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: Our objective was to investigate the effects of iron depletion on adaptation to aerobic exercise , assessed by time to complete a 15-km cycle ergometer test . Forty-two iron-depleted ( serum ferritin < 16 microg/l ) , nonanemic ( Hb > 12 g/dl ) women ( 18 - 33 yr old ) received 100 mg of ferrous sulfate ( S ) or placebo ( P ) per day for 6 wk in a r and omized , double-blind trial . Subjects trained for 30 min/day , 5 days/wk at 75 - 85 % of maximum heart rate for the final 4 wk of the study . There were no group differences in baseline iron status or in 15-km time . Iron supplementation increased serum ferritin and decreased transferrin receptors in the S compared with the P group . The S and P groups decreased 15-km time and respiratory exchange ratio and increased work rate during the 15-km time trial after training . The decrease in 15-km time was greater in the S than in the P group ( P = 0.04 ) and could be partially attributed to increases in serum ferritin and Hb . These results indicate that iron deficiency without anemia impairs favorable adaptation to aerobic exercise BACKGROUND Iron deficiency without anemia has been shown to reduce both muscle-tissue oxidative capacity and endurance in animals . However , the consequences of iron deficiency in humans remain unclear . OBJECTIVE We investigated the effects of iron supplementation on adaptation to aerobic training among marginally iron-depleted women . We hypothesized that iron supplementation for 6 wk would significantly improve iron status and maximal oxygen uptake ( VO(2)max ) after 4 wk of concurrent aerobic training . DESIGN Forty-one untrained , iron-depleted , nonanemic women were r and omly assigned to receive either 50 mg FeSO(4 ) or a placebo twice daily for 6 wk in a double-blind trial . All subjects trained on cycle ergometers 5 d/wk for 4 wk , beginning on week 3 of the study . RESULTS Six weeks of iron supplementation significantly improved serum ferritin and serum transferrin receptor ( sTfR ) concentrations and transferrin saturation without affecting hemoglobin concentrations or hematocrit . Average VO(2)max and maximal respiratory exchange ratio improved in both the placebo and iron groups after training ; however , the iron group experienced significantly greater improvements in VO(2)max . Both iron-status and fitness outcomes were analyzed after stratifying by baseline sTfR concentration ( > and < or = 8.0 mg/L ) , which showed that the previously observed treatment effects were due to iron-status and fitness improvements among subjects with poor baseline iron status . CONCLUSIONS Our findings strongly suggest that iron deficiency without anemia but with elevated sTfR status impairs aerobic adaptation among previously untrained women and that this can be corrected with iron supplementation Zinc and iron compete during intestinal absorption , but postabsorptive interactions between these nutrients are less clear . Underst and ing these interactions is important to determine when supplementation with iron or zinc is proposed . The effect of zinc supplementation ( 22 mg Zn/d as zinc gluconate ) or of iron supplementation ( 100 mg Fe/d as ferrous sulfate ) for 6 wk on iron and zinc metabolism and absorption was evaluated in young women with low iron reserves . Young adult women ( ages 20 - 28 y ) , nonanemic but with low iron stores ( plasma ferritin < 20 microg/L ) , participated in the 70-d study . The women were divided in two groups ( zinc-supplemented , n = 11 ; iron-supplemented , n = 12 ) . The supplements were taken at bedtime .  Iron and zinc biochemical indices and intestinal absorption were measured on d 1 and 56 .  Radioiron and stable isotopes of zinc  were used to measure iron and zinc absorption from a test meal . In the iron-supplemented group , blood hemoglobin , plasma ferritin and the percentage of transferrin saturation increased ( P < 0.01 ) . Zinc indices did not change . In the zinc-supplemented group , plasma ferritin and the percentage of transferrin saturation decreased ( P < 0.05 ) , whereas the plasma transferrin receptor and erythrocyte zinc protoprophyrin levels increased ( P < 0.05 ) . Plasma and urinary zinc also increased ( P < 0.01 ) . Iron absorption ( % ) from the test meal increased ( P < 0.01 ) , whereas zinc absorption ( % ) decreased ( P < 0.01 ) compared with baseline in the Zn-supplemented women . Our results indicate that the use of iron supplements in women with marginal iron status improves iron indices with no effect on zinc status . However , use of a modest zinc supplement improves zinc indices , but also appears to induce a cellular iron deficiency and , possibly , further reduce iron status BACKGROUND Tissue iron depletion may negatively affect endurance performance and muscle fatigability . OBJECTIVE We investigated tissue-level iron depletion and progressive fatigue of the quadriceps during dynamic knee-extension exercise in young women . DESIGN Twenty iron-depleted ( serum ferritin < 20 micro g/L ) , nonanemic ( hemoglobin > 110 g/L ) women ( macro x + /- SEM age : 29.1 + /- 1.2 y ) received iron ( iron group ) or placebo ( placebo group ) for 6 wk in a r and omized , double-blind trial ( n = 10 per group ) . A protocol integrating 2 - 3-s maximal voluntary static contractions ( MVCs ) with dynamic knee extensions was used to assess fatigue . RESULTS No significant differences between the groups in baseline iron status , MVC at rest , or MVC at the end of the protocol were observed . After treatment , serum iron and transferrin saturation increased significantly in the iron group ( P = 0.02 and P = 0.03 , respectively ) . Serum transferrin receptor concentrations increased significantly in the placebo group ( P < 0.01 ) but not in the iron group . After treatment , the rate of decrease in MVC was attenuated in the iron group but not in the placebo group ( P = 0.01 ) . In the iron group , MVC at the sixth minute of the fatigue protocol and MVC at the end of the protocol were approximately 15 % ( P = 0.04 ) and approximately 27 % higher ( P < 0.01 ) , respectively , after treatment . These improvements were not related to changes in iron-status indexes or tissue iron stores , although power was low ( < 0.50 ) to detect these relations . CONCLUSIONS Iron supplementation was associated with a significant improvement in muscle fatigability . Interpretation regarding the direct role of tissue iron status is limited by the study 's low power to detect relations between tissue iron improvement and decreased muscle fatigue This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration . In a r and omized , double-blinded , placebo-controlled study , 90 premenopausal women presenting with fatigue , serum ferritin ≤ 50 ng/mL , and hemoglobin ≥ 120 g/L were r and omized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo . Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks . Median fatigue at baseline was 4.5 ( on a 0 - 10 scale ) . Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group ( P = .07 ) . Efficacy of iron was bound to depleted iron stores : In patients with baseline serum ferritin ≤ 15 ng/mL  , fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group ( P = .005 ) , and 82 % of iron-treated compared with 47 % of placebo-treated patients reported improved fatigue ( P = .03 ) . Drug-associated adverse events were observed in 21 % of iron-treated patients and in 7 % of placebo-treated patients ( P = .05 ) ; none of these events was serious . Intravenous administration of  iron improved fatigue in iron-deficient , nonanemic women with a good safety and tolerability profile . The efficacy of intravenous iron was bound to a serum ferritin concentration ≤ 15 ng/mL. This study was registered at the International St and ard R and omized Controlled Trial Number Register ( www.is rct n.org ) as IS RCT N78430425 Background Unexplained fatigue is often left untreated or treated with antidepressants . This r and omized , placebo-controlled , single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose ( FCM ) in iron-deficient , premenopausal women with symptomatic , unexplained fatigue . Methods Fatigued women ( Piper Fatigue Scale [ PFS ] score ≥5 ) with iron deficiency ( ferritin < 50 µg/L and transferrin saturation < 20 % , or ferritin < 15 µg/L ) and normal or borderline hemoglobin ( ≥115 g/L ) were enrolled in 21 sites in Austria , Germany , Sweden and Switzerl and , blinded to the study drug and r and omized ( computer-generated r and omization sequence ) to a single FCM ( 1000 mg iron ) or saline ( placebo ) infusion . Primary endpoint was the proportion of patients with reduced fatigue ( ≥1 point decrease in PFS score from baseline to Day 56 ) . Results The full analysis included 290 women ( FCM 144 , placebo 146 ) . Fatigue was reduced in 65.3 % ( FCM ) and 52.7 % ( placebo ) of patients ( OR 1.68 , 95%CI 1.05–2.70 ; p = 0.03 ) . A 50 % reduction of PFS score was achieved in 33.3 % FCM- vs. 16.4 % placebo-treated patients ( p<0.001 ) . At Day 56 , all FCM-treated patients had hemoglobin levels ≥120 g/L ( vs. 87 % at baseline ) ; with placebo , the proportion decreased from 86 % to 81 % . Mental quality -of-life ( SF-12 ) and the cognitive function scores improved better with FCM . ‘ Power of attention ’ improved better in FCM-treated patients with ferritin < 15 µg/L. Treatment-emergent adverse events ( placebo 114 , FCM 209 ; most frequently headache , nasopharyngitis , pyrexia and nausea ) were mainly mild or moderate . Conclusion A single infusion of FCM improved fatigue , mental quality -of-life , cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin . Although more side effects were reported compared to placebo , FCM can be an effective alternative in patients who can not tolerate or use oral iron , the common treatment of iron deficiency . Overall , the results support the hypothesis that iron deficiency can affect women ’s health , and a normal iron status should be maintained independent of hemoglobin levels . Trial Registration Clinical Trials.gov This study was conducted to examine the relationship between anemia , supplementation with iron and vitamin C , and productivity . Using the cyanmethemoglobin method , 671 female garment factory workers were examined . On the basis of the World Health Organization ( WHO ) st and ard , 98 were found to be mildly or moderately/severely anemic . An equal number was r and omly chosen from the nonanemic workers . The subjects were then r and omly assigned to either the placebo group or the group receiving 525 mg of ferrous sulfate ( 105 mg elemental iron ) and 500 mg ascorbic acid . Only 118 of the 196 subjects completed the three-month study . The mean hemoglobin ( Hb ) and work output , as indicated by efficiency rating ( ER ) , of the placebo group did not change significantly . Mildly anemic workers with supplements showed a significant improvement in mean Hb , but not in mean ER . The moderately/severely anemic group receiving supplements had significant increases in both Hb and ER PURPOSE The purpose of this study was to find out whether iron repletion leads to an increase in red blood cell volume ( RBV ) and performance capacity in iron-deficient nonanemic athletes . METHODS 40 young elite athletes ( 13 - 25 yr ) with low serum ferritin ( < 20 microg . L-1 ) and normal hemoglobin ( males > 13.5 g.dL-1 , females > 11.7 g.dL-1 ) were r and omly assigned to 12-wk treatment with either twice a day ferrous iron ( equivalent to 2 x 100 mg elemental iron ) or with placebo using a double blind method . Before and after treatment , hematological measures and parameters of iron status were determined in venous blood . RBV , blood volume ( BV ) , and plasma volume ( PV ) were measured by CO rebreathing . For determination of the aerobic and anaerobic capacity ( maximal accumulated oxygen deficit , MAOD ) , the athletes performed an incremental as well as a highly intensive treadmill test . RESULT 
    Output:
    
agent
In IDNA adults  , iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity .
***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: Our objective was to investigate the effects of iron depletion on adaptation to aerobic exercise , assessed by time to complete a 15-km cycle ergometer test . Forty-two iron-depleted ( serum ferritin < 16 microg/l ) , nonanemic ( Hb > 12 g/dl ) women ( 18 - 33 yr old ) received 100 mg of ferrous sulfate ( S ) or placebo ( P ) per day for 6 wk in a r and omized , double-blind trial . Subjects trained for 30 min/day , 5 days/wk at 75 - 85 % of maximum heart rate for the final 4 wk of the study . There were no group differences in baseline iron status or in 15-km time . Iron supplementation increased serum ferritin and decreased transferrin receptors in the S compared with the P group . The S and P groups decreased 15-km time and respiratory exchange ratio and increased work rate during the 15-km time trial after training . The decrease in 15-km time was greater in the S than in the P group ( P = 0.04 ) and could be partially attributed to increases in serum ferritin and Hb . These results indicate that iron deficiency without anemia impairs favorable adaptation to aerobic exercise BACKGROUND Iron deficiency without anemia has been shown to reduce both muscle-tissue oxidative capacity and endurance in animals . However , the consequences of iron deficiency in humans remain unclear . OBJECTIVE We investigated the effects of iron supplementation on adaptation to aerobic training among marginally iron-depleted women . We hypothesized that iron supplementation for 6 wk would significantly improve iron status and maximal oxygen uptake ( VO(2)max ) after 4 wk of concurrent aerobic training . DESIGN Forty-one untrained , iron-depleted , nonanemic women were r and omly assigned to receive either 50 mg FeSO(4 ) or a placebo twice daily for 6 wk in a double-blind trial . All subjects trained on cycle ergometers 5 d/wk for 4 wk , beginning on week 3 of the study . RESULTS Six weeks of iron supplementation significantly improved serum ferritin and serum transferrin receptor ( sTfR ) concentrations and transferrin saturation without affecting hemoglobin concentrations or hematocrit . Average VO(2)max and maximal respiratory exchange ratio improved in both the placebo and iron groups after training ; however , the iron group experienced significantly greater improvements in VO(2)max . Both iron-status and fitness outcomes were analyzed after stratifying by baseline sTfR concentration ( > and < or = 8.0 mg/L ) , which showed that the previously observed treatment effects were due to iron-status and fitness improvements among subjects with poor baseline iron status . CONCLUSIONS Our findings strongly suggest that iron deficiency without anemia but with elevated sTfR status impairs aerobic adaptation among previously untrained women and that this can be corrected with iron supplementation Zinc and iron compete during intestinal absorption , but postabsorptive interactions between these nutrients are less clear . Underst and ing these interactions is important to determine when supplementation with iron or zinc is proposed . The effect of zinc supplementation ( 22 mg Zn/d as zinc gluconate ) or of iron supplementation ( 100 mg Fe/d as ferrous sulfate ) for 6 wk on iron and zinc metabolism and absorption was evaluated in young women with low iron reserves . Young adult women ( ages 20 - 28 y ) , nonanemic but with low iron stores ( plasma ferritin < 20 microg/L ) , participated in the 70-d study . The women were divided in two groups ( zinc-supplemented , n = 11 ; iron-supplemented , n = 12 ) . The supplements were taken at bedtime .  Iron and zinc biochemical indices and intestinal absorption were measured on d 1 and 56 .  Radioiron and stable isotopes of zinc  were used to measure iron and zinc absorption from a test meal . In the iron-supplemented group , blood hemoglobin , plasma ferritin and the percentage of transferrin saturation increased ( P < 0.01 ) . Zinc indices did not change . In the zinc-supplemented group , plasma ferritin and the percentage of transferrin saturation decreased ( P < 0.05 ) , whereas the plasma transferrin receptor and erythrocyte zinc protoprophyrin levels increased ( P < 0.05 ) . Plasma and urinary zinc also increased ( P < 0.01 ) . Iron absorption ( % ) from the test meal increased ( P < 0.01 ) , whereas zinc absorption ( % ) decreased ( P < 0.01 ) compared with baseline in the Zn-supplemented women . Our results indicate that the use of iron supplements in women with marginal iron status improves iron indices with no effect on zinc status . However , use of a modest zinc supplement improves zinc indices , but also appears to induce a cellular iron deficiency and , possibly , further reduce iron status BACKGROUND Tissue iron depletion may negatively affect endurance performance and muscle fatigability . OBJECTIVE We investigated tissue-level iron depletion and progressive fatigue of the quadriceps during dynamic knee-extension exercise in young women . DESIGN Twenty iron-depleted ( serum ferritin < 20 micro g/L ) , nonanemic ( hemoglobin > 110 g/L ) women ( macro x + /- SEM age : 29.1 + /- 1.2 y ) received iron ( iron group ) or placebo ( placebo group ) for 6 wk in a r and omized , double-blind trial ( n = 10 per group ) . A protocol integrating 2 - 3-s maximal voluntary static contractions ( MVCs ) with dynamic knee extensions was used to assess fatigue . RESULTS No significant differences between the groups in baseline iron status , MVC at rest , or MVC at the end of the protocol were observed . After treatment , serum iron and transferrin saturation increased significantly in the iron group ( P = 0.02 and P = 0.03 , respectively ) . Serum transferrin receptor concentrations increased significantly in the placebo group ( P < 0.01 ) but not in the iron group . After treatment , the rate of decrease in MVC was attenuated in the iron group but not in the placebo group ( P = 0.01 ) . In the iron group , MVC at the sixth minute of the fatigue protocol and MVC at the end of the protocol were approximately 15 % ( P = 0.04 ) and approximately 27 % higher ( P < 0.01 ) , respectively , after treatment . These improvements were not related to changes in iron-status indexes or tissue iron stores , although power was low ( < 0.50 ) to detect these relations . CONCLUSIONS Iron supplementation was associated with a significant improvement in muscle fatigability . Interpretation regarding the direct role of tissue iron status is limited by the study 's low power to detect relations between tissue iron improvement and decreased muscle fatigue This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration . In a r and omized , double-blinded , placebo-controlled study , 90 premenopausal women presenting with fatigue , serum ferritin ≤ 50 ng/mL , and hemoglobin ≥ 120 g/L were r and omized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo . Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks . Median fatigue at baseline was 4.5 ( on a 0 - 10 scale ) . Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group ( P = .07 ) . Efficacy of iron was bound to depleted iron stores : In patients with baseline serum ferritin ≤ 15 ng/mL  , fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group ( P = .005 ) , and 82 % of iron-treated compared with 47 % of placebo-treated patients reported improved fatigue ( P = .03 ) . Drug-associated adverse events were observed in 21 % of iron-treated patients and in 7 % of placebo-treated patients ( P = .05 ) ; none of these events was serious . Intravenous administration of  iron improved fatigue in iron-deficient , nonanemic women with a good safety and tolerability profile . The efficacy of intravenous iron was bound to a serum ferritin concentration ≤ 15 ng/mL. This study was registered at the International St and ard R and omized Controlled Trial Number Register ( www.is rct n.org ) as IS RCT N78430425 Background Unexplained fatigue is often left untreated or treated with antidepressants . This r and omized , placebo-controlled , single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose ( FCM ) in iron-deficient , premenopausal women with symptomatic , unexplained fatigue . Methods Fatigued women ( Piper Fatigue Scale [ PFS ] score ≥5 ) with iron deficiency ( ferritin < 50 µg/L and transferrin saturation < 20 % , or ferritin < 15 µg/L ) and normal or borderline hemoglobin ( ≥115 g/L ) were enrolled in 21 sites in Austria , Germany , Sweden and Switzerl and , blinded to the study drug and r and omized ( computer-generated r and omization sequence ) to a single FCM ( 1000 mg iron ) or saline ( placebo ) infusion . Primary endpoint was the proportion of patients with reduced fatigue ( ≥1 point decrease in PFS score from baseline to Day 56 ) . Results The full analysis included 290 women ( FCM 144 , placebo 146 ) . Fatigue was reduced in 65.3 % ( FCM ) and 52.7 % ( placebo ) of patients ( OR 1.68 , 95%CI 1.05–2.70 ; p = 0.03 ) . A 50 % reduction of PFS score was achieved in 33.3 % FCM- vs. 16.4 % placebo-treated patients ( p<0.001 ) . At Day 56 , all FCM-treated patients had hemoglobin levels ≥120 g/L ( vs. 87 % at baseline ) ; with placebo , the proportion decreased from 86 % to 81 % . Mental quality -of-life ( SF-12 ) and the cognitive function scores improved better with FCM . ‘ Power of attention ’ improved better in FCM-treated patients with ferritin < 15 µg/L. Treatment-emergent adverse events ( placebo 114 , FCM 209 ; most frequently headache , nasopharyngitis , pyrexia and nausea ) were mainly mild or moderate . Conclusion A single infusion of FCM improved fatigue , mental quality -of-life , cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin . Although more side effects were reported compared to placebo , FCM can be an effective alternative in patients who can not tolerate or use oral iron , the common treatment of iron deficiency . Overall , the results support the hypothesis that iron deficiency can affect women ’s health , and a normal iron status should be maintained independent of hemoglobin levels . Trial Registration Clinical Trials.gov This study was conducted to examine the relationship between anemia , supplementation with iron and vitamin C , and productivity . Using the cyanmethemoglobin method , 671 female garment factory workers were examined . On the basis of the World Health Organization ( WHO ) st and ard , 98 were found to be mildly or moderately/severely anemic . An equal number was r and omly chosen from the nonanemic workers . The subjects were then r and omly assigned to either the placebo group or the group receiving 525 mg of ferrous sulfate ( 105 mg elemental iron ) and 500 mg ascorbic acid . Only 118 of the 196 subjects completed the three-month study . The mean hemoglobin ( Hb ) and work output , as indicated by efficiency rating ( ER ) , of the placebo group did not change significantly . Mildly anemic workers with supplements showed a significant improvement in mean Hb , but not in mean ER . The moderately/severely anemic group receiving supplements had significant increases in both Hb and ER PURPOSE The purpose of this study was to find out whether iron repletion leads to an increase in red blood cell volume ( RBV ) and performance capacity in iron-deficient nonanemic athletes . METHODS 40 young elite athletes ( 13 - 25 yr ) with low serum ferritin ( < 20 microg . L-1 ) and normal hemoglobin ( males > 13.5 g.dL-1 , females > 11.7 g.dL-1 ) were r and omly assigned to 12-wk treatment with either twice a day ferrous iron ( equivalent to 2 x 100 mg elemental iron ) or with placebo using a double blind method . Before and after treatment , hematological measures and parameters of iron status were determined in venous blood . RBV , blood volume ( BV ) , and plasma volume ( PV ) were measured by CO rebreathing . For determination of the aerobic and anaerobic capacity ( maximal accumulated oxygen deficit , MAOD ) , the athletes performed an incremental as well as a highly intensive treadmill test . RESULT 
    Output:
    