Foshati S, Poursadeghfard M, Heidari Z, Amani R. The effect of ginger (Zingiber officinale) supplementation on clinical, biochemical, and anthropometric parameters in patients with multiple sclerosis: a double-blind randomized controlled trial. Food Funct. 2023;14(8):3701-3711.
To determine if ginger supplementation affects symptoms of multiple sclerosis (MS) over a 12-week period
After 12 weeks, treatment with ginger significantly improved MS disability, objectively and subjectively, but had no significant effect on body mass index (BMI).
Randomized, placebo-controlled, double-blind trial
The final analysis included 52 subjects (aged 18–50 years) with relapsing-remitting multiple sclerosis (RRMS). Investigators assessed 196 adults; 135 did not meet the criteria, and 9 declined to participate. That left 52 participants: 26 in the treatment group and 26 in the placebo group. One participant from the treatment group and 2 from the placebo group were lost to SARS-CoV-2 at week 12 follow-up, but investigators included all 52 in intention-to-treat analysis.
Inclusion criteria: males and nonmenopausal females aged 18 to 50 years, score of <4.5 on the Expanded Disability Status Scale (EDSS), no MS relapse or corticosteroid therapy for the last 3 months, no change in type or dose of MS medications in the last 6 months, and willingness to participate.
Exclusion criteria: other autoimmune diseases, cancer, pregnancy, MS relapse or corticosteroid therapy during the study, change in dose or type of MS medications during study, allergic reaction to ginger or placebo (corn), supplementation with antioxidants or nutrients except vitamin D, or consumption of less than 90% of the ginger or placebo supplements.
Participants took 1 capsule 3 times daily of either ginger (500 mg per capsule) or corn (500 mg per capsule), prepared by Dineh Iran Industries Complex, Tehran, Iran.
Each ginger capsule of 500 mg contained 25 mg gingerols, for a total dosing of 75 mg gingerols per day. A small amount of ginger powder was added to each bottle of placebo capsules to give a similar ginger odor. Participants took ginger or placebo with breakfast, lunch, and dinner, for a total of 1,500 mg per day, for 12 weeks.
Study Parameters Assessed
Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), BMI, neurofilament light chain (NfL), neutrophil-to-lymphocyte ratio (NLR), interleukin 17 (IL-17), and matrix metalloproteinase-9 (MMP-9).
Treatment with 500 mg ginger 3 times daily, with a total daily intake of 75 mg gingerols, after 12 weeks significantly improved MS disability (EDSS), MSIS-29 physical and MSIS-29 psychological scores; it also significantly decreased NLR and IL-17 but had no significant effect on MMP-9 or BMI.
The MSIS-29 physical scale was significantly different, with a higher score in the ginger group, suggesting a higher degree of physical disability in the treatment group. Dietary intake of macro- and micronutrients and energy expenditure were not significantly different between the ginger and placebo groups during the trial.
After ginger supplementation of 1,500 mg/d for 12 weeks, EDSS, MSIS-29 physical and MSIS-29 psychological scores, and IL-17 had significantly decreased. In the placebo group, EDSS, MSIS-29 physical and MSIS-29 psychological, IL-17, NfL, and NLR significantly increased.
There was no significant change in BMI or MMP-9 in either group. In the ginger group, the investigators found no significant change in NfL or NLR. The authors argue that these changes were statistically and clinically significant changes in an MS patient, and they might be, but there were no physical tests or examinations to confirm or deny these outcomes, only the patients’ perspectives obtained by a questionnaire after 12 weeks.
Side effects were reported in 2 treatment patients and 3 control patients. They included heartburn and abdominal pain in the treatment group and, among the control, heartburn in 2 and headache in 1. When we consider the nature of this botanical, the side effects in the treatment group are not unexpected, especially if participants did not follow directions to take it with food. The investigators did not report any subjects who took less than 90% of the required capsules during the trial.
The study authors stated they have no conflicts of interest. The study was funded by Isfahan University of Medical Sciences under grant number 3400357.
Practice Implications & Limitations
Zingiber officinale is a well-known anti-inflammatory botanical and food containing gingerols, shogaols, zingerone, quercetin, alpha-curcumene, and other active constituents.1 Multiple reviews have suggested its potential benefit for MS and other neurodegenerative conditions.2,3 A mouse study showed that gingerol-6 inhibited inflammatory cell migration from the peripheral nervous system to the central nervous system, reduced neuroinflammation and demyelination, suppressed dendritic cell activation by lipopolysaccharides, and inhibited phosphorylation of NF-ĸB (nuclear factor kappa-light-chain-enhancer of activated B cells), all of which could be factors in MS.4
Clinically it has positively affected bacterial infections, colic, atonic dyspepsia, gastric atonia, headaches, rheumatism, inflammation, and diabetes.
A recent trial of Zingiber and Pilates ran for 12 weeks. At the end of the 12 weeks, the ginger-plus-Pilates arm had a significant increase in brain-derived neurotrophic factor (BDNF) and a significant decrease in tumor necrosis factor alpha compared to the Pilates only, ginger only, and control arms.5
Zingiber is native to East and Southeast Asia. The Romans introduced it to Europe from Arab traders, and it became popular in the 9th century. The Spaniard Francesco de Mendoza later carried it to Mexico.6 Cultivation of ginger in India has occurred for more than 3,000 years.6 Within this genus are several species, and the common name ginger includes multiple species in the genera Alpinia, Asarum, and Kaempferia.6 Today it is grown primarily in Nigeria (56.2%), India (23.6%), and China (4.5%).7 Clinically it has positively affected bacterial infections, colic, atonic dyspepsia, gastric atonia, headaches, rheumatism, inflammation, and diabetes.6 It also has antioxidant properties in cooking and roasting.8 It is a botanical with multiple uses, and perhaps multiple sclerosis can be added to the list of conditions that benefit from Zingiber officinale.
In this trial, Zingiber officinale at 500 mg 3 times daily vs a placebo of corn with a similar odor positively affected multiple sclerosis disability (EDSS) and MSIS-29 physical and MSIS-29 psychological scores, along with decreasing IL-17 and NLR, but had no effect on BMI or MMP-9. The 1,500 mg dose was within the generally accepted safe dose of 4,000 mg per day. This study lacked physical examinations or similar assessments of clinical effectiveness. Side effects were minimal and included heartburn and abdominal pain. This may be an effective treatment in the long term for MS patients if researchers can demonstrate in humans the neurological findings from animal studies.
The study was easy to read and follow, but researchers did not describe the exact method of treatment, such as the Zingiber officinale preparation and standardization, which will make replication or parallel studies challenging.