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 Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes , such as chronic daily headache ( CDH ) . High intakes of the omega-6 ( n-6 ) polyunsaturated fatty acids ( PUFAs ) , linoleic acid ( LA ) and arachidonic acid ( AA ) may promote physical pain by increasing the abundance , and subsequent metabolism , of LA and AA in immune and nervous system tissues . Here we describe methodology for an ongoing r and omized clinical trial comparing the metabolic and clinical effects of a low n-6 , average n-3 PUFA diet , to the effects of a low n-6 plus high n-3 PUFA diet , in patients with CDH . Our primary aim is to determine if : A ) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools , compared to baseline ; and B ) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs , compared to the low n-6 diet alone . Secondary clinical outcomes include headache-specific quality -of-life , and headache frequency and intensity .  Methods Adults meeting the International Classification of Headache Disorders criteria for CDH are included . After a 6-week baseline phase , participants are r and omized to a low n-6 diet , or a low n-6 plus high n-3 diet , for 12 weeks . Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day . A research dietitian provides intensive dietary counseling at 2-week intervals . Web-based intervention material s complement dietitian advice . Blood and clinical outcome data are collected every 4 weeks . Results Subject recruitment and retention has been excellent ; 35 of 40 r and omized participants completed the 12-week intervention . Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA , AA and % n-6 in HUFA , and increases in n-3 EPA , DHA and the omega-3 index , indicating adherence . Trial Registration Clinical Trials.gov ( NCT01157208 Few trials have evaluated the metabolic effects and health outcomes of lowering dietary n-6 PUFA . The objectives of the present paper were ( 1 ) to report the methods employed to lower dietary n-6 PUFA , while either increasing or maintaining n-3 PUFA intake and ( 2 ) to vali date our methods with 24 h recalls and erythrocyte fatty acid analyses . A total of sixty-seven subjects were r and omised to either ( 1 ) an average-n-3 PUFA , low-n-6 PUFA ( L6 ) intervention design ed to lower linoleic acid ( LA ; # 2·5 % of energy ( en% ) ) and arachidonic acid ( # 60 mg/d ) , while maintaining an average US intake of n-3 PUFA or ( 2 ) a high-n-3 PUFA , low-n-6 PUFA ( H3-L6 ) intervention design ed to lower n-6 LA , while increasing the n-3 PUFA a-linolenic acid ( ALA ; $ 1·5 en% ) and EPA þ DHA ( $ 1000 mg/d ) . Pre- and intraintervention nutrient intakes were estimated with six 24 h dietary recalls per subject . Both groups achieved the targeted reductions in dietary LA to # 2·5 en% ( median LA 2·45 ( 2·1 , 3·1 ) ; P,0·001 ) . Intakes of n-3 PUFA did not change for the L6 group . Target increases in n-3 ALA ( median 1·6 en% , ( 1·3 , 2·0 ) , P,0·001 ) and EPA þ DHA ( 1482 mg , ( 374 , 2558 ) , P,0·001 ) were achieved in the H3-L6 group . Dietary changes were vali date d by corresponding changes in erythrocyte n-6 and n-3 fatty acid composition . Dietary LA can be lowered to # 2·5 en% , with or without concurrent increases in dietary n-3 PUFA , in an outpatient clinical trial setting using this integrated diet method This study assessed the metabolic response to sweetened dried cranberries ( SDC ) , raw cranberries ( RC ) , and white bread ( WB ) in humans with type 2 diabetes . Development of palatable cranberry preparations associated with lower glycemic responses may be useful for improving fruit consumption and glycemic control among those with diabetes . In this trial , type 2 diabetics ( n= 13 ) received WB ( 57 g , 160 cal , 1 g fiber ) , RC ( 55 g , 21 cal , 1 g fiber ) , SDC ( 40 g , 138 cal , 2.1 g fiber ) , and SDC containing less sugar ( SDC-LS , 40 g , 113 cal , 1.8 g fiber + 10 g polydextrose ) . Plasma glucose ( mmol/L ) peaked significantly at 60 min for WB , and at 30 min for RC , SDC , and SDC-LS at 9.6 ± 0.4 , 7.0 ± 0.4 , 9.6 ± 0.5 , and 8.7 ± 0.5 , respectively , WB remained significantly elevated from the other treatments at 120 min . Plasma insulin ( pmol/mL ) peaked at 60 min for WB and SDC and at 30 min for RC and SDC-LS at 157 ± 15 , 142 ± 27 , 61 ± 8 , and 97 ± 11 , respectively . Plasma insulin for SDC-LS was significantly lower at 60 min than either WB or SDC . Insulin area under the curve ( AUC ) values for RC and SDC-LS were both significantly lower than WB or SDC . Phenolic content of SDC and SDC-LS was determined following extraction with 80 % acetone prior to high-performance liquid chromatography ( HPLC ) and electronspray ionization-mass spectrometry ( ESI-MS ) and found to be rich in 5-caffeoylquinic cid , quercetin-3-galactoside , and quercetin-3-galactoside , and the proanthocyanidin dimer epicatechin . In conclusion , SDC-LS was associated with a favorable glycemic and insulinemic response in type 2 diabetics . Practical Application : This study compares phenolic content and glycemic responses among different cranberry products . The study seeks to exp and the palatable and portable healthy food choices for persons with type 2 diabetes . The novel use of polydextrose as a bulking agent making possible a reduction in caloric content and potential glycemic response is also characterized in this study Given the conflicting results about the positive effects of magnesium and l-carnitine and as there is no report concerning concurrent supplementation of magnesium and l-carnitine on migraine prophylaxis , the effects of magnesium , l-carnitine , and concurrent magnesium – l-carnitine supplementation on migraine indicators were assessed . In this clinical trial , 133 migrainous patients were r and omly assigned into three intervention groups : magnesium oxide ( 500 mg/day ) , l-carnitine ( 500 mg/day ) , and Mg – l-carnitine ( 500 mg/day magnesium and 500 mg/day l-carnitine ) , and a control group . After 12 weeks of supplementation , the checklist of migraine indicators including migraine attacks/month , migraine days/month , and headache severity was completed , and serum concentrations of magnesium and l-carnitine were measured by atomic absorption spectrophotometry and enzymatic UV test , respectively . The results showed a significant reduction in all migraine indicators in all studied groups ( p < 0.05 ) . The ANOVA results showed a significant reduction in migraine frequency across various supplemented and control groups ( p = 0.008 ) . By separating the effects of magnesium supplementation from other confounding factors such as routine treatments using the repeated measures and nested model , it was clarified that magnesium supplementation had a significant effect on all migraine indicators . Oral supplementation with magnesium oxide and l-carnitine and concurrent supplementation of Mg – l-carnitine besides routine treatments could be effective in migraine prophylaxis ; however , larger trials are needed to confirm these preliminary findings BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( < or = 3 months ) myocardial infa rct ion were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration Migraine is a common condition among adults and has become increasingly more recognised as a common condition among children and adolescents . When headaches are frequent or disabling , preventative treatments are indicated . Few studies have addressed the effectiveness of preventative treatments in children and adolescents in a controlled manner . Due to a concern of potential adverse risks , parents are often reluctant to start prophylactic medications and inquire about the use of alternative treatments including vitamin supplementation . Vitamins , in general , are viewed as more ‘ natural ’ and may be involved in the biological pathways underlying migraine . The use of nutraceutical treatment for migraine is a favourable option because they are essentially well tolerated with minimal side effects . Several nutraceuticals have been studied in the literature with some showing positive results in adult patients with migraine ( 1 ) ; however , studies in children and adolescents are scarce with none showing favourable outcomes . As children and adolescents are increasingly diagnosed with migraine , the need for prophylactic or preventative treatment is warranted . Therefore , it is important that headache clinicians and research ers treating paediatric migraine explore therapies that are safe , effective and affordable . Riboflavin , or vitamin B2 , is a co-factor used in mitochondrial function and has been shown to be effective in children with mitochondrial disorders with mild side effects ( 2 ) . In order to achieve this , high doses were required to overcome the mitochondrial impairment . In the pathogenesis of migraine , riboflavin is believed to be a major co-factor in oxidative metabolism as it acts as a precursor to flavin compounds involved in electron transport and generation of energy in the mitochondria ( 3,4 ) . Thus , in theory , low riboflavin levels may be associated with mitochondrial dysfunction linked to migraine . Several studies have shown efficacy and tolerability of riboflavin in migraine prevention in adults ( 5,6 ) ; however . MacLennan et al. ( 7 ) were the first to study the efficacy of high-dose riboflavin ( at least 200mg/day ) in  migraine prevention in children . The results did not show any difference in those who received treatment with riboflavin compared to placebo – although the placebo rate was high . A subsequent , open-label , retrospective study examining high-dose riboflavin in children and adolescents with migraine who failed pharmacological preventative therapy suggested that riboflavin may be effective in migraine , with a more favourable response in boys ( 8) . This sample population was notable for more individuals with severe migraine . A r and omised , placebocontrolled study of a combination of high-dose riboflavin , magnesium and feverfew using low-dose riboflavin ( 25 mg ) , found no difference between high-dose and low-dose riboflavin with equivalent responses ( 9 ) . The study by Bruijn et al. ( 10 ) 
    Output:
    
agent
***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 Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes , such as chronic daily headache ( CDH ) . High intakes of the omega-6 ( n-6 ) polyunsaturated fatty acids ( PUFAs ) , linoleic acid ( LA ) and arachidonic acid ( AA ) may promote physical pain by increasing the abundance , and subsequent metabolism , of LA and AA in immune and nervous system tissues . Here we describe methodology for an ongoing r and omized clinical trial comparing the metabolic and clinical effects of a low n-6 , average n-3 PUFA diet , to the effects of a low n-6 plus high n-3 PUFA diet , in patients with CDH . Our primary aim is to determine if : A ) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools , compared to baseline ; and B ) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs , compared to the low n-6 diet alone . Secondary clinical outcomes include headache-specific quality -of-life , and headache frequency and intensity .  Methods Adults meeting the International Classification of Headache Disorders criteria for CDH are included . After a 6-week baseline phase , participants are r and omized to a low n-6 diet , or a low n-6 plus high n-3 diet , for 12 weeks . Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day . A research dietitian provides intensive dietary counseling at 2-week intervals . Web-based intervention material s complement dietitian advice . Blood and clinical outcome data are collected every 4 weeks . Results Subject recruitment and retention has been excellent ; 35 of 40 r and omized participants completed the 12-week intervention . Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA , AA and % n-6 in HUFA , and increases in n-3 EPA , DHA and the omega-3 index , indicating adherence . Trial Registration Clinical Trials.gov ( NCT01157208 Few trials have evaluated the metabolic effects and health outcomes of lowering dietary n-6 PUFA . The objectives of the present paper were ( 1 ) to report the methods employed to lower dietary n-6 PUFA , while either increasing or maintaining n-3 PUFA intake and ( 2 ) to vali date our methods with 24 h recalls and erythrocyte fatty acid analyses . A total of sixty-seven subjects were r and omised to either ( 1 ) an average-n-3 PUFA , low-n-6 PUFA ( L6 ) intervention design ed to lower linoleic acid ( LA ; # 2·5 % of energy ( en% ) ) and arachidonic acid ( # 60 mg/d ) , while maintaining an average US intake of n-3 PUFA or ( 2 ) a high-n-3 PUFA , low-n-6 PUFA ( H3-L6 ) intervention design ed to lower n-6 LA , while increasing the n-3 PUFA a-linolenic acid ( ALA ; $ 1·5 en% ) and EPA þ DHA ( $ 1000 mg/d ) . Pre- and intraintervention nutrient intakes were estimated with six 24 h dietary recalls per subject . Both groups achieved the targeted reductions in dietary LA to # 2·5 en% ( median LA 2·45 ( 2·1 , 3·1 ) ; P,0·001 ) . Intakes of n-3 PUFA did not change for the L6 group . Target increases in n-3 ALA ( median 1·6 en% , ( 1·3 , 2·0 ) , P,0·001 ) and EPA þ DHA ( 1482 mg , ( 374 , 2558 ) , P,0·001 ) were achieved in the H3-L6 group . Dietary changes were vali date d by corresponding changes in erythrocyte n-6 and n-3 fatty acid composition . Dietary LA can be lowered to # 2·5 en% , with or without concurrent increases in dietary n-3 PUFA , in an outpatient clinical trial setting using this integrated diet method This study assessed the metabolic response to sweetened dried cranberries ( SDC ) , raw cranberries ( RC ) , and white bread ( WB ) in humans with type 2 diabetes . Development of palatable cranberry preparations associated with lower glycemic responses may be useful for improving fruit consumption and glycemic control among those with diabetes . In this trial , type 2 diabetics ( n= 13 ) received WB ( 57 g , 160 cal , 1 g fiber ) , RC ( 55 g , 21 cal , 1 g fiber ) , SDC ( 40 g , 138 cal , 2.1 g fiber ) , and SDC containing less sugar ( SDC-LS , 40 g , 113 cal , 1.8 g fiber + 10 g polydextrose ) . Plasma glucose ( mmol/L ) peaked significantly at 60 min for WB , and at 30 min for RC , SDC , and SDC-LS at 9.6 ± 0.4 , 7.0 ± 0.4 , 9.6 ± 0.5 , and 8.7 ± 0.5 , respectively , WB remained significantly elevated from the other treatments at 120 min . Plasma insulin ( pmol/mL ) peaked at 60 min for WB and SDC and at 30 min for RC and SDC-LS at 157 ± 15 , 142 ± 27 , 61 ± 8 , and 97 ± 11 , respectively . Plasma insulin for SDC-LS was significantly lower at 60 min than either WB or SDC . Insulin area under the curve ( AUC ) values for RC and SDC-LS were both significantly lower than WB or SDC . Phenolic content of SDC and SDC-LS was determined following extraction with 80 % acetone prior to high-performance liquid chromatography ( HPLC ) and electronspray ionization-mass spectrometry ( ESI-MS ) and found to be rich in 5-caffeoylquinic cid , quercetin-3-galactoside , and quercetin-3-galactoside , and the proanthocyanidin dimer epicatechin . In conclusion , SDC-LS was associated with a favorable glycemic and insulinemic response in type 2 diabetics . Practical Application : This study compares phenolic content and glycemic responses among different cranberry products . The study seeks to exp and the palatable and portable healthy food choices for persons with type 2 diabetes . The novel use of polydextrose as a bulking agent making possible a reduction in caloric content and potential glycemic response is also characterized in this study Given the conflicting results about the positive effects of magnesium and l-carnitine and as there is no report concerning concurrent supplementation of magnesium and l-carnitine on migraine prophylaxis , the effects of magnesium , l-carnitine , and concurrent magnesium – l-carnitine supplementation on migraine indicators were assessed . In this clinical trial , 133 migrainous patients were r and omly assigned into three intervention groups : magnesium oxide ( 500 mg/day ) , l-carnitine ( 500 mg/day ) , and Mg – l-carnitine ( 500 mg/day magnesium and 500 mg/day l-carnitine ) , and a control group . After 12 weeks of supplementation , the checklist of migraine indicators including migraine attacks/month , migraine days/month , and headache severity was completed , and serum concentrations of magnesium and l-carnitine were measured by atomic absorption spectrophotometry and enzymatic UV test , respectively . The results showed a significant reduction in all migraine indicators in all studied groups ( p < 0.05 ) . The ANOVA results showed a significant reduction in migraine frequency across various supplemented and control groups ( p = 0.008 ) . By separating the effects of magnesium supplementation from other confounding factors such as routine treatments using the repeated measures and nested model , it was clarified that magnesium supplementation had a significant effect on all migraine indicators . Oral supplementation with magnesium oxide and l-carnitine and concurrent supplementation of Mg – l-carnitine besides routine treatments could be effective in migraine prophylaxis ; however , larger trials are needed to confirm these preliminary findings BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( < or = 3 months ) myocardial infa rct ion were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration Migraine is a common condition among adults and has become increasingly more recognised as a common condition among children and adolescents . When headaches are frequent or disabling , preventative treatments are indicated . Few studies have addressed the effectiveness of preventative treatments in children and adolescents in a controlled manner . Due to a concern of potential adverse risks , parents are often reluctant to start prophylactic medications and inquire about the use of alternative treatments including vitamin supplementation . Vitamins , in general , are viewed as more ‘ natural ’ and may be involved in the biological pathways underlying migraine . The use of nutraceutical treatment for migraine is a favourable option because they are essentially well tolerated with minimal side effects . Several nutraceuticals have been studied in the literature with some showing positive results in adult patients with migraine ( 1 ) ; however , studies in children and adolescents are scarce with none showing favourable outcomes . As children and adolescents are increasingly diagnosed with migraine , the need for prophylactic or preventative treatment is warranted . Therefore , it is important that headache clinicians and research ers treating paediatric migraine explore therapies that are safe , effective and affordable . Riboflavin , or vitamin B2 , is a co-factor used in mitochondrial function and has been shown to be effective in children with mitochondrial disorders with mild side effects ( 2 ) . In order to achieve this , high doses were required to overcome the mitochondrial impairment . In the pathogenesis of migraine , riboflavin is believed to be a major co-factor in oxidative metabolism as it acts as a precursor to flavin compounds involved in electron transport and generation of energy in the mitochondria ( 3,4 ) . Thus , in theory , low riboflavin levels may be associated with mitochondrial dysfunction linked to migraine . Several studies have shown efficacy and tolerability of riboflavin in migraine prevention in adults ( 5,6 ) ; however . MacLennan et al. ( 7 ) were the first to study the efficacy of high-dose riboflavin ( at least 200mg/day ) in  migraine prevention in children . The results did not show any difference in those who received treatment with riboflavin compared to placebo – although the placebo rate was high . A subsequent , open-label , retrospective study examining high-dose riboflavin in children and adolescents with migraine who failed pharmacological preventative therapy suggested that riboflavin may be effective in migraine , with a more favourable response in boys ( 8) . This sample population was notable for more individuals with severe migraine . A r and omised , placebocontrolled study of a combination of high-dose riboflavin , magnesium and feverfew using low-dose riboflavin ( 25 mg ) , found no difference between high-dose and low-dose riboflavin with equivalent responses ( 9 ) . The study by Bruijn et al. ( 10 ) 
    Output:
    