***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: The pharmacokinetics and utilization ( flavocoenzyme synthesis ) of orally and intravenously administered riboflavin in healthy humans were assessed . After the determination of circadian rhythms of riboflavin concentrations in blood plasma and urine of four males and five females ( control period ) , each of these subjects received three different oral riboflavin doses ( 20 , 40 , and 60 mg ) and one intravenous bolus injection of riboflavin ( 11.6 mg ) . Vitamins were administered in a r and omized , cross-over design with 2 wk between each administration . Blood plasma and urine specimens were collected repeatedly over a period of 48 h after each administration . Concentrations of flavocoenzymes and riboflavin were analyzed in blood plasma ; riboflavin was assayed in urine . During the control period , a small circadian variation was observed : plasma concentrations and urinary excretion of riboflavin were low during the afternoon ( P < 0.05 ) . Pharmacokinetics were calculated using a two-compartment open model . The maximal amount of riboflavin that can be absorbed from a single dose was 27 mg per adult . Half-life of absorption was 1.1 h. First-order rate constants describing distribution and elimination of riboflavin were significantly higher after intravenous than after oral administration ( P < 0.01 ) . Release of flavocoenzymes into plasma was low compared with the increase of riboflavin concentrations . 7 alpha-Hydroxyriboflavin was identified in plasma . Clearance data indicated that urinary excretion of riboflavin contributes to one-half of the overall removal of riboflavin from plasma . No sex differences were observed for any of the pharmacokinetic variables ( P > 0.05 ) Background Non-medical , non-pharmacological and pharmacological treatments are recommended for the prevention of migraine . The purpose of this r and omized double-blind placebo controlled , multicenter trial was to evaluate the efficacy of a proprietary nutritional supplement containing a fixed combination of magnesium , riboflavin and Q10 as prophylactic treatment for migraine . Methods 130 adult migraineurs ( age 18 – 65 years ) with ≥ three migraine attacks per month were r and omized into two treatment groups : dietary supplementation or placebo in a double-blind fashion . The treatment period was 3 months following a 4 week baseline period without prophylactic treatment . Patients were assessed before r and omization and at the end of the 3-month-treatment-phase for days with migraine , migraine pain , burden of disease ( HIT-6 ) and subjective evaluation of efficacy . Results Migraine days per month declined from 6.2 days during the baseline period to 4.4 days at the end of the treatment with the supplement and from 6.2.days to 5.2 days in the placebo group ( p = 0.23 compared to placebo ) . The intensity of migraine pain was significantly reduced in the supplement group compared to placebo ( p = 0.03 ) . The sum score of the HIT-6 question naire was reduced by 4.8 points from 61.9 to 57.1 compared to 2 points in the placebo-group ( p = 0.01 ) . The evaluation of efficacy by the patient was better in the supplementation group compared to placebo ( p = 0.01 ) . Conclusions Treatment with a proprietary supplement containing magnesium , riboflavin and Q10 ( Migravent ® in Germany , Dolovent ® in USA ) had an impact on migraine frequency which showed a trend towards statistical significance . Migraine symptoms and burden of disease , however , were statistically significantly reduced compared to placebo in patients with migraine attacks Objective To determine the prevalence and distribution of migraine in the United States as well as current patterns of health care use . Methods A r and om-digit-dial , computer-assisted telephone interview ( CATI ) survey was conducted in Philadelphia County , PA , in 1998 . The CATI identifies individuals with migraine ( categories 1.1 and 1.2 ) as defined by the diagnostic criteria of the International Headache Society with high sensitivity ( 85 % ) and specificity ( 96 % ) . Interviews were completed in 4,376 subjects to identify 568 with migraine . Those with 6 or more attacks per year ( n = 410 ) were invited to participate in a follow-up interview about health care utilization and family impact of migraine ; 246 ( 60.0 % ) participated . Results The 1-year prevalence of migraine was 17.2 % in females and 6.0 % in males . Prevalence was highest between the ages of 30 and 49 . Whereas 48 % of migraine sufferers had seen a doctor for headache within the last year ( current consulters ) , 31 % had never done so in their lifetimes and 21 % had not seen a doctor for headache for at least 1 year ( lapsed consulters ) . Of current or lapsed consulters , 73 % reported a physician-made diagnosis of migraine ; treatments varied . Of all migraine sufferers , 49 % were treated with over-the-counter medications only , 23 % with prescription medication only , 23 % with both , and 5 % with no medications at all . Conclusion Relative to prior cross-sectional surveys , epidemiologic profiles for migraine have remained stable in the United States over the last decade . Self-reported rates of current medical consultation have more than doubled . Moderate increases were seen in the percentage of migraine sufferers who use prescription medications and in the likelihood of receiving a physician diagnosis of migraine If the brain of migraineurs is characterized between attacks by a reduction of mitochondrial phosphorylation potential , riboflavin , which has the potential of increasing mitochondrial energy efficiency , might have prophylactic effects in migraine . In this preliminary open pilot study , 49 patients suffering from migraine ( 45 without aura , 4 with aura ) were treated with 400 mg of riboflavin as a single oral dose for at least 3 months . Twenty-three patients received in addition 75 mg of aspirin .  Mean global improvement after therapy was 68.2 % and there was no difference between the two groups of patients . With the exception of one patient in the riboflavin plus aspirin group who withdrew because of gastric intolerance , no drug-related side effects were reported . High-dose riboflavin could thus be an effective , low-cost prophylactic treatment of migraine devoid of short-term side effects . A placebo-controlled trial of its efficacy seems worthwhile Background : Riboflavin seems to have a promising effect on migraine in adults . The present study examines whether riboflavin has a prophylactic effect on migraine in children . Objective : To investigate whether riboflavin in a dosage of 50 mg/day has a prophylactic effect on migraine attacks in young children . Subjects and methods : This r and omised , placebo-controlled , double-blind , cross-over trial included 42 children ( aged 6–13 years ) with migraine of whom 14 children were also suffering from tension-type headache . Following a 4-week baseline period , all children received placebo for 16 weeks then riboflavin for 16 weeks ( or vice versa ) with a washout period of 4 weeks in between . The primary outcome measure was reduction in mean frequency of migraine attacks and tension-type headache in the last 4 weeks at the end of the riboflavin and placebo phase , compared with the preceding baseline or wash-out period . Secondary outcome measures were mean severity and mean duration of migraine and tension-type headaches in the last 4 weeks at the end of the riboflavin and placebo phase , compared with the preceding baseline or wash-out period . Results : No significant difference in the reduction of mean frequency of migraine attacks in the last month of treatment was found between placebo and riboflavin ( P = 0.44 ) . However , a significant difference in reduction of mean frequency of headaches with a tension-type phenotype was found in favour of the riboflavin treatment ( P = 0.04 ) . Conclusions : In this group of children with migraine , there is no evidence that 50 mg riboflavin has a prophylactic effect on migraine attacks . We found some evidence that 50 mg riboflavin may have a prophylactic effect on interval headaches that may correspond to mild migraine attacks or tension-type headache attacks in children with migraine Objectives : In migraine , an interictal reduction of mitochondrial energy metabolism and a preventive effect of high-dose riboflavin were reported . To explore the relation between the two , we tested if the therapeutic response to riboflavin is associated with specific mitochondrial DNA ( mtDNA ) haplogroups . We focused our attention on haplogroup H , which is known to differ from others in terms of energy metabolism . Methods : Sixty-four migraineurs completed a 4-month open trial with riboflavin ( 400 mg QD ) and were genotyped blindly for mtDNA haplogroups . Results : Forty patients responded to riboflavin treatment and 24 were nonresponders . The mtDNA haplogroup H was found in 29 subjects ( 20 migraine without aura , 9 migraine with aura ) .  Riboflavin responders were more numerous in the non-H group ( 67.5 % ) . Conversely , nonresponders were mostly H ( 66.7 % ) . The difference between the two groups was significant ( χ2 = 7.07 ; p = 0.01 ) . The presence of aura had no influence on riboflavin 's effectiveness ( χ2 = 0.113 ; p = 0.74 ) and was not associated with a particular haplogroup ( χ2 = 0.55 ; p = 0.46 ) . Conclusions : In this pharmacogenetic study , riboflavin appears to be more effective in patients with migraine with non-H mitochondrial DNA haplotypes . The underlying mechanisms are unknown , but could be related to the association of haplogroup H with increased activity in complex I , which is a major target for riboflavin . Our results may have ethnic implication s , since haplogroup H is chiefly found in the European population The familial occurrence and mode of inheritance were analysed in families with migraine without aura ( MO ) and migraine with aura ( MA ) . The prob and s were found among 4000 persons from the general population . All persons with MA were included as prob and s , and an equivalent number of prob and s with MO was selected as a r and om sample among those with MO . Spouses and first-degree relatives were blindly interviewed . All interviews were performed by one neurological research fellow . The distinct familial patterns indicate that MO and MA have a different aetiology . Compared with the general population , the first-degree relatives of prob and s with MO had a 1.9-fold increased risk of MO while spouses had a 1.5-fold increased risk of MO , indicating that both genetic and environmental factors are important in MO . The first-degree relatives of prob and s with MA had a four-fold increased risk of MA while spouses had no increased risk of MA , indicating that MA is determined largely by genetic factors . The complex segregation analysis indicate that both MO and MA have multifactorial inheritance without generational difference A deficit of mitochondrial energy metabolism may play a role in migraine pathogenesis . We found in a previous open study that high-dose riboflavin was effective in migraine prophylaxis . We now compared riboflavin ( 400 mg ) and placebo in 55 patients with migraine in a r and omized trial of 3 months duration . Using an intention-to-treat analysis , riboflavin was superior to placebo in reducing attack frequency ( p = 0.005 ) and headache days ( p = 0.012 ) . Regarding the latter , the proportion of patients who improved by at least 50 % , i.e. “ responders , ” was 15 % for placebo and 59 % for riboflavin ( p = 0.002 ) and the number-needed-to-treat for effectiveness was 2.3 . Three minor adverse events occurred , two in the riboflavin group ( diarrhea and polyuria ) and one in the placebo group ( abdominal cramps ) . None was serious . Because of its high efficacy , excellent tolerability , and low cost , riboflavin is an interesting option for migraine prophylaxis and a c and i date for a comparative trial with an established prophylactic drug OBJECTIVE To determine the efficacy for migraine prophylaxis of a compound containing a combination of riboflavin , magnesium , and feverfew . BACKGROUND Previous studies of magnesium and feverfew for migraine prophylaxis have found conflicting results , and there has been only a single placebo-controlled trial of riboflavin . DESIGN / METHODS R and omized double-blind placebo-controlled trial of a compound providing a daily dose of riboflavin 400 mg , magnesium 300 mg , and feverfew 100 mg . The placebo contained 25 mg riboflavin . The study included a 1-month run-in phase and 3-month trial . The protocol allowed for 120 patients to be r and omized , with a preplanned interim analysis of the data after 48 patients had completed the trial . RESULTS Forty-nine patients completed the 3-month trial . For the primary outcome measure , a 50 % or greater reduction in migraines , there was no difference between active and " placebo " groups , achieved by 10 ( 42 % ) and 11 ( 44 % ) , respectively ( P=.87 ) . Similarly , there was no significant difference in secondary outcome measures , for active versus placebo groups , respectively : 50 % or greater reduction in migraine days ( 33 % and  
    Output:
    
WHAT IS NEW AND CONCLUSION Riboflavin is well tolerated , inexpensive and has demonstrated efficacy in the reduction of adult patient 's migraine headache frequency .