Ann Gaba 1, Kuan Zhang 2,3, Carol B. Moskowitz 2, Carol N. Boozer 3,4, Karen Marder 4 7. Research article

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1 Research article Harris Benedict equation estimations of energy needs as compared to measured 24-h energy expenditure by indirect calorimetry in people with early to mid-stage Ann Gaba 1, Kuan Zhang 2,3, Carol B. Moskowitz 2, Carol N. Boozer 3,4, Karen Marder 4 7 1Department of Food and Nutrition Services, New York Presbyterian Hospital, New York, USA 2Obesity Research Center, St Luke s-roosevelt Hospital Center, New York, USA The Institute of Human Nutrition, 3 Departments of Medicine, 4 Neurology, 5 Psychiatry, 6 Sergievsky Center, 7 Taub Institute, Columbia University College of Physicians and Surgeons, New York, USA Weight loss and energy metabolism are important clinical research areas in understanding the disease mechanisms in. Having an accurate method to estimate expected total energy expenditure would likely facilitate the development of studies about these features of the disease. The Harris Benedict equation is a formula commonly used to estimate basal energy expenditure of individuals, adjusted for height, weight, age and gender. This estimate is then multiplied by a physical activity factor to estimate total daily energy needs to maintain the given weight. Data from 24-h indirect calorimetry was utilized to derive an adjustment formula for the physical activity factor of the Harris Benedict equation for 13 early to mid-stage Huntington s disease patients. The adjusted activity factor provided the most accurate estimate of energy needs. This adjusted formula can be used in clinical assessments of patients, as well as in research studies when indirect calorimetry has not been performed. Keywords:, energy requirements, Harris Benedict equation Introduction Weight loss is very common in people with Huntington s disease, 1 and may occur early in the disease course. Correlates of weight loss include severity of chorea (involuntary dance-like movements), more severe motor impairment in general, less severe depressed mood and decreased functional status. 2 Higher initial body weight may predict slower disease progression; however, a direct Correspondence to: Ann Gaba, Department of Food and Nutrition Services, New York Presbyterian Hospital, New York, USA. angaba@worldnet.att.net Received 30 May 2008, manuscript accepted 10 July 2008 relationship between weight change and calorie intake has not been established for this population. 1 Weight loss, prior to the development of motor manifestations has also been observed in the R6/2 murine model in one study, 3 but not another; 4 however, weight loss consistently occurs when the motor phenotype becomes apparent. 5,6 It has been observed that patients with disease duration of less than 4 years and minimal chorea and dystonia weighed less than age matched controls. 7 In another study of 927 subjects, average weight gain of people with over a 3- year period was less than US population estimates. 2 For studies of looking at specific stage of disease, stage of disease is derived 2008 W. S. Maney and Son Ltd DOI / X Nutritional Neuroscience 2008 Vol 11 No 5 213

2 from the Total Functional Capacity (TFC) score, 8 a global functional measurement designed specifically for. TFC scores range from 13 (no functional impairment) to 0 (severe impairment). TFC scores have been further divided into stages that correlate with disease severity. Stage I represents TFC scores from 11 13; stage II scores of 7 10; stage III scores from 3 6, stage IV scores of 1 and 2; and stage V a score of 0. Total energy expenditure for early to mid-stage (stage 1 and stage 2 as defined above) patients has been examined via 24-h indirect calorimetry. 9,10 These studies showed that early to midstage patients had total energy expenditures that were 11 14% higher than those of matched control subjects. Both studies noted that this difference was primarily due to significantly increased physical activity in the subjects, particularly during waking hours. This increased physical activity, approximately twice that of controls, was due to overall movement measured as displacement of the center of mass of the subjects. 10 Total energy expenditure (TEE) is based on the basal energy expenditure (BEE), thermic energy of food, and physical activity. In hyperkinetic movement disorders such as, the additional calorie requirements due to this increased physical activity are particularly important to determine. Dysphagia is common in mid-to-late stage Huntington s disease posing an additional challenge for weight maintenance. 11 The Harris Benedict equation 12 is a validated method 13 to estimate the basal energy expenditure of individuals adjusted for height, weight, age, and gender. Basal energy expenditure is the energy necessary to maintain body temperature, muscle tone, respiration, and autonomic functions. Physical activity factors have been calculated as the measured total energy expenditure from indirect calorimetry (in kilocalories) divided by the predicted basal energy expenditure using the Harris Benedict equation. In the clinical setting, the physical activity factor is categorized by estimated activity, e.g. bed-bound 1.2, ambulatory 1.3, sepsis 1.6, severe burns Barak et al. 15 derived stress factors for hospitalized patients from indirect calorimetry and BEE estimated by the Harris Benedict equation. The mean stress factor was 1.24 ± 0.25 for men and 1.26 ± 0.26 for women. Estimating the caloric needs of patients by the Harris Benedict equation using physical activity or stress factor estimates based on other conditions would most likely result in estimates too low to meet the actual needs of patients. 10 Very low or high activity factors may result in less accurate estimates of energy needs. 16 Further adjustment of this factor may improve accuracy of these estimates for specific conditions. The current study compares the daily energy needs of weight stable people with as measured by indirect calorimetry, with values estimated by the Harris Benedict equation to derive an activity factor appropriate for estimating total daily calorie needs equal to energy expenditure. Subjects and methods Subjects Thirteen patients who had been weight stable for at least 6 months prior to the study, and met the functional status requirements for 24-h indirect calorimetry, were recruited from the Huntington s Disease Center of Excellence at the New York State Psychiatric Institute. 10 Ten healthy age-, gender-, height-, and weight-matched subjects were also recruited to serve as a control group. Huntington and control subjects did not differ in body composition, as measured by percentage fat (Table 1). Appropriately matched control subjects were not found for three of the subjects. Therefore, comparisons were done between 10 Huntington subjects and their controls, as well as grouped data for all 13 Huntington subjects and the 10 controls. There were no significant differences in the results between groups with or without the three additional Huntington subjects. IRB approval was obtained prior to data collection. Signed informed consent forms were obtained for all study subjects. Confidentiality of data was maintained as required by HIPAA guidelines. Subjects received a small honorarium after participation. Indirect calorimetry The methods of indirect calorimetry have been widely used in the study of energy expenditure. 17,18 They involve the measurement of oxygen consumption with or without concurrent collection of CO 2 produced by a subject breathing into one of several types of apparatus. In the case of the human respiratory chamber, the entire room serves as a collection device, leaving the subject free to move about as he or she wishes, or to perform specified activities according to a study protocol. The human respiratory chamber is considered a reliable and valid method for the study of 24-h energy expenditure in a wide variety of 214 Nutritional Neuroscience 2008 Vol 11 No 5

3 Table 1 Description of matched subjects, and comparisons of activity and chorea Age Height Weight BMI Fat Measured Activity Displacement UHDRS (years) (cm) (kg) (kg/m 2 ) (%) TEE factor of mass chorea score Controls (mean ± SD) 49 ± ± ± ± ± ± ± ± ± 6.3 Control (mean ± SD) 48.6 ± ± ± ± ± ± ± ± 0.23 P-values NS NS NS NS NS NS < < *Unmatched 37* * Subjects 57* NS, not significant. populations, at both low and high levels of physical activity. 22 Each subject spent 24 h in the Human Respiratory Chamber 23 at St Luke s-roosevelt Hospital s Obesity Research Center, to measure 24-h energy expenditure and respiratory quotient (RQ). Individuals were provided with an ad libidum diet, with all portions and left-overs carefully measured to evaluate each subject s 24-h intake. Percentage body fat and lean body mass were obtained via whole body densitometry, utilizing the Obesity Research Center s Bod Pod By the indirect calorimery measurements, the Huntington patients had an average total energy expenditure that was 11% higher than controls. 10 Harris Benedict equation The Harris Benedict equation was used to estimate basal energy expenditure using the height, weight, gender and age obtained for each subject at the same time as the calorimetry studies. It was not possible to derive the BEE from the 24-h indirect calorimetry data, because some of the subjects with extensive chorea were never truly still enough for those measurements to be valid. The Harris Benedict formulas for BEE equations are as follows: 12 Male BEE = (weight in kg) + 5 (height in cm) 6.8 (age in years) Eq. 1 Female BEE = (weight in kg) (height in cm) 4.7 (age in years) Eq. 2 Total energy expenditure minus basal energy expenditure is an estimate of energy expenditure due to physical activity. Large differences in this measurement would indicate that a greater amount of energy is being expended in physical activity as opposed to other factors such as basal metabolism, digestion, or heat production. One would anticipate that, with a hyperkinetic disorder such as, TEE minus BEE would be significantly greater than for controls because of the significantly greater voluntary and involuntary movements as measured by displacement of mass. 10 Calculated BEE values for each of the study subjects were compared to 24-h energy expenditure as Nutritional Neuroscience 2008 Vol 11 No 5 215

4 Table 2 Comparison of TEE by indirect calorimetry with calculated estimates Controls TEE measured BEE by HB calculation TEE by HB 1.5 a TEE by adjusted formula for b (mean ± SD) 2753 ± ± ± ± 439 Control (mean ± SD) 2521 ± P-values NS NS NS a TEE measured correlated with Harris Benedict BEE 1.5; r = b TEE measured correlated with Harris Benedict BEE adjusted activity factor; r = TEE measured correlated with Harris Benedict BEE 1.72; r = (data not shown). NS, not significant. measured by indirect calorimetry. TEE divided by BEE, based on a known (measured) value for TEE, can be used as an estimate of the physical activity factor needed for the Harris Benedict equation to estimated accurately kilocalorie needs to equal 24-h total energy expenditure. Statistical analysis Demographic characteristics of cases and controls were compared using paired t-tests for continuous variables and chi-squared tests for categorical variables. Student s t-tests were also used to compare results for the Huntington and control subjects. Results The mean age of the 8 men and 5 women with was 49.0 ± years, the Total Functional Capacity score was 9.9 ± 2.3 indicating early to mid-stage (stages I and II). Body mass index (BMI) for men with was 30.2 ± 9.78 kg/m 2 (range, kg/m 2 ) and 32.2 ± 6.00 kg/m 2 (range, kg/m 2 ) for women with. Overall results for the 10 Huntington subjects matched to controls and the 10 controls are shown in Table 1. The average physical activity factor for these subjects was 1.72 ± 0.26 and 1.44 ± 0.15 in controls (P < 0.006). The correlation between physical activity factor and the Unified Huntington s Disease Rating Scale (UHDRS) 29 chorea scores for all subjects was not significant (0.42; P < 0.135). However, TEE divided by BEE was correlated with displacement of mass which reflects both voluntary and involuntary activity (r = 0.802; P < ) for Huntington subjects, but not for controls (r = 0.363; P < 0.273). This physical activity factor was inversely correlated with BMI ( 0.53; P < 0.051). Higher BMI was associated with a lower physical activity factor. Based on these results, we derived an equation based on BMI to calculate an adjusted physical activity factor for use with the Harris Benedict 216 Nutritional Neuroscience 2008 Vol 11 No 5

5 equation in estimating total energy expenditure in early to mid-stage. Factor = [ ( BMI)] ( BMI 2 ) Eq. 3 For example, for the first subject in Table 1, with a BMI of 28.6 kg/m 2, the activity factor would be calculated as follows: [ ( )] ( ) = ( ) = ~1.62 (activity factor) Although the Harris Benedict equation takes height and weight into consideration in estimating BEE, BMI adjusted in the formula we derived, gave the most accurate estimates of total energy expenditure when compared with total energy expenditure measured by 24-h indirect calorimetry. Measured total energy expenditure was correlated with energy expenditure calculated by basal energy expenditure multiplied by the average activity factor for Huntington subjects (1.72; r = 0.583); an activity factor typically used for ambulatory patients (1.5; r = 0.621); and by the adjusted activity factors using our formula (r = 0.708). While all of these are positively correlated with measured TEE, the results from the calculations using the adjusted activity factors were the most accurate overall. Discussion We have derived a formula to adjust the activity factor of the Harris Benedict equation to estimate the caloric needs of individuals with early to mid-stage. We determined that an average activity factor of 1.72 was needed to provide an estimate of sufficient calories for most of our Huntington s disease subjects to be in positive energy balance, whereas control subjects only required an average activity factor of 1.44 (P < 0.006). There was greater variability in the activity factors among Huntington subjects. Two patients required an activity factor > 2.0 to maintain their energy balance. While severity of chorea is a contributing factor to increasing calorie needs, surprisingly, the UHDRS chorea score was not a significant predictor of total physical activity. Degree of total physical activity as measured by displacement of mass (Table 1) may have overwhelmed the effect of chorea alone. Direct measurement of total physical activity over 24 h is also likely to be a more accurate evaluation of excessive movement than the UHDRS chorea score, which is based on visual observation during a much more limited time frame. Large differences in measured displacement of mass (and, therefore, the activity factor) were seen between Huntington subjects and controls, and within the Huntington subjects group, but not within the control group. Our formula relies on the correlation of BMI and activity factor in calculating predicted energy needs (Table 2). Differences in physical activity during 24-h energy expenditure studies have also been shown to correlate with usual level of activity while free-living. 30 Therefore, we believe that the differences observed with patients would be comparable under free-living conditions. It has long been known that spontaneous physical activity, fidgeting can make a substantial contribution to total energy expenditure. Ravussin et al. 31 estimated kcal/day in sedentary subjects undergoing 24-h energy expenditure testing in a human respiratory chamber. These authors also identified this variability in spontaneous physical activity as being an inherited trait. This factor has also been shown to be related to resistance to increased fat gain with overfeeding. Levine et al. 32 described their terminology as follows: Physical activity thermogenesis can be subdivided into volitional exercise (sports and fitness-related activities) thermogenesis and what we characterize as non-exercise activity thermogenesis (NEAT). NEAT is the thermogenesis that accompanies physical activities other than volitional exercise, such as the activities of daily living, fidgeting, spontaneous muscle con - tractions, and maintaining posture when not recumbent. The genetic factor(s) that determine spontaneous physical activity (displacement of mass, fidgeting) may operate similarly to whatever causal factor increases this activity in people with. Furthermore, it is known that skeletal muscle work efficiency changes with weight loss or gain, with concurrent changes in resting energy expenditure. 33 While this might have been a confounding variable in interpreting the results of this study, being weight stable prior to participating was one of the inclusion criteria. However, in applying this in clinical settings, it would seem prudent to obtain frequent weights for such patients, and adjust calorie recommendations accordingly. This is especially important for patients dependent on enteral nutrition support. Nutritional Neuroscience 2008 Vol 11 No 5 217

6 Conclusions The data obtained in this study were from a small number of people with early to mid-stage. It is not known whether calorie needs continue to increase with advancing disease or in the presymptomatic stage of this disease. Further assessments of this kind, with larger samples including all stages of disease would likely yield even more specific adjustments to these estimators. The results presented here may be helpful to dietitians and other health professionals caring for patients. Because indirect calorimetry is not routinely performed in individuals with, this formula can readily be used by health providers to estimate caloric needs of patients in early to mid-stage. More accurate values for estimating energy require - ments will facilitate better nutritional care for this challenging population. Acknowledgements This study was funded, in part, by an Initiative Grant from the Huntington s Disease Society of America, and the American Dietetic Association s Gemple Grant for the study of nutrition and neurological disorders. References 1. Myers RH, Saxs DS, Koroshitz WJ. Factors associated with slow progression in. Arch Neurol 1991; 48: Hamilton JM, Wolfson T, Peavy GM, Jacobson MW, Corey-Bloom J. Rate and correlates of weight change in. J Neurol Neurosurg Psychol 2004; 75: Davies SW, Turmaline M, Cazens B et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the mutation. Cell 1997; 90: Carter RJ, Lione LA, Humby T et al. Characterization of progressive motor deficits in mice transgenic for the human mutation. J Neurosci 1999; 19: Mangiarini L, Sathasivam K, Seller M. Exon 1 of the Huntington s disease gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 1996; 87: Cha J-HJ, Kosinski CM, Kerner JA et al. Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human Huntington disease gene. Proc Natl Acad Sci USA 1998; 95: Djousse L, Knowlton B, Cupples LA, Marder K, Shoulson I, Myers RH. Weight Loss in early stage of. Neurology 2002; 59: Shoulson I, Kulan R, Rubin A. Assessment of functional capacity in neuro-degenerative movement disorders: as a prototype. In: Munsat T. (ed) Quantification of Neurological Deficits. Stoneham: Butterworth, Pratley RE, Salbe AD, Ravussin E, Caviness JN. Higher sedentary energy expenditure in patients with. Ann Neurol 2000; 47: Gaba AM, Zhang K, Marder K, Moskowitz CB, Werner P, Boozer CN. Energy balance in early-stage. Am J Clin Nutr 2005; 81: Hunt VP, Walker FO. Dysphagia in. J Neurosci Nurs 1989; 21: Harris JA, Bennedict FG. A Biometric Study of Basal Metabolism in Man. Publication No Washington, DC: Carnagie Institute, Frankenfield DC, Rowe WA, Smith JS, Cooney RN. Validation of several established equations for resting metabolic rate in obese and nonobese people. J Am Dietetic Assoc 2003; 103: Hedberg AM, Garcia N. Macronutrient requirements. In: Skipper A. (ed) Dietitian s handbook of enteral and parenteral nutrition. Gaithersburg, MD: Aspen, 1989; Barak N, Wall-Alonso E, Sitrin MD. Evaluation of stress factors and body weight adjustments currently used to estimate energy expenditure in hospitalized patients. J Parent Ent Nutr 2002; 26: Lin PH, Proschan MA, Bray GA et al. Estimation of energy requirements in a controlled feeding trial. Am J Clin Nutr 2003; 77: Jequier E, Schultz Y. Long-term measurements of energy expenditure in humans using a respiration chamber. Am J Clin Nutr 1983; 38: Fernanini E. The theoretical bases of indirect calorimetry: a review. Metabolism 1988; 37: Ravussin E, Lilloja S, Anderson TE, Christin L, Bogardus C. Determinants of 24-hour energy expenditure in man: methods and results using a respiratory chamber. J Clin Invest 1986; 78: DeBoer JA, Van Es AJH, Vogt JE. Reproducibility of 24 h energy expenditure measurements using a human whole body indirect calorimeter. Br J Nutr 1987; 57: Rumpler WV, Seale JL, Conway JM, Moe PW. Repeatability of 24-h energy expenditure measurements in humans by indirect calorimetry. Am J Clin Nutr 1990; 51: DeJonge L, Nguyen T, Smith SR, Zachwieja JJ, Roy HJ, Bray GA. Prediction of energy expenditure in a whole body indirect calorimeter at both low and high levels of physical activity. Int J Obes 2001; 25: Zhang K, Sun M, Werner P et al. Sleeping metabolic rate in relation to body mass index and body composition. Int J Obes 2002; 3: Dempster P, Aitkens S. A new air displacement method for the determination of body composition. Med Sci Sports Exer 1995; 27: McCrory MA, Gomez TD, Bernauer EM, Mole PA. Evaluation of a new air displacement plethymography for measuring human body composition. Med Sci Sports Exer 1995; 27: McCrory MA, Mole PA, Gomez TD, Dewey KG, Bernauer EM. Body composition by air-displacement plethymography by using predicted and measured thoracic gas volumes. J Appl Physiol 1998; 84: Wagner DR, Heyward VH, Gibson AL. Validation of air displacement plethymography for assessment of body composition. Med Sci Sports Exer 2000; 32: Vescovi JD, Zimmerman SL, Miller WC, Hildebrandt L, Hammer RL, Fernhall B. Evaluation of the BOD POD for estimating percentage of body fat in a heterogeneous group of adults. Eur J Appl Physiol 2001; 85: Huntington Study Group, Unified Huntington s Disease Rating Scale: reliability and consistency. Mov Dis 1996; 11: Snitker S, Tataranni PA, Ravussin E. Spontaneous physical activity in a respiratory chamber is correlated to habitual physical activity. Int J Obes 2001; 25: Ravussin E, Lillioja S, Anderson TE, Christin L, Bogardus C. Determinants of 24-hour energy expenditure in man. J Clin Invest 1986; 78: Levine JA, Eberhardt NL, Jensen MD. Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science 1999; 283: Rosenbaum M, Vandenborne K, Goldsmith R et al. Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects. Am J Physiol 2003; 285: R183 R Nutritional Neuroscience 2008 Vol 11 No 5

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