On the Big Island of Hawaii, under azure skies, rises the Lotus Buddhist Monastery, founded by female monk and dharma master Ji Kwang Dae Poep Sa Nim. Nim discovered a natural way to turn fresh papaya into a potent and novel preparation , one that relies on the principles of slow cooking utilised in Traditional Chinese Medicine.
Originally produced as a home recipe for the temple’s spiritual disciples, the novel papaya fruit preparation (NPFP) is now prepared from organic, ripe fruit in a patented, ten-hour process. The product has been shown in several studies to be effective in helping a wide range of digestive conditions.
“We saw significant benefits,” says Wilhelm Mosgoeller, a Viennese oncologist who served as principal investigator on one study of the supplement’s effect on gastrointestinal complaints of six months or longer. “The preparation has a plethora of interesting bio effects, including enzyme, anti-histamine, anti-microbial and antioxidant effects.”
Fifty-one million Americans visit doctors or hospitals annually because of diseases of the digestive system, according to the CDC’s latest data. Approximately sixty-three million Americans suffer from chronic constipation, which is classed as a functional disorder. Other functional gastrointestinal disorders, such as bloating, diarrhoea, irritable bowel syndrome, reflux, and even fatigue after eating, are widespread. Functional digestive disorders are not only disruptive to daily living, they may be linked to more serious and chronic health conditions, mediated in large part through the gut associated lymphoid tissue (GALT). Over 70% of the human immune system is located in the GALT. Clearly, a supplement with wide application application for the improvement of functional digestive disorders and healthy support of the GALT is of great interest.
Slow-Cooking Yields a Potent Preparation
Traditional Chinese Medicine (TCM) often relies on slowly cooked stews and brews of functional foods and herbs to support the healing of the body. Food in TCM terms can be classified as warming, cooling or neutral, as well as moisturizing or drying to the body. According to TCM, cooking is an energizing process and allows for the release of the healing properties within the food or herbs. TCM minimises the use of cold or raw foods or herbs as this requires the body to expend energy in digestion. The term in Chinese medicine for processing an herb to change its properties is called Pao Zhi.
From this perspective, the process of slow cooking papaya releases its healing potential. Papaya fruits are chosen when ripe and are then prepared over a period of ten hours. The fruits are harvested, washed, and cut in half; the seeds removed by hand and the mature flesh scooped out. The flesh is slow cooked for several hours at 100 degrees centigrade, and air is injected into the mixture while it is cooled. The most studied enzyme in papaya—papain—is known to reach its highest activity at 85 degrees centigrade, and appears to be liberated in this cooking process. Once prepared, the fruits are crushed, mixed and strained into a finished puree.  The final puree has 3.75 times as much papain as the raw, natural fruit pulp.
The slow cooking process results in a concentrate with documented ability to decrease biomarkers of inflammation. In research by Dr. Burkhard Schütz, of the Biovis Institute for naturopathic Diagnosis and Preventive Medicine in Germany, NPFP’s impact on two widely validated markers of bowel inflammation were studied. These are alpha 1-antitrypsin and calprotectin, and can be measured in stool. The concentration of these proteins increases when the gut is inflamed. These markers can be used to monitor the course of inflammatory bowel diseases and the response to therapies.,
Schütz studied these markers in seven patients consuming 40 grams of NPFP daily for a month. Five out of the seven began the study with elevated markers of both proteins, indicating mucosal irritation and inflammation. In four of those patients, both markers declined (in two patients, from about 112 ug/dl to 67; in the third from 112 down to 38, and in the fourth patient, from 55 to 40). In one of the seven, however, the marker significantly increased.
Because this was a short term pilot study, Schütz notes that, “For conclusive results on mucosal and inflammation parameters the alpha 1-antitrypsin/calprotecin have to be monitored more extensively and closely.”9
During the course of the pilot study Schütz also had patients score symptoms from 1 (excellent) to 10 (worse). Those included frequent diarrhoea, constipation, nausea, flatulence, stomach ache, discomfort, and headache, among other symptoms. All seven patients using NPFP reported a decline of the complaints score, with four showing a marked reduction of over 50%. Fat content was reduced in the stool of four of the patients. Says Schütz, “The fat values in stool of healthy people should be below 3.5 g/100 g, which with a daily average stool amount of 150 – 200 grams. This correlates to a fat excretion of 5-7 grams. A fat excretion of 7 grams in 24-hour stool indicates steatorrhoea. For 5 of 7 patients the measured fat excretion in stool before giving NPFP was >3.5grams/100grams, and three patients had a fat concentration of >5grams/100gramsin stool, which indicates steatorrhoea. By giving NPFP the stool excretion decreased in 4 cases by 25-30%. In one case fat excretion remained unchanged at 5.8 grams/100 grams.”
There is a long history of research into papaya’s histamine blocking abilities. Histamines are known to trigger allergic responses, increased vascular permeability, itching, sneezing, and also excess production of stomach acid, leading to peptic ulcers and gastroesophageal reflux disease (GERD). According to a 2006 review of histamine in the 20th century, “histamine has been shown to have a key physiological role in the control of gastric acid secretion and a pathophysiological role in a range of allergic disorders. The synthesis of, and pharmacological studies on, selective agonists and antagonists has established the existence of four types of histamine receptor and histamine receptor antagonists have found very important therapeutic applications.
There are four known histamine receptors:
H1: mainly involved in pain, allergy, smooth muscle cell motility.H1 blockers treat allergic rhinitis and other allergies.
H2: mainly involved in acid production by parietal cells in the gastric lining. H2 blockers treat peptic ulcer and gastric acid diseases.
H3: can cross-react with H1, and blockers have been used for neurological complaints such as vertigo. H3 is still being studied for its role in central nervous system disorders.
H4: detected only recently, its role is still under discussion but may help modulate immune response and possibly treat asthma and inflammation
Studies have found that papaya reduces gastric acid production. A 1981 animal study found that papaya protected against ulcer and significantly lessened acid secretion induced by intravenous infusion of histamine. A 1984 animal study found that gastric acid secretion was reduced as early as two hours after feeding the enzyme papain, lasted up to 48 hours, and waned after 96 hours. A 2009 animal study found that extracts of whole unripe papaya fruit significantly reduced the ulcer index.
An in vitro study in Switzerland tested the binding affinity of NPFP to the histamine H1 receptor. NPFP does not contain histamine, yet it bound to the histamine receptor in a dose-dependent manner. One reason NPFP may help reduce gastritis and GERD could be its ability to bind to or otherwise beneficially modify these receptors.
In further in vitro research, conducted at the University of Vienna, cells called “caco 2”, which are widely used to represent the small intestine’s epithelium, were incubated in NPFP. The researchers report that NPFP “exerts a cytoprotective and cell proliferation promoting effect on Caco-2 cells representing a model of the small intestine. This indicates that [the concentrate] might have a positive effect during inflammation on the one hand and a stabilizing effect on the cells of the small intestine on the other hand.”
Several studies on NPFP have shown it to be a powerful regulator of digestion, able to promote healing of a wide range of functional digestive disorders.
In a 2012 double blind study of 126 individuals with chronic constipation, flatulence and heartburn, NPFP was significantly more effective than placebo in improving symptoms. Both groups took 20 mg of either NPFP or a similar tasting placebo for forty days. A total of 22 symptoms were rated by questionnaire before and after the study. Three symptoms—constipation, bloating/flatulence, and heartburn—were defined as primary. Painful defecation (a consequence of constipation) was defined as secondary. To analyse the data, participants were divided into two groups: those called “early returnees” who filled out their exit questionnaire within two days of the study’s conclusion, and those called “late returnees” who filled out their exit questionnaire between 3 and 16 days after the study concluded. A total of 81 early returnees were actually analysed to produce the data in the study.
This was done because the questionnaire, in simply asking frequency of symptoms recently, was not effective in determining how late returnees were faring. Instead, they experienced the typical washout effect that occurs when you stop most drugs or supplements, says principal investigator, oncologist Wilhelm Mosgoeller, MD.1
An impressive 82% of those taking NPFP, in the early returnees group, benefited while the placebo group improved less than 50%. In the NPFP group, 93% of early returnees experienced improvement in painful defecation, and 78% experienced improvement in flatulence (as compared to a little over 40% in the placebo group). Heartburn showed a trend towards improvement in the NPFP group of early returnees, but it did not reach statistical significance.
Appetite also seemed to be curbed by NPFP. Dr. Mosgoeller notes that “to our surprise in the active treatment group 83% of the participants reported a reduction of “hunger”, compared to only 58% in the placebo group…This beneficial effect fell just short of the level of significance.” Nonetheless, it may be useful for appetite control in some individuals. In addition, Mosgoeller and colleagues replicated the in vitro work on histamine reported by Dr. Büter: “We searched for histamine and histidine…no detectable amounts were found, but [NPFP] bound to, and therefore blocked the histamine H1 receptors.”17
“As a scientist trained in the western tradition,” says Dr. Mosgoeller, “the histamine-related effects are the most intriguing ones. They are straightforward and comprehensible. Histamine triggers gastric acid. NPFP contains a histamine receptor-blocking ingredient, therefore it reduces gastric acid, to the benefit of any patient with GERD.”1
He also notes some interesting patient reports. The official ROME criteria for gastrointestinal complaints notes that relief of discomfort or pain upon defecation is a healthy sign; if there is incomplete relief, there may be irritable bowel syndrome or inflammatory bowel disease. One construction worker reported back that while on the NPFP, he had complete relief of discomfort upon defecation every day. Another participant who was on prescription blood thinners was concerned that NPFP might interfere with their effect, but his doctors monitored him during the trial and there was no change.1
Individuals with irritable bowel syndrome (IBS) have also responded to NPFP.(18) A 2009 study reported on 15 patients suffering from IBS, who took NPFP daily for a month. Dosage began at 40 grams per day, and was altered (down to 20 grams per day, or up to 40 grams twice a day) depending on patient response. IBS symptoms included frequency of bowel movements, stool consistency, abdominal pain and flatulence. Descriptive grading was used: none, slight, modest, moderate, intense, very intense, and complete. To avoid any placebo effect, the authors only acknowledged change as significant if more than 80% of patients improved after four weeks of continuous treatment. Fourteen patients completed the study, and 87% of the participants experienced at least moderate improvement on bowel movements, stomachache, abdominal pain and stool consistency.18
In an informal study, Dr. Heide Seppele, MD, gave NPFP to twenty-seven individuals aged 25 to 70. They took 20 grams for a minimum of 8 days and a maximum of 24 days. All seven individuals suffering from constipation found their bowel movements became regular. Another seven individuals had “mushy” or soft stools which also became normal in consistency. Three individuals suffered from IBS symptoms that alternated between constipation and diarrhea, and elimination became normal. (also see FOCUS TK clinical pearl Seppele page TK)
Dr. Seppele also conducted a study on ten geriatric patients with chronic diarrhea, following them over a seven-week period. For about three weeks, stool consistency was documented—it was “mushy” or soft an average of four days a week, and normal on the other three. After starting NPFP, bowel movement began to normalize, and after about a month, defecation was normal at least five days a week. Therapy was interrupted for a three week washout phase, and then reinstituted at double the dose, but the higher dosage did not change the results.
At another geriatric centre in Vienna, Peter M. Bernecker, MD and Theresa Maier-Dobersberger, MD, studied 40 patients with chronic constipation. Bowel movements were documented over a period of eleven weeks.. During a pre-test phase of three weeks, all laxatives were terminated. NPFP was given for five weeks, resulting in a statistically significant decrease in constipation. Days with bowel movements increased by 50%. At the study’s outset, nine patients needed “escape” medication because they had not had a bowel movement. By the end of the study, only three patients needed “escape” medication.
In the words of Dr. Mosgoeller, the effectiveness of NPFP may be due to the synergy of its various ingredients. “Blocking the gastric histamine receptors reduces gastric acid production, while the enzymes enhance digestion and therefore reduce bloating. If both constipation and diarrhoea are a dysfunction of the physiological-peristaltic movements, they might both be explained by the toxic effect of undigested food, or by bacterial toxins. We noted improved digestion, antimicrobial effects, and antioxidant capacity. Thus it addresses the underlying problems behind many digestive disorders.”1
 Email and skype interview with William Moesgoeller, MD, June and July, 2013.
 CDC statistics, “http://www.cdc.gov/ nchs/fastats/digestiv.htm”
 Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol 2004 Apr:99(4):750-9. PMID: 15089911
 Hwang JS, Im SH. Immune disorders and its correlation with gut microbiome Im¬mune Netw. 2012 Aug;12(4):129-38
 http://www.archpatent.com/patents/8097289US 8097289: “Papaya puree and the use of the same”
 Report from the Institute of Food and Environmental LEFO Arensburg research, findings from May 21, 2004.
 Rodriguez-Otero P, Porcher R, Peffault de Latour R, Contreras M, Bouhnik Y, Xhaard A, An¬dreoli A, Ribaud P, Kapel N, Janin A, Socié G, Robin M. Fecal calprotectin and alpha-1 antitrypsin predict severity and response to corticoste¬roids in gastrointestinal graft-versus-host disease. Blood. 2012 Jun 14;119(24):5909-17. PMID:22555971
 Borkowska A, Liberek A, Plata-Nazar K, Kamińiska B. Utility of fecal markers of inflammation in the diagnostics of inflammatory bowel diseases. Med Wieku Rozwoj. 2010 Jan-Mar;14(1):37-41. Review. Polish. PMID: 20608427
 Report entitled Evaluation of clinical as¬pects of Caricol by Dr. Burkhard Schütz, Biovis: Institute for Naturopathic Diag¬nosed and Preventive Medicine, Limburg, Austria.
 Email interview with Dr. Burkhard Schütz, July 2013
 Parsons ME, Ganellin CR Histamine and its receptors. Br J Pharmacol. 2006 Jan;147 Suppl 1:S127-35.
 Chen, CF, Chen, SM, Chow, SY and Han, PW (1981). Protective effects of Carica pa¬paya Linn on the exogenous gastric ulcer in rats. Am J Chin Med. 9: 205-12.
 Cho, CH and Han, PW (1984). Papain reduces gastric acid secretion induced by histamine and other secretagogues in anesthetized rats. Proc Natl Sci Counc Repub China B. 8: 177-81. 14. Ezike, AC, Akah, PA, Okoli, CO, Ezeuchenne, NA and Ezeugwu, S (2009).
 Carica papaya (Paw-Paw) unripe fruit may be beneficial in ulcer. J Med Food. 12: 1268-73.
 Report entitled Effect of Caricol on binding affinity to Histamine H1 and alpha Adrenogenic 1A receptors, by Dr. Karin Berger Büter, Department Head, Pharma Unit, Vitaplant, Witterswil, Switzerland.
 Report entitled Ex-vivo study to determine cytoprotective function and promotion of cell proliferation by Caricol using Caco-2 cells, by Dr. Franz Gabor and Dr. Michael Wirth, Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna.
 Muss C, Mosgoeller W, Endler T. Papaya preparation (Caricol®) in digestive disorders. Neuro Endocrinol Lett. 2013;34(1):38- 46. PMID:23524622
 Vogelsang H, Brenner FM, Effect of Caricol on Irritable Bowel Syndrome, Wissenschaftliche Arbeiten, JEM Sonderdruck 2 | 2009
 Report entitled Diary Assessments of Papaya-Remedy, a drug against constipation, Heide Seppele, MD, year TK.
 Unpublished study by Heide Seppele, MD and Herta Bayer, MD, at Committee for Assisted Living Residences, Vienna.
 Unpublished study by Peter M. Bernecker MD and Theresia Maier-Dobersberger, MD, at Geriatric Center Baumgarten, Vienna