|Year : 2016 | Volume
| Issue : 3 | Page : 92-97
Effect of lysine supplementation on cardiovascular response to stressors of households in two peri-urban communities in Ghana
Frederick Vuvor1, Thomas Ndanu2
1 Department of Nutrition and Food Science, School of Biological Sciences, College of Basic and Applied Sciences, University of Ghana, Legon, Accra, Ghana
2 Department of Community and Preventive Dentistry, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
|Date of Submission||09-May-2016|
|Date of Acceptance||02-Jun-2016|
|Date of Web Publication||2-Nov-2016|
Department of Nutrition and Food Science, School of Biological Sciences, College of Basic and Applied Sciences, University of Ghana, P.O. Box LG 134, Legon, Accra
Source of Support: None, Conflict of Interest: None
Introduction: Lysine affects the level of stress/anxiety, increases resistance to diseases, and prevents protein deficiency disorders. It is the most limiting amino acid that affects protein quality. The main aim was to study the effect of lysine supplementation on stressor of adults in two peri-urban communities in Ghana. Materials and Methods: It was a double-blind, randomized, placebo-controlled trial involving 90 men and 90 women. At the baseline and after intervention, the subjects' blood pressures (BPs) were measured before and after subjecting them to stressor in the form of blood draw. Halves of the men and women were assigned to lysine and the other assigned to placebo as a control. After taken the initial measurements 1,000 g lysine tablets were daily given to the subjects for 112 days to supplement their dietary lysine intake. Results: No significant variation was observed among the subjects at baseline. However, after the supplementation, there were significant drops in the delta of systolic BP by the margin of 7.26 ± 11.64 mmHg in men and 8.50 ± 14.96 mmHg in women. The mean arterial blood pressure also dropped by 1.09 ± 8.22 mmHg in men; but not in women while the delta in the control remains fairly unchanged in both men and women in the control groups. Conclusion: There were positive effects of lysine supplementation on the outcomes of cardiovascular response to stressors by normalizing and reducing the stress of subjects.
Keywords: Lysine, response, stress, stressor, supplementation
|How to cite this article:|
Vuvor F, Ndanu T. Effect of lysine supplementation on cardiovascular response to stressors of households in two peri-urban communities in Ghana. J Health Res Rev 2016;3:92-7
|How to cite this URL:|
Vuvor F, Ndanu T. Effect of lysine supplementation on cardiovascular response to stressors of households in two peri-urban communities in Ghana. J Health Res Rev [serial online] 2016 [cited 2021 Dec 9];3:92-7. Available from: https://www.jhrr.org/text.asp?2016/3/3/92/193184
| Introduction|| |
Lysine is the most limiting amino acid that affects protein quality, especially in cereal-based diets. The risk of lysine inadequacy is mostly found in regions where low socioeconomic classes rely on traditional cereals for their protein source., Many foods supply lysine but the richest sources include meats, fish, and dairy products. Vegetables are poor sources of lysine, with the exception of legumes.
A stressor may be defined as any situation that tends to disturb the equilibrium between a living organism and its environment. Such situations include increased mental or physical activities, or the exposure to such hostile stimuli as trauma, hypoxia, toxin, or disease. Stress (which is the actual response to stressor) results when something real or perceived, causes one to react when under attack of any kind. When stress occurs, the body prepares to take action. This preparation may be termed “fight-or-flight response to fright.” In the fight-or-flight response, levels of many hormones shoot up. Their net effect is to make a lot of stored energy (glucose and fat) available to cells. These cells are prime to help the body get away from the danger or deal with it.
Serotonin receptors are located mainly in the limbic area of the brain that plays a specific pro-stress roles by enhancing stress responses, such as anxiety. Although lysine does not interfere with the metabolism of serotonin, it acts similar to a receptor antagonist of serotonin and suppresses serotonin receptor-mediated anxiety  but does not affect plasma serotonin. Other articles indicated that persistently administered lysine has sedative influences mediated through the benzodiazepine receptors. At the cellular level, lysine deficiency persistently affects the brain content of lysine major monoamine neurotransmitters in the hypothalamus and the amygdala.,,, The monoamine system in the hypothalamus and amygdala participate in regulation of emotional responses to stress. The disruption of monoamine transmission in the amygdala elevates anxiety and leads to aggression and violence. This indicates that lysine deficiency might be associated with an enhancement of stress-induced anxiety. In another physiological pathway, lysine increases gamma-amino butyric acid (GABA) and reduces stress and anxiety. The synthesis of GABA in the body depends on the availability of lysine. Therefore, the more lysine is available, the more production of GABA is facilitated biologically. The granular neurons in the cerebral cortex of the brain are of two types, one functions as excitatory, releasing mainly the excitatory neurotransmitter (glutamate) and other as inhibitory releasing mainly the inhibitory neurotransmitter (GABA). Therefore, it is clear that there is a strong relationship between diets deprived in lysine and high stress/anxiety levels.
Studies have shown that diet inadequacy of lysine leads to nonspecific protein deficiency symptoms. Some of these deficiency disorders are high levels of stress/anxiety and others., In investigational animals study, where protracted dietary lysine insufficiency upsurges stress-induced nervousness, it suggests that if the similar condition is detected in humans, it would have deep-seated implications for mental health., Stress usually leads to psychopathological disorders where the individuals manifest physical symptoms of diseases that have no biological basis., Studies have indicated that fortification of lysine inadequate diet in low socioeconomic groups have reduced anxiety and improved stress related disorders. Recent studies have indicated that lysine decreases anxiety and regularizes stressor-induced hormonal reactions in healthy people with reasonably high observed anxiety., 10, ,, When comparisons were made about food data from different nations, it was established that there are significant reductions in the availability and affordability of animal protein and increase in the dependence on cereals.
Animal and legumes and protein that could supplement the amino acid pattern of cereals are not affordable by low socioeconomic groups., In Ghana, most households consume high levels of cereals, roots, and tubers. Agricultural households, in the peri-urban areas, produce legumes, and animals that could be used for household consumption, but due to the high market prices of these products, most households prefer to sell them and purchase cheaper foods which are cereals, roots, and tubers to feed their households. It has been noted that rates of malnutrition and morbidity are many times greater in peri-urban areas than in urban areas and rural neighborhoods. Clearly peri-urban communities which subsist on cereal and cereal products are not likely to meet their protein needs vis-à-vis lysine requirements. A study has shown that many countries in the ECOWAS region had a high prevalence of lysine deficiencies.
The main aim of this investigation was to study the effects of lysine supplementation on stress of adults in the poor communities in Ghana. An analysis was conducted on 183 countries using food balance sheet data (FAOSTAT, 2004). The results have shown that there is high prevalence of lysine deficiency in most West African countries including Ghana. Any population with dietary lysine levels below 45 mg/g protein indicates a significant proportion of that population would be at risk.
| Materials and Methods|| |
It has been noted that peri-urban areas are often neglected in terms of research and intervention studies and are nutritionally and socioeconomically worse off than either urban or rural areas. The study was conducted as a community-based, double-blind, randomized controlled trial in two peri-urban areas of Ghana involving adults (aged 18–45 years). Sample size determination was done at the household levels (men and women). To observe at least the same difference as observed in the Syrian data, variance in delta blood cortisol and skin conductance response measurements from Syrian data  were used for the sample size calculations. The power and significance were set at 80% and 95%, respectively. From the determination, a minimum of 15 men and 15 women on lysine and the same number on the control (total = 60) were needed for the acceptance of the study results. However, the numbers were increased to 45 men 45 women on lysine and the same number as control (total = 180).
The study protocol was reviewed and approved by Human Ethical Review Board of Noguchi Memorial Institute for Medical Research (FWA 00001824-IRB000176). The purpose of the study and the potential risks involved were explained to each subject. The trial and consent forms were signed by each eligible subject. A total of 90 households were recruited. Upon receiving the filled informed consent from the household heads, eligible households were assigned randomly to lysine or placebo (control) groups. A responsible person, who was not part of the study, organized the randomization list and preserved the code and were opened only after a preliminary analysis has been performed using dummy group names. The intervention (lysine) group was expected to consume 1,000 mg lysine per day in two equally divided doses for 112 days. Exactly 428 households made of a total of 856 individuals were screened for eligibility [Figure 1].
|Figure 1: Trial profile. *Reflects household number of individuals in brackets|
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Based on the calculations, at 41.1 mg lysine/g protein, lysine availability in Ghanaian diets was marginal. [Table 1] shows the additional lysine required to complete the protein quality of the Ghanaian diets. As per [Table 1], an extra amount of 15.2 mg lysine/g protein or 900 mg of lysine per day would adequately supplement the diets. Each subject was supplied two tablets of lysine-HCl (each tablet equivalent to 500 mg lysine per tablet or 500 mg of dicalcium phosphate as a placebo) per day for 112 days. A total of 1000 mg lysine HCl lysine or 1200 mg placebo was supplied each day.
Collection for baseline data included: Dietary assessment involving repeated 24-h dietary recall for three nonconsecutive days for each subject (1 weekend and 2 weekdays) to obtain a representative data on dietary intake according to standard. Dietary intake was only used as a measure of lysine adequacy since blood lysine is not a poor measure of dietary change. Data on health status and clinical assessments including measurements of blood pressures (BP) before and after blood draw were collected. All clinical measurements were repeated after lysine supplementation.
BP of subjects was taken using the Omron Automatic BP Monitor (with Comfit™ Cuff Model HEM-780 made in China for Omron Healthcare Inc., 1200 Lakeside Drive Bannockburn, Illinois 60015, USA © 2006). Measurement of BP (before and after the blood draw) was taken. Blood drawing was validated to be sufficient stressor in human studies., The BP (ante-stress BP) were measured before the blood draw (Stressor) and after (poststress BP) the differences between pre- and post-stress were computed for each adult subjects. The primary outcome measure was the changes in BP before and after the blood draw. This was measured at baseline and after interventions.
Data management was designed using MS Excel 2007 (Microsoft Corp, Redmond, WA, USA) were used for data calculations, Epi-Info 2000 (Centers for Disease Control, Atlanta, GA, USA) and SPSS version 16 (SPSS Inc, Chicago, IL, USA). Paired t-tests were used for comparing baseline and posttest within groups. Different values were computed for both placebo and lysine groups for men and women using independent sample tests. Significance levels were set at 0.05.
| Results|| |
Dietary data collected were broken down into nutrients using Ghanaian Food Composition Tables  and US Department of Agriculture  due to the absence of amino acid information in the Ghanaian Food Composition Table. Lysine and other nutrient intakes were calculated such as energy, carbohydrate, fat, type of protein (tubers, vegetable, legume, animal, roots), levels of utilizable protein based on the Protein Digestibility Corrected Amino Acid Score technique and expressed as amount of utilizable protein intakes in a day and utilizable protein g/kg body weight, lysine, threonine, tryptophan, and sulphur amino acids (mg/day and mg/g protein). Comparisons of all statistics were made to the WHO standards. The risk of protein insufficiency was in mg per kg body weight, and the mean deficit established on intake by gender versus average needs for protein intake and risk of inadequacy. The expected changes in utilization protein, total nitrogen, lysine (mg/kg/day) and the effect on amino acid balance based on the addition of 1000 mg lysine HCl to the baseline diets in a total lysine group. Http://www.convertunits.com/molarmass/Lysine (cited 2010).
Adequacy of nutrients intake was assessed using Food and Agriculture Organization (FAO)/WHO Recommended Dietary Allowance (RDA) and Estimated Average Requirements (EAR) (FAO, 2004). Adequacy of nutrient intake and population prevalence of inadequate intakes were determined using the EAR cut-point method  to assess the nutrients adequacy of subjects. The population prevalence of insufficiency of a nutrient is the proportion of the people with intakes beneath the EAR. Nutrients intakes were compared to the RDAs for the different physiological groups. Protein intakes were broken down by sources namely cereal protein, legume protein, animal protein, protein from fruits and vegetables, protein from roots and tubers, and protein from other plant sources. Energy intakes were broken down into the percentage contributions from the various sources namely carbohydrate, protein, and fats.
Pre- and post-stress BP differences were critically examined. This (poststress BP minus prestress BP) was tested to find out the effect lysine supplementation has on stress. Here, the BPs of adults were measured 5 min before and after blood draw and delta computed at baseline and after lysine supplementation. This part of the study assessed relationships between effect of lysine supplementation and poststress BP variables. Subject's BP was expected to rise due to the stressor imposed on them. An unpaired t-test was employed to compare the lysine-supplemented and the placebo-supplemented adults. The paired t-test was used to compare the delta of baseline and posttest data of all categories (n = 180) individuals: 44 (men and women) in the placebo group and 46 (men and women) in the lysine group [Figure 1].
The results indicated that in both male and female, no significant differences were detected in nutrition or age. [Table 2] shows that at the start of the study, all subjects and conditions were fairly comparable. Examining the differences in habitual dietary intakes by treatment type, no differences in mean were between the two groups. The addition of 1,000 mg lysine caused a reduction in risk of lysine inadequacy and protein inadequacy in all groups [Table 2]. The addition of lysine enhanced the lysine score. This implies that by providing the limiting amino acid, there was improved the level of protein utilizable that is a function of digestible protein and the score of amino acid in the diet [Table 3].
|Table 3: The amino acid balance in comparison to WHO 2007 reference and on the addition of 1000 mg of supplement at baseline|
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Effect of lysine supplementation on cardiovascular response to stressor
Pre- and post-stress changes in BP of subjects after lysine supplementation was presented in [Table 4]. It was observed that lysine-supplemented men and women had significantly lowered their poststress BP and whereas placebo groups remained significantly unchanged.
|Table 4: Comparison of cardiovascular response (delta blood pressure) to stressor of participants|
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| Discussion|| |
The study indicates that energy intake was generally low among study participants with all groups having a mean energy intake below the recommended RDA. In generally, meeting energy requirements is a problem in developing countries. This is supported by the fact that over 300 million people in Africa consume <2100 calories per day on average.
On the contrary, protein intake was found to be quite adequate among study participants. About 70% of subjects met their EAR for proteins, and all age groups had mean intake values above two-thirds of the RDA. This may be attributed to the availability of animal sourced foods, particularly fish, and eggs in the study area. This observation is contrary to the notion that protein deficiency is a major nutritional problem in Ghana. It, however, implies that nutritional problems in the country differ from community to community, and thus intervention programs should be targeted based on findings in each community and not on generalized perceptions. Among women however, a high proportion (47.7%) had inadequate protein intakes (intake less than their EAR). There is also the likelihood that some subject over-reported their intake of protein-rich foods since frequent consumption of such foods including fish, meat, and eggs were seen as an indicator of wealth.
This findings further showed that nearly equal proportions of total protein intakes came from cereals and animal foods. Main animal foods found in the diets of subjects were fishes, although meats and eggs were also present in significant amounts. The high proportion of proteins from cereals may be attributed to the frequent consumption of these foods and their products in the study population. The proportions of proteins contributed by the different food groups have implications on the protein quality. Thus, protein quality among study participants can be said to be quite adequate.
About one-third of men and about a half of women did not meet their lysine needs (mg/kg/day) that were 37% of men and 57% of women were at risk of protein insufficiency at baseline. The first limiting amino acid is lysine. Among subjects, proteins, fats, and carbohydrates contributed approximately 12%, 25%, and 64% respectively of total energy intake. These values are within the recommended ranges and may imply a healthy eating habit among subjects in this study. However, the fact that total energy intakes were lower than recommended implies that this observation should be interpreted with caution. Subjects might increase their daily energy intake but maintain the proportions of the different energy-yielding macronutrients. There was no significant difference between the lysine-supplemented group and those on the placebo for all background characteristics measured.
Using the multivariate linear regression model, it showed that at baseline, there were no significant variations in the change in BP for all groups (P = 0.72). The models were both significant, with postsupplementation tablet type taken and sex of respondent contributing 63% of the change in BP observed. It were substantiated in some studies that the procedure of blood draw has been an acceptable stressor in human studies., The response to stressor is determined by the values indicated by mean change in BP at baseline for both lysine-supplemented men (5.95 ± 8.04 mmHg) and the control (4.05 ± 9.19 mmHg). The same observation was seen in lysine-supplemented women (13.38 ± 14.80 mmHg) and the control (9.54 ± 10.22 mmHg). However, after the intervention the mean BP dropped significantly (−1.32 ± 11.68 mmHg) for lysine-supplemented subjects but not in control. Pre- and post-stress BP difference of subjects after lysine supplementation clearly showed that lysine-supplemented subjects had their poststress BP significantly reduced as compared with the placebo subjects. This study results have shown that lysine could have positive effect on cardiovascular response to stressors of adults significantly (P = 0.018) as well as mean arterial blood pressure (P = 0.036). Thus, dietary lysine status may affect the stress of adults.
The significance of these analyses was that, if the BP taken before stress was lower than after the stress then the difference was due to the stress. If the difference also drops significantly at postlysine-supplementation, it should be due to the lysine supplementation. The values of the response to stressors showed that the techniques of the collection of blood and its expectation was sufficiently stressful since there was significant change in prestress BP and poststress BP found in lysine-supplemented subjects. This observations also confirmed that blood draw is sufficient stressor in human study.
| Conclusion|| |
The study demonstrated positive effects of lysine supplementation on outcomes of cardiovascular response to stressors of subjects. The change in BP clearly indicated that dietary lysine deficiency may induce and or increases anxiety and heighten cardiovascular response to stressors in adults. Apart from the direct effect of lysine on normalizing BP of individuals, it also reduces stress. These study results indicated that lysine may be used to control abnormal responses to stressors/anxiety and prevent stress-induced abnormalities.
Authors express their appreciation to the study participants, Chief/Elders, Nurses, Pharmacy Assistants, Laboratory Technicians, Teaching/Research Assistants from Prof. Matilda Steiner-Asidu, Prof. Firibu Kwesi Saalia, Dr. William Bruce Owusu, Prof. Emmanuel Ohene Afoakwa and Dr. Agartha Ohemeng all of the Department of Nutrition and Food Science, University of Ghana for their kind support of this work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Song S, Hooiveld GJ, Li M, Zhao F, Zhang W, Xu X, et al.
Distinct physiological, plasma amino acid, and liver transcriptome responses to purified dietary beef, chicken, fish, and pork proteins in young rats. Mol Nutr Food Res 2016;60:1199-205.
Pellett PL, Ghosh S. Lysine fortification: Past, present, and future. Food Nutr Bull 2004;25:107-13.
Liu X, Zheng L, Zhang R, Liu G, Xiao S, Qiao X, et al.
Toxicological evaluation of advanced glycation end product Ne-(carboxymethyl) lysine: Acute and subacute oral toxicity studies. Regul Toxicol Pharmacol 2016;77:65-74.
Pakula B, Carpiano RM, Ratner PA, Shoveller JA. Life stress as a mediator and community belonging as a moderator of mood and anxiety disorders and co-occurring disorders with heavy drinking of gay, lesbian, bisexual, and heterosexual Canadians. Soc Psychiatry Psychiatr Epidemiol 2016;51: 1181-92.
Goto K, Kawahara I, Inada H, Misawa H, Kuniyasu H, Nabekura J, et al.
Activation of 5-HT4 receptors facilitates neurogenesis from transplanted neural stem cells in the anastomotic ileum. J Physiol Sci 2016;66:67-76.
Smriga M, Torii K. L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats. Proc Natl Acad Sci U S A 2003;100:15370-5.
Venzi M, David F, Bellet J, Cavaccini A, Bombardi C, Crunelli V, et al.
Role for serotonin2A (5-HT2A) and 2C (5-HT2C) receptors in experimental absence seizures. Neuropharmacology 2016;108:292-304.
Neudegger T, Verghese J, Hayer-Hartl M, Hartl FU, Bracher A. Structure of human heat-shock transcription factor 1 in complex with DNA. Nat Struct Mol Biol 2016;23:140-6.
Smriga M, Murakami H, Mori M, Torii K. Effects of L-lysine deficient diet on the hypothalamic interstitial norepinephrine and diet-induced thermogenesis in rats in vivo
. Biofactors 2000;12:137-42.
Smriga M, Ghosh S, Mouneimne Y, Pellett PL, Scrimshaw NS. Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria. Proc Natl Acad Sci U S A 2004;101:8285-8.
Smriga M, Kameishi M, Uneyama H, Torii K. Dietary L-lysine deficiency increases stress-induced anxiety and fecal excretion in rats. J Nutr 2002;132:3744-6.
Maselko J. Culture, Genes, and Socioemotional Neurodevelopment: Searching for Clues to Common Mental Disorders. The Oxford Handbook of Cultural Neuroscience 2016;355.
Cain C, Sullivan R. Amygdala contributions to fear and safety conditioning: insights into PTSD from an animal model across development. Posttraumatic Stress Disorder: From Neurobiology to Treatment; 2016. p. 81-104.
Davidson J, De Jong RM. The functional central limit theorem and weak convergence to stochastic integrals II. Econ Theory 2000;16:643-66.
Galili G, Tang G, Zhu X, Gakiere B. Lysine catabolism: A stress and development super-regulated metabolic pathway. Current opinion in plant biology 2001;4:261-6.
Kurpad AV, Regan MM, Raj T, Vasudevan J, Kuriyan R, Gnanou J, et al.
Lysine requirements of chronically undernourished adult Indian men, measured by a 24-h indicator amino acid oxidation and balance technique. Am J Clin Nutr 2003;77:101-8.
Ghosh S, Pellett PL, Aw-Hassan A, Mouneime Y, Smriga M, Scrimshaw NS. Impact of lysine-fortified wheat flour on morbidity and immunologic variables among members of rural families in northwest Syria. Food Nutr Bull 2008;29:163-71.
Arellano RO, Sánchez-Gómez MV, Alberdi E, Canedo-Antelo M, Chara JC, Palomino A, et al.
Axon-to-glia interaction regulates GABAA receptor expression in oligodendrocytes. Mol Pharmacol 2016;89:63-74.
Crocker MA. Enteral and parenteral nutrition support of terminally ill patients: Practical and ethical perspectives. Nutrition and Hydration in Hospice Care: Needs, Strategies, Ethics. 1993;9(2-3):107.
Srinongkote S, Smriga M, Nakagawa K, Toride Y. A diet fortified with L-lysine and L-arginine reduces plasma cortisol and blocks anxiogenic response to transportation in pigs. Nutr Neurosci 2003;6:283-9.
Zhao B, Schneid C, Iliev D, Schmidt EM, Wagner V, Wollnik F, et al.
The circadian RNA-binding protein CHLAMY 1 represents a novel type heteromer of RNA recognition motif and lysine homology domain-containing subunits. Eukaryot Cell 2004;3:815-25.
Jezova D. Control of ACTH secretion by excitatory amino acids: Functional significance and clinical implications. Endocrine 2005;28:287-94.
Hussain T, Abbas S, Khan MA, Scrimshaw NS. Lysine fortification of wheat flour improves selected indices of the nutritional status of predominantly cereal-eating families in Pakistan. Food Nutr Bull 2004;25:114-22.
Manary M, Callaghan M, Singh L, Briend A. Protein quality and growth in malnourished children. Food Nutr Bull 2016;37 Suppl 1:S29-36.
Maxwell D, Levin C, Armar-Klemesu M, Ruel M, Morris S, Ahiadeke C. Urban Livelihoods and Food and Nutrition Security in Greater Accra, Ghana. Washington, DC: International Food Policy Research Institute; 2000.
Luscombe-Marsh ND, Hutchison AT, Soenen S, Steinert RE, Clifton PM, Horowitz M, et al.
Plasma free amino acid responses to intraduodenal whey protein, and relationships with insulin, glucagon-like peptide-1 and energy intake in lean healthy men. Nutrients 2016;8. pii: E4.
Eyeson K, Ankrah E. Composition of Foods Commonly Used in Ghana. Unbuplished; 1975.
Guenther PM, Reedy J, Krebs-Smith SM. Development of the healthy eating index-2005. Journal of the American Dietetic Association 2008;108:1896-901.
WHO. Protein and Amino Acid Requirements in Human Nutrition. Geneva: World Health Organization; 2007.
de Lauzon B, Volatier JL, Martin A. A Monte Carlo simulation to validate the EAR cut-point method for assessing the prevalence of nutrient inadequacy at the population level. Public Health Nutr 2004;7:893-900.
Smolin L, Grosvenor M. Energy balance and weight management. Nutrition Science and Application. 4th
ed. London: Wiley; 2003. p. 176-215.
[Table 1], [Table 2], [Table 3], [Table 4]