Ginger - Anti-Inflammatory and Analgesic in Dysmenorrhea

Zingiber officinale, known commonly as ginger, has been widely recognized for its action as an antinausea remedy. However, traditional Chinese medicine has used ginger as an anti-inflammatory agent for musculoskeletal complaints for more than 2500 years.^[1][2] Ginger is classified as an herb of the Zingiberaceae family, which includes many other anti-inflammatory herbs such as turmeric (Curcuma longa) and galangal (Alpinia galanga).^[3]

Researchers have been investigating the constituents responsible for the analgesic and anti-inflammatory properties of ginger, with some promising results for its pain-related medical applications. Although not conventionally prescribed for pain in Western medicine, ginger may be a novel treatment for dysmenorrhea in women who cannot tolerate, or who have contraindications for, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and oral contraceptive drugs.

Ginger and β‑Endorphins

The use of ginger as an analgesic has been studied in Denmark and the United States for arthritic pain and muscle pain postexercise (delayed-onset muscle soreness).^[4] Its analgesic action has been attributed to its ability to stimulate the release of β‑endorphin, an endogenous opioid neuropeptide.^[2] Interestingly, other studies have also looked at β‑endorphin levels in chronic pelvic pain. Men who were diagnosed with “blood stasis.” by a doctor of traditional Chinese medicine (TCM), which in this case pertained to patients with chronic pelvic pain, showed significantly lower levels of circulating β‑endorphin.^[5] The TCM diagnosis of blood stasis also describes women with dysmenorrhea, endometriosis, dark clots in menstrual flow, and overall sharp and severe throbbing pain. When β‑endorphin levels were tested in women with premenstrual dysphoric disorder (PMDD), it was found that not only did they have lower circulating levels of β‑endorphin, both in the follicular and luteal phases of the menstrual cycle, but patients also experienced decreased pain thresholds and tolerances.^[6] Therefore, lower levels of β‑endorphins may be pathophysiologically significant when addressing chronic pelvic pain.

COX‑Inhibiting and Anti-Inflammatory Effects

Constituents found in ginger root, such as 6‑gingerol and gingerdiones, have been shown to inhibit cyclooxygenase (COX) and lipoxygenase enzymes, which lead to an inhibition of the synthesis of leukotrienes and prostaglandins.^[1][2][4][7] It is by this mechanism that anti-inflammatory effects are seen when used in patients with rheumatoid arthritis,^[10] and also dysmenorrhea.^[2][9][11] Pharmaceutical inhibition of COX has been used for decades for pain and inflammation. Most notable are COX‑2 inhibitors such as celecoxib for arthritic conditions, and NSAIDs such as ibuprofen and naproxen which block both COX‑1 and COX‑2 enzymes.

Research on a specific ginger extract, Eurovita Extract 77 which combines Zingiber officinale with Alpinia galanga, showed that it was able to inhibit the induction of several genes associated with inflammatory responses, including those for cytokines, chemokines, and COX‑2.^[9] One study in patients with osteoarthritis showed that, taken as 225 mg twice daily for six weeks, Eurovita Extract 77 significantly reduced pain and stiffness compared to placebo.^[10] A complementary mechanism of action may be in how ginger affects circulation: As an effective stimulator of peripheral circulation, ginger may help in alleviating cramping pain.^[8] This ties into our TCM theory, whereby stagnation or stasis of blood results in a deep stabbing, throbbing pain; therefore, symptoms may be alleviated with improved circulation, also described in TCM as “smooth flow of blood and qi,.” most notably as liver qi and liver blood, which affect menstrual flow.

Inflammation in Dysmenorrhea

Acting as an inhibitor of inflammatory pathways, an enhancer of peripheral circulation, and an effective analgesic, ginger should be highly considered as an alternative or complementary treatment for dysmenorrhea. Dysmenorrhea is characterized as severe menstrual pain and occurs in up to 50% of menstruating women, most often within the first few days of menses.^[2] Primary dysmenorrhea, specifically, is diagnosed in the absence of any identifiable pathological conditions that would lead to said pain.^[4] Occurrence of pain has been attributed to an increased production of prostaglandins within the endometrium ^[1] and increased activity of COX‑2.^[7] Researchers have found higher levels of prostaglandins F2‑a and E2 as well as of leukotrienes in women who experience dysmenorrhea compared to those who do not experience any menstrual pain.^[11] Activation of these inflammatory-associated substances may also lead to increased pain sensitivity.^[4] Studies have shown that dysmenorrhea can affect academic performance, social activities, and sports activities in young women.^[11] Conventional treatment consists of oral contraceptive medications or progestin-releasing intrauterine devices, and NSAIDs which are typically first-line therapy for acute menstrual pain. Those that have shown efficacy for use include ibuprofen, naproxen, mefenamic acid, and aspirin.^[1] That said, the failure rate for menstrual pain relief with these treatments stands between 20 and 25%.^[2] It’s also common for some women to avoid their use, due to common side effects such as nausea, dyspepsia, and other gastrointestinal disturbances.^[1]

Efficacy of Ginger for Dysmenorrhea

Studies addressed in meta-analyses of ginger’s efficacy in primary dysmenorrhea most commonly used a dried ginger rhizome powder as the treatment form. These preparations, ranging in dose from 1000 to 1500 mg, were standardized for weight of ground ginger powder, but not for gingerol or other constituent concentrations.^[3][4] Nevertheless, positive and statistically significant improvements in menstrual pain were seen almost across the board. A double-blind, placebo-controlled study by Rahnama et al (2012) investigated the efficacy of ginger for pain relief in women with moderate to severe dysmenorrhea.^[7] Treatment consisted of 1500 mg of encapsulated dried ginger powder given daily on days 1–3 of the menstrual cycle. Results showed that ginger elicited a significant decrease in the duration and intensity of pain compared to placebo.^[7] When compared against both ibuprofen and mefenamic acid individually, Ozgoli et al (2009) showed that ginger had a similar efficacy rate.^[1] Patients with moderate to severe dysmenorrhea were allocated to receive one of the three above treatments. Pain severity and satisfaction of pain relief were comparable between the groups with a 62% success rate with ginger, 54% with ibuprofen, and 44% with mefenamic acid.^[1] In contrast to other studies of this kind, Ozgoli et al (2009) used a scale based on the limitations of activities of daily living due to pain as their outcome measure, whereas most other studies employed the Visual Analogue Scale (VAS). Jenabi et al (2013) also found positive results with ginger treatment, where 82% of female subjects found benefit in ginger for the reduction of menstrual pain.^[11] This was a small study (n = 35), with treatment of 1500 mg of dried ginger powder taken in divided doses on days 1–3 of menses; however, the change in perceived pain was quite significant, with a decrease greater than 3 cm on the VAS.^[11] There are limitations to these studies and they warrant further investigations. Many studies tested treatments for only one menstrual cycle. As many women understand, each menstrual cycle may involve a slightly different experience. That is, pain may vary from cycle to cycle; dietary and exercise factors can also influence pain and inflammation, as could hormonal levels of progesterone and estrogens. However, as an acute treatment, ginger may be an excellent substitute for NSAIDs, with a superior safety profile for women.^[4] Grzanna (2005) even goes as far as to suggest that ginger may have a better therapeutic action for pain and inflammation, as it is a dual inhibitor of both COX and 5‑lipooxygenase enzymes,^[9] compared to pharmaceuticals which isolate COX inhibition. This mechanism makes ginger a valuable addition to NSAID use, as the complementary action would enhance that of NSAIDs and therefore allow for a decrease in pharmaceutical dosing.

Safety, Usage, and Dosing

Although ginger’s safety profile outperforms its pharmaceutical counterparts, there are always limitations when it comes to dosing. Human pharmacological studies have shown that in large doses, upwards of 12–14 g, ginger can reduce platelet aggregation and therefore enhance anticoagulant drugs.^[8] That said, this study reported that there was no difference in bleeding times between treatment and placebo groups.^[8] Common dosing for motion sickness or seasickness ranges between 1 and 2 g of dried powder as a single dose.^[12] In TCM, dosing in pregnancy has been prescribed up to a maximum of 2 g per day of dried ginger.^[8] Patients with osteoarthritis found a significant reduction in symptoms with ginger extracts of 340 mg–1020 mg daily, which were found to have similar efficacy to diclofenac.^[1][3] Based on these findings and those in the studies discussed above, it would be reasonable to apply a dosage of 1–2 g of dried ground powder, divided, daily for the treatment of acute menstrual pain. Further studies may be needed to assess the efficacy of daily dosing outside of days 1–3 of menses for other conditions of chronic pelvic pain.

Conclusions

One promising aspect of ginger for pain is that it can help reduce or eliminate the need for NSAIDs. It may also save some women from having to use synthetic hormonal therapy in the absence of irregular cycles or other hormonal imbalances. In general, treatment with ginger was shown to be greater or comparable to pharmaceutical anti-inflammatories in reducing both acute and chronic pain.^[3] This may provide a safe and effective alternative for women who either cannot tolerate the side effects of NSAIDs or who have a contraindication for their use.^[1][12] It may also help to decrease dosing of NSAIDs when used in conjunction with ginger, as they have similar mechanisms of action on inflammatory pathways. Further research is needed to thoroughly investigate the differences in outcomes with dried root powder preparations compared to specific extracts standardized for compounds such as gingerols, which appear to be the active constituents responsible for the inhibition of prostaglandin synthesis, similar to NSAIDs.^[1]