Validating Dietary Intake with Biochemical Markers

Poor nutritional status is common in patients with cystic fibrosis (CF). The North American Cystic Fibrosis Foundation (CFF) has established a goal for all children with CF to be at or above the 50th percentile for body mass index (BMI)-for-age (1). The most recent CFF annual report documents improved BMIs as compared with 1996, but the mean BMI continues to be less than the 50th percentile after age 9 years in most children with CF (1, 2). There is a well-documented relationship between nutrition and pulmonary function (3, 4, 5), and improvement or stabilization of pulmonary function is associated with improved nutritional status (6, 7). Although malnutrition can occur as a consequence of worsening disease, Corey and colleagues (8) have documented malnutrition as an independent predictor of a greater likelihood of mortality. Thus, improving nutrition is imperative.

Malnutrition can be due to inadequate energy intake, but other causes include energy deficits due to increased energy needs, excessive fecal losses, and metabolic losses such as unrecognized CF–related diabetes (9). Furthermore, patients may have adequate energy intake, but still be deficient in one or more macronutrients or micronutrients. Lack of adequate pancreatic enzyme supplementation can lead to malabsorption of fat-soluble vitamins and loss of calories. In addition, protein catabolism has been identified in both adults and children (10, 11, 12) with CF and is worse in patients who are ill (13). Protein catabolism, despite otherwise normal nutritional profiles, could result in protein malnutrition. Any nutritional deficit may be associated with specific clinical consequences. For example, protein malnutrition can lead to impaired immunity (14), decreased strength, and lack of tolerance to exercise (15). Appropriate fat intake and absorption allow the body to create nutritional stores and are also the source of fatty acids, which are needed for normal metabolism. Thus, maximizing nutritional intake in people with CF is of utmost importance.

Centers that specialize in the care of patients with CF generally suggest that patients follow-up every 3 months. Growth should be carefully evaluated at each visit (16). Registered dietitians with specific training in the management of CF generally begin instructing parents and patients on proper dietary intake at a very early age. It is essential to verify that families understand and are following these recommendations because body weight alone does not necessarily constitute dietary adherence. Calculation of percentage ideal body weight can identify patients who are at risk for nutritional failure, yet not all of these patients will have nutritional insufficiency (16). Currently, CF care providers must rely on the family and patient report of dietary consumption to determine level of adherence to dietary recommendations. Dietary records are inaccurate (17, 18, 19), thus there is a great need for accurate and objective measures to assess dietary intake. Olveira and colleagues report on their study of markers of nutritional intake as correlated with dietary history data (20).

Current Research

Olveira and colleagues’ study was conducted in 37 adults with CF and 37 healthy adults well-matched for age, sex, and nutritional status. The investigators collected prospective dietary information consecutively for 1 week. Anthropometric data and a fasting blood sample were collected at baseline. The fasting blood sample was used to measure a potential biochemical marker: serum phospholipid fatty acids. Other biochemical markers included 24-hour urine nitrogen and a 72-hour measure of fecal fat and fecal nitrogen. The ratio of energy intake (EI) to basal metabolic rate (BMR) was calculated by comparing the dietary energy intake to the expected energy requirement measured by age normative intake. Energy intake of CF subjects was also compared with the daily energy requirement as calculated by the CFF equation (21). Results obtained for each of these biochemical markers were carefully correlated with the dietary intake data.

The results suggest that the measurement of fecal fat and nitrogen may be useful for validating dietary intake data, and that the EI/BMR ratio may also be useful. Interestingly, fecal fat and nitrogen correlated with dietary intake of fat and protein, respectively, but also correlated with total energy intake. Furthermore, urine nitrogen correlated with dietary intake of protein and fat and also with fecal nitrogen. The findings from measurement of phospholipid fatty acids differed in control subjects depending on dietary intake, but no consistent pattern was noted in CF patients. Thus, serum phospholipids are not likely to be useful to validate measures of dietary intake in CF.

Relevant Findings

This study presents several possible biomarkers to validate dietary intake in patients with CF. The EI/BMR has been used by others and a ratio of 1.55 or less has been viewed as a marker for underreporting (22). This study validates the accuracy of this cutpoint for underreporting dietary intake in CF patients and thus provides information that clinicians can use to evaluate annual dietary reports. Those who underreported in this study (only three with CF) had a tendency toward higher than normal BMI. Underreporting may be more likely in these groups if they are self-conscious about weight (23).

Another important finding from this study is that measures of fecal fat correlated with total energy intake, but the correlation disappeared in patients who had no malabsorption, thus suggesting that use of fecal fat as a method to validate dietary intake is likely more important in patients with suspected steatorrhea. Urinary nitrogen, although highly correlated with dietary intake in these patients, assumes positive nitrogen balance. Patients who are ill are more likely to be in negative nitrogen balance secondary to increased catabolism; thus, urinary nitrogen measures may not be useful in the face of acute illness. Therefore, if this biochemical marker is selected as a validation tool for dietary intake, it is advisable that the patient’s clinical status be considered. The lack of correlation with serum phospholipid is not particularly surprising given altered fat metabolism in CF (24). Future studies to better understand fat metabolism in these patients may help identify a better biochemical marker.

Overall, the study by Olveira and colleagues provides several useful biochemical markers for validation of dietary intake in CF. Most importantly, they have validated the EI/BMR cutoff for underreporting in this patient group.
Poor nutritional status is common in patients with cystic fibrosis (CF). The North American Cystic Fibrosis Foundation (CFF) has established a goal for all children with CF to be at or above the 50th percentile for body mass index (BMI)-for-age (1). The most recent CFF annual report documents improved BMIs as compared with 1996, but the mean BMI continues to be less than the 50th percentile after age 9 years in most children with CF (1, 2). There is a well-documented relationship between nutrition and pulmonary function (3, 4, 5), and improvement or stabilization of pulmonary function is associated with improved nutritional status (6, 7). Although malnutrition can occur as a consequence of worsening disease, Corey and colleagues (8) have documented malnutrition as an independent predictor of a greater likelihood of mortality. Thus, improving nutrition is imperative.

Malnutrition can be due to inadequate energy intake, but other causes include energy deficits due to increased energy needs, excessive fecal losses, and metabolic losses such as unrecognized CF–related diabetes (9). Furthermore, patients may have adequate energy intake, but still be deficient in one or more macronutrients or micronutrients. Lack of adequate pancreatic enzyme supplementation can lead to malabsorption of fat-soluble vitamins and loss of calories. In addition, protein catabolism has been identified in both adults and children (10, 11, 12) with CF and is worse in patients who are ill (13). Protein catabolism, despite otherwise normal nutritional profiles, could result in protein malnutrition. Any nutritional deficit may be associated with specific clinical consequences. For example, protein malnutrition can lead to impaired immunity (14), decreased strength, and lack of tolerance to exercise (15). Appropriate fat intake and absorption allow the body to create nutritional stores and are also the source of fatty acids, which are needed for normal metabolism. Thus, maximizing nutritional intake in people with CF is of utmost importance.

Centers that specialize in the care of patients with CF generally suggest that patients follow-up every 3 months. Growth should be carefully evaluated at each visit (16). Registered dietitians with specific training in the management of CF generally begin instructing parents and patients on proper dietary intake at a very early age. It is essential to verify that families understand and are following these recommendations because body weight alone does not necessarily constitute dietary adherence. Calculation of percentage ideal body weight can identify patients who are at risk for nutritional failure, yet not all of these patients will have nutritional insufficiency (16). Currently, CF care providers must rely on the family and patient report of dietary consumption to determine level of adherence to dietary recommendations. Dietary records are inaccurate (17, 18, 19), thus there is a great need for accurate and objective measures to assess dietary intake. Olveira and colleagues report on their study of markers of nutritional intake as correlated with dietary history data (20).

Current Research

Olveira and colleagues’ study was conducted in 37 adults with CF and 37 healthy adults well-matched for age, sex, and nutritional status. The investigators collected prospective dietary information consecutively for 1 week. Anthropometric data and a fasting blood sample were collected at baseline. The fasting blood sample was used to measure a potential biochemical marker: serum phospholipid fatty acids. Other biochemical markers included 24-hour urine nitrogen and a 72-hour measure of fecal fat and fecal nitrogen. The ratio of energy intake (EI) to basal metabolic rate (BMR) was calculated by comparing the dietary energy intake to the expected energy requirement measured by age normative intake. Energy intake of CF subjects was also compared with the daily energy requirement as calculated by the CFF equation (21). Results obtained for each of these biochemical markers were carefully correlated with the dietary intake data.

The results suggest that the measurement of fecal fat and nitrogen may be useful for validating dietary intake data, and that the EI/BMR ratio may also be useful. Interestingly, fecal fat and nitrogen correlated with dietary intake of fat and protein, respectively, but also correlated with total energy intake. Furthermore, urine nitrogen correlated with dietary intake of protein and fat and also with fecal nitrogen. The findings from measurement of phospholipid fatty acids differed in control subjects depending on dietary intake, but no consistent pattern was noted in CF patients. Thus, serum phospholipids are not likely to be useful to validate measures of dietary intake in CF.

Relevant Findings

This study presents several possible biomarkers to validate dietary intake in patients with CF. The EI/BMR has been used by others and a ratio of 1.55 or less has been viewed as a marker for underreporting (22). This study validates the accuracy of this cutpoint for underreporting dietary intake in CF patients and thus provides information that clinicians can use to evaluate annual dietary reports. Those who underreported in this study (only three with CF) had a tendency toward higher than normal BMI. Underreporting may be more likely in these groups if they are self-conscious about weight (23).

Another important finding from this study is that measures of fecal fat correlated with total energy intake, but the correlation disappeared in patients who had no malabsorption, thus suggesting that use of fecal fat as a method to validate dietary intake is likely more important in patients with suspected steatorrhea. Urinary nitrogen, although highly correlated with dietary intake in these patients, assumes positive nitrogen balance. Patients who are ill are more likely to be in negative nitrogen balance secondary to increased catabolism; thus, urinary nitrogen measures may not be useful in the face of acute illness. Therefore, if this biochemical marker is selected as a validation tool for dietary intake, it is advisable that the patient’s clinical status be considered. The lack of correlation with serum phospholipid is not particularly surprising given altered fat metabolism in CF (24). Future studies to better understand fat metabolism in these patients may help identify a better biochemical marker.

Overall, the study by Olveira and colleagues provides several useful biochemical markers for validation of dietary intake in CF. Most importantly, they have validated the EI/BMR cutoff for underreporting in this patient group.

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