Effects of high protein diets on metabolic syndrome parameters

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ScienceDirect Effects of high protein diets on metabolic syndrome parameters Jennifer L Wojcik1, Harold M Aukema1,2, Peter Zahradka1,2,3 and Carla G Taylor1,2,3 High protein diets are commonly promoted for the management of metabolic syndrome parameters. However, the current literature is complex with positive, detrimental and no effects being demonstrated. This conflicting evidence has prevented the development of concrete recommendations regarding the effectiveness and safety of high protein diets for managing metabolic syndrome. Furthermore, evidence that different dietary sources of protein have distinct metabolic effects has been obtained, but additional research is needed to extend and clarify the limited information currently available. In particular, future studies are required to determine whether specific protein sources can elicit effects at normal to moderately increased protein intake as a means of avoiding any potential risks associated with high protein diets. Addresses 1 Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada 2 Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Tache´ Avenue, Winnipeg, MB R2H 2A6, Canada 3 Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada Corresponding author: Taylor, Carla G ([email protected])

Current Opinion in Food Science 2016, 8:43–49 This review comes from a themed issue on Functional foods and nutrition Edited by Rotimi Aluko

http://dx.doi.org/10.1016/j.cofs.2016.02.001 2214-7993/# 2016 Elsevier Ltd. All rights reserved.

Introduction Metabolic syndrome (MetS) is a collection of risk factors including obesity, hyperglycemia, hypertension, and dyslipidemia that lead to an increased risk of cardiovascular disease and type 2 diabetes mellitus (T2DM) [1]. While the exact pathogenesis of MetS is unknown, obesity and insulin resistance appear to be the main underlying factors [1]. In addition, non-alcoholic fatty liver disease (NAFLD) is now considered the hepatic manifestation of MetS due to its strong association with obesity and insulin resistance [2]. Currently, there is much interest in utilizing high protein www.sciencedirect.com

diets to manage MetS [3,4]. High protein intake is considered to be 25–35% of energy (E%) from protein, compared to normal protein intake which is approximately 15E% protein. However, results are mixed and not all studies have reported beneficial outcomes [5]. In addition, variations in study designs make it difficult to compare studies of this nature [6]. Also complicating the issue is the increasing evidence that different sources of animal and plant proteins appear to have varying effects on MetS parameters, with studies reporting both positive [7,8,9] and detrimental effects [10,11,12]. This conflicting evidence makes it difficult to develop conclusive recommendations as to whether high protein diets are an effective and safe means to manage MetS. Therefore, this review examines the effects of high protein intake on the individual parameters of MetS and the potential role of different protein sources.

Effects of high protein intake compared to normal protein intake on MetS High protein intake and obesity

Research on the effects of high protein diets on obesity has amplified over the past several years due to the current obesity epidemic and growing public interest in utilizing high protein diets as a weight loss strategy. While the majority of high protein studies focus on weight loss as the primary outcome, other changes in body composition, including reductions in fat mass and preservation of lean body mass, are well established [13]. This was demonstrated in a recent meta-analysis that analyzed 24 short-term trials (study duration 6 months) comparing energy-restricted high protein diets (mean protein content 31%E) and normal protein diets (mean protein content 18%E) in overweight and obese adults. The high protein diets provided greater reductions in body weight and fat mass and mitigated reductions in lean body mass compared to normal protein diets (Table 1) [3]. In another meta-analysis of 74 trials (majority were 6 months in duration) comparing high protein diets (median protein content 27%E) and normal protein diets (median protein content 18%E) in both energy-restricted and ad libitum feeding studies in adults who varied in age and health status, high protein diets led to greater reductions in body weight, body mass index and waist circumference compared to normal protein diets (Table 1) [14]. Finally, in a meta-analysis of 9 shortterm trials (study duration 6 months), high protein diets (median protein content 30%E) led to greater reductions in body weight compared to normal protein diets (median protein content 16%E) in overweight and obese adults Current Opinion in Food Science 2016, 8:43–49

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Table 1 Summary of meta-analyses comparing effects of high protein vs. normal protein diets on MetS parameters. Studies with subjects with hyperlipidemia, hypertension, or MetS were included. Wycherley et al. [3] Total # Studies Study Selection Criteria

Schwingshackl et al. [5]

Santesso et al. [14]

Dong et al. [15]

24 RCT Energy-restricted and isocaloric

15 RCT Energy-restricted and isocaloric or ad libitum

74 RCT Energy-restricted and isocaloric or ad libitum

9 RCT Energy-restricted and isocaloric or ad libitum

Difference in protein between diets 10%E

High protein diets 25%E protein Normal protein diets 20%E protein Total fat intake 30%E for both diets

Difference in protein between diets >5%E

High protein diets 20%E protein Difference in protein between diets >5%E

No meal replacements

No supplements or meal replacements Participant age 18 years

Total fat intake for both diets 30%E Difference in fat between diets 10%E

Participant age 18 years No restrictions on sex, body weight or BMI Studies with subjects with T2DM included

Participant age 18 years No restrictions on sex, body weight or BMI Studies with subjects with T2DM included

Diet Duration

4 weeks to 6 months

12 months

Diets

Normal protein Mean composition: 18%E protein 57%E carbohydrate 25%E fat High protein Mean composition: 31%E protein 42%E carbohydrate 27%E fat

Outcomes (subjects/studies) Body weight + (1010/23) Body mass index NA Waist circumference NA Fat mass + (765/18) Fat free mass + (714/17) Fasting glucose (580/12) Fasting insulin (2510/11) Total cholesterol (716/15) HDL cholesterol (581/13) LDL cholesterol (530/11) Triglycerides + (490/13) Systolic blood pressure (230/5) Diastolic blood pressure (230/5)

Participant age 18 years

All subjects were overweight or obese with T2DM 4 weeks to 6 months

Normal protein Median composition: 15%E protein 55%E carbohydrate 25%E fat

80% of studies were 4 weeks to 6 months Normal protein Median composition: 18%E protein 55%E carbohydrate 26%E fat

Normal protein Median composition: 16%E protein 53%E carbohydrate 30%E fat

High protein Median composition: 30%E protein 40%E carbohydrate 30%E fat

High protein Median composition: 27%E protein 38%E carbohydrate 32%E fat

High protein Median composition: 30%E protein 40%E carbohydrate 30%E fat

(971/13) NA (727/8) (913/10) NA (1357/11) + (1086/11) (1251/12) (1563/14) (1522/13) (1563/14) (1414/11) (1402/11)

+ (2326/38) + (887/16) + (1214/15) NA NA (1089/15) + (718/11)a (1368/21) + (1555/23) a (1576/23) + (1623/24) + (1186/15) + (1186/15)

+ (406/8) NA NA NA NA (316/8) NA (318/8) (318/8) (318/8) (318/8) + (298/4) + (298/4)

‘‘ + ’’ = high protein diets had positive effects compared to normal protein diets; ‘‘ ’’ = no difference between high protein and normal protein diets. %E = percent energy; BMI = body mass index; MetS = metabolic syndrome; NA = not assessed; RCT = randomized controlled trial; T2DM = type 2 diabetes mellitus. a Sensitivity analysis of studies with lower risk of bias eliminated the effect of high protein diets on fasting insulin and HDL cholesterol.

with T2DM in energy-restricted and ad libitum feeding studies (Table 1) [15]. Beneficial effects of high protein diets on weight loss are often attributed to the increased thermogenesis and satiety of high protein foods [16,17]. More recently, there has been increasing interest in the role of dietary protein as an effective stimulus for the release or inhibition of peptides involved in appetite regulation [18]. Current Opinion in Food Science 2016, 8:43–49

However, not all studies have reported improvements in obesity with high protein intake, specifically over the long-term. A meta-analysis of long-term randomized controlled trials (study duration 12 months) reported high protein diets (median protein content 30%E) had no beneficial effects on weight, waist circumference or fat mass compared to normal protein diets (median protein content 15%E) in overweight and obese adults (Table 1) www.sciencedirect.com

High protein diets and metabolic syndrome Wojcik et al. 45

[5]. Moreover, two recent prospective cohort studies concluded that total protein intake >18%E was positively associated with weight gain when protein replaced carbohydrates or fat in adults who varied in age and health status [19,20]. These studies raise questions regarding the long-term effectiveness of high protein diets in the management of obesity. High protein intake and insulin resistance

Research pertaining to the effects of high protein intake on insulin resistance is complex as evidenced by the inconsistent results cited in the literature. This was highlighted in a recent review that discussed 26 shortand long-term human studies comparing the effects of high protein diets (>20%E protein) on insulin resistance [6]. Positive and no effects were observed in studies 6 months in duration, while positive and detrimental effects including an increased risk of T2DM were reported in studies 6 months in duration. The four meta-analyses highlighted in Table 1 all reported no differences in fasting blood glucose between high protein diets (27–31%E protein) and normal protein diets (15–18%E protein) [3,5,14,15]. Two of the meta-analyses reported high protein diets (27–30%E protein) significantly reduced fasting blood insulin levels compared to normal protein diets (15–18%E) [5,14]. However, it is important to recognize that sensitivity analysis of studies with lower risk of bias eliminated this effect in one of the meta-analyses [14]. The majority of high protein studies assess the effects of high protein intake on insulin resistance by measuring fasting blood glucose and insulin levels, which is consistent with the most recent harmonized definition of the metabolic syndrome which uses impaired fasting glucose as its clinical measurement of insulin resistance [21]. When improvements in insulin resistance are observed in high protein studies that have a weight loss component, the positive effects are usually attributed to weight loss rather than the high protein diet itself [6]. This is commonly observed in energy-restricted studies in which similar improvements in insulin resistance for both high and normal protein diet groups are demonstrated due to the expected weight loss in energy-restricted studies [3,22]. However, it is important to note that even if weight loss is achieved on a high protein diet, insulin resistance does not always improve [6]. Another possible explanation for the beneficial effects of high protein diets is that a higher protein intake during weight loss can reduce loss of lean body mass which may lead to improved insulin sensitivity [23]. A lower glycemic load because of a reduced carbohydrate intake is often cited as another mechanism for the beneficial effects of high protein diets on insulin resistance [24]. Others argue that dietary proteins have an insulinotropic effect and promote insulin secretion which enhances glucose clearance from the blood [25]. www.sciencedirect.com

Conversely, studies that demonstrate detrimental effects of high protein diets on insulin resistance often link these effects to an increase in plasma branched chain amino acids derived from dietary protein [6], with studies showing a positive association between plasma branched chain amino acids and T2DM [26–28]. Moreover, the EPIC-NL study concluded that higher total protein and animal protein intake, but not vegetable protein intake, was associated with increased diabetes risk. Specifically, for every 5E% protein that replaced either 5E% carbohydrate or fat, there was a 30% increase in diabetes risk in adults [29]. The EPIC-INTERACT study also concluded that higher total protein and animal protein intake (>20%E protein), but not vegetable protein intake, and compensatory decrease of carbohydrates was associated with an elevated risk of T2DM in a large cohort of European adults [30]. These studies highlight the need for further research on the effects of high protein intake on insulin resistance especially in populations that are already at an increased risk of developing T2DM, and introduce the importance of the source of protein in a high protein diet. High protein intake and dyslipidemia

The most promising effects of high protein intake on blood lipids appear to be on triglyceride levels with two of the meta-analyses highlighted in Table 1 reporting positive effects of high protein diets (27–31%E protein) on triglyceride levels [3,14]. It is unclear whether the positive effects of high protein diets on triglyceride levels were attributed to the high protein diet itself or to the significant reductions in body weight also observed in the high protein diet groups in these two meta-analyses. Interestingly, studies have stated that high protein diets do indeed have a diet effect on blood lipids and this is attributed to the ability of dietary protein to slow lipid absorption and synthesis as well as promote lipid excretion [31]. However, the evidence on high protein diets and triglyceride levels is not conclusive as the two other meta-analyses in Table 1 reported no differences in triglyceride levels between high protein diets (30%E protein) and normal protein diets (15–16%E protein) [5,15]. In addition, two recent randomized controlled trials not included in the above mentioned meta-analyses also reported no differences in triglyceride levels between high protein diets (25–30%E protein) and normal protein diets (15–20%E protein) in overweight and obese adults [22,32]. Only one of the meta-analyses in Table 1 reported positive effects of high protein diets on HDL cholesterol levels, however this effect was eliminated after sensitivity analysis of studies with lower risk of bias [14]. All other studies reviewed reported no differences between high protein diets (25–31%E protein) and normal protein diets (15–20%E protein) on HDL cholesterol, total cholesterol or LDL cholesterol levels [3,5,14,15,22,32]. It is important to recognize that no reports of detrimental effects of high protein diets Current Opinion in Food Science 2016, 8:43–49

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on dyslipidemia were found in the literature, which is in agreement with a recent review examining the safety and efficacy of high protein diets [13].

diets on NAFLD, additional studies, particularly longterm studies, are still required to make a definitive statement.

High protein intake and hypertension

Limitations to studies examining effects of high protein intake on MetS

Two of the meta-analyses highlighted in Table 1 reported positive effects of high protein diets (27–30%E protein) for lowering blood pressure compared to normal protein diets (16–18%E protein) [14,15], while the other two meta-analyses reported no effects [3,5]. In addition, two recent randomized controlled trials not included in the above mentioned meta-analyses also reported conflicting results with positive [33] and no effects [22] of high protein diets (23–28%E protein) on blood pressure being observed in overweight and obese adults. Although some high protein studies attribute improvements in blood pressure to weight loss rather than the high protein diet itself [33], a recent meta-analysis of 40 trials (study duration 12 months) examining the impact of protein intake on blood pressure demonstrated that increased animal and plant protein intake (median protein content 27%E) resulted in significant reductions in blood pressure independent of changes in body weight [34]. The specific antihypertensive effects of dietary protein are thought to be related to various amino acids in protein which help to decrease oxidative stress, improve nitric oxide bioavailability, enhance renal function, and modulate the reninangiotensin system [34,35,36]. Interestingly, detrimental effects have not been observed in current studies examining the effects of high protein diets on hypertension despite evidence suggesting high protein diets may be harmful to renal function [36,37]. Furthermore, while it has been speculated that high protein intake may lead to increased sodium intake and subsequent hypertension [37], current evidence to support this claim was not found. High protein intake and non-alcoholic fatty liver disease

As previously mentioned, NAFLD is considered the hepatic manifestation of MetS, with hepatic steatosis representing the first stage of NAFLD [2]. While the study of high protein intake on NAFLD is relatively new, short-term high protein (35%E protein) animal and high protein (23–35%E protein) human studies thus far have shown high protein diets to have anti-steatotic effects on the liver independent of reductions in body weight [38,39,40,41,42,43]. While possible mechanisms for the beneficial effects of high protein intake on NAFLD are not fully elucidated, it has been proposed that high protein diets reduce hepatic steatosis through synergistic positive effects on lipid metabolism, cell stress and inflammation [42]. There is also interest regarding the corresponding increase in dietary taurine intake when protein intake is increased as taurine supplementation has been found to reduce hepatic lipid accumulation and inflammation [44]. Therefore, while current literature appears promising regarding the effects of high protein Current Opinion in Food Science 2016, 8:43–49

There are several limitations in studies aiming to clarify the effects of high protein diets on individual parameters of MetS. Firstly, it is difficult to determine specific metabolic effects of high protein diets in studies that show improvements in MetS parameters in conjunction with weight loss [4,6,45]. In fact, when trying to determine the metabolic effects of protein, energy-restricted diets are often seen as a limitation since the strict control of energy and subsequent weight loss will conceal any potential metabolic effects of protein [4]. Another limitation is that studies comparing high and normal protein diets have to increase protein at the expense of carbohydrate and/or fat making it difficult to conclude whether it is the increase in protein or reduction in carbohydrate and/or fat that produces favorable effects [6,31,36,46]. Variations in study designs also make it difficult to compare studies due to differences in the type of animal model or characteristics of human subjects, study duration, outcomes measured, whether diets are energy-restricted or ad libitum, whether weight loss is present, and because the amount and sources of protein, carbohydrate and fat vary widely among studies [6]. Long-term compliance to high protein diets is also often challenged in human studies, but this is no different from compliance to any other macronutrient prescription as compliance is often impacted by various behavioral and environmental factors [18]. Lastly, since MetS is a multifactorial condition, it can be difficult to draw conclusions on the overall impact of high protein intake on MetS since varying results are often observed amongst each individual parameter of MetS. However, this may also suggest that dietary recommendations need to be tailored depending on which MetS parameters are present in an individual.

Role of different protein sources on MetS Studies are now focusing on the effects of various protein sources on MetS to clarify their role in modifying relevant parameters. We recently demonstrated that the source of protein within a high protein diet (35%E protein) is critical for the management of certain MetS parameters. Our work has shown that in an animal model, a high protein diet containing a mixture of animal and plant protein sources (complete milk protein, egg white, soy protein isolate and wheat gluten) was more effective than a high protein casein-based diet for modulating reductions in insulin resistance and hepatic steatosis independent of weight loss. A high protein diet containing only soy protein isolate as the protein source also was effective, but not as effective as the high protein mixed diet [43]. www.sciencedirect.com

High protein diets and metabolic syndrome Wojcik et al. 47

In regards to the effects of animal protein sources, emerging evidence has demonstrated that increased consumption of dairy products is associated with a decreased risk of developing MetS and T2DM [8,47]. This is often attributed to the whey protein component in dairy which has been shown to reduce body weight, preserve lean body mass, improve blood glucose, insulin and lipid levels, and reduce blood pressure [9]. Whey protein contains biological compounds such as b-lactoglobulin and a-lactalbumin that are not found in other protein sources such as casein, the primary protein component in dairy, and these are thought to be responsible for the effect of whey protein on health [9]. Interestingly, beneficial effects of dairy have been observed at normal to moderately increased protein intake [8,47] which raises the question as to whether potential negative consequences of high protein intake can be avoided by focusing on specific sources of protein at normal to moderately increased protein levels to manage MetS. Red meat is another commonly researched animal protein source; red meat consumption is associated with weight gain [11], increased risk of MetS [10] and development of T2DM [12,48,49] causing concern for individuals who mainly use red meat to increase protein intake. In addition, substituting just one serving of red meat with other protein sources is associated with healthier profiles of biomarkers for inflammation and glucose metabolism [50]. Finally, fish is also emerging as another commonly researched animal protein source. While data is still scarce regarding the effects of fish on MetS, a recent review suggested that fish consumption may prevent or improve metabolic health and have a protective role in MetS prevention in adults [51]. In regards to plant protein sources, the evidence appears to support that increasing protein intake with plant protein sources is a safe and effective approach for managing MetS. For instance, three recent prospective cohort studies demonstrated that increased plant protein intake was not associated with increased risks of T2DM and cardiovascular disease [20,29,30]. Soy protein is the most commonly researched plant protein source and several studies in humans and animal models have demonstrated that consumption of soy protein reduces body weight, lowers blood cholesterol and blood pressure, improves insulin sensitivity and reduces hepatic steatosis [7,36,52,53,54,55]. Furthermore, these beneficial effects can be observed at normal to moderately increased protein intake and in the absence of weight loss. This again highlights the need for further research on whether specific sources of protein at normal to moderately increased protein intake can be used to safely and effectively manage MetS.

Conclusion Research examining the effects of high protein diets on MetS parameters is complex. While several well-designed www.sciencedirect.com

studies have demonstrated positive effects of high protein diets on obesity, insulin resistance, dyslipidemia, hypertension and NAFLD, the reported detrimental effects of high protein intake on obesity and insulin resistance are of great concern especially since obesity and insulin resistance are the main causative factors for MetS. Further complicating this area of research is the emerging evidence that the source of protein in a high protein diet potentially influences the type of metabolic effect that might be associated with protein intake. This is an important area of future research especially since consumption of specific proteins can elicit positive effects at normal to moderately increased protein levels thereby avoiding the need to consume high protein diets and any potential risks that may be associated with them. In conclusion, high protein diets may be an appropriate dietary intervention to manage certain parameters of MetS, however careful selection of protein sources used to increase protein intake is critical. Longer-term studies that compare the effects of protein intake at various levels with various protein sources on MetS are needed.

Acknowledgements Supported by grants (to HMA, CGT, PZ) from the Canadian Institutes of Health Research (CIHR, MOP 230564) and the Manitoba Health Research Council and graduate scholarships (to JLW) from CIHR, Dietitians of Canada and the University of Manitoba.

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21. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr 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, 120:1640-1645. 22. Tang M, Armstrong CL, Leidy HJ, Campbell WW: Normal vs. highprotein weight loss diets in men: effects on body composition and indices of metabolic syndrome. Obesity (Silver Spring) 2013, 21:E204-E210. 23. Srikanthan P, Karlamangla AS: Relative muscle mass is inversely associated with insulin resistance and prediabetes, Findings from the third National Health and Nutrition Examination Survey. J Clin Endocrinol Metab 2011, 96: 2898-2903. 24. Layman DK, Shiue H, Sather C, Erickson DJ, Baum J: Increased dietary protein modifies glucose and insulin homeostasis in adult women during weight loss. J Nutr 2003, 133:405-410. 25. El Khoury D, Hwalla N: Metabolic and appetite hormone responses of hyperinsulinemic normoglycemic males to meals with varied macronutrient compositions. Ann Nutr Metab 2010, 57:59-67. 26. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C et al.: Metabolite profiles and the risk of developing diabetes. Nat Med 2011, 17:448-453. 27. Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA et al.: A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 2009, 9:311-326. 28. Floegel A, Stefan N, Yu Z, Muhlenbruch K, Drogan D, Joost HG, Fritsche A, Haring HU, Hrabe de Angelis M, Peters A et al.: Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes 2013, 62:639-648. 29. Sluijs I, Beulens JW, van der ADL, Spijkerman AM, Grobbee DE, van der Schouw YT: Dietary intake of total, animal, and vegetable protein and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study. Diabetes Care 2010, 33:43-48. 30. van Nielen M, Feskens EJ, Mensink M, Sluijs I, Molina E, Amiano P,  Ardanaz E, Balkau B, Beulens JW, Boeing H et al.: Dietary protein intake and incidence of type 2 diabetes in Europe: the EPICInterAct Case-Cohort Study. Diabetes Care 2014, 37:1854-1862. A large cohort study that cautions the use of diets high in animal protein sources, but not plant protein sources, due to their association with a elevated risk of T2DM. 31. El Khoury D, Anderson GH: Recent advances in dietary proteins  and lipid metabolism. Curr Opin Lipidol 2013, 24:207-213. An important review on the role of dietary proteins in lipid metabolism that examines the role of protein quantity, the role of protein composition and potential mechanisms. 32. Chiu S, Williams PT, Dawson T, Bergman RN, Stefanovski D, Watkins SM, Krauss RM: Diets high in protein or saturated fat do not affect insulin sensitivity or plasma concentrations of lipids and lipoproteins in overweight and obese adults. J Nutr 2014, 144:1753-1759. 33. Engberink MF, Geleijnse JM, Bakker SJ, Larsen TM, HandjievaDarlesnka T, Kafatos A, Martinez JA, Pfeiffer AF, Kunesova M, Jebb SA et al.: Effect of a high-protein diet on maintenance of blood pressure levels achieved after initial weight loss: the DiOGenes randomized study. J Hum Hypertens 2015, 29:58-63. 34. Rebholz CM, Friedman EE, Powers LJ, Arroyave WD, He J, Kelly TN: Dietary protein intake and blood pressure: a metaanalysis of randomized controlled trials. Am J Epidemiol 2012, 176(Suppl 7):S27-S43. 35. Vasdev S, Stuckless J: Antihypertensive effects of dietary protein and its mechanism. Int J Angiol 2010, 19:e7-e20. www.sciencedirect.com

High protein diets and metabolic syndrome Wojcik et al. 49

36. Teunissen-Beekman KF, van Baak MA: The role of dietary  protein in blood pressure regulation. Curr Opin Lipidol 2013, 24:65-70. An important review on the effects of dietary proteins on blood pressure including the role of different protein sources, possible mechanisms and the safety of increasing protein intake. 37. Marckmann P, Osther P, Pedersen AN, Jespersen B: Highprotein diets and renal health. J Ren Nutr 2015, 25:1-5. 38. Bortolotti M, Kreis R, Debard C, Cariou B, Faeh D, Chetiveaux M, Ith M, Vermathen P, Stefanoni N, Le KA et al.: High protein intake reduces intrahepatocellular lipid deposition in humans. Am J Clin Nutr 2009, 90:1002-1010. 39. Bezerra Duarte SM, Faintuch J, Stefano JT, Sobral de Oliveira MB, de Campos Mazo DF, Rabelo F, Vanni D, Nogueira MA, Carrilho FJ, Marques Souza de Oliveira CP: Hypocaloric highprotein diet improves clinical and biochemical markers in patients with nonalcoholic fatty liver disease (NAFLD). Nutr Hosp 2014, 29:94-101. 40. Garcia Caraballo SC, Comhair TM, Dejong CH, Lamers WH,  Kohler SE: A high-protein diet is anti-steatotic and has no proinflammatory side effects in dyslipidaemic APOE2 knock-in mice. Br J Nutr 2014, 112:1251-1265. An interesting animal study that demonstrated a high protein diet reduces hepatic lipid content in dyslipidaemic mice and lowers the activation status of inflammatory cells in the liver. 41. Garcia Caraballo SC, Comhair TM, Houten SM, Dejong CH,  Lamers WH, Koehler SE: High-protein diets prevent steatosis and induce hepatic accumulation of monomethyl branchedchain fatty acids. J Nutr Biochem 2014, 25:1263-1274. This study provided unique findings as to the effects of a high protein diet on lipid metabolism by illustrating that high protein diets modified hepatic fatty acid composition. 42. Garcia-Caraballo SC, Comhair TM, Verheyen F, Gaemers I, Schaap FG, Houten SM, Hakvoort TB, Dejong CH, Lamers WH, Koehler SE: Prevention and reversal of hepatic steatosis with a high-protein diet in mice. Biochim Biophys Acta 2013, 1832: 685-695. 43. Wojcik JL, Devassy JG, Wu Y, Zahradka P, Taylor CG,  Aukema HM: Protein source in a high-protein diet modulates reductions in insulin resistance and hepatic steatosis in fa/fa Zucker rats. Obesity (Silver Spring) 2016, 24:123-131. An important animal study illustrating the critical role of the source of protein in a high protein diet and that high protein intake with specific protein sources can elicit improvements in insulin resistance and hepatic steatosis in the absence of weight loss.

46. Layman DK, Clifton P, Gannon MC, Krauss RM, Nuttall FQ: Protein in optimal health: heart disease and type 2 diabetes. Am J Clin Nutr 2008, 87:1571S-1575S. 47. Gao D, Ning N, Wang C, Wang Y, Li Q, Meng Z, Liu Y, Li Q: Dairy products consumption and risk of type 2 diabetes: systematic  review and dose-response meta-analysis. PLoS One 2013, 8:e73965. An important review concluding that a modest increase in daily intake of dairy products such as low fat dairy, cheese and yogurt may contribute to the prevention of T2DM. 48. Feskens EJ, Sluik D, van Woudenbergh GJ: Meat consumption, diabetes, and its complications. Curr Diab Rep 2013, 13: 298-306. 49. Micha R, Wallace SK, Mozaffarian D: Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: a systematic review and metaanalysis. Circulation 2010, 121:2271-2283. 50. Ley SH, Sun Q, Willett WC, Eliassen AH, Wu K, Pan A, Grodstein F,  Hu FB: Associations between red meat intake and biomarkers of inflammation and glucose metabolism in women. Am J Clin Nutr 2014, 99:352-360. A good study demonstrating the critical role of the source of protein by demonstrating the effects on health outcomes by substituting just one serving of red meat with poultry, fish, legumes and nuts. 51. Torris C, Molin M, Cvancarova Smastuen M: Fish consumption and its possible preventive role on the development and prevalence of metabolic syndrome — a systematic review. Diabetol Metab Syndr 2014, 6 112-5996-6-112. eCollection 2014. 52. van Nielen M, Feskens EJ, Rietman A, Siebelink E, Mensink M:  Partly replacing meat protein with soy protein alters insulin resistance and blood lipids in postmenopausal women with abdominal obesity. J Nutr 2014, 144:1423-1429. An important study demonstrating that replacing meat with soy meat analogues and soy nuts in a moderately high protein diet improves insulin sensitivity and total and LDL cholesterol, thus suggesting soy products may be important in preventing MetS. 53. Zhang YB, Chen WH, Guo JJ, Fu ZH, Yi C, Zhang M, Na XL: Soy isoflavone supplementation could reduce body weight and improve glucose metabolism in non-Asian postmenopausal women – a meta-analysis. Nutrition 2013, 29:8-14.

44. Gentile CL, Nivala AM, Gonzales JC, Pfaffenbach KT, Wang D, Wei Y, Jiang H, Orlicky DJ, Petersen DR, Pagliassotti MJ, Maclean KN: Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease. Am J Physiol Regul Integr Comp Physiol 2011, 301:R1710-R1722.

54. Xiao CW, Wood CM, Weber D, Aziz SA, Mehta R, Griffin P,  Cockell KA: Dietary supplementation with soy isoflavones or replacement with soy proteins prevents hepatic lipid droplet accumulation and alters expression of genes involved in lipid metabolism in rats. Genes Nutr 2014, 9 373-013-0373-3 [Epub 2013 Nov 30]. An interesting animal study providing evidence that consumption of soy foods or supplements might be an appropriate strategy for the prevention or treatment of fatty liver diseases.

45. Westerterp-Plantenga MS, Lemmens SG, Westerterp KR: Dietary protein – its role in satiety, energetics, weight loss and health. Br J Nutr 2012, 108(Suppl 2):S105-S112.

55. Mueller NT, Odegaard AO, Gross MD, Koh WP, Yu MC, Yuan JM, Pereira MA: Soy intake and risk of type 2 diabetes in Chinese Singaporeans. Eur J Nutr 2012, 51:1033-1040.

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Current Opinion in Food Science 2016, 8:43–49