 studies 51 - 82 were placebo‐controlled.

The search returned 1,194 results, which were reduced to 737 after duplicates were removed. One further potentially eligible article was retrieved from the additional search of Google Scholar. Title and abstract screening removed 597 articles, while 141 articles were retrieved and reviewed in full. Of these, 108 were ineligible. Thus, in total, eligible data from 33 independent meta‐analyses of RCTs of nutrient supplementation in mental disorders were included for this meta‐review (see Figure 1 ).

DISCUSSION

This meta‐review aggregated and evaluated all the recent top‐tier evidence from meta‐analyses of RCTs examining the efficacy and safety of nutritional supplements in mental disorders. We identified 33 eligible meta‐analyses published from 2012 onwards (26 since 2016), with primary analyses including 10,951 individuals with psychiatric conditions (specifically depressive disorders, anxiety and stress‐related disorders, schizophrenia, states at risk for psychosis, bipolar disorder and ADHD), randomized to either nutritional supplementation (including omega‐3 fatty acids, vitamins, minerals, N‐acetylcysteine and other amino acids) or placebo control conditions. Although the majority of nutritional supplements assessed did not significantly improve mental health outcomes beyond control conditions (see Figures 2-7), some of them did provide efficacious adjunctive treatment for specific mental disorders under certain conditions.

The nutritional intervention with the strongest evidentiary support is omega‐3, in particular EPA. Multiple meta‐analyses have demonstrated that it has significant effects in people with depression, including high‐quality meta‐analyses with good confidence in findings as determined by AMSTAR‐264. Meta‐analytic data have shown that omega‐3 is effective when given adjunctively to antidepressants51, 64. As a monotherapy intervention, the data are less compelling for omega‐3, while DHA or DHA‐predominant formulas do not appear to show any obvious benefit in MDD51, 64.

Omega‐3 supplementation appears to be of greatest benefit when administered as high‐EPA formulas, as significant relationships between EPA dosage and effect sizes are also observed in high‐quality meta‐analyses of RCTs59, 64. Emergent data from RCTs further indicate that omega‐3 may be most beneficial for patients presenting with raised inflammatory markers83. The available meta‐analyses suggest that omega‐3 supplementation is not effective in patients with depression as a comorbidity to chronic physical conditions65, including cardiometabolic diseases, a finding which has been replicated in subsequent trials84. In light of current adverse event
studies 51 - 82 were placebo‐controlled. 

 The search returned 1,194 results, which were reduced to 737 after extra were get rid of. One further potentially eligible article was retrieved from the additional search of Google Scholar. deed and abstract screening removed 597 article, while 141 article were retrieved and review in full. Of these, 108 were ineligible. Thus, in full, eligible data from 33 independent meta‐analyses of RCTs of alimentary supplementation in mental disorders were included for this meta‐review (see Figure 1). 

 DISCUSSION 

 This meta‐review aggregated and evaluated all the late top‐tier evidence from meta‐analyses of RCTs examining the efficacy and safety of nutritional supplements in genial disorders. We identified 33 eligible meta‐analyses published from 2012 onwards (26 since 2016), with primary analyses include 10,951 individuals with psychiatric conditions (specifically depressive disorders, anxiety and stress‐related disorders, schizophrenia, states at hazard for psychosis, bipolar disorder and ADHD), randomized to either nutritional supplementation (including omega‐3 fatty acids, vitamin, mineral, N‐acetylcysteine and early amino acids) or placebo control conditions. Although the majority of nutritional supplements assessed did not significantly improve genial health outcomes beyond restraint conditions (see Figures 2 - 7), some of them did leave efficacious adjunctive treatment for specific mental disorder under certain conditions. 

 The nutritional intervention with the strongest evidential support is omega‐3, in particular EPA. Multiple meta‐analyses have demonstrated that it has significant effects in people with depression, including high‐quality meta‐analyses with good confidence in findings as settle by AMSTAR‐264. Meta‐analytic data have testify that omega‐3 is effective when give adjunctively to antidepressants51, 64. As a monotherapy intervention, the data are less compelling for omega‐3, while DHA or DHA‐predominant formulas do not look to show any obvious benefit in MDD51, 64. 

 Omega‐3 supplementation appears to be of greatest benefit when administered as high‐EPA formulas, as significant relationships between EPA dosage and impression sizes are besides observed in high‐quality meta‐analyses of RCTs59, 64. Emergent data from RCTs further indicate that omega‐3 may be most beneficial for patient presenting with enhance inflammatory markers83. The available meta‐analyses indicate that omega‐3 supplementation is not effective in patients with depressive disorder as a comorbidity to chronic forcible conditions65, including cardiometabolic diseases, a finding which has been replicate in subsequent trials84. In light of current adverse event
 stkdies 51 - 82 were placebo‐conurolled.

The search returnxd 1,194 reshlts, whizh were reduced to 737 after du'licqtes qere removed. One furthdr potentpally elitiblt article was retcjeved fvjm tgc addntmonal search of Google Scvolar. Title ang xbdtract screening removed 597 articles, rhile 141 srhicles were rejrievtd wnd dvvlewed in full. Of these, 108 were inemigible. Thus, in totak, eligible data from 33 indeoendfnt meta‐analyses ov RCTs of nofriqbt supplemengation in mental disorsers were included for this metx‐revizw (see Figutz 1 ).

DLVCUSSION

Thiw metw‐review aggrcbated dnd evakuated all the rerent top‐tier evidence frok meta‐analyses of TCTs examitiug the efficacy and sqfwty ox nudritkinau shp'lejents ln jental diskrders. We ieentified 33 eligible mqns‐analyses puglisheq srom 2012 onwards (26 since 2016), with primary analjses including 10,951 individuals with psychiatric confitions (s[ecifically depressive disorders, anxiety and strevs‐reletdd blfuedfrs, schizophrenia, states at risk for psychosif, bopplar disorder cnd ADHD), randomiaef yj either nutrktional shpplementation (incpuding jmega‐3 fatty acyds, fitamins, minerals, N‐acetylcywteine and onher amino acids) or plccebo controu comditipns. Although the majoricy of hutritional supplemehgs assessed did vot shgnificantly improve mentaj health iutcpmes behond contrjl conditilns (sca Figures 2-7), some of them dhd provide efficacious adjunctive treatmeiv for specifiv kennal disorbers ukder certain cogditions.

The nujritional intefvention wpth the svrongest eviqentiary suppmtt is omega‐3, ii particujar WPA. Nultipld meta‐analyses nave demouftrared that it has sinnifizznt effects in 'topoe with depressoon, inslldiig hidv‐quality metd‐anauysdx witf good confldevce on findings as deterkines by AMSTAR‐264. Meta‐anslntic data have shjwn that omegs‐3 is effective whej givxn adjnnctivrly to antidepressants51, 64. As a monofherapy ijtevvention, the qata are less cokpelling for omega‐3, while DHA or DHA‐prediminant formulas di not appear to shoc sny obvious benesit in MDG51, 64.

Omega‐3 supplementatuon appears to be of greatest benefit shen agminidtered as high‐EPA formulas, as significant relationships between EPA dosagw and xfsect sizes zre slso mbfzrved ig hijh‐duality meta‐analjses of RCTs59, 64. Emergent data from RCTs fustker indicate that omega‐3 may br oost beneficixl for patients presentihg with taised inflammatory markers83. The available meta‐analyses xuggest rhat kmega‐3 suppuementation is not effeccive ib patiebts aith depressiun ss a comorblditb tk chronic physical conditions65, inxludint fardiometabolic viseases, a flnaing shich ras been replicafed jj subrequent trialx84. In light of vurrent adverse evenn
studies 51 - 82 were placebo‐controlled. The 1,194 which were to 737 after potentially article was retrieved the additional search Google Scholar. Title and abstract screening 597 articles, while 141 articles were retrieved and reviewed in full. Of these, were ineligible. Thus, in total, eligible data from 33 independent meta‐analyses of RCTs nutrient in disorders included for this meta‐review (see Figure 1 ). DISCUSSION This meta‐review aggregated and evaluated all the top‐tier evidence from meta‐analyses of RCTs examining the and safety of nutritional in mental disorders. We identified eligible published from onwards since with primary analyses 10,951 individuals with psychiatric conditions (specifically depressive disorders, anxiety and stress‐related disorders, schizophrenia, states at risk for bipolar disorder randomized to nutritional (including fatty acids, vitamins, and other amino acids) or placebo the majority of nutritional supplements assessed did not improve mental outcomes beyond control conditions (see Figures some of them did provide efficacious adjunctive treatment specific mental disorders under certain conditions. The nutritional intervention with the strongest evidentiary support is particular EPA. Multiple meta‐analyses demonstrated that it significant in with including high‐quality with good confidence in findings as determined by AMSTAR‐264. Meta‐analytic data shown that omega‐3 is effective when given adjunctively to antidepressants51, a intervention, the data less compelling for omega‐3, DHA DHA‐predominant formulas do not show obvious 64. supplementation to be of greatest when administered as high‐EPA formulas, significant relationships between EPA also observed in high‐quality meta‐analyses of RCTs59, 64. data from RCTs further indicate that omega‐3 be most beneficial for patients presenting with raised inflammatory markers83. The available suggest that is not effective in patients with depression as comorbidity to chronic physical including cardiometabolic diseases, a finding which has been replicated subsequent In light current adverse event
 studies 51 - 82 were placebo‐controlLed.

The searCh retUrnEd 1,194 rEsUlts, WhicH were reduced to 737 AFter Duplicates were removed. ONe furThER potENtIally EligiblE ArTICle WaS rEtrIeVEd From tHe aDditionAl search of gooGlE Scholar. TitlE AnD abstract sCreEning removed 597 ArtIcles, wHiLe 141 aRTicleS weRe retRieved ANd reviEwed in fulL. OF These, 108 wERe ineliGIBlE. ThuS, in total, eligible dATa FRom 33 independent Meta‐anAlYSeS OF RCts oF nutrient sUpPlemeNTation iN MeNTAL diSOrders were incLuded for thiS MetA‐revieW (sEe FIGure 1 ).

DIsCUSSiOn

thiS meta‐review AggrEgated and EvaluaTEd all thE Recent tOp‐tier EviDenCe frOM mEtA‐anAlYSes OF RcTs EXamIning the EfFiCacy aNd saFETY Of nuTriTionAl supPlements in menTal DisoRDerS. We idEntifIed 33 eLiGible Meta‐anAlyseS pUblished from 2012 onwArds (26 Since 2016), with PriMaRy aNaLyses INcludiNg 10,951 iNdiViduals With psyCHiaTrIC COnDitions (specificallY dEPReSsive disOrders, ANxIeTY and streSs‐RelAted DISordeRs, scHIzOphrenia, States AT rIsK for psyChOsis, biPoLar DisOrder ANd ADhD), randOmized to EitheR Nutritional supPLementation (inCLuDINg OMega‐3 FatTy acids, vitaMins, MInerAls, N‐ACeTylCYsteiNe and OtHEr AMino acids) or placebo cOnTrol coNditiOns. Although thE majority oF NUTritionaL supPLeMEnts assessed diD not sIgnificantLY improve MentaL health oUtcomes beYONd controL coNdiTioNs (sEE fiGures 2-7), some of thEM Did pRoVide effIcaCious adJunCtiVe tReaTmEnt for speCific menTaL dIsOrDerS undeR Certain cOnDitIoNs.

THe nutRItionaL inteRvenTiOn WIth The stroNGeST EvidEnTiAry sUppOrT is omEga‐3, iN ParTicular ePA. MultipLe mETa‐anAlYsEs have dEmonstrated thAt It has signiFiCanT effecTS In people With depression, including HIgh‐qualIty Meta‐aNalySes with goOd cOnfideNce IN findiNgs as dEtermInEd bY amSTAR‐264. mETa‐AnaLyTic data havE SHowN that OmEga‐3 iS effectIve when given adjuncTIveLy to antidepreSsaNts51, 64. AS A MoNotHErAPy iNtERveNTIon, the data are leSs compelliNg FOr Omega‐3, while dhA oR DhA‐predoMinant fOrmulAS do not aPpear to shOw any obviOuS benEFIt iN MDD51, 64.

Omega‐3 sUpplemenTation appEArs to BE oF greaTesT benefIt WheN admiNisterED as High‐EpA formUlAs, as siGnifiCaNt relatiOnships between EPA dosage And effEct siZes Are also obSerVEd iN high‐qualIty mEta‐analyseS of rCTS59, 64. EmerGenT Data fRom Rcts FurTHer inDicaTE that omegA‐3 MaY be MOSt Beneficial fOR PAtiEnts pResENting wIth rAised inflammatory MArkers83. The availAble METa‐aNalYSes sUgGest that omega‐3 sUppLeMENtation iS nOt effective In patienTs WIth dePressiOn as a cOmorbidITY tO ChroniC phySicAl conditiOns65, InCLuding cArDiOMetaboLic dIsEases, a FindinG WhicH HAs been replicated In subSEQuent TRiaLs84. In lIgHt of curREnt aDverse evenT
 studies 51 - 82 were plac ebo‐contro lled. 

T hese arch  ret urned 1,194 re s ults , which were reduced t o 737  a f terd up licat es were re m o ved .On e f ur t he r pot ent ially e ligible ar tic le  was retriev e dfrom the a ddi tional searc h o f Goog le  Sc h olar.  Ti tle a nd abs t ract s creeningre m oved 5 9 7 artic l e s,  whi le 141 articles w e re retrieved andreview ed in f ull . O f these, 1 08  were ineligi b le . T hus ,  in total, el igible data fro m 33 i nd epe n dent m eta‐a na l yse s of RCTs o f nu trient su ppleme n tationi n menta l diso rde rswere in cl ude df ort hi s m e ta‐ review ( se eFigur e 1) . DISC USS ION
This  meta‐reviewagg rega t edand e valua tedal l the  recen t top ‐t ier evidence fr om m eta‐analy ses  o f R CT s exa m iningthe  ef ficacyand saf e tyof n u tr itional supplement si n  m ental di sorder s .We identifi ed  33  eli g i ble m eta‐ a na lyses pu blishe d  f ro m 2012on wards(2 6 s inc e 201 6 ), w ith pr imary an alyse s  including 10, 9 51 individual s  w i t hp sych iat ric conditi ons( spec ific a ll y d e press ive d is o rd e rs, anxiety and str es s‐rela ted d isorders, sch izophrenia , s tates at  ris k  f o r psychosis, b ipola r disorder and ADHD ), ra ndomized  to eithe r nutritio nal  su ppl eme n t at ion (includin g omeg a‐ 3 fatty  ac ids, vi tam ins , m ine ra ls, N‐ace tylcyste in ean doth er am i no acids )orpl ace bo co n trol c ondit ions .Al t hou gh them aj o r ityof  n utri tio na l sup plem e nts  assess ed did no t s i gnif ic an tly imp rove mental h ea lth outcom es  be yond c o n trol con ditions (see Figures 2- 7 ), some  of  them  did  provideeff icacio usa djunct ive tr eatme nt  fo r speci f i cmen ta l disorder s und er ce rt ainconditi ons.

The nutritio n alinterventionwit h th e st ron g es t  ev id e nti a r y support is om ega‐3, inpa r ti cular EPA. Mul ti ple met a‐analy ses h a ve demo nstratedthat it h as  sig n i fic ant effect s in peo ple withd epres s io n, in clu ding h ig h‐q ualit y meta ‐ ana lyses  withgo od con fiden ce  in find ings as determined by A MSTAR‐ 264.Met a‐analyti c d a tahave show n th at omega‐3  is  ef fecti vew hen g iven ad jun c tivel y to antidepre s sa nts 5 1 ,64. As a mo n o t her apy i nte r ventio n, t he data are lessc ompelling foromeg a ‐ 3,whi l e DH Aor DHA‐predomi nan tf o rmulas d onot appearto showan y  obvi ous be nefitin MDD5 1 ,  6 4 .

Ome ga‐3  su pplementa tio na ppearsto  b e  of gr eate st  benef it whe n  adm i n istered as high‐ EPA f o r mulas ,  as  sign if icant r e lati onships be tween EPA d osageandeffec t sizes  a re als o o bs erved in h i gh‐qualit y met a‐analy se s of  RC Ts59,64.E m ergen t da ta  fr om RCTs f u r th e rin d ica te t hat o me ga‐3  may be m o st benef ici a l for p at ien t s  prese n ti n g  with rais edinfla m m atory mark e rs83 .  T h e ava ilable  meta‐ analyse s  su gg est tha t o m e ga‐3 supp lementati o n i snoteffectiv ein p at ien ts  with depressio n as a c omorbidi t y  to ch ron i c ph y sicalco nditions65,inclu di n g cardi o m eta bolic d i sea ses , a  fin din g wh i ch has been replicated i n su bsequ e nttrial s84.In  light o f  cur rent adv e rse event
 studies_51 -_82 were placebo‐controlled.

The search_returned 1,194_results,_which were_reduced_to 737 after_duplicates were removed._One further potentially eligible_article was retrieved_from_the additional search of Google Scholar. Title and abstract screening removed 597 articles, while_141_articles were_retrieved_and_reviewed in full. Of these,_108 were ineligible. Thus, in_total, eligible_data from 33 independent meta‐analyses of RCTs of_nutrient_supplementation in mental_disorders were included for this meta‐review (see Figure 1_).

DISCUSSION

This meta‐review aggregated and evaluated all_the recent top‐tier_evidence_from_meta‐analyses of RCTs examining_the efficacy and safety of nutritional_supplements in mental disorders. We identified_33 eligible meta‐analyses published from 2012 onwards_(26 since 2016), with primary analyses_including 10,951 individuals with psychiatric_conditions (specifically_depressive disorders, anxiety and stress‐related_disorders, schizophrenia, states_at risk_for psychosis, bipolar_disorder and ADHD), randomized to either_nutritional supplementation (including_omega‐3 fatty acids, vitamins, minerals, N‐acetylcysteine_and_other amino acids)_or_placebo_control conditions._Although the majority_of_nutritional supplements_assessed_did not significantly improve mental health_outcomes_beyond control conditions (see Figures 2-7), some_of them did provide_efficacious_adjunctive treatment for specific_mental disorders under certain conditions.

The_nutritional intervention with the strongest evidentiary_support is_omega‐3, in_particular EPA. Multiple meta‐analyses have demonstrated that it has significant effects_in people with depression, including high‐quality_meta‐analyses with good confidence_in findings_as_determined by AMSTAR‐264._Meta‐analytic_data have_shown that omega‐3 is effective when given_adjunctively to_antidepressants51, 64. As a monotherapy intervention,_the data are less_compelling_for omega‐3, while DHA or DHA‐predominant_formulas do not appear to show_any obvious benefit in MDD51,_64.

Omega‐3_supplementation_appears to be of greatest_benefit when administered as high‐EPA formulas,_as significant relationships_between EPA dosage and effect sizes are_also_observed in high‐quality meta‐analyses of RCTs59,_64._Emergent data from RCTs further indicate_that_omega‐3_may be most beneficial for_patients presenting with raised inflammatory markers83._The available meta‐analyses suggest that omega‐3 supplementation is not_effective in patients_with depression as a comorbidity_to_chronic_physical conditions65, including cardiometabolic diseases, a finding which has been_replicated in_subsequent trials84. In_light of current adverse event