phytotherapy research

Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials

Affiliations.

• 1 Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
• 2 Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
• 3 Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
• 4 Cognitive Neurology and Neuropsychiatry Division, Psychiatry Department, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
• 5 Geriatric Department, Ziaeeian Hospital, Tehran University of Medical Sciences, Tehran, Iran.
• 6 Hemato-Oncology Ward, Taleghani Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran.
• PMID: 36017529
• DOI: 10.1002/ptr.7598

Clinical trial studies revealed conflicting results on the effect of Ashwagandha extract on anxiety and stress. Therefore, we aimed to evaluate the effect of Ashwagandha supplementation on anxiety as well as stress. A systematic search was performed in PubMed/Medline, Scopus, and Google Scholar from inception until December 2021. We included randomized clinical trials (RCTs) that investigate the effect of Ashwagandha extract on anxiety and stress. The overall effect size was pooled by random-effects model and the standardized mean difference (SMD) and 95% confidence interval (CIs) for outcomes were applied. Overall, 12 eligible papers with a total sample size of 1,002 participants and age range between 25 and 48 years were included in the current systematic review and meta-analysis. We found that Ashwagandha supplementation significantly reduced anxiety (SMD: -1.55, 95% CI: -2.37, -0.74; p = .005; I 2 = 93.8%) and stress level (SMD: -1.75; 95% CI: -2.29, -1.22; p = .005; I 2 = 83.1%) compared to the placebo. Additionally, the non-linear dose-response analysis indicated a favorable effect of Ashwagandha supplementation on anxiety until 12,000 mg/d and stress at dose of 300-600 mg/d. Finally, we identified that the certainty of the evidence was low for both outcomes. The current systematic review and dose-response meta-analysis of RCTs revealed a beneficial effect in both stress and anxiety following Ashwagandha supplementation. However, further high-quality studies are needed to firmly establish the clinical efficacy of the plant.

Keywords: Ashwagandha; anxiety; meta-analysis; stress; systematic review.

© 2022 John Wiley & Sons Ltd.

Publication types

• Meta-Analysis
• Systematic Review
• Anxiety Disorders
• Anxiety* / drug therapy
• Dietary Supplements
• Middle Aged
• Randomized Controlled Trials as Topic
• Ashwagandha

Phytotherapy Research

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• Pharmacology

John Wiley and Sons Ltd

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0951418X, 10991573

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Clinical trials on pain lowering effect of ginger: A narrative review

Mariangela rondanelli, federica fossari, viviana vecchio, clara gasparri, gabriella peroni, daniele spadaccini, antonella riva, giovanna petrangolini, giancarlo iannello, mara nichetti, vittoria infantino, simone perna.

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Correspondence , Vittoria Infantino, Department of Biomedical Science and Human Oncology, University of Bari, Azienda di Servizi alla Persona “Istituto Santa Margherita,” Pavia, 27100 Italy. Email: [email protected]

Corresponding author.

Received 2019 Aug 28; Revised 2020 Apr 8; Accepted 2020 Apr 23; Issue date 2020 Nov.

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Ginger has a pain‐reducing effect and it can modulate pain through various mechanisms: inhibition of prostaglandins via the COX and LOX‐pathways, antioxidant activity, inibition of the transcription factor nf–kB, or acting as agonist of vanilloid nociceptor. This narrative review summarizes the last 10‐year of randomized controlled trials (RCTs), in which ginger was traditionally used as a pain reliever for dysmenorrhea, delayed onset muscle soreness (DOMS), osteoarthritis (AO), chronic low back pain (CLBP), and migraine. Regarding dysmenorrhea, six eligible studies suggest a promising effect of oral ginger. As concerned with DOMS, the four eligible RCTs suggested a reduction of inflammation after oral and topical ginger administration. Regarding knee AO, nine RCTs agree in stating that oral and topical use of ginger seems to be effective against pain, while other did not find significant differences. One RCT considered the use of ginger in migraine and suggested its beneficial activity. Finally, one RCT evaluated the effects of Swedish massage with aromatic ginger oil on CLBP demonstrated a reduction in pain. The use of ginger for its pain lowering effect is safe and promising, even though more studies are needed to create a consensus about the dosage of ginger useful for long‐term therapy.

Keywords: chronic low back pain, dysmenorrhea, ginger, knee osteoarthritis, myalgia, pain

1. INTRODUCTION

Zingiber officinale Roscoe (Zingiberaceae family), commonly known as ginger is a climbing perennial plant, indigenous to southeastern Asia. Ginger extract is a mixture of many biologically active constituents (Grzanna, Lindmark, & Frondoza, 2005 ). These compounds are numerous and vary depending on the place of origin and whether the rhizomes are fresh or dry (Ali, Blunden, Tanira, & Nemmar, 2008 ).

More than 400 chemical substances have been isolated and identified in ginger rhizomes extracts, and new ones are still being discovered (Charles, Garg, & Kumar, 2000 ; Jolad, Lantz, Solyom, & Chen, 2004 ; Ma, Jin, Yang, & Liu, 2004 ). At present, only a few of them have been evaluated for their pharmacological properties (Grzanna et al., 2005 ).

Carbohydrates, lipids, terpenes, and phenolic compounds are between the ones that already have been identified (Peter, 2016 ; Prasad & Tyagi, 2005 ). From the chemical point of view, isolated zingiber's principles are categorized into pungent and flavoring compounds. Pungent ones including gingerols, shogaols, zingerones, gingerdiols, gingerdione, and paradols are known to play a major role in various pharmacological actions (Jolad et al., 2004 ; Mashhadi et al., 2013 ; Peter, 2016 ; Prasad & Tyagi, 2005 ).

Patients suffering from diseases associated with chronic inflammation are turning to alternative compounds for relief of their symptoms or to take advantage of natural drug properties as prophylactic treatments. A complex interplay of inflammatory cells and a large range of chemical mediators are normally associated with the beginning of the inflammatory response, recruiting, and activating other immune cells to the site to subsequently solve it.

Several studies indicate that many different compounds in ginger are active in lowering chronic inflammatory diseases' symptoms:

Inhibition of prostaglandins via COX and LOX pathways

The traditional use of ginger infusions to alleviate rheumatism and arthritis have pushed researchers to investigate the anti‐inflammatory pathways of secondary metabolites of the plant (Baliga et al., 2011 ; Zahedi, Fathiazad, Khaki, & Ahmadnejad, 2012 ). Some authors attributed 6‐gingerol's anti‐inflammatory activity to the inhibition of pro‐inflammatory cytokines and LPS‐activated macrophages antigen presentation (Setty & Sigal, 2005 ; Tripathi, Tripathi, Kashyap, & Singh, 2007 ).

Dugasani et al. demonstrated that shogaols and all gingerols inhibit NO production in LPS‐stimulated RAW 264.7 cells in a dose‐dependent manner (Dugasani et al., 2010 ). Moreover, with their experiments they showed that stimulation of RAW 264.7 cells with LPS (1 g/ml) for 24 hr induced a dramatic increase in PGE2 production, four times the basal level (Dugasani et al., 2010 ).

Antioxidant activity on free radical scavenging cascade

Zingiber officinale active ingredients like gingerols, shogaols, zingerone, and so on exhibit antioxidant activity. Ginger inhibits an enzyme, namely xanthine oxidase, which is mainly involved in the generation of reactive oxygen species (ROS) (Ahmad et al., 2015 ).

Inhibition of the transcription factor, nuclear NF‐kB

Grzanna and his group demonstrated for the first time that ginger inhibits the transcription factor nuclear NF‐kB (Grzanna et al., 2005 ). Nuclear NF‐kB is the principal regulator of pro‐inflammatory gene expression. Activated NF‐kB can be detected at sites of inflammation, and a link among NF‐kB activation, cytokine production, and inflammation is now generally accepted.

6‐gingerol displayed anti‐inflammatory activity by decreasing inducible NO synthase and TNF‐α expression through the suppression of I‐kBα phosphorylation, NF‐kB nuclear activation, and PKC‐α translocation. The compound was also found to control TLR‐mediated inflammatory responses. It inhibited NF‐kB activation and COX‐2 expression by inhibiting the LPS‐induced dimerization of TLR4 (Ahn, Lee, & Youn, 2009 ).

Vanilloid nociceptor agonist

Vanilloid nociceptor agonists are known to be potent analgesics. The moderate pungency of ginger has been attributed to the mixture of gingerol derivatives in the oleoresin fraction of processed ginger. Gingerols possess the vanillyl moiety which is considered important for activation of the VR1 receptor expressed in nociceptive sensory neurones (Dedov et al., 2002 ).

Dedov reported that gingerols act as agonists at vanilloid receptors suggesting an additional mechanism by which ginger may reduce inflammatory pain (Dedov et al., 2002 ). This finding has added gingerols and zingerone to the list of vanilloid receptor agonists.

Moreover, the presence of VR1 receptors throughout the brainstem (Mezey et al., 2000 ), where the nausea center is located, may conceivably be associated in part with the common use of ginger as antiemetic medicine (Dedov et al., 2002 ).

In summary, current evidence in vitro and in animal models demonstrated that many different compounds of ginger have been shown to posses antioxidative and anti‐inflammatory activities that may be active in lowering chronic inflammatory disease symptoms, in particular pain.

However, human studies that were carried out to assess whether oral or topic ginger has a positive effect by reducing pain are not numerous; furthermore, in these studies different dosages and methods of administration were used, as well as disparate products' formulations and different study designs.

Given this background, the aim of this narrative review was to assess the state of the art randomized clinical trials on pain lowering effect of ginger, considering the pathologies in which ginger is traditionally used in order to control pain, such as: dysmenorrhea, delayed onset muscle soreness (DOMS), knee osteoarthritis, chronic low back pain (CLBP), and migraine.

2. MATERIALS AND METHODS

This narrative review was written after a PubMed and SCOPUS research performed with these keywords: “Ginger,” “pain” with the use of Boolean AND operator to establish the logical relation between them. The research was conducted by four skilled operators from July to September 2018 and followed Egger's criteria (Egger, Smith, & Altman, 2001 ; Moher, Liberati, Tetzlaff, Altman,, & PRISMA Group, 2009 ). The research was time limited (from 2008 to 2018) and restricted to English and humans randomized controlled trial (RCT). The keywords were pain, ginger, primary dysmenorrhea, DOMS, knee pain, osteoarthritis (AO), CLBP, and migraine. They were combined with “AND” to search related articles. Furthermore, we selected trials with oral ginger used as a primary, sole or combined therapy and compared with a placebo or active treatment in diseases. The analysis was carried out in the form of a narrative review (Figure 1 ).

Flow chart of literature research [Colour figure can be viewed at wileyonlinelibrary.com ]

Standard datacoding tables were developed for extracting data from individual trials, key characteristics, and the level of evidence of each study (“Oxford Centre for Evidence‐based Medicine ‐ Levels of Evidence (March 2009)—CEBM,” 2009 ). The following data were extracted: participant characteristics, sample size, form and dosage of ginger, control group, assessment of adherence, outcome measures, methods for statistical analysis, study findings, and adverse events reported.

3. RESULTS AND DISCUSSION

3.1. dysmenorrhea.

This review summarizes evidence from six clinical trials (687 patients) evaluating the efficacy of oral ginger use for dysmenorrehea (Table 1 ). Among the six eligible studies, five were conducted in Iran (Jenabi, 2013 ; Kashefi et al., 2014 ; Ozgoli, Goli, & Simbar, 2009 ; Rahnama et al., 2012 ; Shirvani et al., 2017 ) and one in India (Halder, 2012 ). Participants were either college or high school students. Five of the six studies included only women with moderate to severe symptoms (Jenabi, 2013 ; Kashefi et al., 2014 ; Ozgoli, Goli, & Simbar, 2009 ; Rahnama et al., 2012 ). Five studies specified the inclusion of women with primary dysmenorrhea only, excluding women with secondary dysmenorrhea (Jenabi, 2013 ; Kashefi et al., 2014 ; Ozgoli, Goli, & Moattar, 2009 ; Rahnama et al., 2012 ; Shirvani et al., 2017 ); however, it is unclear how secondary dysmenorrhea was defined/diagnosed. Across the studies, the sample sizes of the ginger group ranged from N = 25 to N = 61. The daily dose of powdered ginger ranged from 750 to 2,000 mg. The most common duration and timing of ginger treatment was 3 days (the first 3 days of menstruation) (Halder, 2012 ; Jenabi, 2013 ; Ozgoli, Goli, & Simbar, 2009 ).

Summary of articles about effect of ginger on dysmenorrhea

Dysmenorrhea is characterized by low abdominal or pelvic pain occurring before or during menstruation (Morrow & Naumburg, 2009 ). Better management of dysmenorrhea may not only improve women's quality of life, but also reduce their risk of developing future pain (Berkley & McAllister, 2011 ; Vincent et al., 2011 ). Dysmenorrhea is conventionally treated with nonsteroidal anti‐inflammatory drugs (NSAIDs) or oral contraceptive pills (OCPs) (Dawood, 2006 ), the efficacy of which are supported by research evidence (Wong, Farquhar, Roberts, & Proctor, 2009 ). However, NSAIDs and OCPs have limitations: some women with dysmenorrhea do not respond to NSAIDs or OCPs (with an estimated failure rate of >15% for NSAIDs) (Dawood, 2006 ); some cannot use these medications because of contraindications or adverse effects; some prefer not to use any medications. Therefore, investigation of complementary alternative treatments for dysmenorrhea is warranted. Ginger is one of the most commonly used natural products among women with dysmenorrhea. The exact mechanism of action of ginger in pain relief remains to be elucidated; however, some evidence suggests that the constituents of ginger have anti‐inflammatory and analgesic properties (Ali et al., 2008 ). Furthermore, preclinical research shows that ginger suppresses the synthesis of prostaglandin (through inhibition of cyclooxygenase) and leukotrienes, which are involved in dysmenorrhea pathogenesis (Dawood, 2006 ; Committee on Herbal Medicinal Products (HMPC), 2013 ).

The available data suggest a promising pattern of oral ginger (750 to 2,000 mg for the first 3 days of menstruation) as a potentially effective treatment for pain in dysmenorrhea. All RCTs agree in demonstrating that ginger is more effective for pain relief than placebo, and no significant difference was found between ginger and NSAIDs (Halder, 2012 ; Jenabi, 2013 ; Kashefi et al., 2014 ; Ozgoli, Goli, & Moattar, 2009 ; Rahnama et al., 2012 ). These findings, however, need to be interpreted with caution due to the small number of studies, poor methodological quality, and high heterogeneity across the trials. Moreover, all of the included trials were conducted in Asia.

3.2. Delayed onset muscle soreness

This review summarizes evidence from four randomized clinical trials (194 subjects) evaluating the efficacy of oral or topic ginger use for DOMS (Table 2 ). Three RCT suggested an effective reduction of inflammation due to exercise‐induced muscle damage after daily consumption of 2 g of raw and heat‐treated ginger (Black et al., 2010 ; Manimmanakorn et al., 2016 ). A useful alternative seems to be the topical administration of Zingiber cassumunar in 14% concentration (Manimmanakorn et al., 2016 ). Finally, 4 g of ginger supplementation is the suggested dose to be used to accelerate recovery of muscle strength following intense exercise (Matsumura et al., 2015 ).

Summary of articles about effect of ginger on DOMS

DOMS indicated by muscle pain and tenderness typically occurs after a strenuous workout or undertaking unaccustomed exercise (Gulick & Kimura, 1996 ). The underlying causes of DOMS are related to exercise‐induced muscle damage, including sarcomere disruption, and the ensuing secondary inflammatory response , (Gleeson et al., 1995 ; Warren, Hayes, Lowe, Prior, & Armstrong, 1993 ). Inflammatory processes stimulate prostaglandin E2 release which sensitizes type III and IV pain afferents, and leukotrienes to attract neutrophils, which produce free radicals that further exacerbate muscle cell damage (Connolly, Sayeres, & McHugh, 2003 ). DOMS after eccentric exercise may result in reduction of muscle performance of athletes (Cheung, Hume, & Maxwell, 2003 ). Numerous methods to prevent and reduce DOMS have been suggested, including stretching exercises, massage, and nutritional supplementation. Non‐steroidal anti‐inflammatory drugs (NSAIDs) have been used in an attempt to reduce DOMS by reducing inflammation and pain and improving function.

Ginger and several of its constituents inhibit activity of COX‐1 and COX‐2, block leukotriene synthesis, and block the production of interleukins and tumor necrosis factor alpha in activated macrophages (Black et al., 2010 ). Thus, these antiinflammatory actions that may help reduce inflammation, such as exercise‐induced muscle damage, are recognized as a product of participating in unfamiliar or strenuous physical activity.

Given that ginger has antinflammatory and analgesic properties, it follows that it may be used to reduce the damage and consequent DOMS following high‐intensity exercise. (Black et al., 2010 ; Black & O'Connor, 2008 ).

3.3. Knee osteoarthritis

This review summarizes evidence from nine randomized clinical trials (964 patients) evaluating the efficacy of oral or topical ginger, sole or in combination with other botanicals, use for knee OA (Table 3 ). The three RCTs that considered the efficacy of oral ginger (powder supplementation of 1 g/day) on pain in knee OA demonstrated that efficacy of ginger on knee pain seemed not to have a unique position. Two studies suggested that the use of ginger in subjects with knee pain could decrease pain (Mozaffari‐Khosravi et al., 2016 ; Naderi et al., 2016 ) while other did not find significant differences (Naderi et al., 2016 ; Niempoog et al., 2012 ). The two RCT that assessed the efficacy of the topical use of ginger considered an aromatic essential oil (1% Zingiber officinale and 0.5% Citrus sinesis) (Yip & Tam, 2008 ) and 4% ginger gel (Niempoog et al., 2012 ) and agree in stating that the topical use of ginger seems to have potential as an alternative method for short‐term knee pain relief. Finally, all the four studies that considered the ginger supplementation in combination with other botanicals agree in demonstrating that these combinations are effective in order to decrease knee pain (Chopra et al., 2013 ; Drozdov et al., 2012 ; Nieman et al., 2013 ).

Summary of articles about effect of ginger on knee AO

Osteoarthritis Osteoarthritis (OA) is a joint disease characterized by degeneration of cartilage, pain, inflammation, impaired mobility, and dysfunction, especially in older populations (Heidari, 2011 ).

Current treatment for OA is palliative and is focused on pain relief and improving mobility, including a combination of nonpharmacologic and pharmacologic measures. However, when these therapeutic treatments fail to improve symptoms, a variety of surgical interventions can be used (Haghighi, Tavalaei, & Owlia, 2006 ). With respect to some commonly‐used treatments, such as NSAIDs, there is increasing concern that long‐term consumption may cause gastrointestinal bleeding and cardiovascular risks, mainly hypertension and thrombotic events (Dingle, 1999 ; Mamdani, 2005 ). Thus, an interest in research has been conducted to find care treatments that have negligible adverse effects while offering significant improvements in the symptoms (Zakeri et al., 2011 ).

Ginger is thought to have anti‐inflammatory effects and may modulate the concentration and activity of inflammatory mediators in OA (Ahmad et al., 2015 ).

Only one RCT, that considered the efficacy of oral ginger (powder supplementation of 1 g/day) on pain in knee OA, did not find significant changes (Niempoog et al., 2012 ). These difference in the results between the study by Niempoog et al. and the study by Mozaffari‐Khosravi H, although the dosage used was the same (1 g/day), could be due to numerous reasons: the type of administration (non‐encapsulated powder vs. encapsulated powder), the duration of treatment (2 vs. 3 months), the parameters studied (symptoms and daily activities vs. inflammatory cytokines), number of patients evaluated (30 vs. 120 subjects) (Mozaffari‐Khosravi et al., 2016 ; Niempoog et al., 2012 ).

3.4. Chronic low back pain

As shown in Table 4 , one RCT was sourced using topical ginger. No RCT studies were found regarding oral ginger supplementation and pain in patients with low back pain.

Summary of articles about effect of ginger on migraine and low back pain

CLBP is defined as a chronic condition of lower back pain lasting for at least 3 months or longer (Andersson, 1999 ; Bogduk, 2004 ). Non‐pharmacologic interventions for CLBP are recommended when patients do not show improvement with standard treatment (Deyo, Mirza, & Martin, 2006 ).

Ginger has been used as an anti‐inflammatory and anti‐rheumatic for musculoskeletal pain (Altman & Marcussen, 2001 ; Therkleson, 2010 ). Although CLBP predominantly affects older people, only one study has specifically investigated the effects of Swedish massage with aromatic ginger oil in order to evaluate if improve the level of disability.

The objective of Sritoomma et al. was to investigate the effects of Swedish massage with aromatic ginger oil (SMGO) on CLBP and disability in older adults compared with traditional Thai massage (TTM). This study demonstrated that SMGO was more effective than TTM in reducing pain and improving disability at short‐ and long‐term assessments. It's important to note that there might be a lack of methodology in this study, because the difference might be due to the type of massage not to the use of ginger. Moreover, it is not clear if the benefit of low back pain is due to the massage and ability of the operator itself or the medical principle of ginger drug in the aromatic oil.

3.5. Migraine

One single RCT (Cady et al., 2011 ) on humans could be considered as the first effort to elucidate the use of ginger in this frequently disabling disease that is present in a large slice of the adult population. This multi‐center RCT on feverfew/ginger use seems to suggest an effective treatment to migraine.

Migraine is a complex neurological disease characterized by episodic periods of disabling physiological dysfunction typically recurring over decades of an individual's lifetime (Cady, Schreiber, & Farmer, 2004 ).

Treatment needs for migraine vary considerably from patient to patient and indeed, from attack to attack for the same patient. Pharmacologically, many over the counter and prescription products are effective on treatment in acute migraine (Monteith & Goadsby, 2011 ). Commonly employed acute treatments approved for migraine can be classified as over the counter products, such as acetaminophen/aspirin/caffeine combination products and non‐steroidal anti‐inflammatory medications (Wenzel, Sarvis, & Krause, 2003 ), and prescription products, such as triptans and non‐steroidal anti‐inflammatories (Ng‐Mak, Hu, Chen, & Ma, 2008 ). Various opioid and butalbital‐containing analgesics are also commonly prescribed, but most do not have Food and Drug Administration approval for migraine, and are generally avoided by physicians because of their propensity to produce medication overuse headache (Bigal, Rapoport, Sheftell, Tepper, & Lipton, 2004 ; Snow, Weiss, Wall, & Mottur‐Pilson, 2002 ).

The main limitation of this review is represented by searching just two databases and only English literature.

4. CONCLUSION

Current evidence in vitro and in animal models demonstrated that many different compounds of ginger have been shown to posses antioxidative and anti‐inflammatory activities that may be active in lowering chronic inflammatory disease symptoms, in particular, pain. This pain‐reducing effect of ginger has been modulated through various mechanisms: inibition of prostaglandins via the COX and LOX‐pathways, antioxidant activity, inibition of the transcription factor nf–kB, or acting as agonist of vanilloid nociceptor.

However, human studies that were carried out to assess whether oral or topic ginger has a positive effect by reducing pain are not numerous; furthermore, in these studies different dosages and methods of administration were used, as well as different study designs.

This narrative review summarizes the last 10‐year of RCT, in which ginger was traditionally used as a pain reliever for dysmenorrhea, DOMS, knee AO, CLBP, and migraine.

Regarding dysmenorrhea, six eligible studies suggest a promising effect of oral ginger. As concerns DOMS, the four eligible RCTs suggested a reduction of inflammation after oral and topical ginger administration. Regarding knee AO, eight RCTs agree in stating that oral and topical use of ginger seems to be effective against pain, while others did not find significant differences. One RCT considered the use of ginger in migraine and suggested its beneficial activity. Finally, one RCT evaluated the effects of Swedish massage with aromatic ginger oil on CLBP demonstrated a reduction in pain.

The most of the included trials were conducted in Asia. Pharmacogenetics and outcome expectancy regarding ginger intervention could differ across cultures and ethnicities, and therefore, it is necessary to confirm the promising effects in the worldwide population.

In conclusion, the use of ginger for its pain lowering effect is safe and promising, even if more studies are needed to create a consensus about the amount of ginger useful for long‐term therapy. The positive health benefits need to be interpreted with caution due to the small number of studies, poor methodological quality, and high heterogeneity across the trials. Therefore, new studies, possibly multi‐center RCT in different continents, with an adequate number of patients and with standardized ginger formulations, are necessary to confirm the results of this review.

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

Rondanelli M, Fossari F, Vecchio V, et al. Clinical trials on pain lowering effect of ginger: A narrative review. Phytotherapy Research. 2020;34:2843–2856. 10.1002/ptr.6730

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