Turmeric in the Treatment of Dyspepsia
May 2000; Volume 3; 49-53
By Philippe O. Szapary, MD, and Michael D. Cirigliano, MD, FACP
The medical literature suggests that turmeric (curcuma longa) extracts possess antioxidant, hypolipidemic, choleretic (stimulation of bile flow), cholekinetic (stimulation of gallbladder contraction), anti-inflammatory, anticarcinogenic, and antimicrobial activities.1 Of all these purported benefits, perhaps the best-studied in humans are turmeric’s choleretic and cholekinetic properties, making this ancient herb potentially useful in the treatment of dyspepsia.
Dyspepsia is a common condition seen in general practice, accounting for 2-4% of all primary care office visits.2 The term non-ulcer dyspepsia (NUD) refers to epigastric discomfort not associated with ulcer disease. In modern clinical practice in this country, the mainstay of treatment for NUD includes antacids, H2-blockers, proton pump inhibitors, and antibiotics aimed at Helicobacter pylori, all of which may work in the short term, or may not work at all. In these patients, turmeric when used in doses of 1-3 g/d may improve dyspeptic symptoms.
History
Turmeric and its powdered rhizome were highly valued by early Asian civilizations because of its golden yellow color, reminiscent of sunlight. In Sanskrit, turmeric can be identified by 46 synonyms, including pita (fire/yellow) or gauri (brilliant).3 Turmeric’s distinctive color was thus exploited and used in commercial textile dyes. It was also noted that turmeric powder, because of its antimicrobial and antioxidant properties, preserved foods and prevented spoiling.3 This is one of the reasons turmeric powder is used as a preservative and flavor enhancer in many Indian curry powders. In Western cuisine, turmeric is still used as a preservative in the pickling process, and as a dye and preservative in condiments like yellow mustard.
Extracts from Curcuma longa, also known as turmeric, have been used in Ayurvedic medicine for more than 2,000 years for a wide variety of unrelated medical conditions from parasitic intestinal infections and skin cancer to liver disease. In traditional Chinese medicine, turmeric, also known as Jianghuang, has been used for dyspepsia, liver disease, and hyperlipidemia for more than two millennia and is listed in the Chinese Materia Medica.4
Source and Identification
Curcuma is a perennial herb indigenous to Southeast Asia and like ginger, belongs to the Zingiberaceae family. Of the genus Curcuma, two plants, C. longa and C. xanthorrhiza (Javanese turmeric) have medicinal properties.3 Curcuma longa, also known as C. domestica, is by far the most commonly used and will be the focus of this review. The underground rhizome of C. longa (1/2 inch in diameter) is cultivated, boiled in water, air dried and cured into fingers, and then ground into powder. The major constituents of the powder include curcuminoids (2-5% by weight) and volatile oils (2-6%).5 The majority of the biologic activity is believed to come from the curcuminoids, and to a lesser extent, the volatile oils that give turmeric its characteristic smell and taste.
Pharmacology
The major curcuminoids are curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), and cyclocurcumin.5 The primary volatile oils, of which much less are known, are composed of sesquiterpenoids such as curcumone, turmerone, and zingiberene.5 Of interest, a number of bioactive polypeptides have been identified, including turmerin.
Metabolism
Studies in rats and humans confirm that the majority of orally ingested curcuminoids are excreted in feces and that only very small amounts can be detected in serum and urine.5 In vivo experimentation in rats using a very large oral dose of curcumin have found that 60% of curcumin is absorbed.1
In humans, curcumin is barely detectable in serum after a single 2 g oral dose of curcumin.6 It is possible that curcumin undergoes transformation to unmeasured compounds in intestinal cell walls, and may be effective at very low concentrations. Interestingly, coadministering a small dose of piperine, an extract of black and long pepper used in Ayurveda, increased bioavailability of curcumin by 2,000% in one study.6 The small amounts of curcumin that are absorbed in the serum are quickly metabolized by the liver to glucuronides of tetrahydrocurcumin and actively excreted into bile.5
The following statements about turmeric are correct except:
a. turmeric is a spice.
b. turmeric can be used as a food colorant.
c. turmeric possesses antioxidant properties in vitro.
d. turmerin is the most bioactive constituent of turmeric.
Mechanism of Action
Curcuminoids’ mechanisms of action have been extensively studied and are multifaceted. Curcuminoids have been shown to antagonize the effect of several spasmogens in isolated guinea pig ileum.5 Curcumin may also stimulate the release of GI paracrine hormones from intestinal luminal cells. Curcumin has also been shown to increase hepatic cholesterol-7a-hydroxylase activity in rats, which stimulates bile acid synthesis.7
Turmeric extracts inhibit cyclooxygenase enzymes, like NSAIDs8 and thus may be ulcerogenic, especially at higher doses.
Animal Studies
In a study done in rats fed a flatulent diet, curcumin feeding decreased gas production.5 Curcumin administered at an IV dose of 25 mg/kg increased bile secretion in anesthetized dogs by 100%.5 Other studies have confirmed these findings and also found a cholekinetic effect. Some investigators have found that curcumin prevented the formation of cholesterol gallstones in mice.9
Curcumin has been shown to increase mucin content in gastric juice of rabbits, thus possibly imparting a protective effect on the gastric mucosa.5 This protective gastric effect is controversial, however, as one study has shown that curcumin when administered at high doses (100 mg/kg) PO to albino rats was actually ulcerogenic.10 It appears that the ulcerative index of curcumin is dose dependent and approximately one-third that of the NSAID phenylbutazone.11
Clinical Trials
Searching MEDLINE, PubMed, NCCAM CAM Citation Index, IBIDS database, and the HerbMed database, we identified 12 clinical trials using turmeric or curcuminoids alone or with other herbs in humans. Of these 12 trials, only five of these trials specifically investigated the GI effects of turmeric derivatives and all of these trials were randomized, placebo-controlled trials (RCT).
One multicenter RCT done in Thailand reported the effect of turmeric powder compared with a combination antiflatulence product containing ginger, capsaicin, and cascara with placebo.12 One hundred sixteen patients with clinically diagnosed non-specific dyspepsia were randomized to take 500 mg turmeric powder PO qid in capsule form for seven days.
Fifty-three percent of placebo patients were "improved or cured" compared to 83% of those assigned to the antiflatulence product and 87% of those in the turmeric group (P < 0.008 for either drug vs. placebo). At the end of the study, approximately 50% of subjects across all groups were satisfied with their treatment assignment. Problems with this study include the use of a nebulous, non-endoscopic definition of dyspepsia and the very short treatment period.
When treating a subset of NUD patients with functional biliary tract pain (i.e., no evidence of gallstones), a recent German group found that a proprietary combination product (Cholagogum F Nattermann®) containing 45 mg of curcumin and 4 mg of celandine given orally tid significantly reduced complaints of colicky right upper quadrant (RUQ) abdominal pain when compared to placebo over three weeks (P < 0.01).13 No significant differences were noted in the incidence of early satiety, nausea, or vomiting.
This study implies that increasing bile flow may improve symptoms in these patients. This effect attributable to curcuminoids was recently demonstrated in another RCT in which 12 healthy volunteers received a 20 mg dose of oral curcumin or placebo, and had four serial RUQ ultrasounds over two hours.14 Investigators found a 30% reduction in gallbladder volume two hours after receiving curcumin (P < 0.001).
Another RCT looking specifically at the healing rate of duodenal ulcers found that 6 g of turmeric powder given orally each day was no better than placebo at eight weeks.15 Healing was actually worse in the turmeric group (2% healed) compared to the placebo group (15% healed) at four weeks. By the study’s end, both groups demonstrated a 30% healing rate.
Another RCT compared turmeric powder 250 mg PO qid with a liquid antacid qid in healing endoscopically proven gastric ulcers in 60 patients.16 After six weeks, 33% of gastric ulcers in the turmeric group had completely healed compared with 65% in the antacid group. Fifteen percent of the turmeric group was unchanged or worse compared to 0% in the antacid group. These findings imply that large doses of turmeric may actually be ulcerogenic and retard healing rate in peptic ulcer disease (PUD).
Adverse Effects and Drug Interactions
Most animal studies have found turmeric and curcumin to be safe, even at high doses. For example, one study done in monkeys found no adverse effects at an oral curcumin dose of 800 mg/kg/d for three months.17 There is one report of curcumin causing gastric ulcerations in mice at 50 mg/kg/d for six days10 and another report of hepatotoxicity with exaggerated oral feedings with turmeric over just 14 days.18
In humans, turmeric is a Generally Recognized as Safe (GRAS) spice with typical consumption in Indian culture ranging from 0.1-3.8 g/d.19 Published clinical trials do not report significant adverse events. Specifically, a clinical trial done in rheumatoid arthritis found curcumin to be well tolerated at doses up to 1,200 mg/d for two weeks (approximately 24 g/d turmeric powder).20 Also, a published abstract from a Phase I trial of curcumin in patients with HIV found curcumin safe at doses of up to 2,000 mg PO qd for 18 weeks.21
There are no published reports of curcumin-drug interactions. One review raised the possibility of an interaction with antiplatelet agents as curcumin inhibits platelet aggregation in vitro. Animal studies have found that turmeric is safe in pregnancy but no human studies address this population. It is clear, however, that medicinal use of turmeric should be avoided in pregnancy as it may increase uterine contraction.19
There are several published case reports of contact dermatitis associated with turmeric powder when used topically. A search of the FDA adverse drug reaction (ADR) database identified 12 reports associated with turmeric or curcumin.22 A review of these ADRs found that every case report was associated with multiherbal preparations, which included small amounts of turmeric and often included ma huang.
Formulations and Dosage
Turmeric is widely available commercially as a spice used in Indian cuisine but the doses required for a therapeutic effect in dyspepsia (1-3 g/d) precludes the practical use of this formulation in most Western diets. Turmeric is also available as a concentrated extract in capsule form standardized to curcumin content, as an alcohol extracted tincture, and as a tea. (See Table 1.) Since the curcuminoids and volatile oils are poorly water soluble, teas are not recommended.
| Table 1-Comparison of commercially available turmeric products with other products used for dyspepsia | ||||
| Product/Manufacturer | Active Ingredient | Manufacturer's Suggested Use | Dyspepsia Dosing (Based on RCT) | ail Price/Month (Based on NUD Dosing) |
| Zantac® | Ranitidine 150 mg | 1 tablet PO bid | same | $41.15/month |
| Artichoke Leaf Extract (Enzymatic Therapy) | 13-18% caffeylquinic acid | 1 capsule PO tid | same | $20.50/month |
| Chamomile (Nature's Herb) | German chamomile flowers 354 mg/capsule | 2 capsules PO tid | same | $11.07/month |
| Turmeric-Power (Nature's Herb) | Curcumin 300 mg Standardized to contain 95% curcuminoids | 2-3 capsules qd | 1 capsule qd | $6/month |
| Turmeric Extract (Source Natural) | Curcumin 350 mg/bromelain 50 mg | 1-3 capsules qd | 1 capsule qd | $6/month |
| Source: Hospital of University of Pennsylvania outpatient pharmacy, online mail order companies | ||||
In this country, turmeric and curcumin are found primarily in combination products marketed as antioxidants or for the treatment of arthritis. It is important to note that the anti-inflammatory doses of curcumin used in RCTs for arthritis treatment are at least four times higher than the doses found to be effective in dyspepsia.
All of the following statements about turmeric are true except:
a. turmeric has documented anti-inflammatory activity in humans.
d. turmeric is most useful when used as a tea.
c. turmeric may retard healing of duodenal ulcers.
d. turmeric should not be used in patients with gallstone disease.
International Practice
In Europe, carminative herbs like chamomile, artichoke leaf, and turmeric are frequently used in clinical practice for the treatment of dyspepsia. The German Commission E has approved the use of turmeric alone, and in combination with the herb celandine, for the treatment of dyspepsia.23
Conclusion
For simple NUD, it appears that curcumin or turmeric powder may decrease symptoms over the short run. No data exist to support its long-term use for this chronic condition. Turmeric should not be used in patients with active PUD as it may be ulcerogenic even at doses of 1 g/d. Turmeric should also not be used in patients with known cholelithiasis or chronic cholecystitis as this herb causes biliary contraction and could precipitate an attack. In the subset of patients with biliary dyskinesia, turmeric and curcumin seem to improve pain symptoms. To date, there are no studies directly comparing turmeric to artichoke leaf extract, the most popular herbal cholagogue used in Europe.
Recommendation
We caution against the indiscriminant use of medicinal turmeric for undiagnosed epigastric pain. This is based on data from RCT that suggest turmeric may impede healing of ulcers in PUD. Turmeric should also not be used in patients with known or suspected cholelithiasis. However, in patients whom you believe truly have NUD, turmeric powder 1-3 g/d or curcuminoids 50-150 mg/d is an inexpensive and likely effective remedy.
Which of the following statements about curcumin is/are true?
a. It has been shown to increase bile acid flow.
b. It has been shown to heal peptic ulcers.
c. It has been shown to increase gallbladder contraction.
d. a and c.
Dr. Szapary is Assistant Professor of Medicine at the University of Pennsylvania School of Medicine in Philadelphia.
References
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20. Deodhar SD, et al. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res 1980;71:632-634.
21. Copeland R, et al. Curcumin therapy in HIV-infected patients initially increased CD-4 and CD-8 cell counts. Int Conf AIDS 1994;10:216, abstract no. PB0876.
22. U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Special Nutritionals. Available at: http://vm.cfsan.fda.gov/~tear/aems.cgi. Accessed March 30, 2000.
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May 2000; Volume 3; 49-53
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