Effects of Asparagus officinalis for burning mouth syndrome: A systematic review of randomized controlled trials

Abstract

Background

Burning mouth syndrome (BMS) lacks optimal treatments. This systematic review assessed Asparagus officinalis, a natural product with anti-inflammatory/antioxidant properties, for managing this chronic pain disorder.

Methods

PubMed, the Cochrane Library, EMBASE, Web of Science, Scopus, and four Chinese databases were searched until February, 2025 for randomized controlled trials (RCTs) involving adults with BMS. Asparagus officinalis products alone or in combination with conventional medications were included. Outcomes included pain, symptoms, psychological outcomes and salivary function. The GRADE approach was used to assess evidence certainty.

Results

Six RCTs with 336 participants were included. Compared to vitamin B complex alone, Asparagus officinalis capsules alone significantly improved the pain-intensity-based effective rate (RR 6.00, 95 % CI [1.61, 22.34]). Compared to conventional medicines, Asparagus officinalis capsules with conventional medicines significantly increased subjective pain scores (MD 1.51, 95 % CI [1.19, 1.83]), symptom-based effective rate (RR 1.27, 95 % CI [1.14, 1.42]), daily water intake score (MD 1.32, 95 % CI [1.00, 1.64]), sleep duration score (MD 1.88, 95 % CI [1.61, 2.15]), and decreased anxiety and depression scores, while Asparagus officinalis oral liquid combined with mecobalamin significantly reduced 10-point VAS (MD -1.40, 95 % CI [-2.19, -0.61]) and increased the unstimulated salivary flow rate (USFR).The certainty of evidence was all graded as low.

Conclusions

Asparagus officinalis products may improve pain intensity, symptoms, psychological outcomes, and salivary function in patients with BMS. However, the low certainty of evidence due to study limitations and small sample sizes suggests the need for well-designed, large-scale real-world studies to confirm these findings and establish their clinical applicability.

Protocol registration

PROSPERO (CRD420250651920).

1. Introduction

Burning mouth syndrome (BMS) is a chronic orofacial pain disorder characterized by a burning sensation in the mouth, often accompanied by taste alterations and dry mouth.¹ The prevalence of BMS ranges from 0.1 % to 4.6 % in the general population,² with high rates reported in Europe and lower rates in Asia and North America.³ The condition is more common in postmenopausal females and individuals aged 60 to 70 years old.³ BMS is classified as primary (idiopathic) or secondary (caused by conditions like acid reflux, dental allergies, or psychological factors).⁴ Therefore, accurate diagnosis and classification of BMS require the use of neurophysiologic, psychophysical, and neuropathological methods/tools.⁵ Salivary biomarker alterations (e.g., elevated α-amylase, IgA, MIP-4; decreased uric acid/FRAP) correlate with BMS pain/anxiety, confirming oxidative stress/inflammation in pathogenesis.⁶

Medications for BMS include antidepressants (clonazepam or amitriptyline), antiepileptics (gabapentin), topical oral medications (chlorhexidine mouthwash or mouthwash containing anesthetics), and vitamins and nutritional supplements (such as B Vitamins, iron or folic acid), which are used to temporarily relieve pain symptoms and supplement nutrition. Alpha-lipoic acid (ALA) and capsaicin also have relatively long-lasting relief effects in alleviating mouth pain caused by BMS.⁶ Non-pharmacological therapies such as cognitive behavioral therapy (CBT), low-level laser therapy (LLLT), transcranial magnetic stimulation (rTMS), and acupuncture can provide pain relief and improve quality of life in the short-term.⁷ However, these treatments have limitations. Studies have shown very low-quality evidence that antidepressants used to treat BMS increase dizziness and drowsiness, and alpha-lipoic acid increases headaches and gastrointestinal discomfort.⁸ Alternative approaches such as acupuncture and cognitive-behavioral therapy (CBT) may exhibit limited efficacy, may not be universally accessible, and may not be suitable for all patients.⁹ There is currently no single therapy that can completely cure BMS, and each therapy has its advantages and disadvantages. Therefore, treatment needs to be individually selected according to the patient’s specific situation.

In recent years, there has been increasing interest in the potential therapeutic effects of natural products for BMS.9, 10 This trend reflects a broader shift towards harnessing the power of nature to address complex health issues. One such natural product that has garnered significant attention is Asparagus officinalis. Asparagus officinalis is a widely consumed vegetable, prized not only for its culinary versatility but for its rich nutritional profile. Research has revealed that bioactive compounds found in Asparagus officinalis, such as asparagus saponins and asparagus polysaccharides, possess remarkable anti-inflammatory and antioxidant properties.¹¹ These anti-inflammatory and antioxidant properties may specifically address BMS pathogenesis by reducing oxidative stress and inflammation, potentially alleviating symptoms.¹²

Given the limitations of current treatments for BMS and the potential therapeutic effects of Asparagus officinalis, this study aims to systematically review the effects and safety of Asparagus officinalis on people with BMS. By conducting a systematic review of randomized controlled trials (RCTs), this study will provide evidence-based information on the efficacy and safety of Asparagus officinalis for BMS, which may help guide future research and clinical practice.

2. Methods

2.1. Study design and registration

We conducted a systematic review (SR) and meta-analysis to assess the effects of Asparagus officinalis on BMS, synthesizing data from RCTs. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO, CRD420250651920) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

2.2. Information sources and search strategy

A comprehensive literature search was conducted across multiple electronic databases, including PubMed, the Cochrane Library, EMBASE, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), Wanfang database, Chinese Scientific Journal Database (VIP), and Sinomed. The search covered studies published from the inception of each database up to February 6, 2025. Additionally, manual searches of reference lists from relevant full-text articles were performed to identify additional studies. The detailed search strategy is provided in Supplement 1.

2.3. Eligibility criteria

The SR included RCTs involving adults diagnosed with BMS. Studies investigating the preventive effects of Asparagus officinalis on individuals without a formal diagnosis of BMS were also included. Interventions of interest consisted of Asparagus officinalis or its derivatives, either used alone or in combination with conventional treatments. This included Asparagus officinalis in its natural form (also known as Lusun or Lu Sun), as well as Asparagus officinalis-containing formulations such as patent medicines, medicinal diets, or other preparations, including but not limited to Asparagus officinalis syrup, Asparagus officinalis granules, Asparagus officinalis oral liquid, compound Asparagus officinalis preparations, and Asparagus officinalis juice. Additionally, extracts derived from Asparagus officinalis, such as Asparagus officinalis saponins, Asparagus officinalis polysaccharide, Asparagus officinalis flavones, and compound Asparagus officinalis extract, were included. Comparators considered in the SR were placebo, no intervention, or conventional medicine and other complementary therapies. Primary outcomes included pain intensity reduction [measured by Visual Analogue Scale (VAS) or Visual Numerical Scale (VNS)] and quality of life improvement [assessed using 36-Short Form Health Survey (SF-36) or Oral Health Impact Profile (OHIP-14)]. Secondary outcomes encompassed symptom improvement (burning sensation, taste alterations, oral sensitivity), psychological outcomes [evaluated by Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), Self-Rating Anxiety Scale (SAS) score or Self-Rating Depression Scale (SDS) score], salivary function parameters, and long-term follow-up data regarding treatment sustainability and symptom recurrence. Safety outcomes were assessed by reporting of adverse effects.

2.4. Study selection and data extraction

After removing duplicate records, two reviewers (XFW and XTW) independently screened the titles and abstracts of identified studies. Full-text articles were then reviewed for eligibility. Any disagreements during the screening process were resolved through discussion or consultation with a third reviewer (CS). Data extraction was performed using a pre-designed form, capturing details such as participant characteristics, intervention details, comparators, outcomes, and outcome measures.

2.5. Quality assessment

The methodological quality of included RCTs was assessed using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool. This tool evaluates bias across five domains: randomization process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selection of reported results. Two reviewers (XFW and XTW) independently conducted the risk of bias assessments, with discrepancies resolved through consensus or arbitration by a third reviewer (CS). The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of evidence.¹³ The GRADE approach evaluates the certainty of evidence into four levels: high, moderate, low, and very low. This assessment is based on several critical dimensions, including the risk of bias, which evaluates potential systematic errors in the design and execution of studies; imprecision, which takes into account the precision of effect estimates, influenced by factors such as sample size and confidence intervals (CIs); inconsistency, which examines the degree of variability in results across different studies; indirectness, which assesses how directly the evidence applies to the target population, intervention, or outcomes of interest; and publication bias, which considers the possibility of selective reporting or the non-publication of relevant studies.

2.6. Data synthesis and analysis

Data synthesis was performed using both meta-analysis and narrative synthesis, depending on the homogeneity of the included studies. For meta-analysis, risk ratios (RR) with 95 % CIs were calculated for dichotomous outcomes, while mean differences (MD) with 95 % CIs were used for continuous outcomes. Heterogeneity was assessed using the I² statistic and χ² test, with a random-effects model applied to account for variability across studies. Subgroup analyses were conducted to explore potential effect modifiers, such as different intervention types and follow-up durations. Publication bias was evaluated using funnel plots and Egger’s test when sufficient studies were available (generally considered to be at least 10 studies). When the studies were too heterogeneous, a narrative synthesis was conducted to describe and compare the findings across studies.

3. Results

3.1. Description of included studies

A total of 171 records were identified, and finally, six studies14, 15, 16, 17, 18, 19 were included in the data synthesis (Fig 1). Numbers of articles and reasons for their exclusion can be seen in Fig 1. Table 1 provides an overview of the included studies. A total of 336 participants were involved, with the sample size ranging from 28 to 98. The observed disease duration spanned from 2 months to 6 years. None of the included studies reported any comorbidities. Among the six articles investigating Asparagus officinalis products, five utilized Asparagus officinalis capsules (with the primary component being the extract of fresh Asparagus officinalis), while the remaining study employed Asparagus officinalis Oral Liquid (containing fresh Asparagus officinalis as its main ingredient). The intervention duration consistently spanned four weeks across all six studies.

Fig. 1.

The PRISMA flow of literature search and selection of studies.

Table 1.

Characteristics of the included studies.

ID	Age (mean)		Sample Size	Course of Disease	Presence of Comorbidities	Intervention	Composition of Asparagus officinalis products	Control	Duration of Intervention (weeks)	Outcome	Risk of bias 2 (overall bias)
	T	C
Kou HF 200314	30-70 yr		40	3 mo-3 yr	No	Asparagus officinalis capsules + Conventional medications	Extract of fresh Asparagus officinalis	Conventional medications (Oryzanol, Vitamins, Mouthwashes, etc.)	4	Symptom improvement	High
Li LK 201216	40-70 yr		30	2 mo-3 yr	No	Asparagus officinalis capsules	Extract of fresh Asparagus officinalis	Vitamin B complex	4	Pain intensity reduction	High
Li XL 201517	30-70 yr		80	6 mo-3 yr	No	Asparagus officinalis capsules + Conventional medications	Extract of fresh Asparagus officinalis	Conventional medications (Oryzanol, Vitamins, Mouthwashes, etc.)	4	Symptom improvement	High
Wang L 201815	51.62 yr	53.5 yr	98	>6 mo	No	Asparagus officinalis capsules + Conventional medications	Extract of fresh Asparagus officinalis	Conventional medications (Vitamin Supplements, Nerve-Nourishing Mouthwashes)	4	Pain intensity reduction, Symptom improvement, Psychological outcomes	High
Yan XL 202219	NR		28	>3 mo	No	Asparagus officinalis oral liquid + Mecobalamin	Fresh Asparagus officinalis	Conventional medications (Oryzanol, Vitamin B₂, Vitamin E)	4	Pain intensity reduction, Salivary function	High
Zhou HM 200018	28-70 yr		60	6 mo-6 yr	No	Asparagus officinalis capsules + Conventional medications	Extract of fresh Asparagus officinalis	Conventional medications (Oryzanol, Riboflavin, Vitamin E)	4	Symptom improvement	High

mo: months; NR: not reported; yr: years.

3.2. Risk of bias evaluation

The risk of bias assessment for the six studies showed several limitations (Fig. 2). Only two studies described specific randomization methods, while the other four only mentioned "randomized" without details. None reported allocation concealment, raising concerns about the randomization process. All studies lacked placebo controls, but there was no evidence of deviations from intended interventions, so this risk was low. One study had a high risk of bias due to missing data and no bias-correcting methods, while the others were low risk. All studies used subjective outcomes, leading to a high risk of bias in outcome measurement.

Fig. 2.

Risk of bias assessment result of randomized controlled trials.

3.3. Primary outcomes

3.3.1. Pain intensity reduction

The effectiveness of Asparagus officinalis products in alleviating pain was evaluated using multiple outcome measures across different studies (Table 2). In the comparison of Asparagus officinalis capsules versus vitamin B complex (N=30, 1 RCT ¹⁶), pain intensity was assessed based on a pain-intensity-based effective rate. The criteria included cured (complete disappearance of oral mucosal pain and related symptoms), markedly effective (≥70 % improvement in pain intensity and frequency), effective (30 %-69 % improvement), and ineffective (<30 % improvement). The low certainty of evidence showed a significantly higher effective rate in the Asparagus officinalis capsules alone, with a RR of 6.00 (95 % CI: 1.61 to 22.34).

Table 2.

Meta-analysis results of Asparagus officinalis for burning mouth syndrome.

Outcome measure	Effect size	95 % confidence interval	Sample size	No. of studies	Evidence quality
Outcome: Pain intensity
Comparison: Asparagus officinalis capsules VS vitamin B complex
Pain-intensity-based effective rate	RR 6.00	1.61 to 22.34	30	116	⊕⊕ΟΟ1,2 LOW
Comparison: Asparagus officinalis capsules + conventional medications VS conventional medications
Subjective pain score	MD 1.51	1.19 to 1.83	98	115	⊕⊕ΟΟ1,2 LOW
Comparison: Asparagus officinalis oral liquid + mecobalamin VS conventional medications
Visual Analog Scale (VAS) score	MD -1.40	-2.19 to -0.61	28	119	⊕⊕ΟΟ1,2 LOW
Outcome: Symptoms improvement
Comparison: Asparagus officinalis capsules + conventional medications VS conventional medications
Daily water intake score	MD 1.32	1.00 to 1.64	98	115	⊕⊕ΟΟ1,2 LOW
Sleep duration score	MD 1.88	1.61 to 2.15	98	115	⊕⊕ΟΟ1,2 LOW
Symptom-based effective rate	RR 1.27	1.14 to 1.42	136	414, 15, 16, 17, 18	⊕⊕ΟΟ1,2 LOW
Outcome: Psychological outcomes
Comparison: Asparagus officinalis capsules + conventional medications VS conventional medications
Self-Rating Anxiety Scale (SAS) score	MD -22.32	-24.21 to -20.43	98	115	⊕⊕ΟΟ1,2 LOW
Self-Rating Depression Scale (SDS) score	MD -13.80	-15.61 to -11.99	98	115	⊕⊕ΟΟ1,2 LOW
Outcome: Salivary function
Comparison: Asparagus officinalis oral liquid + mecobalamin VS conventional medications
Unstimulated salivary flow rate (USFR)	MD 0.20 mL/min	0.10 to 0.29	28	1 19	⊕⊕ΟΟ1,2 LOW

Reasons for downgrading in GRADE assessment:

1. Risk of bias: High risk of bias.

2. Imprecision: The total sample size for continuous data is less than 400 or the total number of events for Dichotomous data is less than 300.

Another study ¹⁵ measured pain using a subjective pain score, where 4 points indicated complete pain relief, 3 points indicated pain reduction, 2 points indicated no change, and 1 point indicated worsening pain. As a result, compared to conventional medications, Asparagus officinalis capsules plus conventional medications demonstrated a significant improvement in subjective pain score, with the MD of 1.51 (95 % CI: 1.19 to 1.83). The certainty of evidence was low.

Additionally, pain was assessed using a 10-point VAS scale, where 0 indicated no pain and 10 indicated severe pain.¹⁹ Compared to conventional medications, Asparagus officinalis oral liquid combined with mecobalamin resulted in a significant reduction in pain intensity, with an MD of -1.40 (95 % CI: -2.19 to -0.61). The certainty of evidence was low.

3.4. Secondary outcomes

3.4.1. Symptom improvement

In the evaluation of symptoms, four studies utilized a symptom-based effective rate to assess the impact of Asparagus officinalis products. The assessment was based on a composite scoring system that integrated subjective pain, daily water intake, and sleep duration. Specifically, subjective pain was scored as 4 points for disappearance of pain, 3 points for reduction, 2 points for no change, and 1 point for worsening. Daily water intake was scored as 4 points for a reduction of more than 500 mL, 3 points for a reduction of 200-500 mL, 2 points for no change, and 1 point for an increase of more than 200 mL. Sleep duration was scored as 4 points for an increase of more than 3 hours, 3 points for an increase of 1-2 hours, 2 points for no change, and 1 point for a reduction of more than 1 hour. The total score was calculated by summing the scores of tongue pain, daily water intake, and sleep duration. An overall score of 9-12 was defined as effective, while a score below 9 was considered ineffective. The effective rate was calculated based on the number of participants achieving an effective score.

The low certainty of evidence (Table 1) revealed that the combination of Asparagus officinalis capsules and conventional medications significantly enhanced the symptom-based effective rate compared to conventional medications alone, with a RR of 1.27 [95 % CI: 1.14, 1.42]. For the individual symptom scores (Table 2), Asparagus officinalis capsules plus conventional medications could significantly improve the daily water intake score, with a MD of 1.32 [95 % CI: 1.00, 1.64], while the sleep duration score had an MD of 1.88 [95 % CI: 1.61, 2.15]. Both of the evidence certainty was graded as low.

3.4.2. Psychological outcomes

Table 2 presents the meta-analysis results on psychological outcomes. One study evaluated anxiety using the SAS score, where a lower score indicated reduced anxiety levels. The low certainty of evidence showed that compared to conventional medications, Asparagus officinalis capsules combined with conventional medications significantly reduced the SAS score, with a MD of -22.32 (95 % CI: -24.21 to -20.43).

Similarly, for depression, the SDS score was used, with lower scores indicating reduced depressive symptoms. The combination of Asparagus officinalis capsules and conventional medications demonstrated a significant improvement compared to conventional medications, with an MD of -13.80 (95 % CI: -15.61 to -11.99). The evidence certainty was graded as low.

3.4.3. Salivary function

In the assessment of salivary function, one study measured unstimulated salivary flow rate (USFR) by instructing participants to rinse their mouths with water before saliva collection. During collection, participants were seated with their heads slightly tilted forward, mouth open, and lower jaw resting against the chest. They were asked not to swallow, chew, or speak, allowing saliva to naturally accumulate in the floor of the mouth. Saliva was collected using a sterile funnel and tube for 5 minutes, and the average salivary flow rate per minute was calculated. Compared to conventional medications alone, Asparagus officinalis oral liquid + mecobalamin significantly increased the USFR, with a MD of 0.20 (95 % CI: 0.10 to 0.29). The evidence certainty was evaluated as low (Table 2).

3.5. Safety outcomes

Among the six included RCTs, five studies did not report any data on safety outcomes. Only one study (Wang et al., 2018) specifically documented safety outcomes, reporting no occurrence of adverse effects in either the intervention or control groups.

4. Discussion

4.1. Summary of findings

This systematic review evaluated the effects and safety of Asparagus officinalis on BMS based on six RCTs. The findings suggest that Asparagus officinalis products, particularly in the form of capsules and oral liquid, may provide significant benefits in reducing pain intensity, improving symptoms, and enhancing psychological outcomes. The meta-analysis revealed that Asparagus officinalis capsules alone showed a RR of 6.00 (95 % CI: 1.61 to 22.34) in improving pain-intensity-based effective rate compared to vitamin B complex, while the combination of Asparagus officinalis capsules with conventional approaches demonstrated a MD of 1.51 (95 % CI: 1.19 to 1.83) in subjective pain scores. Additionally, Asparagus officinalis oral liquid combined with mecobalamin resulted in a significant reduction in pain intensity, with an MD of -1.40 (95 % CI: -2.19 to -0.61) on a 10-point VAS. For symptom improvement, the combination of Asparagus officinalis capsules with conventional approaches showed a RR of 1.27 (95 % CI: 1.14 to 1.42) in symptom-based effective rate, with improvements in daily water intake (MD: 1.32, 95 % CI: 1.00 to 1.64) and sleep duration (MD: 1.88, 95 % CI: 1.61 to 2.15). Psychological outcomes also improved, with reductions in anxiety (MD: -22.32, 95 % CI: -24.21 to -20.43) and depression scores (MD: -13.80, 95 % CI: -15.61 to -11.99). However, the certainty of evidence was generally low due to high risk of bias and small sample sizes.

4.2. Agreements and disagreements with previous studies

The findings of this review align with previous studies that have highlighted the potential health benefits of Asparagus officinalis, particularly its anti-inflammatory, antioxidant, and immunomodulatory properties. For instance, Guo et al. (2020) provided a comprehensive review of the bioactive compounds and biological functions of Asparagus officinalis, emphasizing its potential in cancer prevention, immunomodulation, and hypoglycemic effects²⁰. This review supports the notion that Asparagus officinalis contains a variety of bioactive compounds, such as polysaccharides, saponins, and flavonoids, which contribute to its therapeutic potential.

However, this review also highlights the limitations in the current evidence base. Similar to the findings of McMillan et al. (2016), who reported low-quality evidence for the use of natural products in managing BMS, the certainty of evidence in this review is generally low due to small sample sizes and methodological flaws⁸. Additionally, while previous studies have shown promising results for the use of Asparagus officinalis in various health applications, the lack of well-designed, large-scale studies limits the robustness of these findings²¹.

While previous systematic reviews have attempted to establish clinically meaningful thresholds for treatment effects in BMS, notable methodological differences exist between studies. Alvarenga-Brant et al. (2022) provided a valuable reference by defining minimal important differences (MIDs) based on placebo-controlled comparisons.²² Their approach established an MID threshold of MD ≥|1| for continuous outcomes of pain reduction (with negative values indicating superior efficacy to placebo) and RR of 0.32 or 1.68 for dichotomous outcomes in pain response rates. However, a critical limitation of our study emerges from the absence of placebo controls in all included trials, which precludes direct application of these established MID values to interpret our findings. This methodological discrepancy fundamentally limits our ability to define the clinical significance of observed treatment effects using conventional MID frameworks

4.3. Strengths and limitations

This review provides a comprehensive synthesis of the available evidence on the effects of Asparagus officinalis on BMS, using a systematic approach and adhering to the PRISMA guidelines. The inclusion of multiple outcome measures, such as pain intensity, symptom improvement as daily water intake and sleep duration, psychological outcomes as anxiety and depression, and salivary function, offers a holistic view of the potential benefits of Asparagus officinalis in BMS management. The use of the GRADE approach to assess the certainty of evidence provides a clear evaluation of the quality of the findings. The use of both meta-analysis and narrative synthesis allowed for a more nuanced interpretation of the data.

However, several limitations must be acknowledged. The main limitations of this review stem from the methodological shortcomings of the included studies. Only two studies described specific randomization methods, and none reported allocation concealment, which raises concerns about selection bias. The small sample sizes and the use of subjective outcome measures in all studies may have introduced imprecision and measurement bias. Our analysis included six studies employing Asparagus officinalis interventions, with five using capsule formulations (containing extracts of fresh plant material) and one utilizing an oral liquid preparation. While this demonstrates the versatility of Asparagus officinalis delivery methods, it also reveals critical gaps in standardization. None of the included studies provided complete details regarding extraction protocols, quantification of bioactive constituents, and dosage justification based on active compound content. This variability poses challenges for interpreting efficacy outcomes, as differences in extraction methods may significantly influence bioavailability and pharmacological activity.

While we observed statistically significant pain reduction across studies (MD=1.51 in 4-point subjective pain scores, where 4 points indicated complete pain relief; MD=-1.40 on 10-point VAS), the clinical interpretation of these effect sizes is constrained by the absence of established MIDs specifically for BMS- specific outcomes. Notably, while formally established MIDs for BMS-specific outcomes remain lacking, the effectiveness criteria employed by Li et al. (2012) (defining ≥30 % improvement in both pain intensity and frequency as 'effective') are methodologically aligned with contemporary pain research standards. Specifically, this threshold corresponds with the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations²³, which emphasizes the importance of reporting the percentage of trial participants who demonstrate at least a 30 % improvement in pain scores from baseline when numerical rating scales (NRS) /VAS measures are utilized in chronic pain studies. In our analysis, the Asparagus officinalis group demonstrated a significantly higher pain-intensity-based effective rate (defined as ≥30% improvement), resulting in a six-fold increased likelihood of achieving this threshold compared to vitamin B complex (RR=6.00, 95% CI: 1.61-22.34). This finding not only reaches statistical significance but also suggests potential clinical relevance. However, the wide confidence interval underscores the need for confirmation in larger, BMS-specific studies with standardized outcome measures. Additionally, the lack of long-term follow-up data limits the ability to assess the sustainability of treatment effects and the recurrence of symptoms.

4.4. Implications for future research

Future research should address the limitations identified in this review by conducting larger, well-designed RCTs with rigorous randomization and allocation concealment methods. While the majority of studies reported clear clinical definitions of BMS, heterogeneity in diagnostic criteria precludes definitive conclusions about patient homogeneity. Future research should adopt standardized tools (e.g., ICOP criteria) to enhance comparability.²⁴ The use of placebo controls and objective outcome measures, such as biomarkers or physiological assessments, would enhance the reliability of the findings. Additionally, further investigation into the mechanisms of action of Asparagus officinalis in BMS, particularly its anti-inflammatory and antioxidant properties, could provide a stronger theoretical foundation for its use. Future studies on Asparagus officinalis interventions should also prioritize the development of standardized preparation protocols, including consistent plant parts, extraction methods, and quantifiable bioactive markers (e.g., saponins or flavonoids). Additionally, detailed reporting of dosage formulations, concentration metrics, and batch-to-batch validation data would enhance reproducibility and clinical translation of findings.

Long-term follow-up studies are also needed to evaluate the sustainability of its effects and the potential for symptom recurrence. Besides, our findings highlight the critical need to establish BMS-specific MIDs through well-designed anchor-based studies that correlate objective scale changes with patient-reported meaningful improvement. Future trials should incorporate both traditional pain scales (NRS/VAS) and patient-centered anchors (e.g., Patient Global Impression of Change) to validate clinically meaningful thresholds specific to BMS populations, while maintaining consistency with IMMPACT recommendations to enable cross-condition comparisons.²³ Finally, studies should investigate the optimal formulation and dosage of Asparagus officinalis products to maximize therapeutic benefits while minimizing potential side effects.

4.5. Conclusions

In conclusion, this systematic review and meta-analysis provides preliminary evidence that Asparagus officinalis products may be effective in improving pain intensity, symptoms as daily water intake and sleep duration, anxiety and depression, and salivary function in patients with BMS. The findings suggest that Asparagus officinalis, either used alone or in combination with conventional medications, could be a promising therapeutic option for BMS. However, the certainty of evidence is generally low due to limitations in study design and small sample sizes. Future research should focus on conducting well-designed, large-scale real world studies with rigorous methodological standards to provide more robust evidence on the efficacy and safety of Asparagus officinalis in BMS treatment.

Author Contributions

Chen Shen: Conceptualization, Methodology, Validation, Formal analysis, Data Curation, Writing - Original Draft, Writing - Review & Editing, Visualization, Project administration, Funding acquisition. Xue-Feng Wang: Methodology, Software, Validation, Investigation, Resources, Writing - Original Draft, Writing - Review & Editing, Visualization. Xiao-Ti Wu: Software, Validation, Investigation, Resources, Writing - Review & Editing. Xin-Xin Liu: Writing - Review & Editing. Nicola Robinson: Writing - Review & Editing, Funding acquisition. Jian-Ping Liu: Conceptualization, Writing - Review & Editing, Supervision, Funding acquisition.

Declaration of competing interests

NR and JPL are editorial board members of this journal but their editorial board membership had no bearing on the decision of this review article. The authors declared that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.

Funding

This work was supported by the project “Innovative Research on Evidence-Based Evaluation Methods for Clinical Effectiveness of Traditional Chinese Medicine” (90020172120103). Prof. Nicola Robinson is the guest professor of Beijing University of Chinese Medicine (certification number 20210017). Chen Shen is supported by the China Scholarship Council.

Ethics statement

As this review involved the analysis of previously published data, ethical approval was not required.