Lifestyle and dietary interventions for Ménière’s disease

Summary of findings 1. Abundant water intake compared to no treatment for Ménière’s disease

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Abundant water intake compared to no treatment for Ménière’s disease
Patient or population: Ménière’s disease Setting: outpatients Intervention: abundant water intake Comparison: no treatment
Outcomes	Risk with no treatment/placebo	Risk with abundant water intake	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Improvement in frequency of vertigo Assessed with: number of participants with no vertigo attacks from 18 to 24 months	Study population		RR 1.50 (1.18 to 1.91)	140 (1 RCT)	⊕⊝⊝⊝ very low¹	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.
	543 per 1000	814 per 1000 (641 to 1000)	RR 1.50 (1.18 to 1.91)	140 (1 RCT)	⊕⊝⊝⊝ very low¹
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). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
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.
¹Unblinded study. Potential for selective reporting for this outcome. Outcome considers complete resolution of vertigo only, not 'any improvement'. Optimal information size was not reached, taken as > 300 events for dichotomous outcomes as a rule of thumb.

Summary of findings 2. Sleeping in darkness compared to no treatment for Ménière’s disease

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sleeping in darkness compared to no treatment for Ménière’s disease
Patient or population: Ménière’s disease Setting: outpatients Intervention: sleeping in darkness Comparison: no treatment
Outcomes	Risk with no treatment/placebo	Risk with sleeping in darkness	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Improvement in frequency of vertigo Assessed with: number of participants reporting no vertigo episodes between 18 and 24 months	Study population		RR 1.47 (1.15 to 1.89)	130 (1 RCT)	⊕⊝⊝⊝ Very low ¹	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.
	543 per 1000	798 per 1000 (624 to 1000)	RR 1.47 (1.15 to 1.89)	130 (1 RCT)	⊕⊝⊝⊝ Very low ¹
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). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
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.
¹Unblinded study. Potential for selective reporting for this outcome. Outcome considers complete resolution of vertigo only, not 'any improvement'. Optimal information size was not reached, taken as > 300 events for dichotomous outcomes as a rule of thumb.

Summary of findings 3. Specially processed cereals compared to placebo for Ménière’s disease

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Specially processed cereals compared to placebo for Ménière’s disease
Patient or population: Ménière’s disease Setting: outpatients Intervention: specially processed cereals Comparison: placebo
Outcomes	Risk with no treatment/placebo	Risk with specially processed cereals	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Improvement in vertigo	No study assessed this outcome
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). 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.

Background

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). Sufferers may also report a feeling of fullness in the affected ear. Typically, it initially affects 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 affected 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 difficulties in diagnosis, the true incidence and prevalence of the disease are difficult to ascertain. A population‐based 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 affected by the condition (Tyrrell 2016).

Description of the intervention

A variety of different 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, after betahistine (Smith 2005). Restriction of caffeine 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 gluten‐free 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, caffeine or alcohol may work by changing fluid balance, thereby affecting 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 affect water and electrolyte balance more widely (Lange 2001; Ulgheri 2010).

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 difficulties associated with hearing loss.

Why it is important to do this review

Balance disorders can be difficult 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 effective. 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/balance-disorders-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 effective 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 different interventions for Ménière's disease. Through these reviews, we hope to provide a thorough summary of the efficacy (benefits and harms) of the different treatment options, to support people with Ménière's disease (and healthcare professionals) when making decisions about their care.

Objectives

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

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) and quasi‐randomised 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 effect of different 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 different 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 differences between studies that may impact on our ability to pool the data, or affect the applicability of our findings.

We excluded studies where participants had previously undergone destructive/ablative treatment for Ménière's disease in the affected 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 caffeine 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.
Self‐delivered lifestyle intervention versus placebo/no treatment.
Reduction of salt intake versus placebo/no treatment.
Reduction of caffeine intake versus placebo/no treatment.
Reduction of alcohol intake versus placebo/no treatment.
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 effect estimates may be different 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 different 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

Disease‐specific health‐related quality of life
- Measured with the Dizziness Handicap Inventory (DHI, Jacobsen 1990), a validated measurement scale in widespread use. If data from the DHI were unavailable we extracted data from alternative validated measurement scales, according to the order of preference described in the list below (based on the validity of the scales for this outcome):
  - DHI short form (Tesio 1999);
  - DHI screening tool (Jacobsen 1998);
  - Vertigo Handicap Questionnaire (Yardley 1992a);
  - Meniere's Disease Patient Oriented Symptoms Inventory (MD POSI, Murphy 1999);
  - University of California Los Angeles Dizziness Questionnaire (UCLADQ, Honrubia 1996);
  - AAO‐HNS Functional Level Scale (FLS, AAO‐HNS 1995).
Hearing
- Measured with pure tone audiometry and reported as the change in pure tone average (PTA), or (alternatively) by patient report, if data from PTA were not available.
Tinnitus
- Measured using any validated, patient‐reported questionnaire relating to the impact of tinnitus, for example the Tinnitus Handicap Inventory (THI, Newman 1996) or the Tinnitus Functional Index (TFI, Meikle 2012).
Other adverse effects
- We reported the number of participants who discontinued the intervention due to adverse effects, 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:

the Cochrane ENT Trials Register (search via the Cochrane Register of Studies to 14 September 2022);
the Cochrane Central Register of Controlled Trials (CENTRAL) (search via the Cochrane Register of Studies to 14 September 2022);
Ovid MEDLINE(R) Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) (1946 to 14 September 2022);
Ovid Embase (1974 to 14 September 2022);
Web of Knowledge, Web of Science (1945 to 14 September 2022);
ClinicalTrials.gov, www.clinicaltrials.gov (to 14 September 2022);
World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), https://trialsearch.who.int/ (to 14 September 2022).

The Information Specialist modelled subject strategies for databases on the search strategy designed for CENTRAL. The strategy has been designed to identify all relevant studies for a suite of reviews on various interventions for Ménière's disease. Where appropriate, they were combined with subject strategy adaptations of the highly sensitive search strategy designed by Cochrane for identifying randomised controlled trials and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, Box 6.4.b, Handbook 2011). Search strategies for major databases including CENTRAL are provided in Appendix 2.

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 effects. We considered adverse effects described in included studies only.

Data collection and analysis

Selection of studies

The Cochrane ENT Information Specialist used the first two components of Cochrane's Screen4Me workflow to help assess the search results:

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'.
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 differences 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.

Figure 1

Flow chart of study retrieval and selection.

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 sufficiently 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 effect 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 drafting 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 effect. Alternatively, the trustworthiness 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 differences 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 effect of interest for this review is the effect 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 different 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 difference) 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 effect

We summarised the effects of the majority of dichotomous outcomes (e.g. serious adverse effects) 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 Table 1; summary of findings Table 2; summary of findings Table 3) and full GRADE profiles (Table 1; Table 2; Table 3).

Table 1. GRADE profile: Abundant water intake compared to no treatment for Ménière’s disease

Certainty assessment							Number of participants		Effect		Certainty	Comment
№ of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Abundant water intake	No treatment	Relative (95% CI)	Absolute (95% CI)	Certainty	Comment
Improvement in frequency of vertigo (follow‐up: range > 12 months; assessed with: number of participants with no vertigo attacks from 18 to 24 months)
1	Randomised trials	Very serious^a,b	Not serious	Serious^c	Serious^d	None	57/70 (81.4%)	38/70 (54.3%)	RR 1.50 (1.18 to 1.91)	271 more per 1000 (from 98 more to 494 more)	⨁◯◯◯ Very low	Abundant water intake may increase the proportion of people who experience complete resolution of vertigo, but the evidence is very uncertain.
Change in hearing: improvement in hearing (follow‐up: range > 12 months; assessed with: number of participants with improvement of ≥ 10 dB on PTA)
1	Randomised trials	Serious^a	Not serious	Not serious	Serious^d	None	25/70 (35.7%)	5/70 (7.1%)	RR 5.00 (2.03 to 12.31)	286 more per 1000 (from 74 more to 808 more)	⨁⨁◯◯ 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)
1	Randomised trials	Serious^a	Not serious	Serious^e	Very serious^d,f	None	5/70 (7.1%)	4/74 (5.4%)	RR 1.32 (0.37 to 4.72)	17 more per 1000 (from 34 fewer to 201 more)	⨁◯◯◯ 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.

CI: confidence interval; RR: risk ratio

^aUnblinded study.

^bPotential for selective reporting for this outcome.

^cOutcome considers complete resolution of vertigo only, not 'any improvement'.

^dOptimal information size was not reached, taken as > 300 events for dichotomous outcomes, as a rule of thumb.

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

^fConfidence interval ranges from potential benefit to potential harm from the intervention.

Table 2. GRADE profile: Sleeping in darkness compared to no treatment

Certainty assessment							№ of participants		Effect		Certainty	Comment
№ of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Sleeping in darkness	No treatment	Relative (95% CI)	Absolute (95% CI)	Certainty	Comment
Improvement in frequency of vertigo (follow‐up: range > 12 months; assessed with: number of participants reporting no vertigo between 18 and 24 months)
1	Randomised trials	Very serious^a,b	Not serious	Serious^c	Serious^d	None	48/60 (80.0%)	38/70 (54.3%)	RR 1.47 (1.15 to 1.89)	255 more per 1000 (from 81 more to 483 more)	⨁◯◯◯ Very low	Sleeping in darkness may increase the proportion of people who experience complete resolution of vertigo, but the evidence is very uncertain.
Change in hearing: improvement in hearing (follow‐up: range > 12 months; assessed with: number of participants with ≥ 10 dB improvement in hearing on PTA)
1	Randomised trials	Serious^a	Not serious	Not serious	Serious^d	None	19/60 (31.7%)	5/70 (7.1%)	RR 4.43 (1.76 to 11.16)	245 more per 1000 (from 54 more to 726 more)	⨁⨁◯◯ Low	Sleeping in darkness 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)
1	Randomised trials	Serious^a	Not serious	Serious^e	Serious^d	None	14/74 (18.9%)	4/74 (5.4%)	RR 3.50 (1.21 to 10.14)	135 more per 1000 (from 11 more to 494 more)	⨁◯◯◯ Very low	There may be more chance that people allocated to sleeping in darkness will discontinue this intervention, but the evidence is very uncertain.

CI: confidence interval; dB: decibels; PTA: pure tone audiometry; RR: risk ratio

^aUnblinded study.

^bPotential for selective reporting for this outcome.

^cOutcome considers complete resolution of vertigo only, not 'any improvement'.

^dOptimal information size was not reached, taken as > 300 events for dichotomous outcomes or > 400 participants for continuous outcomes, as a rule of thumb.

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

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

Table 3. GRADE profile: Specially processed cereals compared to placebo

Certainty assessment							№ of participants		Effect		Certainty	Comment
№ of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Specially processed cereals	Placebo	Relative (95% CI)	Absolute (95% CI)	Certainty	Comment
Change in disease‐specific health‐related quality of life (follow‐up: range 3 months to < 6 months; assessed with: AAO‐HNS Functional Level Scale; from: 1 to 6, higher scores = worse quality of life)
1	Randomised trials	Serious^a	Not serious	Serious^b	Serious^c	None	27	24	‐	MD 1.35 points lower (2.08 lower to 0.62 lower)	⨁◯◯◯ Very low	The evidence is very uncertain about the effect of specially processed cereals on disease‐specific quality of life.

AAO‐HNS: American Academy of Otolaryngology ‐ Head and Neck Surgery;CI: confidence interval; MD: mean difference

^aMultiple domains at unclear risk of bias, leading to some concerns.

^bIt is unclear whether all participants met the AAO‐HNS 1995 criteria for a diagnosis of Ménière's disease.

^cOptimal information size was not reached, taken as > 400 participants for continuous outcomes, as a rule of thumb.

For continuous outcomes, we expressed treatment effects as a mean difference (MD) with standard deviation (SD). We did not need to use the standardised mean difference to pool any data.

Unit of analysis issues

Ménière's disease is unlikely to be a stable condition, and interventions may not have a temporary effect. 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 differences between them, as well as using the I² statistic and the P value from the Chi² test. However, each of the studies examined a different 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 insufficient 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 sufficient 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.

Data synthesis

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 sufficiently 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:

Different types of lifestyle management.
Use of concomitant treatment.
Diagnosis of Ménière's disease.

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‐effect model instead of a random‐effects 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 effect 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 effect and that further research is very unlikely to change our confidence in the estimate of effect. A rating of very low certainty implies that any estimate of effect obtained is very uncertain.

The GRADE approach rates evidence from RCTs that do not have serious limitations as high certainty. However, several factors can lead to the downgrading of the evidence to moderate, low or very 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 I² 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 offered that may impact on the efficacy 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 effect 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 effect (Zeng 2021). Where possible, we used agreed minimally important differences (MIDs) for continuous outcomes as the threshold for an important difference. Where no MID was identified, we provide an assumed MID based on agreement between the authors. For dichotomous outcomes, we looked at the absolute effects 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 caffeine 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

Description of studies

Results of the search

The searches in September 2022 retrieved a total of 4434 records. This reduced to 3408 after 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).

Included studies

We included two RCTs (Hanner 2010; Kitahara 2016). Details of the individual studies can be found in the Characteristics of included studies.

Study design

Both included studies were parallel‐group randomised controlled trials. The duration of follow‐up ranged from three months (Hanner 2010) to two years (Kitahara 2016). One trial was conducted in Japan (Kitahara 2016) and the other in Sweden (Hanner 2010).

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.

Interventions and comparisons

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 anti‐secretory factor ‐ or standard cereals, without anti‐secretory factor promoting activity.

Outcomes

1. Improvement in vertigo

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

1.1. Global score

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

1.2. Frequency

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

2. Change in vertigo

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

3. Serious adverse events

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

4. 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.

5. 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.

6. Tinnitus

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

7. Other adverse effects

None of the studies provided any details on how or whether adverse effects 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

After 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 self‐identify 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 insufficient 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.

Figure 3

Risk of bias summary (our judgements about each risk of bias item for each included study).

Figure 4

Risk of bias summary (our judgements about each risk of bias item presented as percentages across all included studies).

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 after 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.

Effects of interventions

1. Abundant water intake compared to no treatment

1.1. 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.

1.1.1. Improvement in global score

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

1.1.2. Improvement in frequency

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

1.1.2.1. 3 to < 6 months and 6 to ≤ 12 months

This outcome was not assessed during these time periods.

1.1.2.2. > 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 (CI) 1.18 to 1.91; 1 study; 140 participants; very low‐certainty evidence; Analysis 1.1).

1.2. 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.

1.3. 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.

1.4. Disease‐specific health‐related quality of life

This outcome was not reported.

1.5. 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.

1.1.2.1. 3 to < 6 months and 6 to ≤ 12 months

This outcome was not assessed during these time periods.

1.1.2.2. > 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).

1.6. Change in tinnitus

This outcome was not reported.

1.7. Other adverse effects

No adverse effects 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 effects.

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).

2. Sleeping in darkness compared to no treatment

2.1. Improvement in vertigo

2.1.1. Improvement in global score

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

2.1.2. Improvement in frequency

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

2.1.2.1. 3 to < 6 months and 6 to ≤ 12 months

This outcome was not assessed during these time periods.

2.1.2.2. > 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).

2.2. Change in vertigo

This outcome was not reported.

2.3. 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.

2.4. Disease‐specific health‐related quality of life

This outcome was not reported.

2.5. 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.

2.1.2.1. 3 to < 6 months and 6 to ≤ 12 months

This outcome was not assessed during these time periods.

2.1.2.2. > 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).

2.6. Change in tinnitus

This outcome was not reported.

2.7. Other adverse effects

No adverse effects 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 effects.

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).

3. Specially processed cereals compared to placebo

3.1. Improvement in vertigo

This outcome was not reported.

3.2. Change in vertigo

This outcome was not reported.

3.3. 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.

3.4. 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.

3.4.1. 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 difference 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).

3.4.2. 6 to ≤ 12 months and > 12 months

This outcome was not assessed during these time periods.

3.5. 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 effect in the otoneurological examinations could be demonstrated in response to the dietary treatment, and the PTA levels were unaffected in the majority of patients."

3.6. Change in tinnitus

This outcome was not reported.

3.7. Other adverse effects

No adverse effects 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 effects.

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.

Discussion

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, disease‐specific health‐related quality of life and other adverse effects). 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 effects).

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 effects of reducing salt or caffeine. These interventions are commonly recommended as part of first‐line therapy for Ménière's disease (Basura 2020). We only identified two studies, and they considered different 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 effects of the interventions, and future research may change the effect estimates a great deal.

This review was conducted as part of a suite considering different interventions for Ménière's disease. A number of issues were identified as affecting 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:

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 effects of the interventions, and future research may change the effect estimates a great deal.
We were unable to carry out many meta‐analyses. There were often differences in the actual outcomes assessed in the study, therefore we were unable to pool the data to achieve a more precise estimate of any effect. Study authors also often used different 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.
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 effects of the interventions were also poorly reported or simply not assessed.
We noted that unvalidated rating scales were commonly used in the studies included, particularly when looking at the global impact of treatments for vertigo. When such scales are used, it is difficult to know if they are accurately assessing the outcome, and also what size of change on this scale represents a meaningful difference in the outcome (the minimally important difference).
Finally, studies often failed to report clearly what treatments participants received before joining the trial, what maintenance treatment they continued on during the trial, and whether they received any additional treatments over the course of the trial. The impact of these additional treatments may be considerable, particularly for those studies with longer‐term follow‐up. Without knowing the background details of study participants (for example, the duration of their Ménière's disease, or what treatments they have tried in the past) it is difficult to identify the groups of people who may benefit from these treatments.

Quality of the evidence

We used the GRADE approach to assess the certainty of the evidence in this review. The evidence identified was all low‐ or very low‐certainty, meaning that we are uncertain about the actual effect of these interventions for all of our outcomes. The main issues that affected the certainty of the evidence were the domains of study limitations and imprecision. The different 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 different 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 effect 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 difference 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 difference 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 difference and a small, but important benefit or harm for each outcome? This question is difficult 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 difference 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 different factors when determining this threshold. The invasiveness and burden of taking the treatment would be taken into account, as well as potential side effects 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 affect 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, caffeine 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.

Figure 1

Flow chart of study retrieval and selection.

Figure 2

The Cochrane Pregnancy and Childbirth Trustworthiness Screening Tool

Figure 3

Risk of bias summary (our judgements about each risk of bias item for each included study).

Figure 4

Risk of bias summary (our judgements about each risk of bias item presented as percentages across all included studies).

Analysis 1.1

Comparison 1: Abundant water intake versus no treatment, Outcome 1: Improvement in frequency of vertigo (complete resolution) at > 12 months

Analysis 1.2

Comparison 1: Abundant water intake versus no treatment, Outcome 2: Change in hearing: improvement in hearing at > 12 months

Analysis 1.3

Comparison 1: Abundant water intake versus no treatment, Outcome 3: Other adverse effects: exclusion from follow‐up

Analysis 2.1

Comparison 2: Sleeping in darkness versus no treatment, Outcome 1: Improvement in frequency of vertigo (complete resolution) at > 12 months

Analysis 2.2

Comparison 2: Sleeping in darkness versus no treatment, Outcome 2: Change in hearing: improvement in hearing at > 12 months

Analysis 2.3

Comparison 2: Sleeping in darkness versus no treatment, Outcome 3: Other adverse effects: exclusion from follow‐up

Analysis 3.1

Comparison 3: Specially processed cereals versus placebo, Outcome 1: Disease‐specific health‐related quality of life (Functional Level Scale)

Summary of findings 1. Abundant water intake compared to no treatment for Ménière’s disease

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Abundant water intake compared to no treatment for Ménière’s disease
Patient or population: Ménière’s disease Setting: outpatients Intervention: abundant water intake Comparison: no treatment
Outcomes	Risk with no treatment/placebo	Risk with abundant water intake	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Improvement in frequency of vertigo Assessed with: number of participants with no vertigo attacks from 18 to 24 months	Study population		RR 1.50 (1.18 to 1.91)	140 (1 RCT)	⊕⊝⊝⊝ very low¹	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.
	543 per 1000	814 per 1000 (641 to 1000)	RR 1.50 (1.18 to 1.91)	140 (1 RCT)	⊕⊝⊝⊝ very low¹
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). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
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.
¹Unblinded study. Potential for selective reporting for this outcome. Outcome considers complete resolution of vertigo only, not 'any improvement'. Optimal information size was not reached, taken as > 300 events for dichotomous outcomes as a rule of thumb.

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sleeping in darkness compared to no treatment for Ménière’s disease
Patient or population: Ménière’s disease Setting: outpatients Intervention: sleeping in darkness Comparison: no treatment
Outcomes	Risk with no treatment/placebo	Risk with sleeping in darkness	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Improvement in frequency of vertigo Assessed with: number of participants reporting no vertigo episodes between 18 and 24 months	Study population		RR 1.47 (1.15 to 1.89)	130 (1 RCT)	⊕⊝⊝⊝ Very low ¹	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.
	543 per 1000	798 per 1000 (624 to 1000)	RR 1.47 (1.15 to 1.89)	130 (1 RCT)	⊕⊝⊝⊝ Very low ¹
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). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
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.
¹Unblinded study. Potential for selective reporting for this outcome. Outcome considers complete resolution of vertigo only, not 'any improvement'. Optimal information size was not reached, taken as > 300 events for dichotomous outcomes as a rule of thumb.

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Specially processed cereals compared to placebo for Ménière’s disease
Patient or population: Ménière’s disease Setting: outpatients Intervention: specially processed cereals Comparison: placebo
Outcomes	Risk with no treatment/placebo	Risk with specially processed cereals	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Improvement in vertigo	No study assessed this outcome
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). 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.

Summary of findings 3. Specially processed cereals compared to placebo for Ménière’s disease

Table 1. GRADE profile: Abundant water intake compared to no treatment for Ménière’s disease

Certainty assessment							Number of participants		Effect		Certainty	Comment
№ of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Abundant water intake	No treatment	Relative (95% CI)	Absolute (95% CI)	Certainty	Comment
Improvement in frequency of vertigo (follow‐up: range > 12 months; assessed with: number of participants with no vertigo attacks from 18 to 24 months)
1	Randomised trials	Very serious^a,b	Not serious	Serious^c	Serious^d	None	57/70 (81.4%)	38/70 (54.3%)	RR 1.50 (1.18 to 1.91)	271 more per 1000 (from 98 more to 494 more)	⨁◯◯◯ Very low	Abundant water intake may increase the proportion of people who experience complete resolution of vertigo, but the evidence is very uncertain.
Change in hearing: improvement in hearing (follow‐up: range > 12 months; assessed with: number of participants with improvement of ≥ 10 dB on PTA)
1	Randomised trials	Serious^a	Not serious	Not serious	Serious^d	None	25/70 (35.7%)	5/70 (7.1%)	RR 5.00 (2.03 to 12.31)	286 more per 1000 (from 74 more to 808 more)	⨁⨁◯◯ 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)
1	Randomised trials	Serious^a	Not serious	Serious^e	Very serious^d,f	None	5/70 (7.1%)	4/74 (5.4%)	RR 1.32 (0.37 to 4.72)	17 more per 1000 (from 34 fewer to 201 more)	⨁◯◯◯ 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.
CI: confidence interval; RR: risk ratio ^aUnblinded study. ^bPotential for selective reporting for this outcome. ^cOutcome considers complete resolution of vertigo only, not 'any improvement'. ^dOptimal information size was not reached, taken as > 300 events for dichotomous outcomes, as a rule of thumb. ^eOnly includes those with < 75% compliance. This may be greater than the number of participants who discontinue the intervention completely. ^fConfidence interval ranges from potential benefit to potential harm from the intervention.

Table 1. GRADE profile: Abundant water intake compared to no treatment for Ménière’s disease

Table 2. GRADE profile: Sleeping in darkness compared to no treatment

Certainty assessment							№ of participants		Effect		Certainty	Comment
№ of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Sleeping in darkness	No treatment	Relative (95% CI)	Absolute (95% CI)	Certainty	Comment
Improvement in frequency of vertigo (follow‐up: range > 12 months; assessed with: number of participants reporting no vertigo between 18 and 24 months)
1	Randomised trials	Very serious^a,b	Not serious	Serious^c	Serious^d	None	48/60 (80.0%)	38/70 (54.3%)	RR 1.47 (1.15 to 1.89)	255 more per 1000 (from 81 more to 483 more)	⨁◯◯◯ Very low	Sleeping in darkness may increase the proportion of people who experience complete resolution of vertigo, but the evidence is very uncertain.
Change in hearing: improvement in hearing (follow‐up: range > 12 months; assessed with: number of participants with ≥ 10 dB improvement in hearing on PTA)
1	Randomised trials	Serious^a	Not serious	Not serious	Serious^d	None	19/60 (31.7%)	5/70 (7.1%)	RR 4.43 (1.76 to 11.16)	245 more per 1000 (from 54 more to 726 more)	⨁⨁◯◯ Low	Sleeping in darkness 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)
1	Randomised trials	Serious^a	Not serious	Serious^e	Serious^d	None	14/74 (18.9%)	4/74 (5.4%)	RR 3.50 (1.21 to 10.14)	135 more per 1000 (from 11 more to 494 more)	⨁◯◯◯ Very low	There may be more chance that people allocated to sleeping in darkness will discontinue this intervention, but the evidence is very uncertain.
CI: confidence interval; dB: decibels; PTA: pure tone audiometry; RR: risk ratio ^aUnblinded study. ^bPotential for selective reporting for this outcome. ^cOutcome considers complete resolution of vertigo only, not 'any improvement'. ^dOptimal information size was not reached, taken as > 300 events for dichotomous outcomes or > 400 participants for continuous outcomes, as a rule of thumb. ^eOnly includes those with < 75% compliance. This may be greater than the number of participants who discontinue the intervention completely.

Table 2. GRADE profile: Sleeping in darkness compared to no treatment

Table 3. GRADE profile: Specially processed cereals compared to placebo

Certainty assessment							№ of participants		Effect		Certainty	Comment
№ of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Specially processed cereals	Placebo	Relative (95% CI)	Absolute (95% CI)	Certainty	Comment
Change in disease‐specific health‐related quality of life (follow‐up: range 3 months to < 6 months; assessed with: AAO‐HNS Functional Level Scale; from: 1 to 6, higher scores = worse quality of life)
1	Randomised trials	Serious^a	Not serious	Serious^b	Serious^c	None	27	24	‐	MD 1.35 points lower (2.08 lower to 0.62 lower)	⨁◯◯◯ Very low	The evidence is very uncertain about the effect of specially processed cereals on disease‐specific quality of life.
AAO‐HNS: American Academy of Otolaryngology ‐ Head and Neck Surgery;CI: confidence interval; MD: mean difference ^aMultiple domains at unclear risk of bias, leading to some concerns. ^bIt is unclear whether all participants met the AAO‐HNS 1995 criteria for a diagnosis of Ménière's disease. ^cOptimal information size was not reached, taken as > 400 participants for continuous outcomes, as a rule of thumb.

Table 3. GRADE profile: Specially processed cereals compared to placebo

Comparison 1. Abundant water intake versus no treatment

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Improvement in frequency of vertigo (complete resolution) at > 12 months Show forest plot	1	140	Risk Ratio (M‐H, Random, 95% CI)	1.50 [1.18, 1.91]

1.2 Change in hearing: improvement in hearing at > 12 months Show forest plot	1	140	Risk Ratio (M‐H, Random, 95% CI)	5.00 [2.03, 12.31]

1.3 Other adverse effects: exclusion from follow‐up Show forest plot	1	144	Risk Ratio (M‐H, Random, 95% CI)	1.32 [0.37, 4.72]

Comparison 1. Abundant water intake versus no treatment

Comparison 2. Sleeping in darkness versus no treatment

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Improvement in frequency of vertigo (complete resolution) at > 12 months Show forest plot	1	130	Risk Ratio (M‐H, Random, 95% CI)	1.47 [1.15, 1.89]

2.2 Change in hearing: improvement in hearing at > 12 months Show forest plot	1	130	Risk Ratio (M‐H, Random, 95% CI)	4.43 [1.76, 11.16]

2.3 Other adverse effects: exclusion from follow‐up Show forest plot	1	148	Risk Ratio (M‐H, Random, 95% CI)	3.50 [1.21, 10.14]

Comparison 2. Sleeping in darkness versus no treatment

Comparison 3. Specially processed cereals versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Disease‐specific health‐related quality of life (Functional Level Scale) Show forest plot	1	51	Mean Difference (IV, Random, 95% CI)	‐1.35 [‐2.08, ‐0.62]

Comparison 3. Specially processed cereals versus placebo