Life Extension Magazine®

Man taking dish of food that counters H. pylori

Natural Support For Stomach Health

Almost 40% of Americans are infected with an ulcer/cancer-inducing bacterium called H. pylori. Japanese researchers have developed a unique nutrient combination that counters H. pylori, protects against excess acid, and guards the gastric lining against erosive drugs.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in October 2024. Written by: Michael Downey, Health & Wellness Author.

The discovery that H. pylori infection leads to serious stomach problems enabled two scientists to win the Nobel prize for their breakthrough research.1-3

Perhaps even more meaningful, it was found that eradication of H. pylori can relieve symptoms of stomach distress, including gastritis, and prevent cancer.4

The ulcer-inducing bacteria H. pylori is now believed to affect up to 40% of Americans.5

The good news is that Japanese researchers developed a unique nutrient combination of zinc and carnosine to effectively counter the destructive impact of H. pylori.

Sold as a prescription drug in Japan, this combination is available in the United States as a supplement. Scientists have now gone a step further and enhanced the Japanese formula by adding natural cranberry, licorice extract, and picrorhiza to provide synergistic support for stomach health, without the adverse side effects associated with over-the-counter and prescription stomach aids.

In this article, you will learn how this combination of novel agents protects stomach tissue from acids, the damaging effect of anti-inflammatory drugs, and helps inhibit inflammation and H. pylori.

Protecting Stomach Tissue From Excess Acid Production

Certain individuals have sensitivities that require them to take extraordinary measures to protect their stomach. This includes those who take drugs that damage the gastric lining, and/or suffer chronic gastric infection/inflammation that may lead to cancer.

The extreme acidity of the stomach provides a primary defense against infection and assists in the early stages of digestion. However, keeping these high levels of acidity in check represents a serious biological challenge—and the fact that the body meets this challenge could be described as miraculous.

First, the specialized surface mucous cells in the stomach’s lining secrete a heavy coating of protective mucus. Second, a rapid turnover of cells in the lining itself keeps fresh cell troops always at the ready.

It’s a great system for protecting delicate stomach tissue from the powerful acids it secretes and contains. This organized system, however, requires precise balance.

Any breach in these defenses rapidly grows into a major problem.

Virtually everyone has experienced at least mild gastritis, or the upset stomach that we commonly associate with overindulgence and stress. While these are usually thought of as annoyances, each episode causes a bit more lasting damage—eventually resulting in cellular injury, which in turn causes inflammation.6

This inflammation then produces free radicals that go on to create still more tissue destruction,7,8 eventually damaging DNA and potentially leading to cancers of the stomach, which are among the most lethal malignancies.9-11

Infection with the H. pylori bacterium produces all these effects and more. In fact, H. pylori is now recognized as a major cause of stomach and upper intestinal disorders, including ulcers of the stomach and duodenum (the beginning of the small intestine), gastric cancer, and gastritis.12,13

Once H. pylori takes hold in the stomach lining, it relies on its elaborate defense mechanisms that allow it to survive the potent acids.14

The bacteria produces an influx of inflammatory cells by secreting powerful “virulence factors.”12 In a microscopic one-two punch,15 these bacterial proteins block normal function of free-radical scavengers, while boosting free-radical production from immune cells.16,17 H. pylori extends its damaging effects by stimulating yet another group of immune cells to produce inflammatory cytokines—the messengers that call new inflammatory cells into the region.12

Antibiotic treatment can be effective against H. pylori. But there is powerful evidence for the role of two nutrients in alleviating the misery caused by this bacterium.18,19

Protecting Stomach Tissue From Excess Acid Production
What You Need To Know

Natural Stomach Protection

  • The short-term consequence of a lifestyle of alcohol, medications, fast food, and chronic stress is often gastric distress—but the long-term consequence is serious damage to delicate stomach tissue.
  • Further magnifying these threats is the unrelenting spread of the ulcer-inducing agent H. pylori, now believed to affect up to 40 percent of Americans.
  • Zinc-carnosine, cranberry, licorice extract, and picrorhiza—provide safe, effective, synergistic support for stomach health, without the high cost and adverse side effects associated with over-the-counter and prescription stomach aids.
  • Together, these nutrients powerfully protect stomach tissue from acids—in turn helping to prevent cancer—and inhibit free-radical damage and inflammation, stimulate immunity, fight H. pylori infection, and speed healing.

Zinc-Carnosine

Zinc-Carnosine  

Zinc supplementation has been repeatedly shown to provide potent gastroprotective effects20,21 and to improve the response to therapy of certain cancers.22

Another nutrient called carnosine can boost these effects even further.

Japanese researchers have led the way in developing a unique zinc-carnosine compound, sold as a prescription anti-ulcer drug in Japan.23,24 This simple nutrient compound—comprising zinc and carnosine linked by a chemical bond—is available in the United States as a nonprescription dietary supplement that is safe for long-term use.22,23

Researchers found that this zinc-carnosine combination adheres to the stomach wall much more tightly than either zinc or carnosine alone—allowing beneficial effects of both components to be delivered directly to the site where protection is most needed.25

Some of the mechanisms behind zinc-carnosine’s protective effects against ulcers were found to be its free-radical-neutralizing effects26,27 and its capacity to boost production of a growth factor that may be important for gastric wound repair.28,29 Zinc-carnosine was also found to prevent the fragmentation of DNA in stomach-lining cells that can cause them to become cancerous.30 Animal and laboratory studies showed that zinc-carnosine stabilizes the membranes of inflammatory cells, preventing them from releasing cytokines and enzymes that can cause the stomach to begin digesting itself.31,32

Additionally, this nutrient combination was shown to inhibit stomach inflammation and cytokine release caused by H. pylori infection33 and to speed eradication of the infection itself34—providing a nutritional way to break the infection-inflammation-cancer chain.

Numerous studies showed that in animals given even single doses of zinc-carnosine, ulcers caused by stress, ischemia (poor blood flow), alcohol, and other toxins were either prevented or rapidly healed.35-40

A scientific team tested the effects of zinc-carnosine on rats with gastric cells damaged by stress or indomethacin, a potent NSAID (nonsteroidal anti-inflammatory drug). The nutrient combination reduced rat stomach injury by 75% and mice small-intestine injury by 50%. It also stimulated migration and proliferation of cells at and near the injury sites by almost 3-fold.41

A 2009 preclinical study found that a zinc-carnosine combination induces heme oxygenase-1 (HO-1)—an enzyme involved with protection against inflammation and oxidative stress42,43—in the stomach mucosa and safely provides mucosal protective effects.44

A 2013 preclinical study published in Life Sciences concluded that a zinc-carnosine combination protects against gastric mucosa damage—not only by reducing inflammatory cytokines and increasing expression of free-radical-quelling enzymes and growth factors—but also through the cytoprotective effects of increasing the level of heat shock proteins (HSP).45

In a clinical trial, 10 healthy volunteers took 50 mg of indomethacin three times daily with either a placebo or zinc-carnosine. Indomethacin increased gut permeability—impaired barrier function of the gut’s lining that allows inflammation to get its start—by a factor of three in the placebo group. But in the zinc-carnosine supplemented group, there was no significant increase in permeability. The researchers concluded that zinc-carnosine stabilized the cells of the mucosal lining of the stomach and small intestine, suggesting potent gastroprotective effects.41

Zinc-carnosine is one of the four important nutrients shown to protect gastric tissue from excess acid and the serious risks involved. Let’s now examine the other three.

Cranberries

Cranberries  

Mounting evidence indicates that cranberries and their potent compounds inhibit H. pylori— a dangerous link in the infection-inflammation-cancer chain.46-48

In research reported in the journal Helicobacter, about two cups of cranberry juice or a placebo were given to 189 adults with H. pylori infection per day. After 35 and 90 days of treatment, more than 14% of the cranberry group—but just 5% of the placebo group—showed test results that suggested complete eradication of the H. pylori organism.49

A double-blind, randomized, clinical study was carried out in which 177 patients with H. pylori infection were asked to take 250 mL of either cranberry juice or placebo drink twice daily for three weeks. During the first week only, all participants also took a triple-therapy drug treatment for this infection consisting of two antibiotics (amoxicillin and clarithromycin) and one proton-pump inhibitor (omeprazole). H. pylori was eradicated in more than 95% of the female subjects who took the cranberry juice, compared with only 80 to 86% of the non-supplemented patients. The H. pylori eradication rates were also lower in male subjects supplemented with the juice, but sampling was not large enough for statistical significance.50

A systematic review concluded that regular intake of cranberry juice and other dietary products “might constitute a low-cost, large-scale alternative solution applicable for populations at risk for H. pylori colonization.”51

A later review found that the array of potent compounds in cranberries—anthocyanins, flavonols, flavan-3-ols, proanthocyanidins, and phenolic acid derivatives— “appears to be responsible for the cranberry property of preventing many diseases and infections, including cardiovascular diseases, various cancers, and infections involving the urinary tract, dental health, and Helicobacter pylori-induced stomach ulcers and cancers.”52

Licorice

Licorice extracts provide anti-inflammatory activities, reduce cytokine production, and boost production of stomach mucus.53-55

These extracts were shown to be as effective as the NSAID diclofenac (Voltaren®) in reducing inflammation,56 and human and animal studies demonstrated that deglycyrrhizinated licorice can reduce aspirin-induced damage to the stomach lining57 and promote healing of duodenal ulcers.58

Researchers enrolled 100 patients with endoscopically confirmed gastric ulcers and gave them either a leading antacid medication or a deglycyrrhizinated licorice extract medication called Caved-(S). At 12 weeks, 91% of patients were healed, as proven by endoscopic examination, with no significant difference between the drug and the licorice compound59—and there were still no differences even when long-term effects were examined in a follow-up study several years later.60

Without eradication of H. pylori infection, peptic ulcer disease has a 50 to 80% recurrence rate within six to 12 months after initial healing. A double-blind trial on 60 patients with peptic ulcer disease demonstrated that licorice is as effective as bismuth at eradicating H. pylori—prompting researchers to suggest licorice as a safe alternative for patients for whom bismuth may be contraindicated.61

Picrorhiza  

Picrorhiza

Extracts of a perennial herb called picrorhiza (Picrorhiza kurroa), well-known in Ayurvedic medicine,62 have been found to have potent free-radical-quenching,62-66 immune-stimulating,67-70 and anti-inflammatory71-74 properties—activities central to gastric protection.

Scientists administered this extract to rats with ulcers induced by the potent NSAID indomethacin. Compared with the untreated group, picrorhiza-supplemented rats had much faster rates of ulcer healing, accompanied by a profound drop in levels of oxidized tissue components. And while free-radical-quenching enzyme activity decreased in the untreated animals, it was, in fact, boosted in treated rodents.75

In a study on mice with acute stomach ulceration induced by indomethacin, the healing capacity of picrorhiza was tested. After three days, biochemical analysis of stomach tissues showed that ulcer indices were reduced by 45% in the picrorhiza subjects, compared to the untreated mice.76

Together, zinc-carnosine, cranberry, deglycyrrhizinated licorice, and picrorhiza provide a multi-armed approach to gastric protection, improved stomach health, and cancer prevention.

Side Effects of Common Anti-Acid Drugs

Over-the-counter antacids can be very effective against acid damage. However, they do come with many potentially serious side effects—especially with prolonged use. As an alternative, zinc-carnosine, cranberry, licorice extract, and picrorhiza are natural agents that powerfully protect stomach tissue from acids without notable side effects, even with long-term use. Please note that individuals with esophageal reflux often need to reduce stomach acid and block stomach contents from reaching the delicate tissues of the esophagus. Some of these individuals will require at least temporary use of some of the following drugs:

Class Of Acid-Blocker

Drug Name

Long-Term Effects

Aluminum-Containing
Antacids

Maalox®

Mylanta®

Bone-softening77,78

H2
Blockers

Cimetidine

Ranitidine Famotidine

Vitamin B12 deficiency79,80

Proton-Pump
Inhibitors

Omeprazole

Esomeprazole

Vitamin B12 deficiency80,81

Reduced medication bioavailability82

C. difficile -associated diarrhea82

Pneumonia81,82

Osteoporosis and vertebral and hip fracture81-83

Rebound acid over-secretion83

Summary

Prescription drugs, fast food, alcohol, and chronic stress can lead quickly to gastric distress—and in the long term, can seriously damage delicate stomach tissue.

Worsening this scenario, the unrelenting spread of the ulcer-inducing agent H. pylori is now believed to affect up to 40% of all Americans.

Fortunately, four natural nutrients provide safe, effective, synergistic support for stomach health, without the high cost and adverse side effects of over-the-counter and prescription stomach aids.

Zinc-carnosine, cranberry, licorice extract, and picrorhiza powerfully protect stomach tissue and protect it from acids, in turn helping to prevent cancer. They inhibit free-radical damage and inflammation, stimulate immunity, fight H. pylori infection, and hasten healing.

For convenience, consumers can now obtain the zinc-carnosine compound sold as a drug in Japan, along with standardized cranberry, picrohiza and licorice in one low cost supplement.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Lochhead P, El-Omar EM. Helicobacter pylori infection and gastric cancer. Best Pract Res Clin Gastroenterol. 2007;21(2):281-97.
  2. Wilson KT, Crabtree JE. Immunology of Helicobacter pylori: insights into the failure of the immune response and perspectives on vaccine studies. Gastroenterology. 2007 Jul;133(1):288-308.
  3. Available at: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2005/press.html. Accessed March 27, 2015.
  4. Lesbros-Pantoflickova D, Corthesy-Theulaz I, Blum AL. Helicobacter pylori and probiotics. J Nutr. 2007 Mar;137(3 Suppl 2):812S-8S.
  5. Available at: http://gi.org/guideline/management-of-helicobacter-pylori-infection. Accessed March 27, 2015.
  6. Davidson G, Kritas S, Butler R. Stressed mucosa. Nestle Nutr Workshop Ser Pediatr Program. 2007;59:133-42.
  7. Boeckxstaens GE. Neuroimmune interaction in the gut: from bench to bedside. Verh K Acad Geneeskd Belg. 2006;68(5-6):329-55.
  8. Iezzi A, Ferri C, Mezzetti A, Cipollone F. COX-2: friend or foe? Curr Pharm Des. 2007;13(16):1715-21.
  9. Fox JG, Wang TC. Inflammation, atrophy, and gastric cancer. J Clin Invest . 2007 Jan;117(1):60-9.
  10. Dalal RS, Moss SF. At the bedside: Helicobacter pylori, dysregulated host responses, DNA damage, and gastric cancer. J Leukoc Biol. 2014 Aug;96(2):213-24.
  11. Hardbower DM, Peek RM Jr, Wilson KT. At the Bench: Helicobacter pylori, dysregulated host responses, DNA damage, and gastric cancer. J Leukoc Biol . 2014 Aug;96(2):201-12.
  12. D’Elios MM, Montecucco C, de BM. VacA and HP-NAP, Ying and Yang of Helicobacter pylori-associated gastric inflammation. Clin Chim Acta . 2007 May;381(1):32-8.
  13. Lai LH, Sung JJ. Helicobacter pylori and benign upper digestive disease. Best Pract Res Clin Gastroenterol. 2007;21(2):261-79.
  14. Müller A, Oertli M, Arnold IC. H. pylori exploits and manipulates innate and adaptive immune cell signaling pathways to establish persistent infection. Cell Commun Signal. 2011 Nov 1;9(1):25.
  15. Robinson K, Argent RH, Atherton JC. The inflammatory and immune response to Helicobacter pylori infection. Best Pract Res Clin Gastroenterol. 2007;21(2):237-59.
  16. Gotz JM, van Kan CI, Verspaget HW, et al. Gastric mucosal superoxide dismutases in Helicobacter pylori infection. Gut. 1996 Apr;38(4):502-6.
  17. Gotz JM, Thio JL, Verspaget HW, et al. Treatment of Helicobacter pylori infection favourably affects gastric mucosal superoxide dismutases. Gut. 1997 May;40(5):591-6.
  18. Lin YT, Kwon YI, Labbe RG, Shetty K. Inhibition of Helicobacter pylori and associated urease by oregano and cranberry phytochemical synergies. Appl Environ Microbiol. 2005 Dec;71(12): 8558-64.
  19. O’Mahony R, Al-Khtheeri H, Weerasekera D, et al. Bactericidal and anti-adhesive properties of culinary and medicinal plants against Helicobacter pylori. World J Gastroenterol. 2005 Dec 21;11(47):7499-507.
  20. Varas Lorenzo MJ, Lopez MA, Gordillo BJ, Mundet SJ. Comparative study of 3 drugs (aceglutamide aluminum, zinc acexamate, and magaldrate) in the long-term maintenance treatment (1 year) of peptic ulcer. Rev Esp Enferm Dig. 1991 Aug;80(2):91-4.
  21. Rodriguez de la SA, az-Rubio M. Multicenter clinical trial of zinc acexamate in the prevention of nonsteroidal antiinflammatory drug induced gastroenteropathy. J Rheumatol. 1994 May;21(5):927-33.
  22. Barrera JL, Verastegui E, Meneses A, et al. Combination immunotherapy of squamous cell carcinoma of the head and neck: a phase 2 trial. Arch Otolaryngol Head Neck Surg. 2000 Mar;126(3):345-51.
  23. Matsukura T, Tanaka H. Applicability of zinc complex of L-carnosine for medical use. Biochemistry (Mosc). 2000 Jul;65(7):817-23.
  24. Sakae K, Yanagisawa H. Oral treatment of pressure ulcers with polaprezinc (zinc L-carnosine complex): 8-week open-label trial. Biol Trace Elem Res . 2014 Jun;158(3):280-8.
  25. Furuta S, Toyama S, Miwa M, et al. Residence time of polaprezinc (zinc L-carnosine complex) in the rat stomach and adhesiveness to ulcerous sites. Jpn J Pharmacol. 1995 Apr;67(4):271-8.
  26. Hiraishi H, Sasai T, Oinuma T, et al. Polaprezinc protects gastric mucosal cells from noxious agents through antioxidant properties in vitro. Aliment Pharmacol Ther. 1999 Feb;13(2):261-9.
  27. Nishiwaki H, Kato S, Sugamoto S, et al. Ulcerogenic and healing impairing actions of monochloramine in rat stomachs: effects of zinc L-carnosine, polaprezinc. J Physiol Pharmacol. 1999 Jun;50(2):183-95.
  28. Watanabe S, Wang XE, Hirose M, et al. Insulin-like growth factor I plays a role in gastric wound healing: evidence using a zinc derivative, polaprezinc, and an in vitro rabbit wound repair model. Aliment Pharmacol Ther. 1998 Nov;12(11):1131-8.
  29. Kato S, Tanaka A, Ogawa Y, et al. Effect of polaprezinc on impaired healing of chronic gastric ulcers in adjuvant-induced arthritic rats—role of insulin-like growth factors (IGF)-1. Med Sci Monit. 2001 Jan;7(1):20-5.
  30. Suzuki H, Mori M, Seto K, et al. Polaprezinc, a gastroprotective agent: attenuation of monochloramine-evoked gastric DNA fragmentation. J Gastroenterol. 1999;34 Suppl 1143-6.
  31. Cho CH, Luk CT, Ogle CW. The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats. Life Sci. 1991;49(23):L189-94.
  32. Shimada T, Watanabe N, Ohtsuka Y, et al. Polaprezinc down-regulates proinflammatory cytokine-induced nuclear factor-kappaB activiation and interleukin-8 expression in gastric epithelial cells. J Pharmacol Exp Ther. 1999 Oct;291(1):345-52.
  33. Suzuki H, Mori M, Seto K, et al. Polaprezinc attenuates the Helicobacter pylori-induced gastric mucosal leucocyte activation in Mongolian gerbils—a study using intravital videomicroscopy. Aliment Pharmacol Ther. 2001 May;15(5):715-25.
  34. Kashimura H, Suzuki K, Hassan M, et al. Polaprezinc, a mucosal protective agent, in combination with lansoprazole, amoxycillin and clarithromycin increases the cure rate of Helicobacter pylori infection. Aliment Pharmacol Ther. 1999 Apr;13(4):483-7.
  35. Cho CH, Ogle CW. The pharmacological differences and similarities between stress- and ethanol-induced gastric mucosal damage. Life Sci. 1992;51(24):1833-42.
  36. Arakawa T, Satoh H, Nakamura A, et al. Effects of zinc L-carnosine on gastric mucosal and cell damage caused by ethanol in rats. Correlation with endogenous prostaglandin E2. Dig Dis Sci. 1990 May;35(5):559-66.
  37. Cho CH, Hui WM, Chen BW, Luk CT, Lam SK. The cytoprotective effect of zinc L-carnosine on ethanol-induced gastric gland damage in rabbits. J Pharm Pharmacol. 1992 Apr;44(4):364-5.
  38. Ito M, Tanaka T, Suzuki Y. Effect of N-(3-aminopropionyl)-L-histidinato zinc (Z-103) on healing and hydrocortisone-induced relapse of acetic acid ulcers in rats with limited food-intake-time. Jpn J Pharmacol. 1990 Apr;52(4):513-21.
  39. Seiki M, Ueki S, Tanaka Y, et al. Studies on anti-ulcer effects of a new compound, zinc L-carnosine (Z-103). Nippon Yakurigaku Zasshi. 1990 May;95(5):257-69.
  40. Yoshikawa T, Naito Y, Tanigawa T, et al. Effect of zinc-carnosine chelate compound (Z-103), a novel antioxidant, on acute gastric mucosal injury induced by ischemia-reperfusion in rats. Free Radic Res Commun. 1991;14(4):289-96.
  41. Mahmood A, FitzGerald AJ, Marchbank T, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut. 2007 Feb;56(2):168-75.
  42. Aburaya M, Tanaka K, Hoshino T, et al. Heme oxygenase-1 protects gastric mucosal cells against non-steroidal anti-inflammatory drugs. J Biol Chem. 2006 Nov 3;281(44):33422-32.
  43. Almolki A, Guenegou A, Golda S, et al. Heme oxygenase-1 prevents airway mucus hypersecretion induced by cigarette smoke in rodents and humans. Am J Pathol. 2008 Oct;173(4):981-92.
  44. Ueda K, Ueyama T, Oka M, Ito T, Tsuruo Y, Ichinose M. Polaprezinc (Zinc L-carnosine) is a potent inducer of anti-oxidative stress enzyme, heme oxygenase (HO)-1 - a new mechanism of gastric mucosal protection. J Pharmacol Sci. 2009 Jul;110(3):285-94.
  45. Choi HS, Lim JY, Chun HJ, et al. The effect of polaprezinc on gastric mucosal protection in rats with ethanol-induced gastric mucosal damage: comparison study with rebamipide. Life Sci. 2013 Jul 30;93(2-3):69-77.
  46. Lin YT, Kwon YI, Labbe RG, Shetty K. Inhibition of Helicobacter pylori and associated urease by oregano and cranberry phytochemical synergies. Appl Environ Microbiol. 2005 Dec;71(12): 8558-64.
  47. Vattem DA, Ghaedian R, Shetty K. Enhancing health benefits of berries through phenolic antioxidant enrichment: focus on cranberry. Asia Pac J Clin Nutr. 2005;14(2):120-30.
  48. Burger O, Weiss E, Sharon N, et al. Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice. Crit Rev Food Sci Nutr. 2002;42(3 Suppl):279-84.
  49. Zhang L, Ma J, Pan K, et al. Efficacy of cranberry juice on Helicobacter pylori infection: a double-blind, randomized placebo-controlled trial. Helicobacter. 2005 Apr;10(2):139-45.
  50. Shmuely H, Yahav J, Samra Z,et al. Effect of cranberry juice on eradication of Helicobacter pylori in patients treated with antibiotics and a proton pump inhibitor. Mol Nutr Food Res. 2007 Jun;51(6):746-51.
  51. Gotteland M, Brunser O, Cruchet S. Systematic review: are probiotics useful in controlling gastric colonization by Helicobacter pylori? Aliment Pharmacol Ther. 2006 Apr 15;23(8):1077-86.
  52. Côté J, Caillet S, Doyon G, Sylvain JF, Lacroix M. Bioactive compounds in cranberries and their biological properties. Crit Rev Food Sci Nutr. 2010 Aug;50(7):666-79.
  53. Fukai T, Marumo A, Kaitou K, et al. Anti-Helicobacter pylori flavonoids from licorice extract. Life Sci. 2002 Aug 9;71(12):1449-63.
  54. Krausse R, Bielenberg J, Blaschek W, Ullmann U. In vitro anti-Helicobacter pylori activity of Extractum liquiritiae, glycyrrhizin and its metabolites. J Antimicrob Chemother. 2004 Jul;54(1):243-6.
  55. Emer J, Waldorf H, Berson D. Botanicals and anti-inflammatories: natural ingredients for rosacea. Semin Cutan Med Surg. 2011 Sep;30(3):148-55.
  56. Aly AM, Al-Alousi L, Salem HA. Licorice: a possible anti-inflammatory and anti-ulcer drug. AAPS PharmSciTech. 2005;6(1): E74-E82.
  57. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.
  58. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.
  59. 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.
  60. 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.
  61. Momeni A, Rahimian G, Kiasi A, Amiri M, Kheiri S. Effect of licorice versus bismuth on eradication of Helicobacter pylori in patients with peptic ulcer disease. Pharmacognosy Res. 2014 Oct;6(4):341-4.
  62. [No authors listed] Picrorhiza kurroa. Monograph. Altern Med Rev. 2001 Jun;6(3):319-21.
  63. Chander R, Kapoor NK, Dhawan BN. Effect of picroliv on glutathione metabolism in liver and brain of Mastomys natalensis infected with Plasmodium berghei. Indian J Exp Biol. 1992 Aug;30(8):711-4.
  64. Chander R, Singh K, Visen PK, Kapoor NK, Dhawan BN. Picroliv prevents oxidation in serum lipoprotein lipids of Mastomys coucha infected with Plasmodium berghei. Indian J Exp Biol. 1998 Apr;36(4):371-4.
  65. Sun M, Fan HW, Ma HY, Zhu Q. Protective effect of total glucosides of Picrorhiza scrophulariiflora against oxidative stress in glomerular mesangial cells induced by high glucose. Yao Xue Xue Bao. 2007 Apr;42(4):381-5.
  66. Vaidya AB, Antarkar DS, Doshi JC, et al. Picrorhiza kurroa (Kutaki) Royle ex Benth as a hepatoprotective agent–experimental & clinical studies. J Postgrad Med. 1996 Oct;42(4):105-8.
  67. Gupta A, Khajuria A, Singh J, et al. Immunomodulatory activity of biopolymeric fraction RLJ-NE-205 from Picrorhiza kurroa. Int Immunopharmacol. 2006 Oct;6(10):1543-9.
  68. Puri A, Saxena RP, Guru PY, et al. Immunostimulant Activity of Picroliv, the Iridoid Glycoside Fraction of Picrorhiza kurroa, and its Protective Action against Leishmania donovani Infection in Hamsters1. Planta Med. 1992 Dec;58(6):528-32.
  69. Sharma ML, Rao CS, Duda PL. Immunostimulatory activity of Picrorhiza kurroa leaf extract. J Ethnopharmacol. 1994 Feb;41(3):185-92.
  70. Smit HF, Kroes BH, van den Berg AJ, et al. Immunomodulatory and anti-inflammatory activity of Picrorhiza scrophulariiflora. J Ethnopharmacol. 2000 Nov;73(1-2):101-9.
  71. Barbieri SS, Cavalca V, Eligini S, et al. Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms. Free Radic Biol Med. 2004 Jul 15;37(2):156-65.
  72. Thomas M, Sheran J, Smith N, Fonseca S, Lee AJ. AKL1, a botanical mixture for the treatment of asthma: a randomised, double-blind, placebo-controlled, cross-over study. BMC Pulm Med. 2007;74.
  73. Zhang Y, DeWitt DL, Murugesan S, Nair MG. Novel lipid-peroxidation- and cyclooxygenase-inhibitory tannins from Picrorhiza kurroa seeds. Chem Biodivers. 2004 Mar;1(3):426-41.
  74. Zhang Y, DeWitt DL, Murugesan S, Nair MG. Cyclooxygenase-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds. Life Sci. 2005 Nov 4;77(25):3222-30.
  75. Ray A, Chaudhuri SR, Majumdar B, Bandyopadhyay SK. Antioxidant activity of ethanol extract of rhizome of Picrorhiza kurroa on indomethacin induced gastric ulcer during healing. Indian J Clin Biochem. 2002;17(2):44-51.
  76. Banerjee D, Maity B, Nag SK, Bandyopadhyay SK, Chattopadhyay S. Healing potential of Picrorhiza kurroa (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration. BMC Complement Altern Med. 2008 Jan 31;8:3.
  77. Kassem M, Eriksen EF, Melsen F, Mosekilde L. Antacid-induced osteomalacia: a case report with a histomorphometric analysis. J Intern Med. 1991 Mar;229(3):275-9.
  78. Krewski D, Yokel RA, Nieboer E, et al. Human health risk assessment for aluminium, aluminium oxide, and aluminium hydroxide. J Toxicol Environ Health B Crit Rev. 2007;10 Suppl 1:1-269.
  79. Ruscin JM, Page RL 2nd, Valuck RJ. Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother. 2002 May;36(5):812-6.
  80. Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol. 2004 Apr;57(4):422-8.
  81. Oh S. Proton pump inhibitors--uncommon adverse effects. Aust Fam Physician. 2011 Sep;40(9):705-8.
  82. Heidelbaugh JJ, Goldberg KL, Inadomi JM. Overutilization of proton pump inhibitors: a review of cost-effectiveness and risk [corrected]. Am J Gastroenterol. 2009 Mar;104 Suppl 2:S27-32.
  83. Roulet L, Vernaz N, Giostra E, Gasche Y, Desmeules J. Adverse effects of proton pump inhibitors: Should we worry about long-term exposure? Rev Med Interne. 2012 Aug;33(8):439-45.