic acid ( r = -0.476 , P = 0.03 ) concentrations in P BMC lipids with the ALA diet . Changes in serum ALA were inversely correlated with changes in TNF-alpha produced by P BMC s ( r = -0.423 , P < 0.05 ) . CONCLUSIONS Increased intakes of dietary ALA elicit antiinflammatory effects by inhibiting IL-6 , IL-1beta , and TNF-alpha production in cultured P BMC s. Changes in P BMC ALA and eicosapentaenoic acid ( derived from dietary ALA ) are associated with beneficial changes in TNF-alpha release . Thus , the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines 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 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 (  
    Output:
    
agent
Overall , high-walnut-enriched diets significantly decreased total and LDL cholesterol for the duration of the short-term trials .
***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: BACKGROUND Atherosclerosis is a chronic inflammatory disease . We previously reported that a diet high in alpha-linolenic acid ( ALA ) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects . OBJECTIVE The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells ( P BMC s ) from subjects fed the experimental diets . DESIGN A r and omized , controlled , 3-diet , 3-period crossover study design was used . Hypercholesterolemic subjects ( n = 23 ) were assigned to 3 experimental diets : a diet high in ALA ( ALA diet ; 6.5 % of energy ) , a diet high in linoleic acid ( LA diet ; 12.6 % of energy ) , and an average American diet ( AAD ) for 6 wk . Serum interleukin (IL)-6 , IL-1beta , and tumor necrosis factor-alpha ( TNF-alpha ) concentrations and the production of IL-6 , IL-1beta , and TNF-alpha by P BMC s were measured . RESULTS IL-6 , IL-1beta , and TNF-alpha production by P BMC s and serum TNF-alpha concentrations were lower ( P < 0.05 and P < 0.08 , respectively ) with the ALA diet than with the LA diet or AAD .  P BMC production of TNF-alpha was inversely correlated with ALA ( r = -0.402 , P = 0.07 ) and with eicosapentaenoic acid ( r = -0.476 , P = 0.03 ) concentrations in P BMC lipids with the ALA diet . Changes in serum ALA were inversely correlated with changes in TNF-alpha produced by P BMC s ( r = -0.423 , P < 0.05 ) . CONCLUSIONS Increased intakes of dietary ALA elicit antiinflammatory effects by inhibiting IL-6 , IL-1beta , and TNF-alpha production in cultured P BMC s. Changes in P BMC ALA and eicosapentaenoic acid ( derived from dietary ALA ) are associated with beneficial changes in TNF-alpha release . Thus , the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines 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 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 (  
    Output:
    