Assessment of the feed additive consisting of folic acid for all animal species for the renewal of its authorisation (Chr. Olesen A/S and DSM Nutritional Products Ltd).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for the renewal of the authorisation of folic acid as a nutritional feed additive. The additive is authorised for use in feed and water for drinking for all animal species. The applicant provided evidence that the additive currently in the market complies with the existing conditions of authorisation and the production process has not been modified. The FEEDAP Panel considers that there is no evidence to revise the conclusions reached in the previous assessment for the safety for the terrestrial species, consumers and for the environment. The use of folic acid in aquatic animal species to cover their nutritional needs is considered safe. However, the Panel is not in a position to set a maximum safe level for all fish and crustacean species. Considering the narrow margin between the requirement and the tolerated levels seen in some aquatic animal species, the FEEDAP Panel considers that supplementation should not exceed the requirements of the different aquatic animal species. The additive is neither a skin irritant nor a dermal sensitiser. The exposure through inhalation is likely. Due to the lack of data, the FEEDAP Panel is not in the position to conclude on the potential of folic acid to be harmful to the respiratory system and irritant to eyes. The Panel retains that the previously made conclusion on the efficacy remains valid.

Safety and efficacy of a feed additive consisting of natrolite-phonolite obtained from volcanic rock from Kaiserstuhl for all animal species (Hans G. Hauri Mineralstoffwerk GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of natrolite-phonolite obtained from volcanic rock from Kaiserstuhl as a technological additive (functional group: anticaking) for all animal species. According to the conventional risk assessment, due to the lack of adequate data, the Panel is not in a position to conclude on the safety of the additive for the target species under the proposed conditions of use. However, from the tolerance studies in cattle for fattening and weaned piglets, effects observed in animal performance and blood clinical biochemistry suggest adverse effects on the animals supplemented with the additive. Based on current knowledge, there is no indication of substantial absorption of the components of the additive and, therefore, of concern for the consumer. The FEEDAP Panel is not in the position to conclude on the potential of the additive to be a skin and eye irritant. The additive is considered a respiratory and dermal sensitiser. In the absence of suitable data, the presence of small/nanoparticles cannot be excluded. As no suitable data in line with the requirements of the Guidance on risk assessment of nanomaterials were provided by the applicant, the potential risks associated with the presence of nanoparticles for the target species, the consumer and the user could not be assessed. Due to the lack of sufficient data, the Panel is not in a position to conclude on the efficacy of the additive.

The effect of clinical guidelines on the utilisation of radiographs in chiropractic clinics in Denmark - an interrupted time series analysis.

BACKGROUND: In Denmark, chiropractors have a statutory right to use radiography and the government-funded national Health Insurance provides partial reimbursement. Danish National Clinical Guidelines recommends against routine use of imaging for uncomplicated spinal pain; however, it is not clear if clinical imaging guidelines recommendations have had an effect on the utilisation of spinal radiography. This study aimed to describe the utilisation rate of radiographs in Danish chiropractic clinics in the period from 2010 to 2020 and to assess the impact of clinical guidelines and policy changes on the utilisation of radiographs in Danish chiropractic clinics. METHODS: Anonymised data from January 1st, 2010, to December 31st, 2020, were extracted from the Danish Regions register on health contacts in primary care. Data consisted of the total number of patients consulting one of 254 chiropractic clinics and the total number of patients having or being referred for radiography. Data were used to investigate the radiography utilisation per month from 2010 to 2020. An 'interrupted time series' analysis was conducted to determine if two interventions, the dissemination of 1) Danish clinical imaging guidelines recommendations and policy changes related to referral for advanced imaging for chiropractors in 2013 and 2) four Danish clinical guidelines recommendations in 2016, were associated with an immediate change in the level and/or slope of radiography utilisation. RESULTS: In total, 336,128 unique patients consulted a chiropractor in 2010 of which 55,449 (15.4%) had radiography. In 2020, the number of patients consulting a chiropractor had increased to 366,732 of which 29,244 (8.0%) had radiography. The pre-intervention utilisation decreased by two radiographs per 10,000 patients per month. Little absolute change, but still statistically significant for Intervention 1, in the utilisation was found after the dissemination of the clinical guidelines and policy changes in 2013 or 2016. CONCLUSIONS: The proportion of Danish chiropractic patients undergoing radiography was halved in the period from 2010 to 2020. However, the dissemination of clinical imaging guidelines recommendations and policy changes related to referrals for advanced imaging showed little meaningful change in the monthly utilisation of radiographs in the same period.

Safety of 41 flavouring compounds providing a herbal flavour and belonging to different chemical groups for use as feed additives in all animal species (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of 41 compounds to provide a Herbal flavour and belonging to different chemical groups, when used as sensory additives in feed for all animal species. Fourteen out of the 41 compounds were tested in tolerance studies in chickens for fattening, piglets, cattle for fattening and Atlantic salmon. No adverse effects were observed in the tolerance studies at 10-fold the intended level. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the 14 tested compounds were safe for these species at the proposed use level and conclusions were extrapolated to all animal species. For the remaining 27 compounds, read-across from structurally similar compounds tested in tolerance trials and belonging to the same chemical group was applied. The FEEDAP Panel concluded that these 27 compounds were safe for all animal species at the proposed use level. No safety concern would arise for the consumer and the environment from the use of the 41 compounds up to the maximum proposed use level in feed.

Assessment of the safety of the feed additives acetic acid, calcium acetate and sodium diacetate for fish (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of acetic acid, calcium acetate and sodium diacetate as technological feed additives (preservatives) for salmonids/fish. The additives are already authorised for use for all animal species other than fish. In previous opinions, the FEEDAP Panel concluded that a maximum concentration of 2,500 mg acetic acid/kg complete feed (or 1,000 mg/L water for drinking) was safe for poultry, pigs and pet animals. Ruminants were considered to exhibit a higher tolerance. Due to lack of data for salmonids, the Panel could not conclude on the safety of acetic acid and its salts for fish. The applicant has provided supplementary information consisting in a tolerance study in Atlantic salmon (Salmo salar) and a literature search to support the safety of acetic acid in fish. Considering all the available information, the FEEDAP Panel concluded that acetic acid (and its salts by analogy) is considered safe for fish up to the maximum recommended supplementation level of 2,500 mg acetic acid/kg complete feed.

Scientific opinion on the presence of DNA in the feed additives consisting of concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride produced by Escherichia coliNITE BP-02917 for all animal species (METEX NOOVISTAGO).

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride produced by a genetically modified strain of Escherichia coli (NITE BP-02917) as nutritional and as sensory (flavouring compound) feed additives for all animal species. In 2022, the FEEDAP Panel issued an opinion on the safety and efficacy of these products. In that assessment, the FEEDAP Panel could not exclude the potential presence of recombinant DNA derived from the genetically modified production organism in the products. The applicant provided supplementary data to exclude the presence of recombinant DNA derived from the production organism in the final products. Based on the new data provided, the FEEDAP Panel concluded that no DNA of the production strain E. coli NITE BP-02917 was detected in concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride.

Safety and efficacy of a feed additive consisting of potassium ferrocyanide for all animal species (K + S KALI GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of potassium ferrocyanide as a technological feed additive, functional group anticaking agents, for all animal species. The additive potassium ferrocyanide is intended to be used in potassium chloride with a maximum content of 150 mg ferrocyanide anion/kg salt. The use of potassium ferrocyanide is safe, when added to potassium chloride at a maximum content of 150 mg ferrocyanide anions (anhydrous)/kg for: pigs for fattening and lactating sows, sheep, goats, salmon and dogs. In the absence of a margin of safety, the use of potassium chloride according to the proposed conditions of use is not considered to be safe for chickens for fattening, laying hens, turkeys, piglets, veal calf, cattle for fattening, dairy cows, horse, rabbit and cats. In the absence of information on the use of potassium chloride in the diets for any other animal species, no conclusion on a potentially safe level of potassium chloride, supplemented with 150 mg ferrocyanide/kg, can be made. The use of potassium ferrocyanide in animal nutrition is of no concern for consumer safety. The results of in vivo studies showed that potassium ferrocyanide is not irritant to skin and eye and is not a skin sensitiser. However, due to the presence of nickel, the additive should be considered as a respiratory and dermal sensitiser. The available data do not allow the FEEDAP Panel to conclude on the safety of the additive for the soil and the marine environment, while the use of the additive in land-based aquaculture according to the proposed conditions of use is considered of no concern. Potassium ferrocyanide is considered to be efficacious as an anticaking agent when included in potassium chloride at the proposed use levels.

Safety and efficacy of feed additives consisting of sodium ferrocyanide and potassium ferrocyanide for all animal species (Eusalt a.i.s.b.l.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of potassium and sodium ferrocyanide as technological feed additives for all animal species. The additives sodium- and potassium ferrocyanide are intended to be used in sodium chloride with a maximum content of 80 mg ferrocyanide anion (anhydrous)/kg salt. The FEEDAP Panel concluded that the use of sodium ferrocyanide and potassium ferrocyanide is safe, when added to sodium chloride at a maximum content of 80 mg ferrocyanide anion/kg for: turkey for fattening and laying hens and other laying/breeding birds; all porcine species and categories, all ruminant species and categories, rabbit, horse, salmonids and other minor fin fish, dogs and cats. In the absence of a margin of safety, the use of sodium and potassium chloride according to the proposed conditions of use is not considered to be safe for chickens for fattening and other poultry species for fattening or reared for laying/breeding other than turkeys. In the absence of information on the use of sodium chloride in the diets for any other animal species, no conclusion on a potentially safe level of sodium chloride, supplemented with 80 mg ferrocyanide anions (anhydrous)/kg, could be made. The use of sodium and potassium ferrocyanide in animal nutrition under the conditions of use proposed is of no concern for consumer safety. The results of in vivo studies showed that sodium and potassium ferrocyanide are not irritant to skin and eye and are not skin sensitisers. However, owing to the presence of nickel, sodium ferrocyanide, is considered a dermal and respiratory sensitiser. No conclusions could be reached on the safety of the user exposed via inhalation for potassium ferrocyanide. The use of sodium and potassium ferrocyanide as feed additives is considered safe for the environment. The additives are considered to be efficacious as anticaking agents in sodium chloride at the proposed use level.

Description of recurrent headaches in 7-14-year-old children: Baseline data from a randomized clinical trial on effectiveness of chiropractic spinal manipulation in children with recurrent headaches.

BACKGROUND: Headaches in children are poorly described and diagnosing can be challenging. Objectives are: (1) to describe headache characteristics and child characteristics, (2) to explore whether data can suggest a more diverse way to categorize headaches than traditionally. METHODS: Baseline data for a clinical trial included a questionnaire and a physical screening. Children's characteristics and detailed description of headache symptoms were provided. Children were classified for migraine or tension-type-headache based on questionnaire data reported by children and parents. This required to apply slightly modified classification criteria and a "non-classifiable" group was added. Severity and symptoms, related to the migraine versus tension type distinction, were investigated to define a migraine-tension-type-index. RESULTS: 253 children were included. Mean pain intensity was 5.9/10. Over 2/3 of the children had headache for > 1 year, and > 50% for several days/week. Half of the children were non-classifiable, 22% were classified as migraine and 23% as tension-type headache. A migraine-tension-type-index was constructed and describes a continuous spectrum rather than two distinct groups. CONCLUSIONS: Children with recurrent headaches are often severely affected. A questionnaire-based classification appeared feasible to distinguish between migraine and tension-type headaches in children but leaving many children unclassified. A migraine-tension-type-index can be generated allowing to regard the traditional distinction as a continuum (including mixed headache), and potentially serving as an instrument to improve headache management. Trial registration ClinicalTrials.gov, identifier NCT02684916.

Safety of the feed additive consisting of vitamin B2/riboflavin (produced by Bacillus subtilis KCCM 10445) for all animal species (Hubei Guangji Pharmaceutical Co. Ltd.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the characterisation and safety of vitamin B2/riboflavin produced by fermentation with a genetically modified strain of Bacillus subtilis (KCCM 10445) as a nutritional additive in feed and water for drinking for all animal species. In 2021, the FEEDAP Panel issued an opinion on the safety and efficacy of vitamin B2 98% and vitamin B2 80% in the form of riboflavin produced by B. subtilis KCCM 10445. In that assessment, the Panel could not confirm the correspondence of the deposited strain under accession number KCCM 10445 with the strain used for production owing to discrepancies in the description of the genetic modification steps. Moreover, in the absence of data, no conclusions on the skin sensitisation potential of vitamin B2 98% and vitamin B2 80% nor on the possible risk by inhalation of vitamin B2 98% could be reached. For the present assessment, the applicant provided supplementary information to partially address the limitations identified in that assessment. Based on the results of a bioinformatic analysis between the strain deposited under accession number KCCM 10445 with the strain used for production under assessment, the Panel confirmed the correspondence between the two strains. As no new data have been submitted on the safety of the additives, the conclusions from the Panel remain that the use of vitamin B2/riboflavin produced by B. subtilis KCCM 10445 is safe for the target species, the consumer and the environment. Vitamin B2 80% is not hazardous by inhalation. In the absence of data, no conclusions on the possible risk by inhalation of vitamin B2 98% could be reached. Neither the vitamin B2 98% nor the vitamin B2 80% are irritant to skin or eyes. In the absence of data, no conclusions on the skin sensitisation potential of the additives could be reached.

Safety and efficacy of a feed additive consisting of l-lysine monohydrochloride and l-lysine sulfate produced by fermentation with Corynebacterium glutamicumCGMCC 17927 for all animal species (Barentz Animal Nutrition B.V.).

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on l-lysine monohydrochloride and l-lysine sulfate produced by Corynebacterium glutamicum CGMCC 17927, when used as a nutritional additive in feed and water for drinking for all animal species. The active substance is l-lysine, and it was produced in two different forms: monohydrochloride (HCl) or sulfate salts. The production strain was genetically modified. Neither viable cells nor recombinant DNA of the production strain were detected in the final products. Therefore, the Panel concluded that the additives did not pose any safety concern regarding the production strain. The use of l-lysine HCl and l-lysine sulfate produced by the strain C. glutamicum CGMCC 17927 in supplementing feed to compensate for l-lysine deficiency in feedingstuffs was safe for the target species. The FEEDAP Panel identified risks of nutritional imbalances and hygienic concerns for amino acids when administered simultaneously in feed and in water for drinking. The use of both forms of l-lysine produced by fermentation using C. glutamicum CGMCC 17927 in animal nutrition was considered safe for the consumers and for the environment. Exposure of users through inhalation to l-lysine HCl and l-lysine sulfate produced with C. glutamicum CGMCC 17927 was considered very likely. In absence of data, the FEEDAP Panel could not conclude on the potential of both forms of the additive to be irritant for skin and eyes or to be dermal sensitisers. l-Lysine HCl and l-lysine sulfate were considered as efficacious sources of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen.

Safety and efficacy of a feed additive consisting of concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride produced by Escherichia coliNITE BP-02917 for all animal species (Metex NoovistaGo).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride produced by Escherichia coli NITE BP-02917 as nutritional and as sensory (flavouring compound) feed additives for all animal species. The production strain did not carry ■■■■■ antimicrobial resistance genes and no viable cells of the production strain were detected in the final products. ■■■■■ However, since no sequences of concern remained in the production strain, the potential presence of that DNA did not raise safety concerns. The use of the three forms of l-lysine produced by E. coli NITE BP-02917 in supplementing feed to compensate for l-lysine deficiency in feedingstuffs was safe for the target species. This conclusion would also cover the use as a sensory additive. The FEEDAP Panel identified risks of nutritional imbalances and hygienic concerns for amino acids when administered simultaneously in feed and in water for drinking. The use of the three forms of l-lysine produced by E. coli NITE BP-02917 in animal nutrition was considered safe for the consumers and for the environment. Concentrated liquid l-lysine, l-lysine HCl and concentrated liquid l-lysine HCl were not considered to have the potential to cause respiratory toxicity, or skin sensitisation. l-Lysine HCl and concentrated liquid l-lysine HCl were not considered skin and eye irritants. Concentrated liquid l-lysine, due to its high pH, might be corrosive for skin and eyes. The three forms were considered an efficacious source of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen. The three forms of the additive were also considered efficacious as feed flavouring compounds under the proposed conditions of use.

Safety and efficacy of a feed additive consisting of l-arginine (produced by Corynebacterium glutamicum CGMCC 20516) for all animal species (Eppen Europe SAS).

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of the feed additive consisting of l-arginine produced by fermentation using a non-genetically modified strain of Corynebacterium glutamicum (CGMCC 20516). The additive is intended to be used in feed and water for drinking for all animal species and categories. The production strain was considered suitable for the qualified presumption of safety (QPS) approach to safety assessment. No viable cells of C. glutamicum CGMCC 20516 were detected in the final product. l-Arginine produced using C. glutamicum CGMCC 20516 is safe for the target species when supplemented in appropriate amounts to the diet according to the nutritional needs of the target species, for the consumer and for the environment. In the absence of data, the FEEDAP Panel could not conclude on the safety of l-arginine produced by C. glutamicum CGMCC 20516 for the users. The additive l-arginine produced by fermentation using C. glutamicum CGMCC 20516 is regarded as an efficacious source of the essential amino acid l-arginine for non-ruminant species. For the supplemental l-arginine to be as efficacious in ruminants as in non-ruminant species, it requires protection against degradation in the rumen.

Safety and efficacy of a feed additive consisting of l-lysine sulfate produced by Escherichia coli CGMCC 7.398 for all animal species (Kempex Holland B.V.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l-lysine sulfate produced by the genetically modified strain Escherichia coli CGMCC 7.398 as a nutritional feed additive for all animal species. Neither the production strain nor its recombinant DNA were detected in the final product. The additive does not pose any safety concerns associated with the production strain. The additive under assessment is considered safe for the target species. When using l-lysine sulfate, the background sulfur/sulfate content in the compound feed should be taken into account. l-lysine sulfate produced by E. coli CGMCC 7.398 is safe for the consumers and for the environment. In the absence of data, the FEEDAP Panel cannot conclude on the potential of the additive under assessment to be irritant to skin or eyes, or on its potential to be a dermal sensitiser. The endotoxin activity of the additive represents a risk by inhalation for users handling the additive. The additive l-lysine sulfate is considered as an efficacious source of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as it is in non-ruminant species, this would require protection against degradation in the rumen.

Assessment of the feed additive consisting of potassium diformate for all animal species for the renewal of its authorisation (Addcon GmbH).

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the assessment of the application for renewal of authorisation of potassium diformate for all animal species. The additive was initially evaluated in 2004 and re-evaluated by the Panel in 2012, with the conclusion that the additive (i) was safe for the target species, the consumer and the environment when used under the proposed conditions; (ii) was an eye irritant and (iii) had the potential to increase the storage time of raw fish and fish by-products for feed use in a dose-dependent manner at low temperature. The FEEDAP Panel considered that the use of potassium diformate under the approved conditions of use remains safe for consumers and the environment, and that it is an eye irritant. Due to the absence of data, the FEEDAP Panel could not conclude on the potential of the additive to be a skin irritant or a respiratory or dermal sensitiser. Regarding the safety for the target species, the FEEDAP Panel considered that the mixture of different sources of potassium diformate remains safe for use in sows' feed under the approved conditions of use (12,000 mg/kg complete feed). However, based on a tolerance trial, the Panel concluded that the maximum safe level of potassium diformate in weaned piglets should be reduced to 6,000 mg/kg complete feed and the same conclusion was extended to pigs for fattening. Owing to the lack of information provided, the Panel could not conclude on the safety of the additive for species other than pigs under the approved conditions. The present application does not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive.

The utilisation of regulated standardised care packages by Danish chiropractors: a mixed methods study.

BACKGROUND: In Denmark, chiropractors in primary care work as independent private contractors regulated by the Danish National Health Authorities. The regulation includes partial reimbursement intended for standardised care packages for lumbar and cervical radiculopathy and lumbar spinal stenosis. Random checks have shown lower use than expected. This study aimed to describe and explore the utilisation of standardised chiropractic care packages and identify barriers to uptake. METHODS: A convergent mixed-method design was conceptualised. The use of standardised care packages was collected by register data. Potential determinants of difference in utilisation were assessed using a modified version of the Determinants of Implementation Behaviour Questionnaire (DIBQ) divided into 13 domains and sent to chiropractors in private clinics in Denmark in 2019. An open-ended question was added to the questionnaire, and thematic content analysis was applied. Qualitative findings were used to expand on the DIBQ data providing further insight into the clinicians' perspective on standardised care packages. RESULTS: Registry data of 244 included chiropractic clinics showed limited and inconsistent use of the standardised chiropractic care packages. A total of 269 chiropractors (44%) answered the DIBQ, and 45 provided data for the qualitative analyses. At least 60% of the clinicians answered 'Strongly agree' or 'Agree' in 10 out of 13 DIBQ domains suggesting a positive attitude towards using the standardised care packages. Three domains were identified as 'problematic' as more than 20% of clinicians disagreed or strongly disagreed: 'Socio-political context', 'Goals' and 'Innovation'. Qualitative findings indicated that lack of usage of the standardised care packages was mainly related to the practical organization of standardised care, the chiropractor's role when managing patients, and the patient population of interest to the clinic (e.g., children, athletes). CONCLUSION: In general, Danish chiropractors displayed positive attitudes towards standardised packages of care. However, considerable variation in the use of the standardised care programs was observed. Low utilisation seemed mainly related to logistics, the chiropractor's role, collaboration with GPs, and the patient population of interest to the clinic. These findings should be further explored in more extensive qualitative studies to inform implementation initiatives to increase and rectify utility.

Manual joint mobilisation techniques, supervised physical activity, psychological treatment, acupuncture and patient education in migraine treatment. A systematic review and meta-analysis.

BACKGROUND: Many people suffering from migraine combine pharmacological and non-pharmacological treatments. The purpose of this systematic review is to provide an updated guideline for some widely used non-pharmacological treatment options for migraine. METHODS: We conducted a systematic literature review of randomized studies of adults with migraine treated with manual joint mobilisation techniques, supervised physical activity, psychological treatment, acupuncture and patient education. The main outcomes measured were days with headache and quality of life. Recommendations were formulated based on the Grade of Recommendation, Assessment, Development and Evaluation (GRADE) approach including patient preferences based on expert opinion and questionnaire data. RESULTS: The overall level of certainty of the evidence was low to very low. Manual therapy techniques and psychological treatment did not change the studied outcomes. Supervised physical activity might have a positive impact on quality of life, acupuncture on headache frequency, intensity, quality of life and the use of attack-medicine. Patient education might improve self-rated health and quality of life and increase the number of well-informed patients. CONCLUSION: Based on observed effects, the lack of serious adverse events, and patients' preferences, we make weak recommendations for considering the investigated interventions as a supplement to standard treatment.Protocol registration: Prospero CRD42020220132.