Medicinal Value of Ginger with Focus on its Use in Nausea and Vomiting of Pregnancy

Abstract

Ginger (rhizome of Zingiber officinale) is a well known herb for its culinary and wide range of medicinal uses and is considered an essential component of the kitchen pharmacy. More commonly, ginger has been traditionally used in disorders of the gastrointestinal tract, as a stomachic, laxative, sialogogue, gastric emptying enhancer, appetizer, antiemetic, antidyspepsic, antispasmodic, and antiulcer agent with sufficient scientific support. Similarly, ginger has been shown to exhibit anti-inflammatory, hypoglycemic, antimigraine, antioxidant, hepatoprotective, diuretic, hypocholesterolemic, and antihypertensive activities. Recently, ginger has gained wide attention for its therapeutic role as a safe and effective preventive treatment option for nausea and vomiting of pregnancy. Ginger has a long history of safety, as it has been used for centuries not only for medicinal purposes, but also as a food and spice. Although some health risk and safety concerns exist in the literature about its use by pregnant women, the clinical evidence of harm is lacking. Ginger might, therefore, be used as an effective treatment option for nausea and vomiting during pregnancy. In this article, we focus attention on these aspects of ginger.

Keywords:

• Ginger
• Medicinal value
• Nausea
• Vomiting
• Pregnancy

INTRODUCTION

Ginger (rhizome of Zingiber officinale) is a popular herb for its culinary and medicinal value. In addition to its flavoring effects, ginger is also considered an essential component of the kitchen pharmacy and is particularly used in combination with foods which cause delayed gastric emptying or flatulence such as beans, certain pulses, and vegetables like radish and cauliflower.[1] It is said to be a native of Asia but is now intensively grown throughout the tropical areas of the world. The most expensive and high quality ginger varieties generally come from Australia, South India, and Jamaica; while the most mass-produced ginger is grown in China. Both fresh and dried forms of ginger are well recognized worldwide for their culinary and medicinal properties.[2,3] The odour of ginger is penetrating and aromatic and it tastes spicy, hot and, biting. These properties, however, are either reduced or lost on exposure to light and air.[1,4]

Ginger has been used for thousands of years in Asian and Ayurvedic medicine as an anti-inflammatory and anti-pyretic agent and to treat indigestion, nausea, stomachache, toothache, insomnia, flatulent intestinal colic, respiratory and urinary tract infections, rheumatism, diabetes, infertility, nervous diseases, as well as to strengthen the memory.[1,5] References to ginger as a medicine and as a spice appear in ancient Chinese and Sanskrit writings, and in surviving Persian, Arabic, Greek, and Roman texts.[6] Medieval writings from many European countries indicate that ginger was a standard ingredient in recipes for the kitchen and the apothecary.[7] In the beginning of the 18^th century, the “Electric Physicians” in the United States used ginger to relieve nausea and intestinal disorders. In China and Japan, ginger is used to treat headache, colds, nausea and related stomach problems.[8] Chinese women traditionally eat ginger during pregnancy to combat morning sickness. Similarly, ginger has been considered useful for cardiovascular disorders.[1]

CHEMICAL COMPOSITION

Ginger contains approximately 50% carbohydrate, 6 to 8% fatty acids and triglycerides, and 9% protein, free amino acids, vitamins, and minerals.[9,10] The main bioactive constituents of ginger are volatile oils, soft resins insoluble in ether and oil, gum, starch, lignin, acetic acid, potassium oxalates, acetates, and some sulphur.[5,10] Depending on the rhizome being fresh or dried, it has varying levels of fatty oils, protein, carbohydrate, raw fibre, ash, water, and volatile oils. The volatile oils constitute sesquiterpenes, curcumene, geranyl acetate, terpineol, terpenes, geraniol, alpha pinene, limonene, linalool, zingiberene, beta-besabolene, and alpha-farnesene.[11] The pungent principles are gingerol, shogaol, zingerone and paradol.[6] [6]-Gingerol and [6]-Shogaol are the major active components for ginger's pharmacological effects and pungency respectively.[8,12] The main aroma-defining component is zingiberol while others as gingediol, monoacyldigalactosyl-glycerol, diarylheptanoids, vitamins, and phytosterols have also been identified.[13]

The levels of constituents in ginger can vary considerably depending upon a number of factors including intra-species variations related to the country of origin, and environmental factors such as climate, growing conditions, and the time of harvesting. Post-harvest handling conditions, like storage and processing may also result in a loss of thermo-labile active constituents.[14] Ginger samples derived from different origins showed no qualitative differences in major volatile compounds, although they did show some significant quantitative differences in non-volatile composition, particularly regarding the content of [6]-, [8]-, and [10]-gingerols, the most active anti-inflammatory and antispasmodic components in this species.[15,16]

REPORTED ACTIVITIES

The anti-inflammatory and analgesic properties of ginger have been known and valued for centuries.[17] Young et al.[18] have recently reported that [6]-gingerol possessed analgesic and anti-inflammatory properties. The in-vitro assays, conducted to evaluate the ability of all the extracts from Zingiber species to inhibit the LPS-induced PGE₂ and TNF-α production, suggested that bioactivity may not be easily predicted by either phylogenetic analysis or gross metabolic profiling.[16] Ginger suppresses prostaglandin synthesis through inhibition of cyclooxygenase-1 and cyclooxygenase-2. An important extension of this early work was the observation that ginger also suppresses leukotriene biosynthesis by inhibiting 5-lipoxygenase.[19] Shobana and Naidu[20] reported that aqueous and alcoholic extracts of commonly used spices (garlic, ginger, onion, mint, cloves, cinnamon, and pepper) dose-dependently inhibited the oxidation of linoleic acid in the presence of soybean lipoxygenase. The spice mixes showed cumulative inhibition of lipid peroxidation thus exhibiting their synergistic antioxidant activity. They suggested that in addition to imparting flavor to the food, these spices possess potential health benefits by inhibiting lipid peroxidation.

Ginger extract (EV.EXT.77) derived from Zingiber officinale and Alpina galanga inhibits the induction of several genes (encoding cytokines, chemokines, and the inducible enzyme cyclooxygenase-2) involved in the inflammatory response.[19] This discovery provided the first evidence that ginger modulates biochemical pathways activated in chronic inflammation. The activation of nuclear transcription factor kappa-B (NF-kappaB) has now been linked with a variety of inflammatory diseases, including cancer, atherosclerosis, myocardial infarction, diabetes, allergy, asthma, arthritis, Crohn's disease, multiple sclerosis, Alzheimer's disease, osteoporosis, psoriasis, septic shock, and acquired immune deficiency syndrome (AIDS).[21]

Ginger is also an effective antimicrobial, antifungal, and antiviral agent.[22] It exerts antioxidative, antitumorigenic, anticarcinogenic, antilipidemic, cardiotonic, cytotoxic and apoptotic activities, as well as immunomodulatory effects.[1,23–29] Sharma and Shukla[30] reported a small but significant blood glucose lowering effect of ginger juice in diabetic and non-diabetic animals. Bode et al.[31] reported that feeding 500 mg [6]-gingerol 3 times per week to athymic nude mice injected with human colon cells suppressed the tumor growth, which took longer time to appear and grow as compared to control (mice fed with a placebo). The mechanism is still to be determined however, they suggested that [6]-gingerol may inhibit tumor growth by inhibiting AP1 activation or inducing tumor cell death. Miyoshi et al.[32] provided the biological evidence that specific constituents of ginger, other than curcuminoids, are the potential anticancer agents. Kim et al.[33] demonstrated that [6]-gingerol inhibits angiogenesis and may be useful in the treatment of tumors and other angiogenesis-dependent diseases. Phytochemicals derived from various spices can interrupt the pathway that activates this transcription factor.[21] These studies have now provided an explanation for seasoning of our foods with spices. Ghayur and Gilani[34] reported that ginger lowers blood pressure through calcium antagonist effect and their more recent studies have revealed that ginger can also lower blood pressure through multiple ways.[35]

More commonly, ginger has been traditionally used in disorders of the gastrointestinal tract, as a stomachic, laxative, sialogogue, appetizer, antiemetic and antidyspepsic and at the same time, as an antidiarrheal, antiulcer and antispasmodic agent.[1,5] In general, ginger is used in multiple situations including the treatment of nausea and vomiting of pregnancy.[36–38] Several studies conducted in both animals and humans have shown its gastric prokinetic action with some conflicting reports on the possible mode of action and recently Ghayur and Gilani[39] demonstrated that ginger contains gastric stimulating factor of cholinergic type, along with an antispasmodic component mediated through the calcium antagonist action explaining its wide range of uses in gastrointestinal disorders. Interestingly, ginger extract and some of its active constituents, such as zingeberene and 6-gingerol have been shown to possess anti-ulcerogenic activity.[40,41] Furthermore, the ginger extract containing gingerols inhibits the growth of Helicobacter pylori.[42,43] More recently, it was observed that the co-administration of ginger extract with clarithromycin showed enhanced activity against the H. pylori,[44] and this might be the contributing factor towards its anti-ulcer effect with an added value for its medicinal use as prokinetic in the esophageal reflux disease.[39]

NAUSEA AND VOMITING OF PREGNANCY (NVP)

The majority (50–90%) of pregnant women experience some degree of nausea and/or vomiting (NVP) usually in the first few months of pregnancy, though its cause is largely unknown.[45,46] Westfall[38] observed that almost 74% of pregnant women experienced nausea. This condition, colloquially known as “morning sickness” (though it is rarely restricted to morning) can range from a mild feeling of seasickness to severe nausea and vomiting. Approximately 1–2% of pregnant women experience a debilitating and life-threatening condition called “Hyperemesis gravidarum,” whereby the nausea and vomiting are so severe that they can lead to starvation and dehydration.[47] This condition may also have serious implications for both the maternal and fetal health.[48]

Nausea and vomiting are mediated primarily by visceral stimulation through dopamine and serotonin, by the vestibular and central nervous system. NVP may cause a decrease or an increase in food intake. Poor appetite and reduced food intake sometimes accompany NVP.[49] NVP can also result in changes in food choices/selection and may affect the quality of the diet. Studies have shown that cravings and aversions are more common in women with NVP than those without.[50] Undernutrition during these critical periods of fetal development may lead to changes, which can program later health risks such as cardiovascular disease, hypertension, and non-insulin dependent diabetes mellitus.[51]

SAFETY AND EFFECTIVENESS OF GINGER IN THE TREATMENT OF NVP

In addition to a range of pharmaceutical drugs, several alternative and complimentary therapies including sea bands (acupressure on the inside of the wrist) and various herbal medicines are used to treat the conditions of nausea and vomiting. At present, no drug is licensed for the treatment of nausea and vomiting of pregnancy in the United Kingdom.[52] In Canada, Diclectin (doxylamine 10mg + pyridoxine 10mg) is the only antinauseant approved for such conditions.[48] Complementary and alternative therapies, such as ginger, acupressure, and vitamin B₆, have shown variable effectiveness in the treatment of pregnancy-induced nausea.[53,54] Vitamin B₆ and ginger are attractive alternative treatments for NVP.[55,56] A survey conducted under the Motherisk Program in Toronto, Canada, indicated that over 50% of the women used ginger tea or tablets.[57] A number of other studies indicated that between 6–12% of pregnant women used ginger or other anti-emetic herbal remedies to treat nausea and vomiting.[58–61]

A significant decrease in nausea and vomiting was observed in pregnant women who used ginger.[62,63] Smith et al.[52] demonstrated that ginger is as effective as vitamin B₆ in improving the symptoms of nausea, retching, and vomiting in early pregnancy. They also observed that the risk of pregnancy loss was lower in the ginger group. Portnoi et al.[64] studied the safety and effectiveness of ginger for nausea and vomiting of pregnancy (NVP). They suggested that ginger does not appear to increase the rates of major malformations above the baseline rate of 1–3% and that it has mild effect on the treatment of NVP. Jewell and Young[65] concluded that anti-emetic medication appears to reduce the frequency of nausea in early pregnancy. There is some evidence of adverse effects but there is very little information on their effects on fetal outcomes from randomized controlled trials. The studies suggest no evidence of teratogenicity from any of these treatments.[65]

There is a general belief that herbal medicines are gentle and safe as they contain multiple types of phytochemicals which can exert both the synergistic and antagonistic effects either enhancing or neutralizing the effects in combinations.[66] However, sufficient scientific basis for such actions is still lacking and no rigorous scientific studies have been conducted on the safety of herbal preparations and dietary supplements for their use during pregnancy. The Teratology Society has stated that it should not be assumed that herbal medicines and dietary supplements are safe for the embryo or fetus.[67] Among many anti-emetic herbal remedies (ginger, peppermint, and Cannabis), only ginger has been subjected to clinical trials in pregnant women. Animal studies in rats did not show any evidence of teratogenicity,[68,69] Vutyavanich et al.[63] also did not observe any adverse effects of ginger on the outcome of pregnancy.

As ginger has been found to be a potent thromboxane synthetase inhibitor, it has been hypothesized that it may affect the testosterone binding receptor in the fetus and could theoretically alter the sex steroid-dependent differentiation of the fetal brain. Backon,[70] therefore, suggested that until its effect on testosterone binding receptors is not thoroughly studied; ginger should not be recommended for use in pregnant women. However, later studies[71,72] did not find any significant change in thromboxane synthesis over a treatment period of up to 2 weeks and at a maximum dose of 40 g cooked ginger. Dietary supplementation of ginger not only inhibited the platelet aggregation but also improved the biosynthesis of prostacyclin.[73,74] Confirmatory clinical studies are however required to exclude any interaction of ginger preparations with platelet aggregation. Similarly, long-term consumption studies are also required to rule out the potential toxicity of ginger.

The contradictory findings in the literature concerning the safety of ginger could be due to a large variation in the chemical composition of tested extracts. Murphy[36] and Fischer-Rasmussen et al.[62] concluded that ginger might be of benefit as a safe and effective antinauseant. The recommended dose for alleviation of morning sickness is 0.5 to 1.0 g per day. Bryer[75] reviewed the 4 recent well-controlled, double blind, randomized clinical studies. She concluded that these studies provide the convincing evidence for the effectiveness of ginger in treating nausea and vomiting of pregnancy.[52,62,63,76] A more recent study concluded that ginger might be an effective treatment for nausea and vomiting in pregnancy.[77] Although clinical and experimental studies suggest that ginger has some antiemetic properties, clinical evidence beyond doubt is only available for pregnancy related nausea and vomiting.[23,78,79] The Meta analysis could not demonstrate any antiemetic effectiveness for postoperative and in-motion sickness or the nausea/vomiting of other etiologies. Though safety concerns exist in the literature about the use of anti-emetic herbal remedies by pregnant women, the clinical evidence of harm is lacking for ginger.[38] Overall the studies suggest that ginger is a safe and effective treatment option for nausea and vomiting of pregnancy. It has been used for centuries for medicinal purposes and as a food and spice. However, more observational and controlled studies, with higher doses and larger sample sizes, are needed to confirm the encouraging preliminary data on ginger safety.

MODE OF ACTION

Ginger's efficacy is believed to be a result of its aromatic carminative and absorbent properties.[62,80,81] Ginger is thought to mediate its action through gastric effects, to increase the tone and peristalsis. However, the exact mechanism of action is not clear.[82–85] Recent studies have shown that ginger selectively exhibits the gastric stimulation along with enhancement of gastric emptying mediated through cholinergic action while exhibiting the antispasmodic properties through calcium antagonist effect in the lower intestine of laboratory animals.[39] Studies on isolated gut preparations from different species revealed that both the gut stimulating and inhibitory effects were species-specific with preparations from guinea-pigs showing enhanced spasmogenicity while reduced spasmolytic effects.[15] This demonstrates that further studies are required to draw a meaningful conclusion. Ginger acts directly on the digestive tract avoiding the CNS side effects, which are common to the centrally acting antiemetics.[83–85] [6]-gingerol and 6-shogaol are the principle components implicated in ginger's anti-nauseant properties as they are found to suppress gastric contraction and increase both gastrointestinal motility and spontaneous peristaltic activity.[15,86] These effect reduce the gastrointestinal feedback to central chemoreceptors reducing the feeling of nausea.

CONCLUSION

Ginger has been safely used for centuries not only for medicinal purposes but also as a food and spice. It is well known for its multiple activities with a proven efficacy in gastrointestinal and inflammatory conditions. Preliminary studies suggest that ginger may also be safe and effective for nausea and vomiting of pregnancy when used at recommended doses for short periods of time. Some safety concerns have been raised when pregnant women used ginger in large doses. However, no clinical evidence on its harmful effects has yet been demonstrated. Clearly more observational and randomized controlled studies, with higher doses of ginger and larger sample size, are needed to confirm the encouraging preliminary data on ginger's safety.