Lifestyle and dietary interventions for Ménière’s disease (Review)

are the benefits and risks of different lifestyle and dietary changes for Ménière's disease


A B S T R A C T Background
Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. Lifestyle or dietary modifications (including reducing the amount of salt or ca eine in the diet) are sometimes suggested to be of benefit for this condition. The underlying cause of Ménière's disease is unknown, as is the way in which these interventions may work. The e icacy of these di erent interventions at preventing vertigo attacks, and their associated symptoms, is currently unclear.

Objectives
To evaluate the benefits and harms of lifestyle and dietary interventions versus placebo or no treatment in people with Ménière's disease.

Search methods
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 September 2022.

Selection criteria
We included randomised controlled trials (RCTs) and quasi-RCTs in adults with Ménière's disease comparing any lifestyle or dietary intervention with either placebo or no treatment. We excluded studies with follow-up of less than three months, or with a cross-over design (unless data from the first phase of the study could be identified). Abundant water intake may result in an increase in the proportion of people who report no vertigo episodes at > 12 months, but the evidence is very uncertain.

Change in vertigo
No study assessed this outcome Serious adverse events No study assessed this outcome *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Sleeping in darkness may result in an increase in the proportion of people who report no vertigo episodes at > 12 months, but the evidence is very uncertain.

Change in vertigo
No study assessed this outcome Serious adverse events No study assessed this outcome *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. Cochrane Database of Systematic Reviews

Description of the condition
Ménière's disease was first described by Prosper Ménière in 1861 as a condition characterised by episodes of vertigo, associated with hearing loss and tinnitus (Baloh 2001). Su erers may also report a feeling of fullness in the a ected ear. Typically, it initially a ects one ear, although some individuals may progress to develop bilateral disease. A hallmark of the condition is that symptoms are intermittent -occurring as discrete attacks that last from minutes to several hours, then resolve. However, over time there is usually a gradual deterioration in hearing, and there may be progressive loss of balance function, leading to chronic dizziness.
The diagnosis of Ménière's disease is challenging, due to the episodic nature of the condition, clinical heterogeneity and the lack of a 'gold standard' diagnostic test. Even the agreed, international classification system has scope for two categories of diagnosis -'definite ' and 'probable' (Lopez-Escamez 2015). In brief, a diagnosis of definite Ménière's disease requires at least two episodes of vertigo, each lasting 20 minutes to 12 hours, together with audiometrically confirmed hearing loss and fluctuating aural symptoms (reduction in hearing, tinnitus or fullness) in the a ected ear. 'Probable' Ménière's disease includes similar features, but without the requirement for audiometry to diagnose hearing loss, and with scope for the vertigo episodes to last longer (up to 24 hours). Both categories ('definite' and 'probable') require that the symptoms are not more likely to be due to an alternative diagnosis, due to the recognised challenges in distinguishing between balance disorders.
Given the di iculties in diagnosis, the true incidence and prevalence of the disease are di icult to ascertain. A populationbased study in the UK using general practice data estimated the incidence to be 13.1 per 100,000 person-years (Bruderer 2017), and the prevalence of the disease has been estimated at 190 per 100,000 people in the US (Harris 2010). It is a disorder of mid-life, with diagnosis typically occurring between the ages of 30 and 60 (Harcourt 2014). Some studies report a slight female preponderance, and there may be a familial association, with approximately 10% of patients reporting the presence of the disease in a first, second or third degree relative (Requena 2014).
The underlying cause of Ménière's disease is usually unknown. Ménière's disease has been associated with an increase in the volume of fluid in the inner ear (endolymphatic hydrops). This may be caused by the abnormal production or resorption of endolymph (Hallpike 1938;Yamakawa 1938). However, it is not clear whether this is the underlying cause of the condition, or merely associated with the disease. Some authors have proposed other underlying causes for Ménière's disease, including viral infections (Gacek 2009), allergic (Banks 2012) or autoimmune disease processes (Greco 2012). A genetic predisposition has also been noted (Chiarella 2015). Occasionally, the symptoms may be secondary to a known cause (such as a head injury or other inner ear disorder) -in these cases it may be referred to as Ménière's syndrome.
Although Ménière's disease is relatively uncommon, it has a profound impact on quality of life. The unpredictable, episodic nature of the condition and severe, disabling attacks of vertigo cause a huge amount of distress. Quality of life (including physical and psychosocial aspects) is significantly reduced for those with Ménière's disease (Söderman 2002). The costs of the condition are also considerable, both in relation to medical interventions (appointments, diagnostic tests and treatments) and loss of productivity or sick days for those a ected by the condition (Tyrrell 2016).

Description of the intervention
A variety of di erent interventions have been proposed to treat people with Ménière's disease. These include dietary or lifestyle changes, oral treatments, treatments administered by injection into the ear (intratympanic) and surgical treatments. This review focuses on lifestyle and dietary modifications.
Lifestyle interventions have been proposed to be of benefit in Ménière's disease. Lifestyle medicine has been defined as the "evidence-based practice of assisting individuals and families to adopt and sustain behaviors that can improve health and quality of life" (Lianov 2010). Therefore for the purposes of this review we consider lifestyle interventions to include any intervention that aims to modify physical activity, sleep patterns or stress management. This may include psychological interventions, such as stress counselling or cognitive behavioural therapy. Some of these interventions may require input from a therapist, whilst others can be self-delivered.
Many dietary changes have been suggested to benefit patients with Ménière's disease. Salt restriction has been suggested to be of benefit for many years, with dietary intake of sodium usually recommended to be less than 2000 mg per day (Sharon 2015). A survey of UK-based ENT surgeons found that restriction of salt was the second most common 'medical intervention' recommended to patients with Ménière's disease, a er betahistine (Smith 2005). Restriction of ca eine and alcohol has also been said to benefit individuals with Ménière's disease, although there does not appear to be a consensus on the level of intake that is acceptable.
More recently, intake of specially processed cereals has been suggested as a potential therapy for Ménière's disease. These are eaten as a dietary supplement, and have also been used in the treatment of inflammatory bowel disease (Bjorck 2000). Other dietary changes have been proposed, such as following a glutenfree diet (di Berardino 2012).
At present, there is no agreement on which is the ideal treatment for people with Ménière's disease -consequently there is no 'gold standard' treatment with which to compare these interventions.

How the intervention might work
As the underlying cause of Ménière's disease is poorly understood, so too are the ways in which the interventions may work.
Restriction of salt, ca eine or alcohol may work by changing fluid balance, thereby a ecting the volume of endolymphatic fluid. There has also been interest in 'specially processed cereals', which are thought to promote the release of a protein known as antisecretory factor. This protein was initially identified in the intestine (and the pituitary gland) during diarrhoeal diseases, where it acts to reduce excessive fluid secretion. However, it is now thought to a ect water and electrolyte balance more widely (Lange 2001; Ulgheri 2010).

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Cochrane Database of Systematic Reviews
Psychological factors have been recognised to play a part in Ménière's disease (van Cruijsen 2003), and many patients identify stress as a trigger for their attacks (Kirby 2012). Stress management, improving sleep patterns and counselling may help patients to manage anxiety or mood disturbance associated with their disease and therefore assist with improving overall quality of life. They may also help patients to develop coping strategies for their symptoms, including reducing the distress associated with acute vertigo and the communication di iculties associated with hearing loss.

Why it is important to do this review
Balance disorders can be di icult to diagnose and treat. There are few specific diagnostic tests, a variety of related disorders with similar symptoms and a limited number of interventions that are known to be e ective. To determine which topics within this area should be addressed with new or updated systematic reviews we conducted a scoping and prioritisation process, involving stakeholders (https://ent.cochrane.org/balancedisorders-ent). Ménière's disease was ranked as one of the highest priority topics during this process (along with vestibular migraine and persistent postural perceptual dizziness).
Although Ménière's disease is a relatively uncommon condition, the significant impact it has on quality of life demonstrates the clear importance of identifying e ective interventions to alleviate the symptoms. There is considerable variation in the management of Ménière's disease on both a national and international scale, with a lack of consensus about appropriate first-line and subsequent therapies.
This review is part of a suite of six that consider di erent interventions for Ménière's disease. Through these reviews, we hope to provide a thorough summary of the e icacy (benefits and harms) of the di erent treatment options, to support people with Ménière's disease (and healthcare professionals) when making decisions about their care.

O B J E C T I V E S
To evaluate the benefits and harms of lifestyle and dietary interventions versus placebo or no treatment in people with Ménière's disease.

Types of studies
We included randomised controlled trials (RCTs) and quasirandomised trials (where trials were designed as RCTs, but the sequence generation for allocation of treatment used methods such as alternate allocation, birth dates etc).
Ménière's disease is known to fluctuate over time, which may mean that cross-over trials are not an appropriate study design for this condition. However, no cross-over RCTs or cluster-RCTs were identified as relevant for inclusion in this review.
We included studies reported as full-text, those published as conference abstracts only and unpublished data.
Ménière's disease is characterised by episodic balance disturbance -the frequency of attacks may change over time (Huppert 2010).
For studies to obtain accurate estimates of the e ect of di erent interventions, we considered that follow-up of participants should be for at least three months -to ensure that participants are likely to have experienced a number of attacks during the follow-up period. Studies that followed up participants for less than three months were excluded from the review.

Types of participants
We included studies that recruited adult participants (aged 18 years or older) with a diagnosis of definite or probable Ménière's disease, according to the agreed criteria of the American Academy Otolaryngology -Head and Neck Surgery (AAO-HNS), the Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology and the Bárány Society. These criteria are outlined in Appendix 1 and described in Lopez-Escamez 2015.
If studies used di erent criteria to diagnose Ménière's disease, we included them if those criteria were clearly analogous to those described in Lopez-Escamez 2015. For example, studies that used earlier definitions of Ménière's disease (from the AAO-HNS guidelines of 1995) were also included.
We anticipated that most studies would include participants with active Ménière's disease. We did not exclude studies if the frequency of attacks at baseline was not reported or was unclear, but we planned to highlight if there were di erences between studies that may impact on our ability to pool the data, or a ect the applicability of our findings.
We excluded studies where participants had previously undergone destructive/ablative treatment for Ménière's disease in the a ected ear (such as vestibular neurectomy, chemical or surgical labyrinthectomy), as we considered that they were unlikely to respond to interventions in the same way as those who had not undergone such treatment.

Types of interventions
We included the following interventions: • Therapist-delivered lifestyle interventions (including any lifestyle intervention that requires interaction with/guidance from a therapist). • Self-delivered lifestyle interventions (including any lifestyle intervention that can be self-delivered, such as through reading a booklet, watching a video etc.). • Modification of salt intake.
• Modification of ca eine intake.
• Modification of alcohol intake.
• Modification of water intake. • Dietary modifications (e.g. use of specially processed cereals, gluten free diet etc.).
The main comparisons were as follows: • Therapist-delivered lifestyle intervention versus placebo/no treatment.

Cochrane Database of Systematic Reviews
• Increase in water intake versus placebo/no treatment.
• Dietary modifications versus placebo/no treatment.

Concurrent treatments
There were no limits on the type of concurrent treatments used, providing these were used equally in each arm of the study. We planned to pool studies that included concurrent treatments with those where participants did not receive concurrent treatment. We planned to conduct subgroup analysis to determine whether the e ect estimates may be di erent in those receiving additional treatment. However, due to the small number of studies included in the review this was not possible (see Subgroup analysis and investigation of heterogeneity).

Types of outcome measures
We assessed outcomes at the following time points: • 3 to < 6 months; • 6 to ≤ 12 months; • > 12 months.
The exception was for adverse event data, when we used the longest time period of follow-up.
We searched the COMET database for existing core outcome sets of relevance to Ménière's disease and vertigo, but were unable to find any published core outcome sets. We therefore conducted a survey of individuals with experience of (or an interest in) balance disorders to help identify the outcomes that should be prioritised. The review author team used the results of this survey to inform the choice of outcome measures in this review.
We analysed the following outcomes in the review, but did not use them as a basis for including or excluding studies.

Primary outcomes
• Improvement in vertigo • Measured as a dichotomous outcome (improved/not improved), according to self-report, or according to a change of a specified score (as described by the study authors) on a vertigo rating scale.

• Change in vertigo
• Measured as a continuous outcome, to identify the extent of change in vertigo symptoms.

• Serious adverse events
• Including any event that causes death, is life-threatening, requires hospitalisation, results in disability or permanent damage, or in congenital abnormality. Measured as the number of participants who experience at least one serious adverse event during the follow-up period.
Vertigo symptoms comprise a variety of di erent features, including frequency of episodes, duration of episodes and severity/ intensity of the episodes. Where possible, we included data for the vertigo outcomes that encompassed all of these three aspects (frequency, duration and severity/intensity of symptoms). However, we anticipated that these data may not be available from all studies. We therefore extracted data on the frequency of vertigo episodes as an alternative measure for these outcomes.

Secondary outcomes
• • We reported the number of participants who discontinued the intervention due to adverse e ects, or for other reasons. • We also used an exploratory approach to adverse events, and recorded any specific adverse events described in the studies.

Search methods for identification of studies
The Cochrane ENT Information Specialist conducted systematic searches for randomised controlled trials and controlled clinical trials in October 2021 and September 2022. There were no language, publication year or publication status restrictions. The date of the latest search was 14 September 2022.

Electronic searches
The Information Specialist searched: •

Searching other resources
We scanned the reference lists of identified publications for additional trials and contacted trial authors where necessary. In addition, the Information Specialist searched Ovid MEDLINE to retrieve existing systematic reviews relevant to this systematic review, so that we could scan their reference lists for additional trials. In addition, the Information Specialist ran a non-systematic search of Google Scholar to identify trials not published in mainstream journals.
We did not perform a separate search for adverse e ects. We considered adverse e ects described in included studies only.

Selection of studies
The Cochrane ENT Information Specialist used the first two components of Cochrane's Screen4Me workflow to help assess the search results: 1. Known assessments -a service that matches records in the search results to records that have already been screened in Cochrane Crowd and been labelled as 'a RCT' or as 'not a RCT'. 2. The machine learning classifier (RCT model) (Wallace 2017), available in the Cochrane Register of Studies (CRS-Web), which assigns a probability of being a true RCT (from 0 to 100) to each citation. Citations that were assigned a probability score below the cut-point at a recall of 99% were assumed to be non-RCTs. We manually dual screened the results for those that scored on or above the cut-point.
At least two review authors (BG, KG, AL, KW) independently screened the remaining titles and abstracts using Covidence, to identify studies that may be relevant for the review. Any discrepancies were resolved by consensus, or by retrieving the full text of the study for further assessment.
We obtained the full text for any study that was considered possibly relevant and two authors (BG, KG, AL, KW) again independently checked this to determine whether it met the inclusion criteria for the review. Any di erences were resolved by discussion and consensus, or through recourse to a third author if necessary.
We excluded any studies that were retrieved in full text but subsequently deemed to be inappropriate for the review (according to the inclusion/exclusion criteria), according to the main reason for exclusion.
The unit of interest for the review is the study, therefore multiple papers or reports of a single study are grouped together under a single reference identification. The process for study selection is recorded in Figure 1. Cochrane Database of Systematic Reviews

Screening eligible studies for trustworthiness
We assessed studies meeting our inclusion criteria for trustworthiness using a screening tool developed by Cochrane Pregnancy and Childbirth. This tool includes specified criteria to identify studies that are considered su iciently trustworthy to be included in the review (see Appendix 3 and Figure 2). If studies were assessed as being potentially 'high-risk', we attempted to contact the study authors to obtain further information or address any concerns. We planned to exclude studies from the main analyses of the review if there were persisting concerns over trustworthiness, or we were unable to contact the authors.

Figure 2. The Cochrane Pregnancy and Childbirth Trustworthiness Screening Tool
However, both of the included studies had some concerns when using the tool -due to the large e ect size seen for the primary outcome measures, despite the relatively small size of the trials, and also because only limited baseline information was reported (preventing full assessment of the randomisation process).
We had not anticipated this issue when dra ing the protocol for our review, but it is likely to be a widespread issue for reviews that incorporate older studies, and has been a persistent problem through this suite of reviews on Ménière's disease.
There are several possible explanations for the large number of studies across the suite that had concerns when using the tool. One is that there are issues with the trustworthiness of the studies identified in this review, and the data included may not give reliable estimates of the true e ect. Alternatively, the trustworthiness Library Trusted evidence. Informed decisions. Better health.
Cochrane Database of Systematic Reviews screening tool may be excessively sensitive, and flag studies that are trustworthy, but where information has not been fully reported. We note that this tool (and others used for the same purpose) has not yet been validated for use.
We therefore took the decision to include the studies in the review, despite the potential concerns over trustworthiness. The uncertainty in the results is captured as part of our GRADE rating in the certainty of the evidence, using the domain 'study limitations'.

Data extraction and management
Two review authors (BG, AL) independently extracted outcome data from each study using a standardised data collection form.
Where a study had more than one publication, we retrieved all publications to ensure that we had a complete data set. We checked any discrepancies in the data extracted by the two authors against the original reports, and resolved di erences through discussion and consensus. If required, we contacted the study authors for clarification.
We extracted data on the key characteristics of the studies, including the following information: • study design, duration of the study, number of study centres and location, study setting and dates of the study; • information on the participants, including the number randomised, those lost to follow-up or withdrawn, the number analysed, the age of participants, gender, severity of the condition, diagnostic criteria used, inclusion and exclusion criteria for the individual studies; • details of the intervention, comparator, and concomitant treatments or excluded medications; • the outcomes specified and reported by the study authors, including the time points; • funding for the study and any conflicts of interest for the study authors; • information required to assess the risk of bias in the study, and to enable GRADE assessment of the evidence.
Once the extracted data were checked and any discrepancies resolved, a single author (KW) transferred the information to Review Manager 5 (RevMan 2020).
The primary e ect of interest for this review is the e ect of treatment assignment (which reflects the outcomes of treatment for people who were assigned to the intervention) rather than a per protocol analysis (the outcomes of treatment only for those who completed the full course of treatment as planned). For the outcomes of interest in this review, we extracted the findings from the studies on an available case basis, i.e. all available data from all participants at each time point, based on the treatment to which they were randomised. This was irrespective of compliance, or whether participants had received the intervention as planned.
In addition to extracting pre-specified information about study characteristics and aspects of methodology relevant to risk of bias, we extracted the following summary statistics for each study and outcome: • For continuous data: the mean values, standard deviation and number of patients for each treatment group at the di erent time points for outcome measurement. Where change-from-baseline data were not available, we extracted the values for endpoint data instead. If values for the individual treatment groups were not reported, where possible we extracted summary statistics (e.g. mean di erence) from the studies. • For binary data: we extracted information on the number of participants experiencing an event, and the number of participants assessed at that time point. If values for the individual treatment groups were not reported, where possible we extracted summary statistics (e.g. risk ratio) from the studies. • For ordinal scale data: if the data appeared to be normally distributed, or if the analysis performed by the investigators indicated that parametric tests are appropriate, then we treated the outcome measure as continuous data. Alternatively, if data were available, we converted these to binary data for analysis -for example, for analysis of improvement in disease-specific health-related quality of life, when rated using the AAO-HNS 1995 Functional Level Scale. • For time-to-event data: we did not identify any time-to-event data for the outcomes specified in the review.
If necessary, we converted data found in the studies to a format appropriate for meta-analysis, according to the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2021).
We pre-specified time points of interest for the outcomes in this review. Where studies reported data at multiple time points, we planned to take the longest available follow-up point within each of the specific time frames. However, the studies included in this review only reported at one time-point.

Assessment of risk of bias in included studies
Two authors (BG, AL) undertook assessment of the risk of bias of the included studies independently, with the following taken into consideration, as guided by the Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2011): • sequence generation; • allocation concealment; • blinding; • incomplete outcome data; • selective outcome reporting; and • other sources of bias.
We used the Cochrane risk of bias tool (Handbook 2011), which involves describing each of these domains as reported in the study and then assigning a judgement about the adequacy of each entry: 'low', 'high' or 'unclear' risk of bias.

Measures of treatment e ect
We summarised the e ects of the majority of dichotomous outcomes (e.g. serious adverse e ects) as risk ratios (RR) with 95% confidence intervals (CIs). We have also expressed the results as absolute numbers based on the pooled results and compared to the assumed risk in the summary of findings tables (Summary of findings 1; Summary of findings 2; Summary of findings 3) and full GRADE profiles (Table 1; Table 2; Table 3).
For continuous outcomes, we expressed treatment e ects as a mean di erence (MD) with standard deviation (SD). We did not need to use the standardised mean di erence to pool any data.

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Unit of analysis issues
Ménière's disease is unlikely to be a stable condition, and interventions may not have a temporary e ect. If cross-over trials are identified then we planned to use the data from the first phase of the study only. If cluster-randomised trials were identified then we would have ensured that analysis methods were used to account for clustering in the data (Handbook 2021). However, we did not identify any cross-over studies, or cluster-randomised trials.
We did identify one study with four arms (Kitahara 2016). One arm was not relevant for this review, and is included in a separate review of surgical interventions for Ménière's disease (Webster 2021a). The remaining arms comprised two active interventions, and one comparator. As both active interventions were relevant for separate comparisons in this review (sleeping in darkness and abundant water intake), we have included the 'no treatment' arm as the comparator for both of the active interventions.

Dealing with missing data
We planned to contact study authors via email whenever the outcome of interest was not reported, if the methods of the study suggest that the outcome had been measured. We did the same if not all data required were reported (for example, standard deviations), unless we were able to calculate them from other data reported by the study authors.

Assessment of heterogeneity
We planned to assess clinical heterogeneity by examining the included studies for potential di erences between them, as well as using the I 2 statistic and the P value from the Chi 2 test. However, each of the studies examined a di erent comparison, and we could not conduct any meta-analysis.

Assessment of reporting biases
We assessed reporting bias as within-study outcome reporting bias and between-study publication bias.

Outcome reporting bias (within-study reporting bias)
We assessed within-study reporting bias by comparing the outcomes reported in the published report against the study protocol or trial registry, whenever this could be obtained. If the protocol or trial registry entry was not available, we compared the outcomes reported to those listed in the methods section. If results are mentioned but not reported adequately in a way that allows analysis (e.g. the report only mentions whether the results were statistically significant or not), bias in a meta-analysis is likely to occur. We then sought further information from the study authors. If no further information was found, we noted this as being a 'high' risk of bias with the risk of bias tool. If there was insu icient information to judge the risk of bias we noted this as an 'unclear' risk of bias (Handbook 2011).

Publication bias (between-study reporting bias)
We did not have su icient studies to create funnel plots for any analysis. Any studies identified through trial registries and other sources (Searching other resources) that remain unpublished are noted in the Ongoing studies section.

Meta-analysis of numerical data
We planned to conduct a meta-analysis of numerical data where possible and appropriate (if participants, interventions, comparisons and outcomes are su iciently similar in the trials identified). However, we only identified a single study for each comparison in this review, therefore no meta-analysis was possible.

Synthesis using other methods
If we were unable to pool numerical data in a meta-analysis for one or more outcomes we planned to provide a synthesis of the results using alternative methods, following the guidance in chapter 12 of the Handbook 2021. However, this was not necessary, as results were provided by a single study.

Subgroup analysis and investigation of heterogeneity
If statistical heterogeneity was identified for any comparison, we planned to assess this considering the following subgroups: • Di erent types of lifestyle management.
• Use of concomitant treatment.
However, due to the paucity of data available, we did not carry out any subgroup analysis.

Sensitivity analysis
We planned to carry out a number of sensitivity analyses for the primary outcomes in this review. However, the paucity of data and the lack of meta-analyses has meant that this was not possible.
We intended to carry out sensitivity analyses for the primary outcomes only, considering: • the use of a fixed-e ect model instead of a random-e ects model; • the diagnostic criteria used for Ménière's disease; • the inclusion/exclusion of studies with identified concerns using the Cochrane Pregnancy and Childbirth Group Screening Tool.

Summary of findings and assessment of the certainty of the evidence
Two independent authors (KG, KW) used the GRADE approach to rate the overall certainty of evidence using GRADEpro GDT (https:// gradepro.org/) and the guidance in chapter 14 of the Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2021). Disagreements were resolved through discussion and consensus. The certainty of evidence reflects the extent to which we are confident that an estimate of e ect is correct, and we have applied this in the interpretation of results. There are four possible ratings: high, moderate, low and very low. A rating of high certainty of evidence implies that we are confident in our estimate of e ect and that further research is very unlikely to change our confidence in the estimate of e ect. A rating of very low certainty implies that any estimate of e ect obtained is very uncertain. Cochrane Database of Systematic Reviews low. The degree of downgrading is determined by the seriousness of these factors: • Study limitations (risk of bias): • This was assessed using the rating from the Cochrane risk of bias tool for the study or studies included in the analysis. We rated down either one or two levels, depending on the number of domains that had been rated at high or unclear risk of bias. • Inconsistency: • This was assessed using the I 2 statistic and the P value for heterogeneity for all meta-analyses, as well as by visual inspection of the forest plot. For results based on a single study we rated this domain as no serious inconsistency. • Indirectness of evidence: • We took into account whether there were concerns over the population included in these study or studies for each outcome, as well as whether additional treatments were o ered that may impact on the e icacy of the intervention under consideration. • Imprecision: • We took into account the sample size and the width of the confidence interval for each outcome. If the sample size did not meet the optimal information size (i.e. < 400 people for continuous outcomes or < 300 events for dichotomous outcomes), or the confidence interval crossed the small e ect threshold we rated down one level. If the sample size did not meet the optimal information size and the confidence interval includes both potential harm and potential benefit we rated down twice. We also rated down twice for very tiny studies (e.g. 10 to 15 participants in each arm), regardless of the estimated confidence interval. • Publication bias: • We considered whether there were likely to be unpublished studies that may impact on our confidence in the results obtained.
We used a minimally contextualised approach, and rated the certainty in the interventions having an important e ect (Zeng 2021). Where possible, we used agreed minimally important di erences (MIDs) for continuous outcomes as the threshold for an important di erence. Where no MID was identified, we provide an assumed MID based on agreement between the authors. For dichotomous outcomes, we looked at the absolute e ects when rating imprecision, but also took into consideration the GRADE default approach (rating down when a RR crosses 1.25 or 0.80).
We have justified all decisions to downgrade the certainty of the evidence using footnotes, and added comments to aid the interpretation of the findings, where necessary.
We planned to provide a summary of findings tables for the following comparisons: • reduction of salt intake versus placebo/no treatment; • reduction of ca eine intake versus placebo/no treatment; • reduction of alcohol intake versus placebo/no treatment.
However, as we did not identify data for these comparisons then we have presented a summary of findings table for the other comparisons included in the review. We have included all primary outcomes in the summary of findings tables.

Results of the search
The searches in September 2022 retrieved a total of 4434 records. This reduced to 3408 a er the removal of duplicates. The Cochrane ENT Information Specialist sent all 3408 records to the Screen4Me workflow. The Screen4Me workflow identified 122 records as having previously been assessed: 83 had been rejected as not RCTs and 39 had been assessed as possible RCTs. The RCT classifier rejected an additional 1427 records as not RCTs (with 99% sensitivity). We did not send any records to the Cochrane Crowd for assessment. Following this process, the Screen4Me workflow had rejected 1510 records and identified 1898 possible RCTs for title and abstract screening.

Possible RCTs Rejected
Known assessments 39 83 RCT classifier 1859 1427 Total 1898 1510 We identified 89 additional duplicates. We screened the titles and abstracts of the remaining 1809 records. We discarded 1786 records and assessed 23 full-text records.
We excluded 18 records (linked to 16 studies) with reasons recorded in the review (see Excluded studies). We included two completed studies (three records) where results were available. Two additional records are listed as ongoing studies (see Characteristics of ongoing studies for details).

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Participants
Kitahara 2016 recruited adult participants with a diagnosis of definite Ménière's disease, according to the AAO-HNS 1995 criteria. Hanner 2010 stated that participants with "definite Ménière's disease" were included, and cites the AAO-HNS 1995 guidelines elsewhere in the article. However, there is no explicit description of the use of the AAO-HNS 1995 criteria for inclusion in the study. Although the majority of participants in the Hanner 2010 study were adults, we note that the inclusion criteria were from age 12 to 80, and it appears that at least one 12-year-old was included in the study. We therefore have some uncertainty regarding the population included in this study.

Features of Ménière's disease
The study Kitahara 2016 included individuals with unilateral Ménière's disease, in whom three to six months of medical treatment had not improved their symptoms. The treatment used before entry to the study varied for each individual, but included diuretics, betahistine, diphenidol, dimenhydrinate and diazepam. The mean duration of Ménière's disease in the participants was approximately 2.5 years, and the average attack frequency at baseline was 1.6 to 1.7 attacks per month.
Hanner 2010 included participants with a longer duration of Ménière's disease on average (12 to 14 years, but with a range from 1 to 37 years). No information was provided on the attack frequency at baseline or therapy used before entry to the trial.

Background interventions
Participants in Kitahara 2016 all continued to receive "traditional oral medications" throughout the course of the trial. As described previously, this varied for individual participants, but may have included diuretics, betahistine, diphenidol, dimenhydrinate and/or diazepam.
Hanner 2010 stated that "no changes were made in the patient's ordinary medication", but no information was provided regarding the types of medication used.

Abundant water intake versus no treatment
Kitahara 2016 assessed this comparison, comparing water intake of 35 mL/kg/day plus standard, oral medications to oral medications alone.

Sleeping in darkness versus no treatment
This comparison was also assessed by Kitahara 2016, comparing sleeping in darkness (defined as lying in bed in an unlit room less than 0.1 lux for six to seven hours per night) plus standard, oral medications to oral medications alone.

Specially processed cereals versus placebo
Hanner 2010 considered this comparison, and randomised participants to receive either specially processed cereals -which are intended to promote an increase in production of antisecretory factor -or standard cereals, without anti-secretory factor promoting activity.

Improvement in vertigo
For this outcome we included dichotomous data -assessed as the proportion of participants whose vertigo had 'improved' or 'not improved'.

Global score
Neither study reported the improvement of vertigo using a global score that considered the frequency, duration and intensity of vertigo attacks.

Frequency
One study assessed improvement in vertigo frequency (Kitahara 2016), but actually considered complete resolution of vertigo, rather than any improvement.

Change in vertigo
This outcome included data on the change in vertigo using a continuous numerical scale. However, neither study reported on this outcome.

Serious adverse events
Neither study provided any details on how or whether serious adverse events were monitored and reported.

Disease-specific health-related quality of life
One study considered this outcome, and reported the Functional Level Scale (FLS) from the AAO-HNS 1995 guidelines (Hanner 2010). This ranges from 1 to 6, with higher scores representing worse quality of life.

Hearing
Kitahara 2016 assessed hearing using pure tone audiometry at an average of four frequencies (0.5 kHz, 1 kHz, 2 kHz and 4 kHz). This was reported as a dichotomous outcome (improved/not improved) with a threshold of a decrease of 10 dB HL representing improvement.
Hanner 2010 stated that audiometry was also used, but no numerical results are reported.

Tinnitus
This outcome was not reported by any of the included studies.

Other adverse e ects
None of the studies provided any details on how or whether adverse e ects were monitored. No adverse events are reported in the studies. The study Kitahara 2016 provided some data regarding discontinuation of the intervention. The authors stated the following: "At their monthly check-ups, patients were excluded if, according to a self-declaration visual analogue scale, they had been <75% compliant with the rules for their group". We presume that this refers to following the instructions according to the study protocol. However, we note that some participants were also excluded in the control group, and it is not clear what would have constituted a lack of adherence in this group.

Excluded studies
A er assessing the full text, we excluded 16 articles (linked to 18 records) from this review. The main reason for exclusion for each article is listed below.
One study was a narrative review article on Ménière's disease (Richards 1971) and another was a systematic review that contained no primary data (Hussain 2018). One study was not a randomised controlled trial (NCT05355610).
Three studies assessed an incorrect population, and included participants who had conditions other than Ménière's disease (Faag 2017; Lee 2019; Shin 2017). One further study aimed to include participants with Ménière's disease, but required patients to selfidentify as having the disease in order to participate in the trial (Yardley 2006). No diagnostic criteria were applied at trial entry. We considered that this may result in a mixed population of participants, and therefore it could not be included in this review.
Three studies assessed a form of traditional Chinese medicine (Hong 2011;Sun 2014;Zhong 2008), one considered transauricular cutaneous nerve stimulation (NCT05328895), and one considered vestibular rehabilitation (Cui 2022), which were not relevant interventions for this review. Two further studies did not follow up participants for at least three months (Garcia 2013;Liu 2020).
Finally, we identified two cross-over trials (Ingvardsen 2016;Leong 2013). Although the study population and intervention (specially processed cereals) were relevant for the review, we were unable to extract data from the first period of the trial. In addition, one of the studies had an insu icient duration of follow-up (two months; Ingvardsen 2016)

Risk of bias in included studies
See Figure 3 for the risk of bias summary (our judgements about each risk of bias item for each included study) and Figure 4 for the risk of bias summary (our judgements about each risk of bias item presented as percentages across all included studies). Both studies had some concerns regarding the risk of bias, with at least one domain rated at high risk of bias. Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews

Figure 4. Risk of bias summary (our judgements about each risk of bias item presented as percentages across all included studies).
Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding of participants and personnel (performance bias): All outcomes Blinding of outcome assessment (detection bias): All outcomes Incomplete outcome data (attrition bias): All outcomes Selective reporting (reporting bias) Other bias 0% 25% 50% 75% 100% Low risk of bias Unclear risk of bias High risk of bias

Allocation
Both included studies reported an adequate method to generate a random sequence (either simple drawing of lots, or computer-generated random numbers). However, only Kitahara 2016 described the methods used to ensure concealment of group allocation, with Hanner 2010 being rated at unclear risk for this domain.

Blinding
Kitahara 2016 was an open-label study, with no attempts made to blind participants to the intervention received. This may be understandable, given the nature of the interventions (sleeping in darkness and abundant water intake), although it still presents a risk of performance bias. Study personnel and outcome assessors were also not blinded to the group allocation for each participant. We therefore rated it at high risk of performance and detection bias.
Hanner 2010 used a placebo intervention to blind participants to their group allocation, but it was unclear whether study personnel were also blinded, therefore we rated the risk of performance bias as unclear. As the primary outcome was assessed by the participants themselves we considered this study to be at low risk of detection bias.

Incomplete outcome data
We rated both studies at low risk of attrition bias.

Selective reporting
We rated both studies at high risk of selective reporting bias. We did identify a prospective trial registration for the study Kitahara 2016. However, the only outcome listed here was 'all cause mortality'. Therefore we could not fully assess whether the study was reported according to a pre-specified analysis plan. In addition, the methods for this study indicated that improvement in vertigo would be assessed using the ratio of attacks before and a er treatment, with a ratio of ≤ 0.8 representing improvement. However, the results only report the number of people in whom vertigo completely resolved, rather than those in whom there was some improvement.
For Hanner 2010, no trial protocol or registration was available for assessment, but we considered it unusual to conduct a trial of Ménière's disease and only assess vertigo using a quality of life score (not using any assessment of specific vertigo symptoms).
In addition, hearing was assessed as part of this study, but the outcome was not reported fully.

Other potential sources of bias
We rated this domain as low risk for Kitahara 2016. For Hanner 2010, we rated this domain at unclear risk of bias, as there was very limited detail on the conduct of the study, and we had some concerns over the diagnostic criteria used for Ménière's disease, as described above.

E ects of interventions
See: Summary of findings 1 Abundant water intake compared to no treatment for Ménière's disease; Summary of findings 2 Sleeping in darkness compared to no treatment for Ménière's disease; Summary of findings 3 Specially processed cereals compared to placebo for Ménière's disease

Improvement in vertigo
For this outcome we included any data that were reported as a dichotomous (binary) outcome -i.e. classifying participants as having improved or not improved.

Improvement in global score
Global improvement in vertigo was not assessed (taking account of the frequency, severity or intensity and duration of symptoms).

Improvement in frequency
Kitahara 2016 assessed improvement in vertigo frequency, by recording the number of participants in whom vertigo symptoms had completely resolved.

3 to < 6 months and 6 to ≤ 12 months
This outcome was not assessed during these time periods.

> 12 months
The study Kitahara 2016 did not assess 'any improvement' in vertigo -only complete resolution was reported (having no vertigo attacks for a period of six months, i.e. between 18 and 24 months of follow-up). Complete resolution of vertigo was more common in the group who received abundant water than the control group, with a risk ratio (RR) of 1.50 (95% confidence interval Cochrane Database of Systematic Reviews (CI) 1.18 to 1.91; 1 study; 140 participants; very low-certainty evidence; Analysis 1.1).

Change in vertigo
For this outcome we included any continuous data -where the change in vertigo was measured on a continuous scale (such as with a numerical scoring system, or the actual number of vertigo episodes experienced in a given time period). However, this outcome was not reported.

Serious adverse events
No serious adverse events were reported. It is unclear whether this is because they did not occur, or because the authors did not monitor and report adverse events.

Disease-specific health-related quality of life
This outcome was not reported.

Change in hearing
Improvement in hearing was assessed by Kitahara 2016, considering the number of participants in whom hearing improved by at least 10 dB over the course of the study.

3 to < 6 months and 6 to ≤ 12 months
This outcome was not assessed during these time periods.

> 12 months
More participants in the 'abundant water' group experienced an improvement in hearing, with a risk ratio of 5.00 (95% CI 2.03 to 12.31; 1 study; 140 participants; low-certainty evidence; Analysis 1.2).

Change in tinnitus
This outcome was not reported.

Other adverse e ects
No adverse e ects were reported. As above, it is unclear whether this is because they did not occur, or because the authors did not monitor and report adverse e ects.
We also aimed to assess how many participants discontinued the intervention. These data were not available from the report, although the authors did specify the number of people who were excluded from analysis because they had been "<75% compliant with the rules for their group". Four out of 74 participants were excluded from the control group (5.4%), and 5 out of 75 (6.7%) were excluded from the group who were allocated to abundant water intake (RR 1.32, 95% CI 0.37 to 4.72; 1 study; 149 participants; very low-certainty evidence; Analysis 1.3).

Improvement in global score
Global improvement in vertigo was not assessed (taking account of the frequency, severity or intensity and duration of symptoms).

Improvement in frequency
Kitahara 2016 assessed improvement in vertigo frequency, by recording the number of participants in whom vertigo symptoms had completely resolved.

3 to < 6 months and 6 to ≤ 12 months
This outcome was not assessed during these time periods.

> 12 months
The study Kitahara 2016 did not assess 'any improvement' in vertigo -only complete resolution was reported. Complete resolution of vertigo was more common in the group who slept in darkness than the control group, with a risk ratio of 1.47 (95% CI 1.15 to 1.89; 1 study; 130 participants; very low-certainty evidence; Analysis 2.1).

Change in vertigo
This outcome was not reported.

Serious adverse events
No serious adverse events were reported. It is unclear whether this is because they did not occur, or because the authors did not monitor and report adverse events.

Disease-specific health-related quality of life
This outcome was not reported.

Change in hearing
Improvement in hearing was assessed by Kitahara 2016, considering the number of participants in whom hearing improved by at least 10 dB over the course of the study.

3 to < 6 months and 6 to ≤ 12 months
This outcome was not assessed during these time periods.

> 12 months
More participants in the 'sleeping in darkness' group experienced an improvement in hearing, with a risk ratio of 4.43 (95% CI 1.76 to 11.16; 1 study; 130 participants; low-certainty evidence; Analysis 2.2).

Change in tinnitus
This outcome was not reported.

Other adverse e ects
No adverse e ects were reported. As above, it is unclear whether this is because they did not occur, or because the authors did not monitor and report adverse e ects.
As described above, data on the number of participants who discontinued the intervention were not available from the report. However, the authors did specify the number of people who were excluded from analysis because they had been "<75% compliant with the rules for their group". Four out of 74 (5.4%) participants were excluded from the control group, and 14 out of 74 (18.9%) were excluded from the group who were allocated to sleeping in darkness (RR 3.50, 95% CI 1.21 to 10.14; 1 study; 148 participants; very low-certainty evidence; Analysis 2.3).

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Improvement in vertigo
This outcome was not reported.

Change in vertigo
This outcome was not reported.

Serious adverse events
No serious adverse events were reported. It is unclear whether this is because they did not occur, or because the authors did not monitor and report adverse events.

Disease-specific health-related quality of life
This was assessed by Hanner 2010 using the AAO-HNS 1995 Functional Level Scale, which ranges from a score of 1 to 6, with higher scores representing worse quality of life.

3 to < 6 months
Those receiving specially processed cereals had, on average, an improvement in their quality of life as compared to those receiving placebo, with a mean di erence of -1.35 points, but the evidence was very uncertain (95% CI -2.08 to -0.62; 1 study; 51 participants; very low-certainty evidence; Analysis 3.1).

6 to ≤ 12 months and > 12 months
This outcome was not assessed during these time periods.

Change in hearing
No numerical data were reported for this outcome. The authors state that pure tone audiometry was used to assess hearing, and that "No consistent e ect in the otoneurological examinations could be demonstrated in response to the dietary treatment, and the PTA levels were una ected in the majority of patients."

Change in tinnitus
This outcome was not reported.

Other adverse e ects
No adverse e ects were reported. As above, it is unclear whether this is because they did not occur, or because the authors did not monitor and report adverse e ects.
No data were reported regarding the number of people who discontinued the intervention. Outcomes were reported for all participants, but it is unclear whether this is simply because an intention-to-treat analysis was conducted, or whether all participants continued their intervention as allocated throughout the trial.

Summary of main results
We identified one study that assessed abundant water intake or sleeping in darkness compared to no intervention. Data from 223 participants were included. Although the proportion of people who experience improvement in their vertigo may be increased by sleeping in darkness or abundant water intake, the evidence was very uncertain. No data were identified that considered a change in vertigo (as a continuous variable), or serious adverse events. Sleeping in darkness or abundant water intake may increase the number of people who experience an improvement in their hearing, however other outcomes were not assessed (tinnitus, diseasespecific health-related quality of life and other adverse e ects). The evidence on discontinuation of treatment was also very uncertain for both interventions. However, the risk of being excluded from the study due to poor adherence to the intervention was similar between the abundant water intake and the control group, but was higher in those who were allocated to sleeping in darkness.
We also identified one study of 51 participants that assessed the use of specially processed cereals. This study did not report on any of our primary outcome measures (improvement in vertigo, change in vertigo or serious adverse events). Specially processed cereals may result in an improvement in disease-specific health-related quality of life, but the evidence is very uncertain. No other outcomes were reported in this study (such as tinnitus, hearing or other adverse e ects).

Overall completeness and applicability of evidence
There was a dearth of evidence for this review, despite lifestyle and dietary changes being commonly recommended as first-line treatments for Ménière's disease. In particular, we identified no studies that considered the e ects of reducing salt or ca eine. These interventions are commonly recommended as part of firstline therapy for Ménière's disease (Basura 2020). We only identified two studies, and they considered di erent interventions -therefore we were unable to carry out any meta-analysis. All the evidence we found was of very low or low certainty, showing that we are unsure of the e ects of the interventions, and future research may change the e ect estimates a great deal.
This review was conducted as part of a suite considering di erent interventions for Ménière's disease. A number of issues were identified as a ecting the completeness and applicability of the evidence in all the reviews in this suite. These have been described in the companion review on systemic pharmacological interventions for Ménière's disease (Webster 2021b), and are replicated here, as they relate to this review: 1. There is a paucity of evidence about all of these interventions, despite some of them being in common use for Ménière's disease. All the evidence we found was of very low or low certainty, showing that we are unsure of the e ects of the interventions, and future research may change the e ect estimates a great deal. 2. We were unable to carry out many meta-analyses. There were o en di erences in the actual outcomes assessed in the study, therefore we were unable to pool the data to achieve a more precise estimate of any e ect. Study authors also o en used di erent ways of measuring the same outcome, which prevented data from being combined. For example, vertigo was assessed with either a global score, or a frequency score, which could not be combined. 3. Certain outcomes were only assessed by some included studies.
Some studies did not assess the impact of the disease on quality of life or tinnitus at all. Potential adverse e ects of the interventions were also poorly reported or simply not assessed. 4. We noted that unvalidated rating scales were commonly used in the studies included, particularly when looking at the global

Quality of the evidence
We used the GRADE approach to assess the certainty of the evidence in this review. The evidence identified was all lowor very low-certainty, meaning that we are uncertain about the actual e ect of these interventions for all of our outcomes. The main issues that a ected the certainty of the evidence were the domains of study limitations and imprecision. The di erent domains addressed by GRADE are considered in more detail below.

Study limitations/risk of bias
Both studies included in this review had at least some concerns regarding the potential for bias in the study design, conduct or reporting. Kitahara 2016 was an open-label study, with concerns over performance and detection bias. We had concerns over the potential for selective reporting bias with Hanner 2010, and we also rated several domains at unclear risk of bias.

Inconsistency
We did not conduct any meta-analyses for this review, therefore we did not reduce the certainty of evidence due to inconsistency.

Indirectness
We rated down for indirectness if the outcome measured was di erent from that specified in our protocol. This was the case for the study Kitahara 2016, where the authors reported complete resolution of vertigo, rather than 'any improvement' in vertigo.

Imprecision
All of the included studies are very small and we were unable to carry out any meta-analyses. Therefore, the total sample size for each of our outcomes of interest was small, reducing the certainty of the evidence. For some outcomes the resulting confidence intervals for the e ect size were also extremely wide -meaning that there was uncertainty over whether the intervention was beneficial or harmful. This further impacted on the certainty of the evidence.
The GRADE approach involves rating down the certainty of the evidence if the threshold for an important di erence is crossed. For example, if the confidence interval for a result includes the possibility of an important benefit of treatment and the possibility of a trivial di erence then we would reduce the certainty of the evidence by one level. If the confidence interval includes the possibility of both an important benefit and an important harm then the certainty would be reduced further. Therefore, it is important to agree on thresholds for this rating, i.e. where is the threshold, or cut-point, between a trivial di erence and a small, but important benefit or harm for each outcome? This question is di icult to answer, and requires input from people with balance disorders. As part of this review process, one of the author team (KW) joined some discussion groups for people with balance disorders, to try and obtain their views on quantifying an important and meaningful di erence in treatment outcomes. However, the main theme that emerged from these discussions was that people were unable to give a specific threshold for each outcome. Instead, individuals tended to weigh up a variety of di erent factors when determining this threshold. The invasiveness and burden of taking the treatment would be taken into account, as well as potential side e ects and the severity of their symptoms at that time. The GRADE working group would likely refer to this as a "fully contextualised approach", accounting for all aspects of the specific intervention in order to set thresholds for benefit (Zeng 2021). For this review we adopted a "minimally contextualised approach" and rated imprecision for each outcome according to specific, defined thresholds (as described in Methods). However, if the thresholds used are inappropriate then this may a ect the certainty of the evidence (by a maximum of one level).

Other considerations
We did not rate down the certainty of the evidence for other reasons. Publication bias is usually assessed as part of this domain.
Although we are aware that this is an issue with many systematic reviews, we did not find strong indications of publication bias with this review.

Potential biases in the review process
We planned to use the Cochrane Pregnancy and Childbirth Trustworthiness Tool to assess the included studies. We had intended to exclude any study where there were concerns (as identified with this tool) from the main analyses. However, as described above, we were unable to determine whether most of the included studies would pass the screening tool, either due to a lack of reporting in the original articles, or because we were unable to contact the authors to resolve any issues. If these studies were subsequently found to have genuine concerns over research integrity then this would further undermine our confidence in the findings of the review. However, as the evidence for these interventions is all low-or very low-certainty, we considered that this would not greatly impact the findings of the review.

Agreements and disagreements with other studies or reviews
We identified one previous Cochrane Review that considered similar interventions (Hussain 2018). However, this review contained no included studies. This is an identical finding to our review, where we did not identify any evidence on salt, ca eine or alcohol reduction in Ménière's disease.
A clinical practice guideline, Basura 2020, identified one RCT that compared salt restriction to medical therapies for Ménière's disease (Acharya 2017), but as no placebo arm was included in this study it has not been included in our review.

Implications for practice
There are very few randomised controlled trials (RCTs) that consider the use of lifestyle or dietary interventions for Ménière's disease. We identified a small amount of information regarding abundant water intake, sleeping in darkness or the consumption of specially processed cereals. However, the evidence available is all low-or very low-certainty, therefore we cannot be sure if these interventions have any beneficial e ects, nor whether they may be associated with any harm.

Implications for research Further research on lifestyle and dietary interventions for Ménière's disease
There are some specific challenges associated with conducting RCTs that consider lifestyle and dietary modifications (Hébert 2016). These interventions may be complex, requiring a collection of lifestyle or dietary changes for their full e ect. Consequently, adherence to such interventions requires commitment from trial participants -perhaps considerably more than trials of a oneo surgical procedure, or a daily medication. Substantial dropout may be anticipated in these circumstances, leaving trials at risk of attrition bias, and underpowered to detect an e ect. Furthermore, some e ects of lifestyle and dietary interventions may be modest, requiring very large studies to identify any possible benefits. RCTs are costly to conduct, and it may be di icult to obtain funding for such a trial.
Numerous confounders may cause di iculties in assessing the impact of these interventions. Dietary intake, lifestyle and behaviours of specific individuals may vary considerably at the baseline of the trial. The e ects of any intervention in a specific subgroup of participants may then be masked by the mixed population included in the study. Reduction in salt intake, for example, may have di erent e ects in those with a higher baseline intake of salt than those with relatively modest salt intake at the start of a trial.
It is o en impossible to blind participants to their allocated intervention in trials of lifestyle or dietary intervention. Typically, these interventions involve multiple modifications to diet, or specific lifestyle interventions, and it is di icult to establish a suitably blinded 'placebo' arm. Performance bias will therefore be a risk with these types of studies.
Finally, studies of lifestyle and dietary interventions may require assessment of additional outcomes when compared to trials of other interventions. Many of these interventions may be burdensome or time-consuming to undertake, and the acceptability of this to people with Ménière's disease must also be considered.
Even if lifestyle or dietary interventions were of only modest benefit for Ménière's disease, as these interventions may be relatively inexpensive (or free) to implement, the potential for impact is considerable. Therefore further research in this area is clearly warranted. However, it may be that evidence for these interventions will need to be established through study designs other than RCTs. The authors of future systematic reviews may need to consider data from non-randomised studies, in order to establish whether there is any evidence for these interventions.

Further research on other interventions for Ménière's disease
This review was conducted as part of a suite regarding a number of di erent interventions for Ménière's disease. Many of the conclusions below are relevant to all of these reviews and are replicated across the suite.
The lack of high-certainty, RCT evidence suggests that wellconducted studies with larger numbers of participants are required to appropriately assess the e icacy (and potential harms) of these interventions. However, there also needs to be more clarity on which outcomes studies should assess, when and how to assess them. Vertigo is a notoriously di icult symptom to assess, and there is great variety in the methods used to record and report this symptom in the studies we have identified.
There is a clear need for consensus on which outcomes are important to people with Ménière's disease, so that future studies can be designed with this in mind. Development of a core outcome set would be preferable as a guide for future trials. We understand that development of a core outcome set for Ménière's disease was underway, with a project registered on the COMET website (https:// www.comet-initiative.org/Studies/Details/818), but we have been unable to identify any results of this project, or ascertain whether it is ongoing. If a core outcome set is developed, this should include details on the recommended methods used to measure outcomes, ensuring that these are validated, reliable tools. Monitoring and reporting of adverse e ects should be considered a routine part of any study, and should always occur -this is inconsistent at present. Agreement is also needed on the appropriate times at which outcomes should be measured to adequately assess the di erent interventions.
Any decisions about which outcomes to measure, how to measure them and when to measure them must be made with input from people with Ménière's disease, to ensure that the outcomes reported by trialists (and future systematic reviews) are relevant to those with the disease.
For those considering development of a core outcome set, we would highlight that the use of the dichotomous outcome 'improvement' or 'no improvement' of vertigo may cause di iculties when interpreting the results. Individuals with Ménière's disease typically experience fluctuations in disease severity over time. Furthermore, they may have enrolled in a clinical trial at a time when their symptoms were severe. Therefore there is likely to be a natural tendency to improve over time, even for those who do not receive an intervention. The high rate of improvement in those who receive no treatment means that smaller studies are likely to be underpowered to detect a true e ect of treatment. Ideally, agreement should be reached on what constitutes a meaningful improvement in vertigo symptoms, rather than simply considering any improvement as a positive outcome.
Trialists should also be clear about the treatments that participants received before entry to the trial, throughout the trial, and the need for additional treatment during the course of the trial. People with Ménière's disease need to be able to understand whether interventions work in all people with the disease, or whether they might work best during certain phases of the disease -perhaps as Cochrane Database of Systematic Reviews a first-line therapy, or for people in whom other treatments have failed.

A C K N O W L E D G E M E N T S
This project was supported by the National Institute for Health Research, via Cochrane Infrastructure, Cochrane Programme Grant or Cochrane Incentive funding to Cochrane ENT, as well as an Evidence Synthesis Programme grant (NIHR132217). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Evidence Synthesis Programme, NIHR, NHS or the Department of Health.
The development of the protocol (including the prioritisation of outcomes) for this review was informed by responses to a survey to encourage patient and public involvement in the review process. The development and distribution of this survey would not have been possible without the support of the Ménière's Society and the Migraine Trust, and the authors wish to thank them for their help. We would also like to thank the members and a iliates of the Ménière's Society who contributed to discussions about minimally important di erences in vertigo outcomes.
The authors would like to thank Lee Yee Chong for her work on generic text that has been used and adapted (with permission) in the methods section of this protocol. We would also like to extend our thanks to Frances Kellie and Cochrane Pregnancy and Childbirth for their permission to use and reproduce the Cochrane Pregnancy and Childbirth Trustworthiness Screening Tool in this review.

Intervention (n = 27 randomised, n = 27 completed)
Specially processed cereal flakes. The SPC flakes were taken as a dietary supplement for a 3-month long experimental period. The cereals were consumed together with milk, twice daily as a dietary supplement, at a dose of 1 g/kg body weight/day.

Comparator (n = 24 randomised, n = 24 completed)
Placebo flakes (cereals without anti-secretory factor inducing activity). The placebo flakes were taken as a dietary supplement for a 3-month long experimental period. The cereals were consumed together with milk twice daily as a dietary supplement, at a dose of 1 g/kg body weight/day.

Background interventions administered to all participants
None; no changes were made to the participant's routine medication Cochrane Database of Systematic Reviews • No retractions/expressions of concern were identified • Limited information on baseline characteristics of participants was reported. However, there are no concerns regarding excessive similarity based on the details we can assess. • No loss to follow-up was reported • A very marked effect size is seen in the FLS score changes, despite the small sample size • No concerns over the adequacy of randomisation

Bias
Authors' judgement Support for judgement Random sequence generation (selection bias) Low risk Quote: "The patients were randomized by lottery to receive either active treatment with SPC-flakes or placebo".
Comment: simple drawing of lots.

Allocation concealment (selection bias)
Unclear risk Comment: insufficient details regarding allocation process to be confident about this. Authors do state that the "the study code [was] kept secret at the Department of Audiology, Sahlgrenska University Hospital, until all data had been processed".
Blinding of participants and personnel (performance bias) All outcomes Low risk Quote: "Neither the physician nor the patients knew which package contained SPC-flakes or placebo." (E. Jennische, personal communication) Comment: placebo cereals used. Unlikely that participants could have identified the active from placebo versions of the cereals. Study personnel were also blinded to group allocation.
Blinding of outcome assessment (detection bias) All outcomes Low risk Comment: outcomes were assessed by (blinded) participants themselves.
Incomplete outcome data (attrition bias) All outcomes Low risk Comment: no missing outcome data.
Selective reporting (reporting bias) High risk Comment: very limited outcome data, no assessment of vertigo episodes other than through a quality of life score, and these would be considered key outcomes for a study of Ménière's disease. Audiometry outcomes were assessed but not reported in sufficient detail to be included in a meta-analysis. No protocol was available for comparison.
Other bias Unclear risk Comment: insufficient detail on the methods and conduct of study, and baseline details regarding participants to judge. It is unclear whether the AAO-HNS 1995 guidelines for diagnosis of Meniere's disease were used.

Study characteristics
Methods 4-arm, parallel-group, open-label RCT with 24 months total duration of treatment and follow-up.

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Single-centre study. Recruitment took place in the vertigo and dizziness department of Osaka Rosai Hospital in Japan from January 2010 until December 2013.
Sample size: • Number randomised: 223 participants included in the 3 arms relevant to this review (297 total in the trial) • Number completed: 200 participants included in the 3 arms relevant to this review (263 total in the trial)

Participant baseline characteristics
• Age: • Abundant water intake group: mean 46.7 years (SD 13.7) • Sleeping in darkness group: mean 49.7 years (SD 11.9) • Control group: mean 49.7 years (SD 16.5) • Gender: • Abundant water intake group: 28 male ( • Abundant water intake group: mean 1.7 attacks per month (SD 1) • Sleeping in darkness group: mean 1.7 attacks per month (SD 1.1) • Control group: mean 1.6 attacks per month (SD 1) • Hearing loss at baseline: • Abundant water intake group: mean 48.7 dB hearing level (SD 14.9) • Sleeping in darkness group: mean 49.1 dB hearing level (SD 15.1) • Control group: mean 47.3 dB hearing level (SD 13.4) • Measure of tinnitus at baseline: • Not reported • Number of participants with bilateral disease: • None (table of demographics reports laterality of disease for each participant; no participant is listed as having bilateral disease, therefore we assume all were unilateral)

Inclusion criteria:
Definite MD according to the AAO-HNS 1995 criteria. Age ≥ 20 years. Eligible patients were those in whom 3 to 6 months of "basically fixed forms of medical treatment" had produced insufficient benefit (i.e. recurrent vertigo attacks and/or no improvement in sensorineural hearing loss) and for whom surgical treatment would otherwise be considered. Medical treatments included diuretics, betahistine, diphenidol, dimenhydrinate and diazepam. No further information on doses or treatments in each group was provided.

Exclusion criteria:
Cardiac disease; renal dysfunction; middle ear problems; nyctophobia (those who cannot sleep in darkness)

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Cochrane Database of Systematic Reviews
Interventions Intervention A (n = 75 randomised, n = 70 completed) Abundant water intake plus medication. Participants were required to have abundant water intake: 35 mL/kg/day with a self-check diary of water volume/day. They also continued traditional medication as per the control group.
Intervention B (n = 74 randomised, n = 60 completed) Sleeping in darkness plus medication. Participants were given advice to sleep in darkness to maintain the hormonal circadian rhythm, defined as lying in bed in an unlit room less than 0.1 lux for 6 to 7 hours per night with a self-check diary using an illuminometer (Panasonic Corp., Osaka, Japan). They also continued traditional medication as per the control group.

Comparator (n = 74 randomised, n = 70 completed)
Medication only. Participants continued to receive traditional oral medications: "Medical treatments were fixed basically including diuretics, betahistine, diphenidol, dimenhydrinate, and diazepam, all considered effective for persistent symptoms of Meniere's disease".

Background interventions administered to all participants
As described above, all 3 groups received oral medication Outcomes Primary outcomes relevant to this review: • Improvement in vertigo • Improvement of vertigo was assessed using the control of vertigo scale, according to the AAO-HNS 1995, with a score of < 0.8 being regarded as improvement. However, the article only reports the proportion of participants who had complete resolution of vertigo.

• Change in vertigo
• Not reported • Serious adverse events • Not reported; trial registration document does list "all cause mortality" as the primary outcome measure Secondary outcomes relevant to this review: • Disease-specific health-related quality of life • Not assessed or reported • Hearing • Assessed with pure tone audiometry with an average of four frequencies (0.5 kHz, 1 kHz, 2 kHz and 4 kHz). Reported as a dichotomous outcome: improved/not improved, with a threshold of a decrease of 10 dB representing improvement.

• Tinnitus
• Not assessed or reported • Other adverse effects • Not assessed or reported Other outcomes reported in the study: • Blood results for stress (pAVP and cortisol) • Questionnaires measuring psychological factors  Funding sources This study was supported in part by JSPS KAKENHI Grant (2016-2018 and by Grant-in-Aid for Research on Intractable Vestibular Disorder from Japan AMED (2015-2017). The funders above had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Aged over 18 years Serum levels of 25 (OH) vitamin D3 less than 30 ng/mL and more than 10 ng/mL Interventions Intervention group: in addition to receiving betahistine, Pearl vitamin D supplement 50,000 units, one per week for 8 weeks will be prescribed Control group: the placebo, which is exactly the same as the vitamin D supplement in shape and colour, will be delivered once a week for 8 weeks. (It is unclear whether participants in the control group will also receive betahistine).

Footnotes
(1) Functional Level Scale, range 1-6, higher scores = worse quality of life. Change from baseline data at 3 months.

Risk of bias legend
(A) Random sequence generation (selection bias) (B) Allocation concealment (selection bias) (C) Blinding of participants and personnel (performance bias) (D) Blinding of outcome assessment (detection bias) (E) Incomplete outcome data (attrition bias) (F) Selective reporting (reporting bias) (G) Other bias

⨁⨁◯◯ Low
Abundant water intake may increase the number of people who experience an improvement in hearing.
Other adverse events: discontinuation (follow-up: range > 12 months; assessed with: number of participants excluded from follow-up due to < 75% compliance)

Very low
There was little difference between the groups in the proportion of people who discontinued their allocated intervention, but the evidence is very uncertain.

Very low
There may be more chance that people allocated to sleeping in darkness will discontinue this intervention, but the evidence is very uncertain.

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e Only includes those with < 75% compliance. This may be greater than the number of participants who discontinue the intervention completely.