Sickly Sweet: The Development of a Standardized Method Testing for Lactose and Fructose Intolerance and Malabsorption

Taylor Lawless East Carolina University Faculty Mentor: Kimberly B. Myers East Carolina University

ABSTRACT Lactose intolerance has been a known cause of gastrointestinal distress for many years. Recently, scientists have discovered that fructose intolerance elicits many of the same symp- toms as lactose intolerance. The consumption of fructose has more than doubled in the past twenty years; similarly, the instances of fructose intolerance have also increased. Fructose and lactose intolerance are measured using similar methods. While there are common prac- tices and guidelines used when testing for fructose and lactose intolerance and malabsorptive issues, there is no official standard method including precise practices for before, during, and after the test. Therefore, in the present study a standardized form and set of recommendations were suggested by comparing methods used in previous studies. If used on a wide scale, the standard system would enable researchers to compare results of different studies. Ultimately, this would help researchers gain a better understanding of lactose and fructose intolerance and malabsorptive issues and to measure the frequency of diagnoses for each condition in order to develop improved treatments and potential cures.

actose intolerance has been a popular are not completely understood, there is re- Ltopic in the study of nutrition for many search being conducted on the different types years. Many people suffer from irritable of sugar malabsorption and intolerance. bowel syndrome (IBS) due to the sugar lac- Malabsorption refers to sugar not being prop- tose found in dairy1. Interestingly, as fructose erly broken down in the gastrointestinal tract4 has become more prevalent in the human di- and intolerance implies that the body is inca- ets, people have begun suffering similar mal- pable of breaking down the sugar5. Thus, re- absorpitve effects. searchers are interested in questions regard- Lactose intolerance can cause an array ing the relation between the type of sugars of painful and irritating symptoms such as individuals are consuming and the way the gas, bloating, diarrhea, vomiting and nau- sugars are absorbed and metabolized. sea2. These same symptoms have been ob- Fructose consumption has more than served in those with fructose intolerance3. doubled in the past 20 years due to the use Because the causes of sugar malabsorption of the inexpensive sweetener high fructose

92 Taylor Lawless corn syrup3. Fructose is naturally found in ambiguity of varied extant testing systems. fruits and some vegetables. It is also part The research questions for the present of the simple sugar sucrose, which is a di- study were 1) what are the common charac- saccharide commonly known as table sugar. teristics of the methods and results published Sucrose is comprised of glucose and fructose in the current literature, and 2) could the molecules, which are both monosaccharides. common features of testing be combined to High fructose corn syrup contains a higher create a standard method for testing? A lit- percentage of fructose than glucose. Its use erature review on fructose and lactose malab- is controversial as it is added to many foods sorption studies was conducted. The review as a sweetener because it is less expensive, was conducted after analyzing published arti- but not necessarily healthier, than table sugar. cles about fructose and lactose malabsorption It has been said that the increase in instances and intolerance in order to build a knowledge of intolerance is because it fructose is now in foundation about common practices. The pri- more foods6. mary focus of the review was on the methods While the full effect of this increase of used for diagnosis, and the results obtained fructose in foods is not yet known, more in- in the treatment studies. The methods used stances of fructose malabsorption are being for diagnosis often affected the conclusions diagnosed. Some attribute this malabsorp- about the results, thus, we reviewed methods tion to the metabolic pathway of fructose, and results together. speculating that fructose is absorbed by fa- cilitated diffusion or that fructose can only be Literature Review absorbed with glucose5. While the absorp- tion of fructose is still being studied, it is One of the most referenced studies was known that the enzyme lactase breaks lactose one by Choi et al. 3. The objective of this into the simple sugars galactose and glucose study was to determine how common fruc- in the human body7. tose intolerance was in the sample popula- Fructose and lactose malabsorption and in- tion and to see if lifestyle changes regarding tolerance can impact the life of an individual fructose intake would have an effect on IBS tremendously, and misdiagnosis of these con- experienced by the patients. The research- ditions can also have negative implications. ers questioned how effective the fructose If a person is incorrectly diagnosed with an restricted diets would be for limiting IBS. intolerance, the individual may eliminate the Those with positive hydrogen breath test re- sugar from the diet unnecessarily2,8. That is sults were deemed fructose intolerant. The particularly concerning with lactose because patients who produced a positive breath test restriction of lactose can lead to calcium de- were then given a kit that contained informa- ficiencies9. A diagnosis implying the person tion regarding a fructose restricted diet and is not intolerant when the person is can be were asked to implement the diet. After one dangerous as well since the person will con- year, patients were asked to return and repeat tinue to consume the sugar and experience the same tests and surveys. In addition, the discomfort1. patients answered questions regarding how Hydrogen breath tests are the primary tool strictly the diet was followed according to used to measure fructose and lactose malab- the guidelines and how much time was spent sorption and intolerances. The inconsisten- following the guidelines3. cies associated with conducting such tests The results showed that of the 80 partici- have raised questions regarding the validity pants, 31 had a positive fructose breath test. of the results1. Testing differences also makes Greater than 90% of those with a positive test it difficult for scientists to compare results. claimed that the test caused the usual gastro- For these reasons, we recommend a stan- intestinal discomfort symptoms, which have dard system of measurement to alleviate the been attributed to fructose intolerance. The

93 Explorations |Natural Science and Engineering patients reported that the lifestyle changes Review of best practices: Comparison and had a mild to moderate effect on their life- analysis style (a rating of 2.93 on a 5-point scale). The researcher concluded that there was a corre- Best practices from several reviewed lation between the lifestyle changes and the studies were used to create a “standardized symptoms of those in the positive test group3. method and tool.” Inclusion criterion for the Da Silva Mederios, et al. 2 reported on a studies were 1) publication dates between pediatric population. In the pretest proce- 2008 and 2012 and 2) the use of a hydrogen dure, the children’s height and weight were breath test and the measurement of the sugars measured and parents were asked to fill out fructose, lactose or lactulose. Representative a symptom form for their children2. This is studies reviewed are included in Table 1. a potential source of bias as the parents can- The six variables noted for each study were not feel exactly what their children do. The Primary Researcher; Publication; Year; Sugar children were given a hydrogen breath test Tested; Subjects; Pre-Test; During Test; and which was used to determine whether or not Results. “Primary researcher and publication they were an absorber of lactose or malab- year” were used to identify the study. The sorber. The night before, they were asked to “sugar tested” variable noted whether the eat white rice with chicken and not to eat af- study examined fructose, lactose, lactulose ter the meal2. or a combination of the three. The “subjects” Calcium deficiencies were examined in this variable identified the age group, gender, and study. While most of the studies on calcium general information about the participants in absorption focus on adult populations, this the study. The “pre-test” variable described study is one of the few that has examined a the practices and procedures before the test. younger population. Other studies found that The “during test” variable detailed how the the calcium intake was much lower among test was conducted. The “results” variable the lactose intolerant; however, this study did was used to list the findings of each study. not support that theory; there was no statis- The results of the compilation can be found tical difference in bone density between the in Table 1. Common trends were observed two groups (absorbers and malabsorbers)2. and the most effective methods were deter- The lives of individuals could be improved mined by the researchers. We determined by the results of the studies about fructose the most consistent methods according to the and lactose. For example, researchers sug- table. Then the best practices were selected gest that by limiting lactose in the diet, the to be compiled for the creation of a standard- pain suffered by afflicted children could be ized tool. reduced10. Other researchers4 determined that The standardized tool can be seen in Figure fructose and lactose malabsorption can be the 1. The standardized tool is a form with proce- cause of recurrent abdominal pain and that re- dures that are to be followed and is to be com- moving the malabsorbed sugar from the diet pleted by the physician or researcher. Each of the patient can help alleviate the symp- step of the tool was added to ensure each test toms4. Similar results were noted by Choi,et produces accurate results. Additional steps al3 and Gomara, et al5. Further, Gomara, et were developed in order to create consistency al. found that fructose restriction can reduce between different test administrators. These IBS in pediatric patients5. In addition, there simple preventative steps make it possible appears to be a relationship between age and to compare test results from different medi- the ability to absorb fructose and lactose; cal or research sites. If the steps are properly results suggested a positive correlation for followed and the data are accurately entered fructose, but none for lactose11. into the form, then the results across studies will be more comparable. It was common in the studies reviewed

94 Taylor Lawless for the subjects to be asked to avoid high day having followed the procedures properly. fat meals and foods containing fructose and Thus, the standard form (see Figure 1) has lactose the day before testing (Table 1). The a specific box asking if the patient has- fol purpose of the request was to avoid results be- lowed the dietary restrictions. ing skewed from hydrogen production from We also recommend that the patients the breakdown of the meals of the previous should fast from 10:00 pm until after the test- day. For example, in the study of children ing time. The studies described in Table 1 in San Paulo2, the researchers requested that suggested different times, such as after last children eat white rice with ground chicken meal or from midnight. We recommend that had been fried or roasted as the last meal 10:00 pm for its convenience for varying pa- before the test. The simplicity of that meal tient schedules. The 10:00 pm fast start al- made it easy for participants to comply and lows ample fasting time, while still pinpoint- the meal is also low in fat and does not con- ing a standard time for patients to stop eating. tain lactose2. The fact that all of the patients We recommend that smoking and exercis- had the same last meal added to the interpret- ing are prohibited from bedtime until after ability of the study. the test has been completed. This was con- Therefore, in order to increase consistency sistent in many of the studies because these and decrease stress to the patients trying to activities affect the volume of hydrogen follow the dietary guidelines on the day be- produced and excess hydrogen can skew the fore the test, we suggest that prepackaged results3,11,14. meals should be provided. Three square We further note that the sex of each pa- meals and optional snacks should be given to tient should be recorded as should the height, the patient to consume on the day before the weight and waist circumference for compara- test. The meals would be prescribed by the tive analysis. Fasting blood glucose and iron physician and will be low fat and lactose free. levels should be measured as well because There should be a list of meal options from the tests are easy to perform and may prove which the patients can select meals. Then the useful in later studies. Recording those mea- meals will be known to the physician and sures for later analysis is not time consuming the nutrient content will be easily accessible. and is relatively inexpensive. Trends relating The patient will not be required to consume iron and glucose levels to intolerance may be the entire meal as the meals are only to en- observed if they are regularly recorded. As sure that the low fat, lactose free guidelines shown in several of the studies2,14, the mouths are followed. of the patient should be sanitized in order to We further suggest that compilation of prevent the bacteria in the mouth from affect- fructose recipes and appendices from The ing the results. Teeth should be thoroughly Sugar Fix 6 would be a great reference to pro- brushed and antiseptic mouthwash should be vide patients for the day before the test and generously used. The standard form provides for a fructose free diet. The Sugar Fix by de- a safeguard to ensure that this is done. scribes the negative influence fructose has on The majority of studies used solutions of the human body6. The recipes that contain fructose or lactose in water. Several studies lactose or that are high fiber should be- ex used lactulose as a constant as it is always cluded or the problematic ingredient should malabsorbed. The sugar solutions posed an be substituted. issue in some studies when patients refused We also suggest that all meals consumed to drink the solution4. In order to combat should be recorded. Notes may be added re- that issue and to more accurately reflect the garding how much of the food was consumed, ways the sugars are found in nature, it was but it is not necessary. If high fat foods or suggested that natural food should be used foods containing lactose were consumed, the for the tests13. For example, raisins could patient must come back for testing another be used to measure fructose intolerance and

95 Explorations |Natural Science and Engineering milk to measure lactose intolerance. The an identification number known only to the sugar solutions are highly concentrated and physician providing analysis. do not reflect their naturally found counter- parts13. However, using natural foods would Conclusion pose many issues such as making sure the same concentration of sugar was in each dose There have been significant advances in and the other component of the natural food the study of sugar malabsorption and intoler- may affect the results. Thus, we recommend ance issues. While more studies have been that the sugar solution (fructose or lactose in conducted on lactose, fructose related issues water) continue to be used. are becoming more prevalent. The increased Several of the studies assigned sugar intake prevalence is likely due to the increase of based on body mass in kilograms2,10,11. The fructose consumption3. Removing sources of most common assignments were 0.5 g per kg fructose such as fruits and vegetables could of body weight for fructose and 2 g of lactose result in vitamin deficiencies and low fiber per kilogram of bodyweight2,10. However, we intake, just as several of the lactose studies disagree with this method. We recommend suggested that calcium deficiencies could re- that a standard amount of sugar solution is sult in the avoidance of dairy9,12. administered, as this can reflect a standard A standard test and reporting system for serving. lactose and fructose intolerance and malab- Based on the review of studies, we recom- sorption should be adopted. Based on our mend that breath hydrogen be measured ev- review of best practices, the test should begin ery 30 minutes for three hours. An increase with a night of fasting. A hydrogen breath of 20 ppm over baseline constitutes a positive test using lactulose should be conducted for result. continuity. The results of the test could be Finally we recommend that all data col- used as the control or baseline hydrogen val- lected should be entered into the form pro- ues of the patient. A standard food frequency vided (see Figure 1). This form should be questionnaire should be distributed to gather completed electronically so that it can be data regarding the sources and quantities of saved by the doctor and submitted to a da- fructose and lactose consumed. In addition, tabase. Each patient should be given an ID follow up hydrogen breath tests using fruc- number so the information is confidential. tose and lactose should also be conducted. If electronic, the form can be submitted to a By using a standard test, it would be easier database where all of the results across the to analyze and compare the results. In addi- world can be compiled. This compilation of tion a standard diagnosis could be created. information will allow researchers to analyze This would make it easier to determine the data and observe trends. Such trends can be sugar absorption of an individual. After a used to better understand malabsorption and standard is set, more studies on fructose and intolerance. lactose could be conducted. If the causes of This process could be facilitated by creat- sugar malabsorption and intolerance are all ing an app. The app would contain the meal determined, researchers could work towards choices, the test form and the procedure a solution to avoid the negative effects pro- instructions. During the test the physician duced by the malabsorption and intolerance. could enter the patient data directly into the This tool will be helpful in consistently app form which would be loaded on to an determining cases of fructose and lactose icloud database. By creating a database via intolerance and malabsorption. By adopting the icloud all physicians would have access a standard procedure, people will be able to to the data, allowing them to compare re- more easily understand tests and the results of sults. Patient identities would remain con- the test1. This is especially important during fidential as each patient would be assigned this time where there has been an increase in

96 Taylor Lawless cases of fructose intolerance3. The standard- information that would lead to further studies ized method will also be beneficial to those involving the control and treatment of fruc- with lactose intolerance. tose and lactose intolerance and malabsorp- In order to be successful, this system tive issues. The overall quality of life of those must be adopted and used on a wide scale. who have such issues would be improved as By having an app created for physicians symptoms such as gas, bloating, diarrhea, and researchers to use, they could save the vomiting and nausea2,3 would decrease or be data to the database and access information alleviated altogether. By standardizing the from other patients to compare and contrast. testing procedures, scientists would be one Due to the standardized protocol, results step closer to being able to treat lactose and from all studies would be possible to com- fructose intolerance and malabsorption. pare. Hopefully, this database would provide

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Figure 1 Fructose and Lactose Malabsorption and Intolerance Test Sheet

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Taylor Lawless Table 1 1 Table

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Works Cited

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