A high-protein total diet replacement increases energy expenditure and leads to negative fat balance in healthy, normal-weight adults

Camila L P Oliveira, Normand G Boulé, Arya M Sharma, Sarah A Elliott, Mario Siervo, Sunita Ghosh, Aloys Berg, Carla M Prado, Camila L P Oliveira, Normand G Boulé, Arya M Sharma, Sarah A Elliott, Mario Siervo, Sunita Ghosh, Aloys Berg, Carla M Prado

Abstract

Background: High-protein diets and total diet replacements are becoming increasingly popular for weight loss; however, further research is needed to elucidate their impact on the mechanisms involved in weight regulation.

Objective: The aim of this inpatient metabolic balance study was to compare the impact of a high-protein total diet replacement (HP-TDR) versus a control diet (CON) on select components of energy metabolism in healthy adults of both sexes.

Methods: The acute intervention was a randomized, controlled, crossover design with participants allocated to 2 isocaloric arms: 1) HP-TDR: 35% carbohydrate, 40% protein, and 25% fat achieved through a nutritional supplement; 2) CON: 55% carbohydrate, 15% protein, and 30% fat. Participants received the prescribed diets for 32 h while inside a whole-body calorimetry unit (WBCU). The first dietary intervention randomly offered in the WBCU was designed to maintain energy balance and the second matched what was offered during the first stay. Energy expenditure, macronutrient oxidation rates and balances, and metabolic blood markers were assessed. Body composition was measured at baseline using DXA.

Results: Forty-three healthy, normal-weight adults (19 females and 24 males) were included. Compared with the CON diet, the HP-TDR produced higher total energy expenditure [(EE) 81 ± 82 kcal/d, P <0.001], protein and fat oxidation rates (38 ± 34 g/d, P <0.001; 8 ± 20 g/d, P = 0.013, respectively), and a lower carbohydrate oxidation rate (-38 ± 43 g/d, P <0.001). Moreover, a HP-TDR led to decreased energy (-112 ± 85 kcal/d; P <0.001), fat (-22 ± 20 g/d; P <0.001), and carbohydrate balances (-69 ± 44 g/d; P <0.001), and increased protein balance (90 ± 32 g/d; P <0.001).

Conclusions: Our primary findings were that a HP-TDR led to higher total EE, increased fat oxidation, and negative fat balance. These results suggest that a HP-TDR may promote fat loss compared with a conventional isocaloric diet. These trials were registered at clinicaltrials.gov as NCT02811276 and NCT03565510.

Keywords: adults; energy metabolism; metabolic biomarkers; protein; total diet replacement.

Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.

Figures

FIGURE 1
FIGURE 1
Overview of the experimental protocol (A) and variables assessed during each 32-h test (B). CON, control diet; EE, energy expenditure; HP-TDR, high-protein total diet replacement; N/A, not applicable; REE, resting energy expenditure; WBCU, whole-body calorimetry unit.
FIGURE 3
FIGURE 3
Change in resting energy expenditure (∆ EE) following ingestion of the isocaloric HP-TDR and CON breakfasts on the second day of intervention while participants were inside the whole-body calorimetry unit. Values are mean ± SD. Left panels (A, C, and E) indicate 30-min means; right panels (B, D, and F) indicate the total AUC over 360 minutes. Top panels (A and B) contain data from all participants (n = 43); middle panels (C and D) contain data from females (n = 19); and bottom panels (E and F) contain data from males (n = 24). *Significant difference between the HP-TDR and CON conditions, P <0.05 as assessed by a mixed ANOVA. Although there was no statistically significant interaction between the interventions and sex on the total AUC (P = 0.115), the main effect of sex showed a significant difference in females and males (P  = 0.003), as assessed by a mixed analysis of variance. CON, control; HP-TDR, high-protein total diet replacement.
FIGURE 2
FIGURE 2
CONSORT flow diagram for crossover trials. CON, control diet; CONSORT, Consolidated Standards of Reporting Trials; HP-TDR, high-protein total diet replacement; WBCU, whole-body calorimetry unit.
FIGURE 4
FIGURE 4
Correlation between protein and fat balances in all participants (n = 43, panels A and B), females (n = 19, panels C and D), and males (n  = 24, panels E and F). Black squares (▓) represent the HP-TDR condition and empty circles (○) represent the CON condition. CON, control, HP-TDR, high-protein total diet replacement.

References

    1. Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6–10.
    1. Brown A, Dornhorst A, McGowan B, Omar O, Leeds AR, Taheri S, Frost GS. Low-energy total diet replacement intervention in patients with type 2 diabetes mellitus and obesity treated with insulin: a randomized trial. BMJ. 2020;8:e001012.
    1. McCombie L, Brosnahan N, Ross H, Bell-Higgs A, Govan L, Lean MEJ. Filling the intervention gap: service evaluation of an intensive nonsurgical weight management programme for severe and complex obesity. J Hum Nutr Diet. 2019;32(3):329–37.
    1. Ard JD, Lewis KH, Rothberg A, Auriemma A, Coburn SL, Cohen SS, Loper J, Matarese L, Pories WJ, Periman S. Effectiveness of a Total Meal Replacement Program (OPTIFAST Program) on weight loss: results from the OPTIWIN Study. Obesity. 2019;27(1):22–9.
    1. Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KGet al. . Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet North Am Ed. 2018;391(10120):541–51.
    1. Kahathuduwa CN, Davis T, O'Boyle M, Boyd LA, Chin SH, Paniukov D, Binks M. Effects of 3-week total meal replacement vs. typical food-based diet on human brain functional magnetic resonance imaging food-cue reactivity and functional connectivity in people with obesity. Appetite. 2018;120:431–41.
    1. Astbury NM, Aveyard P, Nickless A, Hood K, Corfield K, Lowe R, Jebb SA. Doctor Referral of Overweight People to Low Energy total diet replacement Treatment (DROPLET): pragmatic randomised controlled trial. BMJ. 2018;362:k3760.
    1. Li Z, Tseng CH, Li Q, Deng ML, Wang M, Heber D. Clinical efficacy of a medically supervised outpatient high-protein, low-calorie diet program is equivalent in prediabetic, diabetic and normoglycemic obese patients. Nutr Diabetes. 2014;4(2):e105–e.
    1. Henry RR, Wiest-Kent TA, Scheaffer L, Kolterman OG, Olefsky JM. Metabolic consequences of very-low-calorie diet therapy in obese non-insulin-dependent diabetic and nondiabetic subjects. Diabetes. 1986;35(2):155–64.
    1. Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). Washington, DC: The National Academies Press; 2005, 1357.
    1. Drummen M, Tischmann L, Gatta-Cherifi B, Adam T, Westerterp-Plantenga M. Dietary protein and energy balance in relation to obesity and co-morbidities. Front Endocrinol. 2018;9(443):443.
    1. Mikkelsen PB, Toubro S, Astrup A. Effect of fat-reduced diets on 24-h energy expenditure: comparisons between animal protein, vegetable protein, and carbohydrate. Am J Clin Nutr. 2000;72:1135.
    1. Lejeune MP, Westerterp KR, Adam TC, Luscombe-Marsh ND, Westerterp-Plantenga MS. Ghrelin and glucagon-like peptide 1 concentrations, 24-h satiety, and energy and substrate metabolism during a high-protein diet and measured in a respiration chamber. Am J Clin Nutr. 2006;83(1):89–94.
    1. Bray GA, Smith SR, de Jonge L, Xie H, Rood J, Martin CK, Most M, Brock C, Mancuso S, Redman LM. Effect of dietary protein content on weight gain, energy expenditure, and body composition during overeating: a randomized controlled trial. JAMA. 2012;307(1):47–55.
    1. Bray GA, Redman L, de Jonge L, Covington J, Rood J, Brock C, Mancuso S, Martin CK, Smith SR. Effect of protein overfeeding on energy expenditure measured in a metabolic chamber. Am J Clin Nutr. 2015;101(3):496–505.
    1. Sutton EF, Bray GA, Burton JH, Smith SR, Redman LM. No evidence for metabolic adaptation in thermic effect of food by dietary protein. Obesity. 2016;24(8):1639–42.
    1. Oliveira CLP, Boulé NG, Sharma AM, Elliott S, Siervo M, Ghosh S, Berg A, Prado CM. Examining the effects of a high-protein total diet replacement on energy metabolism, metabolic blood markers, and appetite sensations in healthy adults: protocol for two complementary, randomized, controlled, crossover trials. Trials. 2019;20(1):787.
    1. U.S. National Library of Medicine. [Internet] Available from: (accessed 16 April, 2020).
    1. U.S. National Library of Medicine. [Internet] Available from: (accessed 16 April, 2020).
    1. Canadian Institutes of Health Research; Natural Sciences and Engineering Research Council of Canada; Social Sciences and Humanities Research Council. [Internet] Available from: (accessed 16 April, 2020).
    1. Koohkan S, McCarthy DH, Berg A. The effect of a soy-yoghurt-honey product on excess weight and related health risk factors – a review. J Nutrition Health Food Sci. 2017;5(2):1–10.
    1. Smith SR, de Jonge L, Zachwieja JJ, Roy H, Nguyen T, Rood JC, Windhauser MM, Bray GA. Fat and carbohydrate balances during adaptation to a high-fat diet. Am J Clin Nutr. 2000;71(2):450–7.
    1. Brouwer E On simple formulae for calculating the heat expenditure and the quantities of carbohydrate and fat oxidized in metabolism of men and animals, from gaseous exchange (oxygen intake and carbonic acid output) and urine-N. Acta Physiol Pharmacol Neerl. 1957;6:795–802.
    1. Koohkan S, Golsorkhi M, Schaffner D, Konig D, Deibert P, McCarthy HD, Berg A. Effect of different isoenergetic breakfast compositions on blood glucose regulation, energy allocation and satiety. J Nutrition Health Food Sci. 2014;2(4):1–9.
    1. Prentice AM. Manipulation of dietary fat and energy density and subsequent effects on substrate flux and food intake. Am J Clin Nutr. 1998;67(3 Suppl):535S.
    1. Feinman RD, Fine EJ. "A calorie is a calorie" violates the second law of thermodynamics. Nutr J. 2004;3:9.
    1. Feinman RD, Fine EJ.. Thermodynamics and metabolic advantage of weight loss diets. Metab Syndr Relat Disord. 2003;1(3):209–19.
    1. Fine EJ, Feinman RD.. Thermodynamics of weight loss diets. Nutr Metab (Lond). 2004;1:15.
    1. Hall KD, Guo J. Obesity energetics: body weight regulation and the effects of diet composition. Gastroenterology. 2017;152(7):1718–27..e3.
    1. Leidy HJ, Clifton PM, Astrup A, Wycherley TP, Westerterp-Plantenga MS, Luscombe-Marsh ND, Woods SC, Mattes RD. The role of protein in weight loss and maintenance. Am J Clin Nutr. 2015;101(6):1320S–9S.
    1. Gardner CD, Trepanowski JF, Del Gobbo LC, Hauser ME, Rigdon J, Ioannidis JPA, Desai M, King AC. Effect of low-fat vs low-carbohydrate diet on 12-month weight loss in overweight adults and the association with genotype pattern or insulin secretion: the dietfits randomized clinical trial. JAMA. 2018;319(7):667–79.
    1. Hall KD, Guyenet SJ, Leibel RL. The carbohydrate-insulin model of obesity is difficult to reconcile with current evidence. JAMA Intern Med. 2018;178(8):1103–5.
    1. Ludwig DS, Ebbeling CB.. The carbohydrate-insulin model of obesity: beyond "calories in, calories out". JAMA Intern Med. 2018;178(8):1098–103.
    1. Wycherley TP, Moran LJ, Clifton PM, Noakes M, Brinkworth GD. Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2012;96(6):1281–98.
    1. Jebb SA, Prentice AM. Physiological regulation of macronutrient balance. In: International Textbook of Obesity, Björntorp P, editor. West Sussex, UK: John Wiley & Sons Ltd; 2001. p. 125–35.
    1. Abbott WG, Howard BV, Christin L, Freymond D, Lillioja S, Boyce VL, Anderson TE, Bogardus C, Ravussin E. Short-term energy balance: relationship with protein, carbohydrate, and fat balances. Am J Physiol. 1988;255(3 Pt 1):E332–7.
    1. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963;1(7285):785–9.
    1. Hue L, Taegtmeyer H.. The Randle cycle revisited: a new head for an old hat. Am J Physiol Endocrinol Metab. 2009;297(3):E578–91.
    1. Jones PJ, Pappu AS, Hatcher L, Li ZC, Illingworth DR, Connor WE. Dietary cholesterol feeding suppresses human cholesterol synthesis measured by deuterium incorporation and urinary mevalonic acid levels. Arterioscler Thromb Vasc Biol. 1996;16(10):1222–8.
    1. Parks EJ. Effect of dietary carbohydrate on triglyceride metabolism in humans. J Nutr. 2001;131(10):2772S.
    1. Wolfe BM, Piche LA.. Replacement of carbohydrate by protein in a conventional-fat diet reduces cholesterol and triglyceride concentrations in healthy normolipidemic subjects. Clin Invest Med. 1999;22(4):140–8.
    1. Reshef L, Olswang Y, Cassuto H, Blum B, Croniger CM, Kalhan SC, Tilghman SM, Hanson RW. Glyceroneogenesis and the triglyceride/fatty acid cycle. J Biol Chem. 2003;278(33):30413–16.
    1. Swiger KJ, Martin SS, Blaha MJ, Toth PP, Nasir K, Michos ED, Gerstenblith G, Blumenthal RS, Jones SR. Narrowing sex differences in lipoprotein cholesterol subclasses following mid-life: the very large database of lipids (VLDL-10B). JAHA. 2014;3(2):e000851.
    1. Wang X, Magkos F, Mittendorfer B. Sex differences in lipid and lipoprotein metabolism: it's not just about sex hormones. J Clin Endocrinol Metab. 2011;96(4):885–93.
    1. Schaefer EJ, Foster DM, Zech LA, Lindgren FT, Brewer HB Jr, Levy RI. The effects of estrogen administration on plasma lipoprotein metabolism in premenopausal females. J Clin Endocrinol Metab. 1983;57(2):262–7.
    1. Berg A, Koohkan S, Baer M, König D, Deibert P, Bisse E. [Internet] Available from: (accessed 06 May, 2020).

Source: PubMed

3