Gastroesophageal reflux disease

Introduction

A deficiency of gastric acid has the potential to cause clinically relevant consequences such as: (1) diminished sterilizing capacity favoring enteric pathogens; (2) absorption problems of various nutrients; (3) abnormal morphological changes of the gastric mucosa; (4) hypergastrinemia; and (5) the initiation of neoplastic mucosal changes. (1) The clinical signs and symptoms of deficient gastric acid states have been well described by this author in previous publications. (2,3) Diseases associated with deficient gastric acidity includes, but are not limited to the following: Addison's disease, alcoholism, anemia/pernicious anemia, asthma (of children), diabetes mellitus. eczema, hyperthyroidism, lupus erythematosis, psoriasis, rosacea, urticaria, and vitiligo. (4)

When evaluating patients with gastrointestinal symptoms indicative of deficient gastric acid states (i.e., hypo- and achlorhydria), many options exist to help in the work-up of such patients. (5) One method of gastric analysis, the Heidelberg radiotelemetric device, is very accurate but demands approximately 90 minutes for its operation. (6,7) Furthermore, the Heidelberg method costs around $675US per analysis. (8) Another method is direct gastric intubation that is both costly and time consuming, in addition to being very invasive and uncomfortable. The simplest, most cost effective and least invasive test for gastric pH would be the Gastro-Test[R], (9) which costs approximately $20US per analysis. (10) This simple in-office test would spare both patient and doctor numerous inconveniences and the likely discomfort associated with gastric intubation.

To critically appraise the efficacy of the Gastro-Test[R] the following sources of information were analyzed: (1) Experimental data that compared pH values from the Gastro-Test[R] to pH values obtained from direct gastric intubation; (2) a 1968 study that used a "string test" for the determination of gastric pH in 500 subjects; (3) two studies that used the Gastro-Test[R] as a screening test for gastroesophageal reflux disease; and (4) data that compared pH values from the Gastro-Test[R] using different time intervals (15 minutes versus 1 minute).

1. Review data comparing pH values obtained from the Gastro-Test[R] to those obtained from direct gastric intubation

Three fasting, healthy male subjects (Table 1) participated in a small study examining the comparability of pH values obtained from the Gastro-Test[R] and from direct gastric intubation. (11)

Materials and Methods

The Gastro-Test[R] consists of a weighted gelatin capsule with 70cm of highly absorbent cotton floss attached within the capsule, and a protruding free portion of cotton floss at the other end of the capsule. The string unwinds as the capsule descends into the stomach. The capsule is weighted by having a ball bearing made of stainless steel embedded in a thin film of silicone rubber (as is the whole capsule). When the gelatin capsule dissolves in the gastrointestinal tract, the silicone rubber covering the stainless steel ball forms a micro-bag around the ball bearing. Thus, the ball bearing never comes in direct contact with the gastric contents, never gets absorbed, and presumably exits the body via the feces. The test kit also includes a surface marking pH stick and a pH color chart. The gastric intubation was performed with a 3Fr. silicone rubber nasogastric feeding tube. The gastric contents were aspirated with a 10cc syringe, and the pH readings were done with a Perkin Elmer pH meter.

Each of the 3 subjects volunteered to be a part of this study. No eligibility criteria were established for the selection of the subjects, except for their declaration of being healthy and free of disease. None of the subjects received compensation for participating in the study. Each subject had fasted for 12 hours prior to testing, after which each swallowed the floss-filled Gastro-Test[R] capsule followed by intubation with a 3Fr. silicone rubber nasogastric feeding tube. The subjects were instructed to lie down on their left side for 15 minutes to allow the gastric contents to saturate the end of the string. They were then instructed to stand up and the string was pulled from their stomach. The string was then rubbed with the pH stick provided and the resultant color change was then compared to the pH color chart. With the nasogastric tube still in the stomach, 3cc of aspirate was obtained from each of the three subjects using a 10cc syringe. Each subject's aspirate was diluted to 10cc with sterile water and tested on a Perkin Elmer pH meter. The pH meter results were recorded and compared to the pH results obtained from using the Gastro-Test[R] (Table 2).

Subsequent to the tests above, each subject took 2 caffeine alkaloid tablets (400mg in total) with 1/4 cup (60ml) of water. After 30 minutes the procedure outlined above was repeated, and the results recorded (Table 3). No side effects occurred from the oral administration of the caffeine alkaloid tablets or from the Gastro-Test[R] procedure. No gagging or vomiting was observed in any of the 3 subjects.

Results & Discussion

The data clearly indicated that in these three subjects, the Gastro-Test[R] produced the same pH readings as did direct gastric intubation. It is not clear why the gastric contents were more alkaline among the two African American subjects. It should be noted that neither had any gastrointestinal problems at the time of this study. Considering the very small sample size, a larger number of subjects might have reinforced the pH accuracy of the Gastro-Test[R] if more data was available for analysis. By contrast, a larger sample size might have also weakened the validity of the test because more data might have demonstrated pH inaccuracies between the Gastro-Test[R] and direct gastric intubation. Despite the limited data here, it can be concluded that the Gastro-Test[R] was comparable to gastric intubation in the three, healthy male subjects who were studied.

2. Review study on a "string test" that is strikingly similar to the Gastro-Test[R]

A literature search was conducted on tubeless methods of gastric analysis to address the pH accuracy of the Gastro-Test[R]. Among the nine articles sampled, (12-20) only one was identified that had data relating to the accuracy of the Gastro-Test[R]. (20)

In this study, a "string test," with striking similarities to the Gastro-Test[R], was compared to two substantiated methods of gastric analysis, i.e., gastric intubation and the indirect Azure-A carboxylic resin (Azuresin, Diagenex Blue) urine test. Both the Gastro-Test[R] and "string test" use a pharmaceutical grade gelatin capsule with cotton floss coiled within, leaving a protruding end at one end of the capsule. In the study using the "string test" the length of the coiled cotton floss was not specified, (20) although a personal communication with one of the founders of the HDC Corporation stated that the length was 90cm long. (21) The information leaflet that comes with the Gastro-Test[R] states that the length of the cotton floss is 70cm long, (9) leaving a 20cm difference in the cotton floss lengths. Each of these tests requires that the subjects lie down so that the cotton floss can saturate within the gastric pool. In both of these tests the gelatin capsule dislodges from the cotton floss prior to retrieving (i.e., pulling out) the floss.

One of the main differences between the "string test" and the Gastro-Test[R] is that in the former, the cotton floss is pulled gently from the stomach after being in contact with the gastric pool for 1 minute instead of being within the gastric pool for 15 minutes. The other difference is that in the "string test" there is no need for a pH stick since the string itself changes color depending on the pH of the gastric contents it comes in contact with. In the Gastro-Test[R], it is necessary to rub a pH stick along the floss upon retrieval to provide the color change representative of a specific pH reading.

In the "string test" study, a total of 500 tests were performed on medical students, patients, and employees of a medical center. (20) Of the 500 "string tests" performed, a total of 136 were compared to other methods of gastric analysis. Only 7 of the 136 participants were given the azuresin test. The other 129 participants had their pH measurements via the "string test" compared to the pH measurements obtained through gastric intubation. Upon reviewing the study data further, the confidence interval was calculated to be 93.3% {95% CI, 87.8-96.4%} correlated to other methods of gastric analysis (Table 4). (22)

The confidence interval was calculated a second time without the azuresin test data to compare the results to gastric intubation only. (22) The correlation was found to be 93% {95% CI, 87.2-96.2%}, thus demonstrating the accuracy of the "string test" to direct intubation (Table 5). Overall, the "string test" is a very reliable indicator of gastric pH.

3. Using the Gastro-Test[R] to diagnose Gastroesophageal Reflux Disease (GERD)

On the cotton floss there are blue markings every 10cm that help to determine the anatomical location of the cotton floss. The esophagus typically extends from the incisors (i.e., mouth) to the third or fourth blue markings. (9) Normally, the pH along the esophageal location should be greater than 3. If the pH is shown to be a 3 or less at these markings, it could be stated that the gastric contents have escaped into the esophagus and are likely responsible for symptoms of GERD such as chest pain, heartburn, dysphagia, and regurgitation.

In one report, the pH probe (modified Tuttle) test was compared to the Gastro-Test[R] in 5 infants and children with suspected GERD. (23) The 3 patients with a positive pH probe test also had a pH of 3 or less with the Gastro-Test[R]. The author concluded that the Gastro-Test[R] "may provide an accurate, simple alternative to other methods for detection of acid reflux."

In a subsequent report, the sensitivity of the Gastro-Test[R] to detect GERD in 15 infants and children was assessed. (24) The patient ages ranged from 5 months to 11 years of age (mean, 2.7 years), and symptoms were vomiting, regurgitation, or lower respiratory symptoms. The Gastro-Test[R] results were compared to barium esophagram, esophageal manometry, and the acid reflux test (pH probe). The barium esophagram demonstrated reflux in 4/15 patients, pH probe in 7/15, and the Gastro-Test[R] in 6/15. It was concluded that the Gastro-Test[R] is a simple, rapid, safe, and efficient screening method for patients suspected of having GERD.

Another reason for using the Gastro-Test[R] when screening for GERD is because the symptoms of gastric acid deficiency can also mimic the symptoms associated with GERD. It has been reported that low gastric acidity, even complete achlorhydria, can manifest symptoms as though too much acid is present. (25) Thus, the Gastro-Test[R] can help to differentially diagnose between deficiency of gastric acid and GERD.

4. Further analysis of the Gastro-Test[R] using different time intervals

The "string test" study used a 1 minute time period during which the cotton floss would be in direct contact with the gastric pool. The previous 3 subjects who were studied used a 15 minute time period when the cotton floss was assumed to be in the gastric pool.

To further examine the Gastro-Test[R], 3 fasting, healthy female subjects (Table 6) participated in a small study examining pH values obtained from a 15 minute Gastro-Test[R] versus a 1 minute Gastro-Test[R].

Materials and Methods

Each of the three subjects volunteered to be a part of this study. No eligibility criteria were established for the selection of the subjects, except for their declaration of being healthy and free of disease. None of the subjects received compensation for participating in the study. Each subject had fasted for 10-12 hours prior to testing. Thirty minutes before swallowing the floss-filled gelatin capsule, each subject ingested 4 caffeine alkaloid tablets (100mg each; 400mg in total) in order to stimulate the production of hydrochloric acid. Once the 30 minute period was over, each subject swallowed the floss-filled Gastro-Test[R] capsule with approximately one-eighth to one-quarter (30-60ml) of water.

The subjects were instructed to lie down on their left side for 15 minutes to allow the gastric contents to saturate the end of the floss. The subjects were then instructed to stand up and the floss was pulled from their stomach. The floss was then rubbed with the pH stick provided and the resultant color change was then compared to the pH color chart.

The same procedure was administered 1 week later, except that the 3 subjects were instructed to lie on their left side for only 1 minute. No side effects occurred from the oral administration of the caffeine alkaloid tablets and from the Gastro-Test[R] procedures. No severe gagging or vomiting was observed in any of the 3 subjects. Some gagging did occur in 1 of the subjects, but it did not prevent her from being able to perform the tests.

Results & Discussion

The data (Table 7) demonstrates that the Gastro-Test[R] does not provide comparable results when 15 minutes were compared to 1 minute. In 2 of the subjects, the pH was 1 point greater. In the other subject, the pH was dramatically different and no explanation can adequately explain large pH discrepancy. It is possible that in this subject the cotton floss did not descend properly into the stomach and stayed within the esophagus, thus giving a high pH value. The accuracy of the Gastro-Test[R] seems to be time dependent. One minute is probably not sufficient in terms of saturation of the cotton floss with the gastric contents. More time appears to be necessary for precise results. However, these are mere assumptions since none of the pH results were compared to gastric intubation. The only way to truly assess the accuracy of the different time intervals would have been comparisons to gastric intubation.

Conclusion

The 15 minute Gastro-Test[R] appears to be the procedure of choice. It is known that the Gastro-Test[R] does compare very well to gastric intubation in the 3 healthy male subjects who were evaluated. It can also be stated, that a similar "string test" compares very well to gastric intubation. The Gastro-Test[R] appears to be an excellent screening test for GERD.

Overall, the Gastro-Test[R] is inexpensive, minimally invasive, and easy to administer in the office. It probably compares very well to other methods of gastric analysis, such as gastric intubation. When working-up patients with gastrointestinal symptoms suggestive of deficient gastric acid states and GERD, this test can be very useful as part of the entire evaluation process due to the short time commitment, low side effects, and ease of administration.

Additional Remarks on the Gastro-Test[R] Procedure

To optimize the Gastro-Test[R], it is the author's contention, after having done this test on more than 200 patients in the past 3 years, that the following procedure should be used:

1. The patient should fast for ten to twelve hours prior to the administration of the Gastro-Test[R].

2. Water, but not food, is allowed anytime during the fast.

3. 30-minutes prior to the Gastro-Test[R] the patient should be given 400mg of caffeine alkaloid in pill form. A 240ml cup of black coffee can be used instead of the caffeine alkaloid pill, but standardizing the dose is preferable.

4. For a patient who is very sensitive to caffeine, an alternative is to take 15ml of the botanical medicine, Gentiana lutea, 15 minutes prior to the Gastro-Test[R] since its bitter properties should stimulate the secretion of gastric juices.

5. The patient needs to be seated and the floss-filled capsule is then placed in the patient's mouth.

6. The protruding string, at one end of the capsule, is taped to the patient's cheek.

7. The patient then drinks one-to-two small cups (approximately 30-60 ml) of water and swallows the capsule.

8. The patient then lies on his/her left side for 15 minutes. Lying down allows for maximal contact between the floss and the gastric pool.

9. 15 minutes later, the patient is instructed to sit in a comfortable chair with his/her head slightly extended.

10. The tape is removed from the cheek and the floss withdrawn from the mouth.

11. The floss is then placed on a piece of white exam paper to augment visualization of the color change.

12. The pH stick is rubbed along the floss, beginning at the incisors, working distally until the end of the floss is reached.

13. The resultant color change is then compared to the pH color chart.

14. A pH of 3 or less extending from the incisors to the third or fourth blue markings indicates the presence of acid in the esophagus, thus helping in the diagnosis of GERD.

15. A pH of 3 or less on any part of the distal half of the floss indicates

that the stomach is secreting hydrochloric acid properly. A pH greater than 3 indicates hypochlorhydria, whereas a pH of 5 or above indicates achlorhydria.

Acknowledgements & Competing Interests

Consent was obtained from the patients for publication of this study. The author would like to thank Nick DeGroot, BSc, ND, and Matthew Gowan, BSc, ND, for their assistance and thorough review of this document. Additionally, the author would like to thank Mr. Len Ross from HDC Corporation for providing the comparative study data on the Gastro-Test[R] and gastric intubation. Mr. Len Ross did not provide financial remuneration or influence/oversee any of the comments made within this report.

References

1. Modlin IM, Goldenring JR, Lawton GP, Hunt R, Aspects of the theoretical basis and clinical relevence of low acid states. Am J Gustroenterol 1994;89:308-318.

2. Prousky J. Seely D, A case report on the successful use of inositol hexaniacinate for the treatment of achlorhydria: its possible mechanism of action upon the central nervous system and parietal cell-adenosine triphosphate-dependent [K.sup.+]/[H.sup.+] pump. TLfDP 2003;235/236:72-75.

3. Prousky J, Kerwin C, Niacin (Nicotinic Acid) a putative treatment for hypochlorhydria: re-analysis of two case reports. J Orthomol Med 2002;17:163-169.

4. Kelly GS, Hydrochloric acid: physiological functions and clinical implications. Altern Med Rev, 1997;2:116-127.

5. A deficient gastric acid state is a better term to use than hypochlorhydria or achlorhydria. It simply means a gastric luminal pH above 3.

6. Barrie S, Heidelberg pH capsule gastric analysis. Eds. Pizzorno J & Murray MT. Textbook of Natural Medicine. 2nd ed. New York, NY, Churchill Livingstone, 1999;173-176.

7. Wright JV, ABCs of nutritional testing. Dr. Wright's Guide to Healing Nutrition. New Canaan, CT, Keats Publishing, Inc, 1990;92-128.

8. The patient cost of the Heidelberg radiotelemetric device was obtained from a United States medical center.

9. HDC Corporation, 628 Gibraltar Court. Milpitas, CA 95035. 1-800-227-8162. www.hdccorp.com.

10. The patient cost of the Gastro-Test[R] was obtained from a naturopathic outpatient clinic in Canada. The Canadian cost was converted to US dollars.

11. This study was undertaken in 1974 at the HDC Corporation, previously located at 2109 O'Toole Avenue (San Jose, CA).

12. Segal HL, Miller LL, Morton JJ, Determination of gastric acidity without intubation by use of cation exchange indicator compounds. Proc Soc Exper Biol & Med 1950;74:218-220.

13. Segal HL, Miller LL, Detection of achlorhydria by tubeless gastric analysis. J Nat Cancer Inst 1953;13:1079-1086.

14. Sharp GS, Hazlet JW, Shankman S, Gastric analysis without intubation. Cancer 1954;7:289-290.

15. Sharp GS, Fister HW. The diagnosis and treatment of achlorhydria: ten-year study. J Amer Ger Soc 1967;15(8):786-791.

16. Feldman M, Barnett C, Fasting gastric pH and its relationship to true hypochlorhydria in humans. Dig Dis Sci 1991;36(7):866-869.

17. Russell TL, Berardi RR, Barnett JL, et al, Upper gastrointestinal pH in 79 healthy, elderly, North American men and women. Pharm Res 1993;10(2):187-196.

18. Hurwitz A, Brady DA, Schaal SE, et al, Gastric acidity in older adults. JAMA 1997;278(8):659-662.

19. Morihara M, Aoyagi N, Kaniwa N, Kojima S, Ogata H, Assessment of gastric acidity of Japanese subjects over the last 15 years. Biol Pharm Bull 2001;24(3):313-315.

20. Beal CB, Brown JE, A rapid screening test for gastric achlorhydria. Am J Dig Dis 1968;13(2):113-122.

21. Mr. Len Ross, Personal Comm., October 30, 2003.

22. I calculated the confidence intervals since they had not been reported and calculated in the original study.

23. Liebman WM, Tests for gastroesophageal reflux. Lancet 1978;2(8093):787.

24. Liebman WM, Rosenthal P, The string test for gastroesophageal reflux. Am J Dis Child. 1980;134(8):775-776.

25. Slanger A, Management of gastric achlorhydria and hypochlorhydria. Geriatrics 1966;21(8):193-198.

by Jonathan E. Prousky, ND, FRSH

Correspondence:

Dr. Prousky is the Chief Naturopathic Medical Officer and Associate Dean, Clinical Education at The Canadian College of Naturopathic Medicine. Please send correspondence to: J. Prousky, ND, FRSH, CCNM, 1255 Sheppard Ave. E., Toronto, Ontario, M2K 1E2; Email: jprousky@ccnm.edu.

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