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Branched-Chain amino acids intake is negatively related to body adiposity in individuals at cardiometabolic risk

Consumo de aminoácidos de cadeia ramificada está negativamente relacionado com adiposidade corporal em indivíduos com risco cardiometabólico

ABSTRACT

Objective

To assess the relationship between branched-chain amino acids intake in the current diet and the metabolic and body adiposity markers in a population at cardiovascular risk.

Methods

This is a cross-sectional study with 282 adults and elderly people from the Cardiovascular Health Care Program of the Universidade Federal de Viçosa. Sociodemographic, anthropometric and body composition data, as well as metabolic biomarkers were collected using standardized protocols. Dietary intake of branched amino acids was assessed using a 24-hour recall.

Results

Individuals with a higher branched-chain amino acids intake (≥2.6g/day, median value) had lower body fat (29.6 vs 32.2%; p=0.019), and higher serum ferritin (113.2 vs. 60.1mg/dL; p=0.006) and uric acid concentrations (4.4 vs. 4.0; p=0.023). In addition, a lower prevalence of overweight and excessive abdominal fat (p<0.05) was found in the individuals with higher branched-chain amino acids intake. They also had a higher daily intake of fiber, copper, zinc, magnesium, and iron, as well as a lower intake of total lipids.

Conclusion

In the present study, the intake of branched amino acids is negatively related to total and central adiposity, but more studies are needed to fully elucidate this possible relationship. (Brazilian Registry of Clinical Trials, code RBR-5n4y2g).

Keywords
Cardiovascular diseases; Feeding behavior; Isoleucine; Leucine; Overweight; Valine

RESUMO

Objetivo

Avaliar a relação entre o consumo de aminoácidos de cadeia ramificada na dieta atual e os marcadores de adiposidade metabólica e corporal em uma população com perfil de elevado risco cardiovascular.

Métodos

Trata-se de um estudo transversal com 282 adultos e idosos do Programa de Atenção Cardiovascular da Universidade Federal de Viçosa. Dados sociodemográficos, antropométricos e de composição corporal, além de biomarcadores metabólicos, foram coletados utilizando protocolos padronizados. O consumo alimentar de aminoácidos ramificados foi avaliado através de um recordatório de 24 horas.

Resultados

Indivíduos com maior consumo de aminoácidos de cadeia ramificada (≥2,6g/dia, valor da mediana) apresentaram menores valores de gordura corporal (29,6 vs 32,2%; p=0,019) e maiores valores de séricos de ferritina (113,2 vs. 60,1mg/dL; p=0,006) e ácido úrico (4,4 vs. 4,0; p=0,023). Além disso, foi encontrada uma menor prevalência de sobrepeso e excesso de gordura abdominal (p<0,05) nos indivíduos com maior consumo de aminoácidos de cadeia ramificada. Eles também apresentaram um maior consumo diário de fibra, cobre, zinco, magnésio e ferro, além de um menor consumo de lipídios totais.

Conclusão

No presente estudo, o consumo de aminoácidos ramificados está negativamente relacionado à adiposidade total e central, porém mais estudos são necessários para elucidar completamente essa possível relação. (Registro Brasileiro de Ensaios Clínicos, código RBR-5n4y2g)

Palavras-chave
Doenças cardiovasculares; Comportamento alimentar; Isoleucina; Leucina; Sobrepeso; Valina

INTRODUCTION

Excess weight is the main risk factor for the development of Cardiovascular Diseases (CVD), being one of the biggest public health problems worldwide. It should be noted that eating habits are an important modifiable risk factor for such changes [11 Ruiz-Canela M, Toledo E, Clish CB, Hruby A, Liang L, Salas-Salvadó J, et al. Plasma branched-chain amino acids and incident cardiovascular disease in the PREDIMED trial. Clin Chem. 2016;62(4):582.

2 Dégano IR, Marrugat J, Grau M, Salvador-González B, Ramos R, Zamora A, et al. The association between education and cardiovascular disease incidence is mediated by hypertension, diabetes, and body mass index. Sci Rep. 2017;7(1):12370.

3 Zhao X, Han Q, Liu Y, Sun C, Gang X, Wang G. The Relationship between branched-chain amino acid related metabolomic signature and insulin resistance: a systematic review. J Diabetes Res. 2016:2794591.

4 Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, et al. Restoration of metabolic health by decreased consumption of branched-chain amino acids. J Physiol. 2018;596(4):623-45.
-55 Zheng Y, Ceglarek U, Huang T, Li L, Rood J, Ryan DH, et al. Weight-loss diets and 2-y changes in circulating amino acids in 2 randomized intervention trials. Am J Clin Nutr. 2016;103(2):505-11.].

In this context, dietary Branched-Chain Amino Acids (BCAA), such as leucine, isoleucine, and valine, are essential for a healthy cellular and organ function [11 Ruiz-Canela M, Toledo E, Clish CB, Hruby A, Liang L, Salas-Salvadó J, et al. Plasma branched-chain amino acids and incident cardiovascular disease in the PREDIMED trial. Clin Chem. 2016;62(4):582.,66 Siomkajlo M, Rybka J, Mierzchala-Pasierb M, Gamian A, Stankiewicz-Olczyk J, Bolanowski M, et al. Specific plasma amino acid disturbances associated with metabolic syndrome. Endocrine. 2017;58(3):553-62.

7 Rousseau M, Guénard F, Garneau V, Allam-Ndoul B, Lemieux S, Pérusse L, et al. Associations between dietary protein sources, plasma BCAA and short-chain acylcarnitine levels in adults. Nutrients. 2019;11(1):173.

8 Green CR, Wallace M, Divakaruni AS, Phillips SA, Murphy AN, Ciaraldi TP, et al. Branched chain amino acid catabolism fuels adipocyte differentiation and lipogenesis. Nat Chem Biol. 2016;12(1):15-21.
-99 Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol. 2014;10(12):723-36.]. The impact of BCAA intake on cardiometabolic risk factors, such as overweight and body fat, has been investigated in previous studies [1010 Cocate PG, Natali AJ, Oliveira A, Alfenas RC, Hermsdorff HH. Consumption of branched-chain amino acids is inversely associated with central obesity and cardiometabolic features in a population of Brazilian middle-aged men: potential role of leucine intake. J Nutr Health Aging. 2015;19(7):771.

11 Giglio BM, Schincaglia RM, Silva AS, Fazani ICS, Monteiro PA, Mota JF, et al. Whey protein supplementation compared to collagen increases blood nesfatin concentrations and decreases android fat in overweight women: a randomized double-blind study. Nutrients. 2019; 11(9):pii:E2051. https://doi.org/10.3390/nu11092051
https://doi.org/10.3390/nu11092051...
-1212 Novin ZS, Ghavamzadeh S, Mehdizadeh A. The weight loss effects of branched chain amino acids and vitamin B6: a randomized controlled trial on obese and overweight women. Int J Vitam Nutr Res. 2018;88(1-2):80-9.].

A recent meta-analysis [1313 Okekunle AP, Zhang M, Wang Z, Onwuka JU, Wu X, Feng R, et al. Dietary branched-chain amino acids intake exhibited a different relationship with type 2 diabetes and obesity risk: a meta-analysis. Acta Diabetol. 2019;56(2):187-95.] reported that a higher dietary intake of BCAA was inversely related to the prevalence of overweight and obesity in adults. The possible mechanisms for the effect of BCAA on body weight are still poorly understood, however it is known that BCAA, especially leucine, can act in ways to control cellular metabolism, providing a decrease in food intake and body weight [1414 Li YC, Li Y, Liu LY, Chen Y, Zi TQ, Du SS, et al. The ratio of dietary branched-chain amino acids is associated with a lower prevalence of obesity in young Northern Chinese adults: an internet-based cross-sectional study. Nutrients. 2015;7(11):9573-89.

15 Qin LQ, Xun P, Bujnowski D, Daviglus ML, Horn LV, Stamler J, et al. Higher branched-chain amino acid intake is associated with a lower prevalence of being overweight or obese in middle-aged East Asian and Western adults. J Nutr. 2011;141(2):249-54.
-1616 Okekunle AP, Li Y, Liu L, Du S, Wu X, Chen Y, et al. Abnormal circulating amino acid profiles in multiple metabolic disorders. Diabetes Res Clin Pract. 2017;132:45-58.]. However, few studies have assessed BCAA intake, especially in the Brazilian population and, to date, few studies have assessed the relationship of these nutrients with metabolic and adiposity markers in a population at cardiovascular risk [1010 Cocate PG, Natali AJ, Oliveira A, Alfenas RC, Hermsdorff HH. Consumption of branched-chain amino acids is inversely associated with central obesity and cardiometabolic features in a population of Brazilian middle-aged men: potential role of leucine intake. J Nutr Health Aging. 2015;19(7):771.]. Therefore, the aim of this article is to assess the relationship between BCAA intake, included in the current diet, and metabolic and adiposity biomarkers in a population at cardiovascular risk.

METHODS

A cross-sectional study with 282 patients included in the Programa de Atenção à Saúde Cardiovascular da Universidade Federal de Viçosa (PROCARDIO-UFV, Cardiovascular Health Care Program of the Universidade Federal de Viçosa), who had their first medical appointment until July 2016, with complete data concerning their BCAA intake. The PROCARDIO-UFV performs nutritional intervention to promote cardiovascular health in the academic community of the Universidade Federal de Viçosa (UFV), registered in the Registro Brasileiro de Ensaios Clínicos (ReBEC, Brazilian Registry of Clinical Trials), code RBR-5n4y2g [1717 Ministério da Saúde (Brasil). Registro Brasileiro de Ensaios Clínicos. Brasília: Ministério; 2013 [citado 2 fev 2017]. Disponível em: http://www.ensaiosclinicos.gov.br/rg/RBR-5n4y2g/.
http://www.ensaiosclinicos.gov.br/rg/RBR...
].

The criteria for inclusion in the program are: age =20 years; both sexes; being a student, worker, or a dependent family member of UFV workers; present cardiovascular diseases or the occurrence of cardiometabolic risk factors such as overweight or obesity (Body Mass Index (BMI) =25 or 27kg/m2) or/and dyslipidemia (Triglycerides (TG) =150mg/dL; Total Cholesterol (TC) = 200 mg/dL or/and High Density Lipoprotein (HDL-c) <40 or <50mg/dL for men and women, respectively), or/and blood pressure =130/=85mmHg or diagnosed arterial hypertension or/and fasting blood glucose =100mg/dL or diagnosed diabetes mellitus. The data used were related to the first medical consultation at the PROCARDIO-UFV. Among the 417 users of the program, 282 were selected for having complete data on their BCAA intake.

The study was approved by the UFV’s Human Research Ethics Committee (Protocol number 066/2012/CEPH), in accordance with Resolution 466/2012 of the Conselho Nacional de Saúde (CNS, National Health Council/Ministry of Health, Brazil) and with the principles of the Helsinki Declaration. All study participants read and signed the informed consent form.

The participants responded to a 24-hour food recall (R24h), reporting all the food and drinks consumed the day before (weekday or weekend) the medical consultation, as well as their quantities. In the present study, the daily intake of calories, carbohydrates, proteins, lipids, fibers, vitamins A, C, D and E, selenium, copper, manganese, magnesium, zinc, calcium, iron, and sodium were assessed using the DietPRO software, version 5.0i [1818 Dietpro. Dietpro: soluções em Nutrição. Viçosa: Dietpro; 2019.].

The determination of BCAA intake (leucine, isoleucine, and valine) was performed using the National Nutrient Database for Standard Reference (USDA, 2015), as such data are not available in the Brazilian tables [1919 Department of Agriculture (United States). FoodData Central. Washington: Department; 2016 [cited 2016 Aug 8]. Available from: https://fdc.nal.usda.gov/
https://fdc.nal.usda.gov/...
]. The foods reported in the R24h and not listed in the USDA table had their estimated composition considering the foods that showed nutritional composition and similar cooking methods. The preparations were broken down into their constituent ingredients and, if there was no choice of composition for the prepared food, the composition of the raw foods was used. The intake of each amino acid was performed in an electronic spreadsheet (Microsoft Excel®), developed especially for this purpose.

Anthropometric measurements (body weight, height, hip, and waist circumference) were measured using a standardized, previously established protocol [2020 Silva HA, Carraro JCC, Bressan J, Hermsdorff HHM. Relação entre ácido úrico e síndrome metabólica em uma população com risco cardiometabólico. Einstein (Sao Paulo). 2015;13(2):202-8.]. Waist-to-Hip (WHR) and Waist-to-Height (WHtR) ratios were calculated. Total Body Fat (BF%) was assessed by tetrapolar electrical bioimpedance (Biodynamics 310 model, Washington, USA), according to the manufacturer’s protocol. Excess weight was classified according to a BMI greater than or equal to 25 (adults) and 27 (elderly) kg/m2 [2121 World Health Organization. Obesity: preventing and managing the global epidemic: report of a World Health Organization Consultation. Geneva: Organization; 2000(284):256.,2222 Lipschitz DA. Screening for nutritional status in the elderly. Prim Care. 1994;21:55-67.]. Excess abdominal fat was assessed using waist circumference values equal to or greater than 80 cm and 90 cm for women and men, respectively [2323 Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640-5.].

Fasting blood glucose, triglycerides, total and fraction cholesterol (Low Density Lipoprotein [LDL-c], High Density Lipoprotein [HDL-c], and Very Low Density Lipoprotein [VLDL-c>]), ferritin, uric acid, total leukocytes, and Ultrasensitive C-Reactive Protein (Us-CRP) were determined at the Clinical Analysis Laboratory of the Health Department of the UFV, according to its standardized protocol.

Insulin resistance was estimated using the Homeostasis-Insulin Resistance Model (HOMA-IR), calculated as follows: HOMA-IR=[fasting glucose (mmol/L)] fasting insulin (µUI/ml)]/22.5 and the triglycerides/glycemia (TyG) index, calculated using the formula: Ln [fasting triglycerides (mg/dl)×fasting glycemia (mg/dL)/2] [2424 Mohammadabadi F, Vafaiyan Z, Hosseini SM, Aryaie M, Eshghinia S. Assessment of insulin resistance with two methods: HOMA-IR and TyG index in Iranian obese women. Iran J Diabetes Obes. 2014;6(1):23-7.].

The age, sex, educational level, relationship to the UFV, income, smoking, regular practice of physical activities, and intake of alcoholic beverages variables were collected by interviewing participants through a questionnaire.

The results were presented in absolute and relative frequencies, mean±standard deviation, and/or median (25th-75th percentile). The normality of each variable was assessed using the Kolmogorov-Smirnov test. To assess the possible association of BCAA intake and other variables of interest, the sample of the present study was categorized according to the median BCAA intake (2.6g/day). The use of the median as a cut-off point for statistical analysis has been used before [2525 Carraro JC, Hermsdorff HH, Mansego ML, Zulet MÁ, Milagro FI, Bressan J, et al. Higher fruit intake is related to TNF-? hypomethylation and better glucose tolerance in healthy subjects. J Nutrigenet Nutrigenomics. 2016;9(2-4):95-105.,2626 Santos Epifânio AP, Balbino KP, Jorge MP, Ribeiro SMR, Moreira AVB, Oliveira JM, et al. Metabolic, inflammatory and oxidative stress markers in the nitric oxide variation of hemodialysis subjects. Nutr Hosp. 2018;10;35(1):176-84.]. All food intake variables were adjusted for total caloric intake using the residual method [2727 Willett W. Overview of nutritional epidemiology. In: Willett W. Nutritional epidemiology. 2nd. ed. New York: Oxford University Press; 1998:514.].

The Student t and Mann-Whitney-U tests were used to compare the two groups, when appropriate. Pearson’s Chi-square, linear trend chi-square or Fischer’s exact test were used when appropriate to verify associations between sociodemographic and body composition variables, and the median BCAA intake. Spearman’s correlation was used to assess the relationship between BCAA intake and other nutrients with variables of interest. All statistical analyses were performed using the SSPS 21.0® program, considering the level of statistical significance as 5%.

RESULTS

Of the individuals who had a higher BCAA intake (=2.6g/day), 28.4% (n=40) were male, 28.2% (n=40) were employees of the university, and 75.9% (n=107) were not smokers (Table 1). Regarding food intake, those with a BCAA intake =2.6g/day had a higher intake of fibers, copper, zinc, magnesium, and iron (Table 2).

Table 1
Sociodemographic characteristics, according to the Branched-Chain Amino Acids intake (median value).
Table 2
Current dietary habits according to the branched-chain amino acids intake (median value).

Individuals with the highest BCAA intake (=2.6g/day) had higher concentrations of ferritin and uric acid, in addition to lower body fat and HDL-c values (Table 3).

Table 3
Adiposity indicators and cardiometabolic risk markers, according to branched-chain amino acids intake (median value).

Moreover, there was a higher prevalence of overweight and excessive abdominal fat in individuals with a lower BCAA intake (Figure 1). In addition, BCAA intake was negatively correlated with body fat (Figure 2).

Figure 1
.Prevalence of overweight (BMI>25 and 27kg/m2 for adults and elderly individuals) and excess abdominal fat (Waist circumference =80 and 90cm for women and men, respectively), according to the branched amino acids intake (median: 2.6 g/day). p-values according to the Chi-Square test.
Figure 2
Spearman’s correlation between the branched amino acids intake and total body fat (%) in individuals at cardiometabolic risk (n=206).

DISCUSSION

Amino acids can play an important role in the development of CVD [1010 Cocate PG, Natali AJ, Oliveira A, Alfenas RC, Hermsdorff HH. Consumption of branched-chain amino acids is inversely associated with central obesity and cardiometabolic features in a population of Brazilian middle-aged men: potential role of leucine intake. J Nutr Health Aging. 2015;19(7):771.,2828 Shin AC, Fasshauer M, Filatova N, Grundell LA, Zielinski E, Zhou JY, et al. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. Cell Metab. 2014;20(5):898-909.

29 Du X, You H, Li Y, Wang Y, Hui P, Qiao B, et al. Relationships between circulating branched chain amino acid concentrations and risk of adverse cardiovascular events in patients with STEMI treated with PCI. Sci Rep. 2018;8:15809.

30 Prodhan UK, Milan AM, Thorstensen EB, Barnett MPG, Stewart RAH, Benatar JR, et al. Altered dairy protein intake does not alter circulatory branched chain amino acids in healthy adults: a randomized controlled trial. Nutrients. 2018;10(10):1510.

31 Zheng Y, Li Y, Qi Q, Hruby A, Manson JE, Willett WC, et al. Cumulative consumption of branched-chain amino acids and incidence of type 2 diabetes. Int J Epidemiol. 2016;45(5):1482-92.

32 Mangge H, Zelzer S, Prüller F, Schnedl WJ, Weghuber D, Enko D, et al. Branched-chain amino acids are associated with cardiometabolic risk profiles found already in lean, overweight and obese young. J Nutr Biochem. 2016;32:123-7.

33 Grajeda-Iglesias C, Aviram M. Specific amino acids affect cardiovascular diseases and atherogenesis via protection against macrophage foam cell formation: review article. Rambam Maimonides Med J. 2018;9(3):e0022. https://doi.org/10.5041/RMMJ.10337
https://doi.org/10.5041/RMMJ.10337...

34 Palmer ND, Okut H, Hsu FC, Ng MCY, Chen YDI, Goodarzi MO, et al. Metabolomics identifies distinctive metabolite signatures for measures of glucose homeostasis: the Insulin Resistance Atherosclerosis Family Study (IRAS-FS). J Clin Endocrinol Metab. 2018;103(5):1877-88.
-3535 Tobias DK, Lawler PR, Harada PH, Demler OV, Ridker PM, Manson JE, et al. Circulating branched-chain amino acids and incident cardiovascular disease in a prospective cohort of US women. Circ Genom Precis Med. 2018;11(4):e002157. https://doi.org/10.1161/CIRCGEN.118.002157.
https://doi.org/10.1161/CIRCGEN.118.0021...
]. This relationship can be justified by the food source of these nutrients (legumes, oilseeds, eggs, fish, meat, milk, and dairy products). In fact, the cardiometabolic effects related to animal protein food sources are probably better explained by the non-protein components than by the protein components of these foods [3636 Merz B, Frommherz L, Rist MJ, Kulling SE, Bub A, Watzl B. Dietary pattern and plasma BCAA-variations in healthy men and women: results from the KarMeN Study. Nutrients. 2018;10(5):623.

37 Briggs MA, Petersen KS, Kris-Etherton PM. Saturated fatty acids and cardiovascular disease: replacements for saturated fat to reduce cardiovascular risk. Healthcare. 2017;5(2):29.
-3838 Haring B, Gronroos N, Nettleton JA, von Ballmoos MCW, Selvin E, et al. Dietary protein intake and coronary heart disease in a large community based cohort: results from the Atherosclerosis Risk in Communities (ARIC) Study. Plos One. 2014;9(10):e109552. https://doi.org/10.1371/journal.pone.0109552
https://doi.org/10.1371/journal.pone.010...
].

The first relevant result of this study was the higher body fat (%) in those individuals with a lower BCAA intake. Other results also were towards the inverse relationship between BCAA intake and body adiposity, as well as the results of other cross-sectional studies, carried out in Brazil, China, Japan, the United Kingdom and the United States [1010 Cocate PG, Natali AJ, Oliveira A, Alfenas RC, Hermsdorff HH. Consumption of branched-chain amino acids is inversely associated with central obesity and cardiometabolic features in a population of Brazilian middle-aged men: potential role of leucine intake. J Nutr Health Aging. 2015;19(7):771.,1414 Li YC, Li Y, Liu LY, Chen Y, Zi TQ, Du SS, et al. The ratio of dietary branched-chain amino acids is associated with a lower prevalence of obesity in young Northern Chinese adults: an internet-based cross-sectional study. Nutrients. 2015;7(11):9573-89.,1515 Qin LQ, Xun P, Bujnowski D, Daviglus ML, Horn LV, Stamler J, et al. Higher branched-chain amino acid intake is associated with a lower prevalence of being overweight or obese in middle-aged East Asian and Western adults. J Nutr. 2011;141(2):249-54.,3939 Jennings A, MacGregor A, Pallister T, Spector T, Cassidy A. Associations between branched chain amino acid intake and biomarkers of adiposity and cardiometabolic health independent of genetic factors: a twin study. Int J Cardiol. 2016;223:992-8.]. Probably, leucine is the most influential BCAA regarding energy balance [4040 McAllan L, Cotter PD, Roche HM, Korpela R, Nilaweera KN. Impact of leucine on energy balance. J Physiol Biochem. 2013;69(1):155-63.]. When these amino acids are released into the gastrointestinal tract after the hydrolysis of dietary proteins, the production of anorexigenic hormones is stimulated and thus the production of orexigenic hormone is inhibited. In addition, leucine induces the activation of the pro-opiomelanocortin, hypothalamic neuropeptide, as well as negatively regulating neuropeptide Y signaling.

In the central nervous system, these signals can affect food intake, increasing satiation and satiety. Also, leucine can act directly on adipocyte, liver, and muscle cells, influencing the expression of fatty acid synthase (adipocytes) and lipid catabolism (adipocytes, liver and muscle cells), favoring, subsequently, the reduction of adiposity [4040 McAllan L, Cotter PD, Roche HM, Korpela R, Nilaweera KN. Impact of leucine on energy balance. J Physiol Biochem. 2013;69(1):155-63.]. Leucine is also a potent activator of mTOR, a serine/threonine kinase involved in many cellular processes, which includes protein synthesis and cell growth. Central leucine administration can increase hypothalamic mTOR signaling and decrease food intake and body weight [1414 Li YC, Li Y, Liu LY, Chen Y, Zi TQ, Du SS, et al. The ratio of dietary branched-chain amino acids is associated with a lower prevalence of obesity in young Northern Chinese adults: an internet-based cross-sectional study. Nutrients. 2015;7(11):9573-89.]. Another possible mechanism for the effect of BCAA on body weight is the improvement of glucose tolerance, since impaired glucose tolerance may be related as one of the possible causes of obesity [1515 Qin LQ, Xun P, Bujnowski D, Daviglus ML, Horn LV, Stamler J, et al. Higher branched-chain amino acid intake is associated with a lower prevalence of being overweight or obese in middle-aged East Asian and Western adults. J Nutr. 2011;141(2):249-54.].

As shown in Table 2, individuals with a higher BCAA intake also had a higher intake of fibers and minerals (iron, copper, zinc, and magnesium) (p<0.05), as well as a lower intake of total fats (p<0.05). We also observed a negative correlation between the percentage of body fat and the current intake of fibers, iron, zinc, and copper (r=-0.16 and p=0.02; r=-0.206 and p=0.003; r=-0,16 and p=0.03; r=-0.16 and p=0.02, respectively). Therefore, the lower body fat in these individuals with a higher BCAA intake may also be related to a better quality of food in general.

Still, in the present study, serum ferritin and uric acid concentrations were significantly higher in the individuals with higher BCAA intake. However, these concentrations, even though higher, are still within normal values. They do not represent an increase in the cardiometabolic risk for these individuals [2020 Silva HA, Carraro JCC, Bressan J, Hermsdorff HHM. Relação entre ácido úrico e síndrome metabólica em uma população com risco cardiometabólico. Einstein (Sao Paulo). 2015;13(2):202-8.,4141 Klip IT, Voors AA, Swinkels DW, Bakker SJ, Kootstra-Ros JE, Lam CS, et al. Serum ferritin and risk for new-onset heart failure and cardiovascular events in the community. Eur J Heart Fail. 2017;19(3):348-56.,4242 Zacharski LR, Shamayeva G, Chow BK, DePalma RG. Ferritin and percent transferrin saturation levels predict type 2 diabetes risk and cardiovascular disease outcomes. Curr Diabetes Rev. 2017;13(4):428-36.].

In addition, HDL-c concentrations were lower in those individuals with higher BCAA intake. The opposite result was observed in the study by Cocate et al., in which HDL-c concentrations were higher in the third tertile, when compared to the first tertile of BCAA intake [1010 Cocate PG, Natali AJ, Oliveira A, Alfenas RC, Hermsdorff HH. Consumption of branched-chain amino acids is inversely associated with central obesity and cardiometabolic features in a population of Brazilian middle-aged men: potential role of leucine intake. J Nutr Health Aging. 2015;19(7):771.]. BCAA can act as signaling molecules to control energy homeostasis involving the disposition of glucose and lipid metabolism. Any changes in their intake could also lead to changes in the lipid profile [11 Ruiz-Canela M, Toledo E, Clish CB, Hruby A, Liang L, Salas-Salvadó J, et al. Plasma branched-chain amino acids and incident cardiovascular disease in the PREDIMED trial. Clin Chem. 2016;62(4):582.,4343 Yang P, Hu W, Fu Z, Sun L, Zhou Y, Gong Y, et al. The positive association of branched-chain amino acids and metabolic dyslipidemia in Chinese Han population. Lipids Health Dis. 2016;15:120.], but additional studies that assess this relationship are necessary.

The present study has some limitations. First, its cross-sectional design makes impossible to infer about a cause-effect relationship in the results presented. However, the authors used the statistical tests that are suitable for this type of study and performed the interpretations of the results with scientific relevance. Another factor is the use of only a 24-hour recall, as it provides information only about the individual’s current and unusual intake. However, this food survey has been used in epidemiological studies that evaluated the relation between food intake and cardiometabolic risk factors with promising results and acceptance by the scientific community [4444 Silveira BKS, Novaes JFN, Reis NA, Lourenço LP, Capobiango AHM, Leal ACG, et al. Sociodemographic and lifestyle factors are associated with diet quality in cardiometabolic risk subjects. J Food Nutr Res. 2019;7(2):141-7.

45 Meneguelli TS, Hinkelmann JV, Novaes JF, Rosa COB, Filgueiras MS, Silveira BKS, et al. Dietary inflammatory index is associated with excessive body weight and dietary patterns in subjects with cardiometabolic risk. J Food Nutr Res. 2019;7(7):491-9.

46 Almeida AP, Rocha DMUP, Moreira AVB, Lima HCFM, Hermsdorff HH. Personalized nutrition using PROCARDIO to reduce cardiometabolic risk in the academic community: a study protocol with preliminary results. J Am Coll Nutr. 2020;1-10.
-4747 Silva JT, Bersch-Ferreira ÂC, Torreglosa CR, Weber B, Levy RB. Development of a dietary index based on the Brazilian cardioprotective nutritional program (BALANCE). Nutr J. 2018;17(1):49.].

CONCLUSION

The results of the present study indicate that a higher BCAA intake (>2.6g/day) has an inverse association with excess weight and body fat, in addition to a positive association with biomarkers (ferritin and uric acid) in individuals at cardiometabolic risk. Further studies are needed to assess the relationship between BCAA intake and chronic diseases.

ACKNOWLEDGMENTS

To the Programa de Atenção à Saúde Cardiovascular da Universidade Federal de Viçosa (PROCARDIO-UFV, Cardiovascular Health Care Program of the Universidade Federal de Viçosa) patients, for their participation in this study, and for the professionals for the excellent support they provided. HHM Hermsdorff has a Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, National Council for Scientific and Technological Development) Research Productivity fellowship (1D-level).

  • Support: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, National Council for Scientific and Technological Development) (Process number 408279/2017-6) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes, Coordination for Higher Education Staff Development) (Code 001).

How to cite this article

  • Almeida AP, Fortes FS, Silveira BKS, Reis NA, Hermsdorff HHM. Branched-Chain amino acids intake is negatively related to body adiposity in individuals at cardiometabolic risk. Rev Nutr. 2020;33:e190208. https://doi.org/10.1590/1678-9865202033e190208

REFERENCES

  • 1
    Ruiz-Canela M, Toledo E, Clish CB, Hruby A, Liang L, Salas-Salvadó J, et al Plasma branched-chain amino acids and incident cardiovascular disease in the PREDIMED trial. Clin Chem. 2016;62(4):582.
  • 2
    Dégano IR, Marrugat J, Grau M, Salvador-González B, Ramos R, Zamora A, et al The association between education and cardiovascular disease incidence is mediated by hypertension, diabetes, and body mass index. Sci Rep. 2017;7(1):12370.
  • 3
    Zhao X, Han Q, Liu Y, Sun C, Gang X, Wang G. The Relationship between branched-chain amino acid related metabolomic signature and insulin resistance: a systematic review. J Diabetes Res. 2016:2794591.
  • 4
    Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, et al Restoration of metabolic health by decreased consumption of branched-chain amino acids. J Physiol. 2018;596(4):623-45.
  • 5
    Zheng Y, Ceglarek U, Huang T, Li L, Rood J, Ryan DH, et al Weight-loss diets and 2-y changes in circulating amino acids in 2 randomized intervention trials. Am J Clin Nutr. 2016;103(2):505-11.
  • 6
    Siomkajlo M, Rybka J, Mierzchala-Pasierb M, Gamian A, Stankiewicz-Olczyk J, Bolanowski M, et al Specific plasma amino acid disturbances associated with metabolic syndrome. Endocrine. 2017;58(3):553-62.
  • 7
    Rousseau M, Guénard F, Garneau V, Allam-Ndoul B, Lemieux S, Pérusse L, et al Associations between dietary protein sources, plasma BCAA and short-chain acylcarnitine levels in adults. Nutrients. 2019;11(1):173.
  • 8
    Green CR, Wallace M, Divakaruni AS, Phillips SA, Murphy AN, Ciaraldi TP, et al Branched chain amino acid catabolism fuels adipocyte differentiation and lipogenesis. Nat Chem Biol. 2016;12(1):15-21.
  • 9
    Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol. 2014;10(12):723-36.
  • 10
    Cocate PG, Natali AJ, Oliveira A, Alfenas RC, Hermsdorff HH. Consumption of branched-chain amino acids is inversely associated with central obesity and cardiometabolic features in a population of Brazilian middle-aged men: potential role of leucine intake. J Nutr Health Aging. 2015;19(7):771.
  • 11
    Giglio BM, Schincaglia RM, Silva AS, Fazani ICS, Monteiro PA, Mota JF, et al Whey protein supplementation compared to collagen increases blood nesfatin concentrations and decreases android fat in overweight women: a randomized double-blind study. Nutrients. 2019; 11(9):pii:E2051. https://doi.org/10.3390/nu11092051
    » https://doi.org/10.3390/nu11092051
  • 12
    Novin ZS, Ghavamzadeh S, Mehdizadeh A. The weight loss effects of branched chain amino acids and vitamin B6: a randomized controlled trial on obese and overweight women. Int J Vitam Nutr Res. 2018;88(1-2):80-9.
  • 13
    Okekunle AP, Zhang M, Wang Z, Onwuka JU, Wu X, Feng R, et al Dietary branched-chain amino acids intake exhibited a different relationship with type 2 diabetes and obesity risk: a meta-analysis. Acta Diabetol. 2019;56(2):187-95.
  • 14
    Li YC, Li Y, Liu LY, Chen Y, Zi TQ, Du SS, et al The ratio of dietary branched-chain amino acids is associated with a lower prevalence of obesity in young Northern Chinese adults: an internet-based cross-sectional study. Nutrients. 2015;7(11):9573-89.
  • 15
    Qin LQ, Xun P, Bujnowski D, Daviglus ML, Horn LV, Stamler J, et al Higher branched-chain amino acid intake is associated with a lower prevalence of being overweight or obese in middle-aged East Asian and Western adults. J Nutr. 2011;141(2):249-54.
  • 16
    Okekunle AP, Li Y, Liu L, Du S, Wu X, Chen Y, et al Abnormal circulating amino acid profiles in multiple metabolic disorders. Diabetes Res Clin Pract. 2017;132:45-58.
  • 17
    Ministério da Saúde (Brasil). Registro Brasileiro de Ensaios Clínicos. Brasília: Ministério; 2013 [citado 2 fev 2017]. Disponível em: http://www.ensaiosclinicos.gov.br/rg/RBR-5n4y2g/
    » http://www.ensaiosclinicos.gov.br/rg/RBR-5n4y2g/
  • 18
    Dietpro. Dietpro: soluções em Nutrição. Viçosa: Dietpro; 2019.
  • 19
    Department of Agriculture (United States). FoodData Central. Washington: Department; 2016 [cited 2016 Aug 8]. Available from: https://fdc.nal.usda.gov/
    » https://fdc.nal.usda.gov/
  • 20
    Silva HA, Carraro JCC, Bressan J, Hermsdorff HHM. Relação entre ácido úrico e síndrome metabólica em uma população com risco cardiometabólico. Einstein (Sao Paulo). 2015;13(2):202-8.
  • 21
    World Health Organization. Obesity: preventing and managing the global epidemic: report of a World Health Organization Consultation. Geneva: Organization; 2000(284):256.
  • 22
    Lipschitz DA. Screening for nutritional status in the elderly. Prim Care. 1994;21:55-67.
  • 23
    Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640-5.
  • 24
    Mohammadabadi F, Vafaiyan Z, Hosseini SM, Aryaie M, Eshghinia S. Assessment of insulin resistance with two methods: HOMA-IR and TyG index in Iranian obese women. Iran J Diabetes Obes. 2014;6(1):23-7.
  • 25
    Carraro JC, Hermsdorff HH, Mansego ML, Zulet MÁ, Milagro FI, Bressan J, et al Higher fruit intake is related to TNF-? hypomethylation and better glucose tolerance in healthy subjects. J Nutrigenet Nutrigenomics. 2016;9(2-4):95-105.
  • 26
    Santos Epifânio AP, Balbino KP, Jorge MP, Ribeiro SMR, Moreira AVB, Oliveira JM, et al Metabolic, inflammatory and oxidative stress markers in the nitric oxide variation of hemodialysis subjects. Nutr Hosp. 2018;10;35(1):176-84.
  • 27
    Willett W. Overview of nutritional epidemiology. In: Willett W. Nutritional epidemiology. 2nd. ed. New York: Oxford University Press; 1998:514.
  • 28
    Shin AC, Fasshauer M, Filatova N, Grundell LA, Zielinski E, Zhou JY, et al Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. Cell Metab. 2014;20(5):898-909.
  • 29
    Du X, You H, Li Y, Wang Y, Hui P, Qiao B, et al Relationships between circulating branched chain amino acid concentrations and risk of adverse cardiovascular events in patients with STEMI treated with PCI. Sci Rep. 2018;8:15809.
  • 30
    Prodhan UK, Milan AM, Thorstensen EB, Barnett MPG, Stewart RAH, Benatar JR, et al Altered dairy protein intake does not alter circulatory branched chain amino acids in healthy adults: a randomized controlled trial. Nutrients. 2018;10(10):1510.
  • 31
    Zheng Y, Li Y, Qi Q, Hruby A, Manson JE, Willett WC, et al Cumulative consumption of branched-chain amino acids and incidence of type 2 diabetes. Int J Epidemiol. 2016;45(5):1482-92.
  • 32
    Mangge H, Zelzer S, Prüller F, Schnedl WJ, Weghuber D, Enko D, et al Branched-chain amino acids are associated with cardiometabolic risk profiles found already in lean, overweight and obese young. J Nutr Biochem. 2016;32:123-7.
  • 33
    Grajeda-Iglesias C, Aviram M. Specific amino acids affect cardiovascular diseases and atherogenesis via protection against macrophage foam cell formation: review article. Rambam Maimonides Med J. 2018;9(3):e0022. https://doi.org/10.5041/RMMJ.10337
    » https://doi.org/10.5041/RMMJ.10337
  • 34
    Palmer ND, Okut H, Hsu FC, Ng MCY, Chen YDI, Goodarzi MO, et al Metabolomics identifies distinctive metabolite signatures for measures of glucose homeostasis: the Insulin Resistance Atherosclerosis Family Study (IRAS-FS). J Clin Endocrinol Metab. 2018;103(5):1877-88.
  • 35
    Tobias DK, Lawler PR, Harada PH, Demler OV, Ridker PM, Manson JE, et al Circulating branched-chain amino acids and incident cardiovascular disease in a prospective cohort of US women. Circ Genom Precis Med. 2018;11(4):e002157. https://doi.org/10.1161/CIRCGEN.118.002157.
    » https://doi.org/10.1161/CIRCGEN.118.002157
  • 36
    Merz B, Frommherz L, Rist MJ, Kulling SE, Bub A, Watzl B. Dietary pattern and plasma BCAA-variations in healthy men and women: results from the KarMeN Study. Nutrients. 2018;10(5):623.
  • 37
    Briggs MA, Petersen KS, Kris-Etherton PM. Saturated fatty acids and cardiovascular disease: replacements for saturated fat to reduce cardiovascular risk. Healthcare. 2017;5(2):29.
  • 38
    Haring B, Gronroos N, Nettleton JA, von Ballmoos MCW, Selvin E, et al Dietary protein intake and coronary heart disease in a large community based cohort: results from the Atherosclerosis Risk in Communities (ARIC) Study. Plos One. 2014;9(10):e109552. https://doi.org/10.1371/journal.pone.0109552
    » https://doi.org/10.1371/journal.pone.0109552
  • 39
    Jennings A, MacGregor A, Pallister T, Spector T, Cassidy A. Associations between branched chain amino acid intake and biomarkers of adiposity and cardiometabolic health independent of genetic factors: a twin study. Int J Cardiol. 2016;223:992-8.
  • 40
    McAllan L, Cotter PD, Roche HM, Korpela R, Nilaweera KN. Impact of leucine on energy balance. J Physiol Biochem. 2013;69(1):155-63.
  • 41
    Klip IT, Voors AA, Swinkels DW, Bakker SJ, Kootstra-Ros JE, Lam CS, et al Serum ferritin and risk for new-onset heart failure and cardiovascular events in the community. Eur J Heart Fail. 2017;19(3):348-56.
  • 42
    Zacharski LR, Shamayeva G, Chow BK, DePalma RG. Ferritin and percent transferrin saturation levels predict type 2 diabetes risk and cardiovascular disease outcomes. Curr Diabetes Rev. 2017;13(4):428-36.
  • 43
    Yang P, Hu W, Fu Z, Sun L, Zhou Y, Gong Y, et al The positive association of branched-chain amino acids and metabolic dyslipidemia in Chinese Han population. Lipids Health Dis. 2016;15:120.
  • 44
    Silveira BKS, Novaes JFN, Reis NA, Lourenço LP, Capobiango AHM, Leal ACG, et al Sociodemographic and lifestyle factors are associated with diet quality in cardiometabolic risk subjects. J Food Nutr Res. 2019;7(2):141-7.
  • 45
    Meneguelli TS, Hinkelmann JV, Novaes JF, Rosa COB, Filgueiras MS, Silveira BKS, et al Dietary inflammatory index is associated with excessive body weight and dietary patterns in subjects with cardiometabolic risk. J Food Nutr Res. 2019;7(7):491-9.
  • 46
    Almeida AP, Rocha DMUP, Moreira AVB, Lima HCFM, Hermsdorff HH. Personalized nutrition using PROCARDIO to reduce cardiometabolic risk in the academic community: a study protocol with preliminary results. J Am Coll Nutr. 2020;1-10.
  • 47
    Silva JT, Bersch-Ferreira ÂC, Torreglosa CR, Weber B, Levy RB. Development of a dietary index based on the Brazilian cardioprotective nutritional program (BALANCE). Nutr J. 2018;17(1):49.

Publication Dates

  • Publication in this collection
    30 Oct 2020
  • Date of issue
    2020

History

  • Received
    08 Oct 2019
  • Reviewed
    05 May 2020
  • Accepted
    08 Aug 2020
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