Journal of the American College of Nutrition, Vol. 17, No. 4, 392-397 (1998)
Published by the American College of Nutrition
Growth Hormone and IGF-I Plasma Concentrations and Macronutrient Intake Measured in a Free-Living Elderly Population During a One-Year Period
Maurine Darling-Raedeke, MS, RD,
William H. Thornton, Jr, MS and
Ruth S. MacDonald, PhD, RD
Nutritional Sciences Program, University of Missouri, Columbia, Missouri
Address reprint requests to: Ruth S. MacDonald, PhD, RD, Food Science and Human Nutrition, 122 Eckles Hall, University of Missouri, Columbia, MO 65211
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ABSTRACT
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Objective: To determine seasonal variations in circulating concentrations of growth hormone and IGF-I in healthy, free-living elderly and to identify correlates between dietary intake, growth hormone and IGF-I concentrations in this population.
Methods: Seven-day diet records and plasma samples were collected throughout a 1-year period. Plasma growth hormone and IGF-I were determined by RIA. Dietary macronutrient intake was determined using Nutritionist IV.
Results: The dietary intake of the population corresponded to the established recommendations for percentage of fat, carbohydrate and protein. Carbohydrate intake differed significantly during the year, but protein and fat did not. Hormone concentrations were constant throughout the year, with no significant differences observed. No correlation between plasma growth hormone and IGF-I was observed. Growth hormone and IGF-I concentrations did not correlate with macronutrient intake, however subjects with the lowest energy intakes tended to have higher growth hormone and lower IGF-I than those with higher energy intakes.
Conclusion: This study provides important information on the dietary intake and hormone concentrations in normal, healthy elderly which will be useful in comparison with persons of similar age with complicating illnesses or nutrient deficiencies.
Key words: growth hormone, IGF-I, elderly, diet, macronutrients, free-living
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INTRODUCTION
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Circulating concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I) decrease with increasing age in humans [13]. GH, which is secreted by the pituitary, stimulates the synthesis of IGF-I by the liver. IGF-I circulates in the blood bound to IGF binding proteins. Many of the growth promoting effects of GH appear to be mediated by IGF-I activation of IGF-I receptors found in the plasma membrane of most cells [4]. IGF-I is also produced locally, and has paracrine and autocrine activity. Advancing age is associated with decreased lean muscle mass, increased percent body fat and loss of bone density [5,6]. Hence, the lower concentrations of the mitogenic hormones that occur with age are thought to be related to these changes in body composition [7].
Nutritional status is a primary regulator of circulating IGF-I concentration [8,9]. Specifically, suboptimal total energy or protein intake are associated with decreased circulating concentrations of IGF-I [10,11]. Reduced IGF-I concentrations are associated with several conditions of compromised nutritional status, such as marasmus, anorexia nervosa, inflammatory bowel disease and celiac disease [12]. In conditions of starvation, GH resistance is common with circulating GH concentrations elevated or normal.
The nutritional status of elderly persons is often compromised by illness, socioeconomic factors and living conditions. Limited information is currently available from which nutrient requirements for the elderly can be determined, particularly for healthy, non-institutionalized elderly persons. However, it is generally found that people require less energy and macronutrients as they age, although requirements for micronutrients may not decrease [13]. Studies in which dietary intake, and circulating concentrations of GH and IGF-I in healthy, free-living elderly during an extended period have not been done. Because of the importance of nutritional status on circulating IGF-I concentrations, maintaining adequate nutritional status of the elderly would appear to be helpful in maintaining more youthful concentrations of GH and IGF-I. This study was undertaken to define the concentrations of IGF-I and GH in a healthy, free-living elderly population during a 1-year period. The normal dietary intake of the subjects was determined by periodic 7-day dietary records in order to identify seasonal variations in macronutrient intake and to identify correlations between the mitogenic hormones and dietary intake.
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MATERIALS AND METHODS
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Individuals living in the Lenoir Retirement Village in Columbia, Missouri were recruited for voluntary participation in the study. A general survey instrument was completed by potential participants to provide demographic, health and pharmacological information prior to acceptance in the study, and medical records were also screened. Accepted participants were free-living, generally healthy and prepared their own meals. Individuals with dietary restrictions or digestive diseases were excluded, as were persons on chronic hormone therapy (e.g., insulin, thyroid or steroids) or antibiotics. Voluntary participation adhered to guidelines established by the Institutional Review Board at the University of Missouri.
Participants were instructed by a registered dietitian (MDR) in identifying food components and estimating portion sizes prior to beginning the study. The training included visual examples and written materials. Participants completed a diet record for 7 consecutive days in March, July, September and January, to reflect seasonal variation in food availability and intake. Dietary analysis was completed using Nutritionist IV (N-Squared Computing, Salem, OR).
Blood samples were obtained from the participants in March, May, July, September, November, and January. Participants refrained from eating and drinking (except water) 2 hours before blood sampling. Blood was drawn between 8:30 a.m. and noon into EDTA-treated tubes and held on ice. Blood samples were centrifuged, the plasma was removed, aliquoted and immediately frozen at -20°C.
Plasma growth hormone was measured by immunoradiometric assay (IRMA; Nichols Institute Diagnostics, San Juan Capistrano, CA). For each assay a standard curve and internal standard were determined. Samples were assayed in duplicate. The intra-assay variation was 3.68% and the inter-assay variation was 5.2%. IGF-I was measured by radioimmunoassay (RIA) in acid-ethanol extracted plasma (Monsanto, 1989). 125I was purchased from Amersham (Arlington Heights, IL) and human anti IGF-I antibody was purchased from Nichols Institute Diagnostics (San Juan Capistrano, CA). A standard curve and internal standard were determined for each assay. The intra-assay variation was 8% and the inter-assay variation was 11.4%. GH and IGF-I values were corrected for albumin and reported as ng hormone/mg albumin, in order to correct for blood volume variation which may occur in elderly subjects. Plasma albumin was measured by spectrophotometric analysis using bromcresol green (Sigma Chemical Co., St. Louis, MO). The intra-assay variation was 3% and the inter-assay variation was 7%.
Body fat was measured at the end of the study by bioelectrical impedance (BIA; RJL Systems, Mt. Clemmons, MI). Participants consumed eight glasses of non-caffeine, non-alcohol-containing beverages 24 hours prior to the test, and avoided caffeine and alcohol sources and heavy exercise 12 hours prior to testing. A single BIA was performed on each of the participants in a prone position with the exception of two who remained seated because of physical impairments. Height, weight, age and activity levels were determined prior to testing. Percent body fat was determined using a standard equation based on ages 18 to 84 years.
Data are expressed as means ± SEM. Analysis of variance (ANOVA) and linear regression were performed on the data by SAS [14] with significance determined by LS means.
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RESULTS
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Characteristics of the study population are summarized in Table 1. A total of 35 subjects completed the study. The mean age of the participants was 77.6 years, and 86% of the subjects were between 71 to 90 years of age. Women represented 77% of the participants. Mean length of participation was 14 months. Attrition due to death was two. The use of medication and supplements was minimal among subjects with some participants reporting no use. Common medications were laxatives and stool softeners, while supplements were usually a multivitamin.
Plasma albumin concentrations fell within the expected normal range and were consistent throughout the study (Table 2). Mean plasma GH concentrations were highly consistent in the subjects over the 4 months tested (Table 2). Although not statistically different, GH concentrations tended to be higher during July and lower during May. Similarly, mean plasma IGF-I concentrations were consistent throughout the year (Table 2), with no statistical differences observed. As observed for GH, IGF-I concentrations tended to be higher during July. The overall mean IGF-I and GH concentrations in the subjects, expressed as ng/ml, were 44.69±1.40 and 2.11±0.287, respectively.
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Table 2. Circulating Concentrations of Albumin, Growth Hormone (GH) and Insulin-Like Growth Factor-I (IGF-I) in Lenoir Participants by Month
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Individual participant values for plasma GH and IGF-I from the March sample were examined by linear regression (Fig. 1). The Pearson Correlation Coefficient was 0.0915 for the 34 observations, indicating no correlation between GH and IGF-I. Similar lack of correlation were observed for the May, July, and September time points (data not shown).

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Fig. 1. Scatter plot of plasma growth hormone and insulin-like growth factor-I concentrations in the March sample obtained from the Lenoir participants. Hormone concentrations are expressed per mg albumin measured simultaneously in the samples. The Pearson Correlation Coefficient was 0.0915 for the 34 observations, indicating no correlation between the two hormone concentrations.
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Significant differences in carbohydrate intake by the participants during the year were observed (Table 3). LS mean carbohydrate intake determined from 7-day diet records, expressed as g carbohydrate consumed per day, was higher in September and January compared to July. The greatest difference in carbohydrate intake occurred between July and January. Energy intake was also calculated (Table 3), and expressed as MJ consumed per day. Although there was a trend toward higher mean energy intake in September and January, no statistical differences were observed. Mean energy intake was lowest during July (7.1 MJ/day) and highest during January (7.99 MJ/day). Mean protein and fat intake, expressed as g consumed per day (Table 3) were not different in the participants during the months of March, July, September and January. Overall, carbohydrate, fat and protein comprised 58, 29 and 15% of total energy, respectively.
The relationship between dietary factors and plasma GH and IGF-I concentrations during the months of March, July, September and January (when blood samples and food records were both collected) was examined. Data from the March comparison are shown in Figs. 2 and 3 as representative of the four analyses. The energy intake of the participants was designated as low (5 MJ/day), moderate (57.5 MJ/day) or high (>7.5 MJ/day) and the data presented in quartiles. As energy intake increased, GH concentration tended to decrease, although the values did not reach statistical significance (Fig. 2). Conversely, as energy intake increased, IGF-I concentration tended to increase, but without statistical significance (Fig. 3).

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Fig. 2. Quartile distribution (2575 percentile) of plasma growth hormone concentration in the Lenoir participants consuming three levels of energy. Data from individual participants obtained during the month of March are included in the analysis. T-bars represent SD of the analysis, with mean shown within each box. The number of individuals with intakes <5 MJ/day=3, 5 to 7.5 MJ/day=16 and >7.5 MJ/day=13.
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Fig. 3. Quartile distribution (2575 percentile) of plasma insulin-like growth factor concentration in the Lenoir participants consuming three levels of energy. Data from individual participants obtained during the month of March are included in the analysis. T-bars represent SD of the analysis, with mean shown within each box. Dots represent individual outliers within the sample population. The number of individuals with intakes <5 MJ/day=3, 5 to 7.5 MJ/day=16 and >7.5 MJ/day=13.
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The mean body fat determined by bioelectrical impedece was 33% for men and 44% for women (Table 4). The mean body mass index (BMI) was 23.83 kg/m2. Mean BMI for women was 23.7 and 24.7 for men. No correlation between body fat and GH or IGF-I were observed (data not shown).
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DISCUSSION
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With the increased relative availability of recombinant human GH, administration of GH to elderly people has been attempted to improve muscle strength, and reduce age-related loss of lean body mass and bone density [1719]. Positive improvements in body composition have been observed in elderly men given GH for 6 months, including an 8.8% increase in lean body mass and 1.6% increase in lumbar vertebrae density [17]. A decrease in percent body fat and increased bone turnover, with evidence of decreased bone loss, was observed in elderly women given GH for 6 months [19]. However, side effects did occur in some subjects, including edema, fluid retention carpal tunnel syndrome, and gynecomastia. Exogenous GH treatment produces an increase in plasma concentrations of IGF-I [17,20]. Therefore, direct administration of IGF-I to elderly people has also been attempted as a more direct therapy. Administration of a low dose of rhIGF-I (3060 µg/kg-day) to postmenopausal women increased bone turnover [21]. However, a higher dose of 120180 µg/kg-day resulted in significant side effects in the women, including edema, weight gain, sinus tachycardia and postural hypotension. Hence, pharmacological administration of mitogenic hormones may be counterproductive in some elderly patients.
The overall 1-year mean GH concentration of 2.11 ng/ml observed in the Lenoir population was consistent with, but slightly higher, than literature values. According to Rudman [7] people between 70 to 80 years of age, which encompasses the mean age of the Lenoir participants, have less than 2 ng/ml plasma immunoreactive GH throughout the day. Others have measured 0.9 and 0.8 ng/ml concentrations in elderly men [1,22]. Ironically, among the Lenoir participants the highest single GH value, 20 ng/ml, was obtained in the oldest participant (91 year old female). Individuals exhibit unique circadian rhythms for GH release, and single GH measurements do not provide details concerning peak GH concentrations, total GH release or patterns of GH secretion. Because participants were free-living it was not feasible to obtain multiple, daily GH measurements. To reduce variability, blood sampling was done at approximately the same time each day, and participants were diligent in refraining from eating prior to the blood sampling. Given the narrow variation among the overall mean GH concentrations each month, consistency in sampling was achieved. The mean values obtained over a year period were also highly consistent, indicating reliability in the data. GH measurements at a single daily time point is an accepted method for GH measurement as indicated by the frequent use of this sampling method [23].
Corpas et al [22] reported plasma IGF-I concentrations of 144 ng/ml in men aged 60 to 79. Guler et al [23] observed plasma IGF-I concentrations of 102 and 154 ng/ml in healthy men aged 57 and 60 years, respectively. And Bando et al [1] found a mean basal IGF-I concentration of 86.7 ng/ml in males with a mean age or 77.8 years. In the Lenoir population the mean IGF-I concentration was 44.69 ng/ml, which is lower than these previous reports. Measurement of plasma IGF-I concentrations are often confused by differences in assay techniques, including specificity of antibodies, and binding protein extraction methods [24]. Our assay was found to recover 88% of exogenously added IGF-I, and to be reliable in measuring standard IGF-I concentrations.
In this elderly population no significant correlations between energy or macronutrient intake and GH or IGF-I concentrations were observed. The Recommended Dietary Allowances suggest consumption of 9.6 MJ/day for men and 7.9 MJ/day for women 51 years and older [18]. Our subjects averaged 7.55 MJ/day. The RDA values are, however based on an average person who would be heavier, taller and younger than the average Lenoir participant. It is therefore suggested that the RDA values overestimate caloric needs of this population. Lamon-Fava et al [25] found elderly free-living persons to consume 7.77 (men) or 6.15 (women) MJ of energy per day, which correlates well with our results. Since it is generally agreed that 5.0 MJ/day is needed to maintain basal metabolic rate, inadequate caloric intake would be defined as less than 5.0 MJ/day. Frequency distribution revealed that GH was higher in the subjects who did consume less than 5.0 MJ/day (Fig. 2), although this was not statistically significant due to the limited number of subjects. These findings are consistent with the literature which suggests that during moderate energy restriction such as fasting, GH concentrations increase [26]. During a mild energy restriction the number of GH binding sites decreases [27], thus GH is left to circulate in the blood and GH levels increase.
Conversely, IGF-I concentration tended to be lower in subjects who consumed less than 5.0 MJ/day (Fig. 3). A reduction in GH receptors seen during fasting is one mechanism by which IGF-I concentrations may decrease with energy deprivation. According to Thissen et al [27], nutritional deprivation may decrease hepatic IGF-I production by diminishing IGF-I gene expression. IGF-I gene expression may be nutrient regulated at either the level of transcription or translation, although no mechanism has been described.
Mean protein intake for the Lenoir subjects was 1.11 g protein/kg body weight throughout the year. This is greater than the estimated requirement of 0.8 g protein/kg body weight [18], although Pemberton et al [28] have suggested that protein needs for the elderly are higher than 0.8 g protein/kg body weight. Protein intake in these subjects may be higher than other elderly populations as the Lenoir residents represent a financially secure and highly educated elderly population. High quality protein foods, such as meats and dairy products, were affordable to this population. Although no specific dietary recommendations or advice was given to the participants, the overall consumption was 58, 15, and 29% of total energy as carbohydrate, protein and fat, respectively. These fall very well within the recommended ranges 55 to 60, 15 to 20 and 25 to 39% of total calories as carbohydrates, protein and fat, respectively [28]. A comparable group of elderly free-living subjects was found to consume more fat (35%) and less carbohydrate (48%) than our population [25]. Hence, our population was consuming a well-balanced and adequate diet throughout the study and therefore provides a useful comparison to other populations.
The mean BMI and percentage of body fat of the population was within the normal range for that age group [7]. No correlations between body fat and GH or IGF-I could be found in this population, likely due to the narrow range of the body fat in the population. However, evidence suggests that BMI is not a predictor of plasma IGF-I concentrations. Kelly et al [29] found only a weak positive correlation in normal middle aged women between BMI and IGF-I.
In rats a direct association between protein intake and serum concentrations of growth factors has been observed [30,8]; and adequate energy intake is required to maintain IGF-I concentrations [31]. These studies were performed in animal models, where severe protein or energy restrictions were induced. In our population, protein and energy intake was not restricted, nor at the extremes thus the lack of correlation between nutrient intake and GH or IGF-I likely reflect this limited range of intakes. Positive correlations between physical fitness, as measured by VO2max capacity, in middle-aged women and both IGF-I and GH were previously reported [29]. However, neither IGF-I nor GH correlated with bone turnover. The authors speculate that the age-related decline in IGF-I and GH may be more related to declining levels of physical fitness rather than to the aging process. However, Rudman and Mattson [32], found physically active older men to have lower serum IGF-I concentrations than sedentary older men and young men (168, 219.6 and 363.7 ng/ml, respectively). In both young and old men, serum IGF-I did not correlate with level of physical activity nor BMI. These authors conclude that the observed decline in IGF-I with age is independent of decreased physical activity. In neither of these studies was diet or nutritional status measured.
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CONCLUSION
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Prior to this study, no correlations between the circulating levels of GH and IGF-I with nutritional intake have been performed in a non-intervention study of a human, elderly population. Although the number of subjects was small, the participants were exceptionally cooperative, thorough in their diet records and explicit in following instructions. Therefore, overall trends in the data are strong indicators of response in a larger population. The objective to study a healthy, elderly population was clearly achieved. Albumin levels ranged from 4.55 to 4.74 g/dL which are within the expected normal range of 3.5 to 5.5 g/dL [33]. This study provides important information regarding the endocrine status of free-living healthy elderly persons during a 1-year period. The data collected will be useful in comparing other elderly populations with nutritional deficiencies or illness. It also provides a baseline from which dietary intervention studies, aimed at increasing GH and IGF-I concentrations in an elderly population, may be performed.
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ACKNOWLEDGMENTS
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Contribution from the Missouri Agricultural Experiment Station. Journal Series Number 12,610. We thank all of the dedicated residents of the Lenoir Retirement Village in Columbia, MO who participated in this study, and the Lenoir Clinic for allowing us to use their facilities. Also we thank Jackie Baker for performing the blood drawing.
Funding provided by the University of Missouri Research Board and Food for the 21st Century Nutrition Cluster.
Received May 1, 1997.
Accepted December 1, 1997.
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