Effectiveness and Safety
Although they are effective in providing symptomatic relief, Zantac®, Tagamet®, and other H2 receptor antagonists have the highest recurrence rate among anti-ulcer treatments. In addition, both drugs are associated with numerous side effects. Because H2-receptor antagonists block the vital bodily function involved in digestion, digestive disturbances are quite common and can include nausea, constipation, and diarrhea. Nutrient deficiencies can appear as a result of impaired digestion. Other possible side effects include liver damage, hair loss, breast enlargement in men, dizziness, allergic reactions, headaches, osteoporosis, depression, insomnia, and impotence. Cost: A month's supply of Zantac® or Tagamet® at therapeutic levels typically costs between $40 and $60.

Clinical Trials
The use of Deglycyrrhizinated Licorice (DGL) compared to standard drug therapy is a classic example of addressing the underlying cause of a condition rather than simply blocking an effect. Most people do not get ulcers because of over secretion of acid. The cause in most cases is a breakdown in the integrity of the intestinal lining. While drugs like Zantac® and Tagamet® can block symptoms and promote temporary healing, they don't address the underlying cause. DGL addresses the underlying factors and promotes true healing. Rather than inhibit the release of acid, licorice stimulates the normal defense mechanisms that prevent ulcer formation. Specifically, flavonoids present in DGL inhibit the growth of H. pylori in vitro, while the whole extract improves both the quantity and the quality of the protective substances which line the intestinal tract, increases the life span of intestinal cells, and improves blood supply to the intestinal lining.

Numerous clinical studies over the years have found DGL to be an effective anti-ulcer compound. For example in one study, 33 gastric ulcer patients were treated with either DGL or a placebo for one month. At the end of the study, there was a significantly greater reduction in ulcer size in the DGL group (78%) than in the placebo group (34%). Complete healing occurred in 44% of those receiving DGL, but in only 6% of the placebo group. In several head to head comparison studies, DGL has been shown to be more effective than either Tagamet® or Zantac® in both short-term treatment and maintenance therapy of peptic ulcers. However, while these drugs are associated with significant side effects, DGL is extremely safe and is only a fraction of the cost.

References

i. Morgan AG, McAdam WA, Pacsoo C, Darnborough A. "Comparison between cimetidine and Caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy." Gut 1982 Jun; 23(6): 545-51.

ii. Morgan AG, Pacsoo C, McAdam WA. "Maintenance therapy: a two year comparison between Caved-S and cimetidine treatment in the prevention of symptomatic gastric ulcer recurrence." Gut 1985 Jun; 26(6): 599-602.

iii. Turpie AG, Runcie J, Thomson TJ. "Clinical trial of deglydyrrhizinized liquorice in gastric ulcer." Gut. 1969 Apr; 10(4): 299-302.

iv. D'Imperio N, Giuliani Piccari G, Sarti F, Soffritti M, Spongano P, Benvenuti C, Dal Monte PR. "Double-blind trial in duodenal and gastric ulcers. Cimetidine and deglycyrrhizinized liquorice." Acta Gastroenterol Belg. 1978 Jul-Aug; 41(7-8): 427-34.

v. Brogden RN, Speight TM, Avery GS. "Deglycyrrhizinised liquorice: a report of its pharmacological properties and therapeutic efficacy in peptic ulcer." Drugs. 1974; 8(5): 330-9.

vi. van Marle J, Aarsen PN, Lind A, van Weeren-Kramer J. "Deglycyrrhizinised liquorice (DGL) and the renewal of rat stomach epithelium." Eur J Pharmacol 1981 Jun 19; 72(2-3): 219-25.

Antiviral effects of Glycyrrhiza species.
Phytother Res. 2007 Sep 20;
Department of Medical and Surgical Sciences Endocrinology,
University of Padua, Padova, Italy.
Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, Armanini D, Bielenberg J.

Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus-induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV-1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus.Mechanisms for antiviral activity of Glycyrrhiza spp. include reduced transport to the membrane and sialylation of hepatitis B virus surface antigen, reduction of membrane fluidity leading to inhibition of fusion of the viral membrane of HIV-1 with the cell, induction of interferon gamma in T-cells, inhibition of phosphorylating enzymes in vesicular stomatitis virus infection and reduction of viral latency.Future research needs to explore the potency of compounds derived from licorice in prevention and treatment of influenza A virus pneumonia and as an adjuvant treatment in patients infected with HIV resistant to antiretroviral drugs. Copyright (c) 2007 John Wiley & Sons, Ltd.


In vitro and in vivo antiallergic effects of Glycyrrhiza glabra and its components.
Planta Med. 2007 Mar;73(3):257-61. Epub 2007 Feb 28.
Shin YW, Bae EA, Lee B, Lee SH, Kim JA, Kim YS, Kim DH.

Licorice (Glycyrrhiza glabra L., Leguminosae) is frequently used in traditional medicine to treat inflammatory and allergic diseases. In this study, the main components (glycyrrhizin, 18beta-glycyrrhetinic acid, isoliquiritin, and liquiritigenin) were isolated from licorice, and their anti-allergic effects, such as antiscratching behavior and IgE production-inhibitory activity, were evaluated both in vitro and in vivo. Liquiritigenin and 18beta-glycyrrhetinic acid most potently inhibited the degranulation of RBL-2H3 cells induced by IgE with the antigen (DNP-HSA) and rat peritoneal mast cells induced by compound 48/80. Liquiritigenin and 18beta-glycyrrhetinic acid potently inhibited the passive cutaneous anaphylactic reaction as well as the scratching behavior in mice induced by compound 48/80. These components inhibited the production of IgE in ovalbumin-induced asthma mice but liquiritigenin had little effect. This suggests that the antiallergic effects of licorice are mainly due to glycyrrhizin, 18beta-glycyrrhetinic acid, and liquiritigenin, which can relieve IgE-induced allergic diseases such as dermatitis and asthma.


Preventive effects of glycyrrhizin on estrogen-related endometrial carcinogenesis in mice.
Oncol Rep. 2007 Mar;17(3):617-22.
Niwa K, Lian Z, Onogi K, Yun W, Tang L, Mori H, Tamaya T.

We have previously reported on the inhibitory effect of Glycyrrhizae radix (Gl radix) on mouse endometrial carcinogenesis. The present study was performed to clarify the effects of Gl radix and glycyrrhizin (GL), the main part of Gl radix, on estradiol (E2)-related endometrial carcinogenesis. Both Gl radix and GL exerted a significant decrease in the COX-2, IL-1alpha and TNF-alpha mRNA expressions. GL generated a significant decrease in the incidence of endometrial adenocarcinoma. Accordingly, the preventive effects of Gl radix may be attributable to GL, thus being related with the suppression of COX-2, IL-1alpha and TNF-alpha. Gl radix and GL could therefore be a promising formula for the chemoprevention of human endometrial cancer.


Comparison between cimetidine and Caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy.
Gut 1982 Jun; 23(6): 545-51.
Morgan AG, McAdam WA, Pacsoo C, Darnborough A.

One hundred patients with benign gastric ulceration were treated in a single-blind, endoscopically controlled trial to assess the relative efficacy of cimetidine (1 g daily) and Caved-S (six tablets daily). Ulcer healing was assessed after six weeks' treatment, and, if incomplete, after a further six weeks. There was no significant difference between the two drug regimens (approximately 63% at six weeks and 91% at 12 weeks). If an ulcer remains unhealed after 10 weeks' treatment the patient should undergo surgery. There was no difference in the relief of day pain between the two drug regimens but cimetidine was more effective over the first two weeks of treatment relieving night pain, than was Caved-S (p less than 0 . 02). After ulcer healing, drug dosage was reduced (cimetidine to 400 mg at night and Caved-S to two tablets twice daily). So far, 56 patients, 28 in each group, have completed the first year's maintenance treatment, and there have been four ulcer recurrences in each group (14%).


Maintenance therapy: a two year comparison between Caved-S and cimetidine treatment in the prevention of symptomatic gastric ulcer recurrence.
Gut 1985 Jun; 26(6): 599-602.
Morgan AG, Pacsoo C, McAdam WA.

Eighty two patients with an endoscopically healed gastric ulcer, were treated for two years with either Caved-S tablets, two twice daily or cimetidine 400 mg at night. During the first year, 12% (four out of 34) of the Caved-S group and 10% (four out of 41) of the cimetidine group had an ulcer recurrence. By the end of the second year, the recurrence rate was 29% (nine out of 31) in the Caved-Sgroup, and 25% (eight out of 32) for the cimetidine group. Ulcer relapse occurred frequently in patients with either a dyspeptic history of over six months (p less than 0.05), or a past history of a gastric ulcer (p less than 0.001). Ulcers recurred rapidly after maintenance therapy; Caved-S two out of 22; cimetidine seven out of 23, within four months (NS). This study shows that long term maintenance therapy is safe and reasonably effective. The high recurrence rate after stopping treatment suggests that therapy in high risk or elderly patients should be for life.


Clinical trial of deglydyrrhizinized liquorice in gastric ulcer.
Gut. 1969 Apr; 10(4): 299-302.
Turpie AG, Runcie J, Thomson TJ.

In a double-blind clinical trial of deglycyrrhizinized liquorice 16 patients with gastric ulcer received the active drug for four weeks in a dose of 760 mg thrice daily and 17 the placebo. All patients, except four from each group who remained ambulant, were treated as outpatients. The results of the trial were assessed by the change in the size of the ulcer crater on barium meal before and after treatment. Of the patients given the active drug, on average the size of the ulcer niche was reduced by 78%; in six patients (44%) the crater disappeared radiologically. In contrast the average reduction in size of the ulcer niche of the placebo group was 34% and in only one (6%j did the ulcer disappear. The difference in the reduction in ulcer size in favour of the treated group compared with the control group is statistically significant (P<0.001). None of the patients developed oedema and there was no excessive weight gain. A pilot trial using Caved-(S) in a dose containing 760 mg of deglycyrrhizinized liquorice thrice daily for one mont showed no toxic effects on fluid and electrolyte balance in 10 patients.


Double-blind trial in duodenal and gastric ulcers. Cimetidine and deglycyrrhizinized liquorice.
Acta Gastroenterol Belg. 1978 Jul-Aug; 41(7-8): 427-34.
D'Imperio N, Giuliani Piccari G, Sarti F, Soffritti M, Spongano P, Benvenuti C, Dal Monte PR.

Among the patients receiving cimetidine, 43% with DU and 14.3% with GU had healed ulcers after two weeks; among the patients treated with Caved'S, 31% with DU and 43% with GU recovered. At 4 weeks the percentages recovery were 93% and 57% patients, respectively treated with cimetidine, 64% and 43% patients receiving Caved'S. At 8 weeks, after 4 weeks' therapy with cimetidine, the recovered subjects were 100% of patients with DU and 79% of those with GU. After recovery all the patients were admitted to an open trial of the same drugs and have been followed every 2 months. At present this follow-up is still in course, (Acta gastro-ent. belg., 1978, 41, 427-434). The purpose of our trial is the comparison between cimetidine and deglycyrrhizinized liquorice activity in the treatment of duodenal and benign gastric ulcers. We used Caved'S because, as you probably know, the fundamental pharmacological activity of this product is claimed to be due to deglycyrrhizinized liquorice in dose of 380 mg/tablet. Moreover, we have checked the relapse percentage and rate during the maintenance therapy with the same drugs.


Deglycyrrhizinised liquorice: a report of its pharmacological properties and therapeutic efficacy in peptic ulcer.
Drugs. 1974; 8(5): 330-9.
Brogden RN, Speight TM, Avery GS.

Glycyrrhizinic acid-reduced (deglycyrrhizinated) liquorice compound consists of liquorice from which all by 3% of the glycyrrhizinic acid has been removed, plus antacids, and powdered frangula bark. Another liquorice derivative, carbenoxolone, is synthesized from glycyrrhetinic acid (the aglycone of glycyrrhizinic acid) and is of proven value in the treatment of gastric ulcer. Glycyrrhizinic acid-reduced liquorice is less well established, although results of therapeutic trials suggest that it can accelerate the healing of gastric ulcers in ambulatory patients. It may be of particular value in patients in whom there is a high risk of side-effects with carbenoxolone therapy. Results of trials in duodenal ulcer are less convincing, and although the frequency of relapse over a 1-year period was clearly reduced by a higher than usual dose, further suitably designed studies are needed to confirm these findings. Side-effects have been minimal and there has been no evidence of adverse effects of electrolyte metabolism, as are sometimes seen with carbenoxolone.


Deglycyrrhizinised liquorice (DGL) and the renewal of rat stomach epithelium.
Eur J Pharmacol 1981 Jun 19; 72(2-3): 219-25.
van Marle J, Aarsen PN, Lind A, van Weeren-Kramer J.

Deglycyrrhizinised liquorice (DGL) stimulated proliferation in the forestomach of the rat but did not stimulate and possibly even inhibited proliferation in the glandular part. DGL increased the number of fundus glands in which labeled mucus secreting cells occur as well as the total number of labelled mucus cells per gland. The mechanism of action proposed for DGL is that DGL stimulates and/or accelerates the differentiation to glandular cells as well as mucus formation and secretion. The accelerated proliferation observed in the forestomach is ascribed to an improved environment in the stomach as a consequence of the enhanced mucus secretion under the influence of DGL.