n-6 gla together with fishoil concentrate containing n-3 epa and dha showed significant overall improvement in symptoms and rbc essential fatty acid levels. however a subsequent rct trying to replicate this study found no significant differences between the treatment and placebo group after treatment, and no significant differences in pre-treatment red-cell membrane lipids between the two groups. the different results may be explained by the patient selection: the first trial tested people with pvfs, whereas the second used the oxford criteria for cfs. also, the first trial used paraffin while the second trial used sunflower oil which is better tolerated and less likely to adversely affect the placebo group. magnesium positive results from a trial of magnesium delivered by injection to magnesium-deficient cfs patients were published in 1991, but three subsequent studies did not find magnesium deficiency as a general problem in cfs patients. a 2008 review concluded that there is no good evidence that intramuscular magnesium is of benefit in cfs. vitamin b12 both oral and injected vitamin b12 have been suggested as treatments for generalized fatigue since the 1950s, however recent studies do not suggest any benefit from it, either for generalized fatigue or cfs specifically. further research is needed, however, as studies to date have been small and used inconsistent dosing regimens. controversy pace trial controversy the pace trial was a large-scale five-year trial funded by the uk government which compared the efficacy and safety of four treatments: specialist medical care (smc), smc with cbt, smc with get, and smc with adaptive pacing therapy (apt). the results were published in february 2011 and showed that cbt and get were, when combined with smc, each "moderately" effective compared to smc alone. apt was not found to be effective when added to smc. cbt was done on the basis of the fear avoidance theory of chronic fatigue syndrome. this theory regards cfs as being reversible and that cognitive responses (fear of engaging in activity) and behavioural responses (avoidance of activity) are linked and interact with physiological processes to perpetuate fatigue. the aim of treatment was to change the behavioural and cognitive factors assumed to be responsible for perpetuation of the participant's symptoms and disability. graded exercise therapy (get) was done on the basis of deconditioning and exercise intolerance theories of chronic fatigue syndrome. these theories assume that cfs is perpetuated by reversible physiological changes of deconditioning and avoidance of activity; these changes result in the deconditioning being maintained and an increased perception of effort during exertion and increased symptoms after unaccustomed activity, leading to further inactivity. the aim of treatment was to help the participant gradually return to appropriate physical activities, reverse the deconditioning, and thereby reduce fatigue and disability. 641 patients meeting the oxford criteria for cfs were recruited, and were assigned approximately evenly to the four treatment conditions. two weeks after the commencement of the trial, self-reported fatigue scores were significantly lower and self-rated physical function scores significantly higher for the get and cbt groups than for the smc and apt groups. at 52 weeks post-treatment, average scores on a 6-minute walking distance test were significantly higher for the get group than for the other groups. however, the mean distance walked (334 metres) was still well below the mean for healthy elderly people (631 metres). the cbt group did not perform significantly differently from the smc and apt groups on this measure. a subsequent paper presented results from a step fitness test, but at 52 weeks, there were no significant differences in performance across groups on this measure. the trial reported that cbt and get were "safe". a serious adverse event was defined as either: death, life-threatening, hospitalisation, increased severe disability for at least 4 weeks duration, any episode of deliberate self-harm. serious adverse reactions to the therapies were recorded in two (1%) of the 159 patients in the apt group, three (2%) of the 161 patients in the cbt group, 2 (1%) of the 160 patients in the get group and two (1%) of the 160 patients in the smc group. a subsequent paper examined the proportion of patients who could be classified as recovered after the trial. a patient was considered recovered if they obtained a specified threshold score on the fatigue and physical function self-report scales, if they rated their health as "much better" or "very much better", and if they also failed to meet the authors' case definition of cfs. according to the primary measures of recovery reported in the paper, 22% recovered after cbt, 22% after get, but only 8% after apt and 7% after smc. a follow-up conducted 2.5 years after the commencement of the trial reported no significant differences between the various treatment groups on the primary self-report measures. that is, the treatment-specific effects evident at 52 weeks were no longer evident at 2.5 years. the publication of the trial results generated a vigorous response. letters to the editor by some specialists and patient advocates expressed concern over generalisability of the results and questioned protocol changes during the course of the trial that resulted in some participants meeting criteria for "trial recovery" at baseline. the authors of the paper responded in a letter which stated that the protocol changes and other decisions were approved by the trial steering committee. patient groups expressed disappointment over news media interpreting the definition of "recovery to normal by trial criteria" as "cured". professor malcolm hooper submitted complaints to the medical research council and the lancet . the mrc and the lancet considered the submissions but rejected them. a lancet editorial expressed suspicions of an active campaign to discredit the research." controversy has arisen from the authors' and the lancet's refusal to share data from the study; according to an article in slate: "starting in 2011, patients analyzing the study filed freedom of information act requests to learn what the trial's results would have been under the original protocol. those were denied along with many other requests about the trial, some on the grounds that the requests were 'vexatious.' the investigators said they considered the requests to be harassment. ... richard horton, the editor of the lancet, defended the trial, calling the critics 'a fairly small, but highly organized, very vocal and very damaging group of individuals who have, i would say, actually hijacked this agenda and distorted the debate so that it actually harms the overwhelming majority of patients.'" in 2016, the pace trial data were made publicly available after a ruling in the uk.