The term “high-protein diet” (otherwise defined as “protein diet”) is generically used to identify several commercial dietary regimes for slimming purposes (e.g. Atkins, Zona, Dukan, Tisanoreica, etc.), very popular among the public. Their popularity largely depends on advertising and the continuous offer of new products, particularly appreciated by those looking for an easy way to lose weight and unwilling to follow a "weighted foods" diet.
Since most (but not all) of these regimes combine the increase in the protein percentage with the reduction in the intake of carbohydrate-based foods, the program appears simpler to follow (compared to the “weighted foods”diet) as it is based on the exclusion of whole food groups (pasta, pizza, bread..). The consequent caloric cut and depletion of glycogen deposits, leads to a rapid drop in initial weight, which increases the treatment satisfaction. The potential superiority of high-protein regimens in obtaining and maintaining better control of body weight has been related to an increase in satiating power, an increase in energy expenditure due to postprandial thermogenesis and to the maintenance of lean mass (Westerterp-Plantenga et al. 2012), as well as to the possible (but not proven) satiating effect of ketosis (see last paragraph). Some of these programs have in fact been defined as “ketogenic” in an erroneous way given that the protein portion of the diet is "anti-ketogenic" being the majority of the amino acids precursors of gluconeogenesis. Mild ketosis (about 1 mmol / L of beta-hydroxybutyrate) is a marker of strong caloric restriction (combined with carbohydrate restriction) in the Very Low Calorie Ketogenic Diet (VLCKD). Higher ketosis values are induced by classic Ketogenic Diet (a normocaloric, adequate protein, very low-carb and high-fat diet (Kirkpatrick et al 2019), indicated for drug-resistant epilepsy and some rare metabolic diseases (Martin-McGill 2012, Pong 2012, Veggiotti et al 2011).
However, given the importance of identifying effective strategies for weight control, there is a growing scientific interest in evaluating the real effectiveness of different metabolic mixtures proposed as part of a low-calorie diet on short and long-term weight loss and their metabolic effects.
A first difficulty for the correct scientific evaluation of these approaches consists in the poor standardization, as there is no univocal definition of a high-protein diet. In fact, most studies consider "high-protein" a low-calorie diet with over 20% of the energy deriving from proteins but the intake of proteins in grams per kg of body weight, which would allow a more accurate definition, is rarely indicated (Westerterp et al 2007). As already described, most of the high-protein commercial regimens are also low-carb, therefore the metabolic mixture of the macronutrients can vary a lot, thus making a comparison difficult, in particular regarding the effects on the metabolic framework.
Even with these methodological limitations, the effects of "high-protein" diets on weight loss and cardiovascular risk are discussed in the very recent umbrella review carried out by the SINU Giovani Working Group (Dinu M et al, 2020). The authors considered all the meta-analyses published to date on the effects of diets of various kinds on anthropometric and metabolic risk parameters.
The analysis showed that the quality of the meta-analyses published on "high protein" diets (8 in all with protein percentages ranging from 25 to 35% of energy) is critically low and the number of participants relatively small. Little or no evidence is reported regarding the reduction in anthropometric parameters and blood pressure values while the data on the lipid and glycemic profile are discordant. The elevated intake of saturated fatty acids and the reduced fiber content may help explain the increases observed in LDL cholesterol, blood sugar and HbA1c levels and cast doubt on the health outcomes of this type of diet in the long term.
Regarding the maintenance of weight loss, the international Diogenes study concluded that a moderate increase in protein content and reduction in the glycemic index represent a useful tool to prevent weight re-gain following a low-calorie diet aimed at weight loss. (Larsen et al 2010). However, it is important to note that in this study, weight loss was achieved with the use of meal replacements and not with foods available on the market; the conclusions of the study therefore do not seem extensible to other dietary regimens. Subjects who are educated to the correct use of food products on the market may be able to achieve the goal of maintaining their weight even with a normoproteic diet. Finally, it is important to underline that the study did not take into account the long-term side effects that make diets with a moderate increase in protein intake contraindicated in overweight or obese subjects with comorbidities.
2) Low-carb-diets: is there the need to exclude carbohydrates from the diet for weight loss?
The study of the amount of carbohydrate intake in the diet is a different and complex topic. In the past the human brain was thought to be entirely dependent upon glucose, in the ‘60s circulating ketones were discovered to replace glucose as the brain’s major fuel during the marked hyperketonemia of prolonged fasting. Nowadays a hyperketonemic diet can allow growth and maintenance in subjects who lack the brain glucose transporter and, for these subjects, a very low- carb diet is a life-saving therapy (Pong et al 2012). However, low-carb diets are mainly known as weight loss diets used for this purpose since the ‘70s. As previously indicated, most commercial weight loss diets defined as "high protein" are actually also low-carb.
There has recently been a renewed scientific interest in assessing the impact of these diets on glycemic control and other cardiovascular risk factors in patients with prediabetes and type 2 diabetes, but little data on their long-term efficacy and safety is still available ( Kirkpatrick et al 2019; Bolla et al 2019).
Most reviews about the effects of low-carb diets on weight loss and metabolic parameters distinguish moderately low-carb diets, equivalent to 26–44% energy from CHO (130–225 grams per 2000 kcal reference intake), low-carb diets equal to 10-25% energy from CHO (50-130 grams) and very low-carb diets, less than 10% energy from CHO (<50 grams) (Feinman 2015, Kirkpatrick 2019). However, they do not distinguish the type of carbohydrates (starch or sugars) nor the quality of the nutrients that complete the metabolic mixture (type of fat? animal or vegetable protein?). For these reasons, many review conclusions based on this classification may be inappropriate. Limiting our attention to weight loss effects, we can refer again to the recent review (Dinu M et al, 2020) which shows greater short-term weight loss (6 months) with higher carbohydrate restriction diets, an outcome which fades as the duration of follow-up increases. Taking into account that obesity therapy is long-term, the usefulness of this approach therefore appears limited. Proponents of low-carb diets attribute the greater satiating effect of these regimens to the induction of ketosis. However, most commercial diets are not actually ketogenic. The restriction of carbohydrates is a necessary but not sufficient condition to induce a level of therapeutic ketosis (Kirkpatrick 2019): for this purpose, it is also necessary to maintain the protein intake in physiological quantities by supplementing the caloric share with lipids. The ketogenic potential of a diet can be expressed in a simplified way by the ratio (in grams) between ketogenic (fat) and non-ketogenic (proteins and carbohydrates) nutrients. This ratio must be at least equal to or greater than 2 to achieve a therapeutic level of ketosis. The highest levels of ketosis necessary for the treatment of some rare congenital diseases and for drug resistant epilepsy (Martin-McGill 2018, Pong et al 2012) are obtained with ratios of 3: 1 and 4: 1 (International Study Group on Ketogenic diet - International League Against Epilepsy https://www.ilae.org/patient-care/ketogenic-diets/international-centers)
The effects of ketosis on satiety are not completely elucidated (Gibson et al 2015). The long-term maintenance of a classic ketogenic diet (normocaloric, normoproteic, very low-carb and very high-fat ketogenic diet) does not alter ghrelin values and does not compromise weight and linear growth as demonstrated by recent studies conducted in children suffering from rare metabolic disease who require long-term ketogenc dietary treatment (Ferraris et al 2019; D'Amicis et al 2019).
In short:
High protein diets (not otherwise specified) are not necessary to lose weight, they often require expensive commercial products and have long-term side effects High-protein diets are not ketogenic (this is a publicity stunt from companies selling high-protein low-carb products for weight loss, based on the widespread concept that ketogenic = anorexant = slimming). The only ketogenic weight loss regimens are very low calorie ketogenic diet in which ketosis is induced by extreme calorie restriction .
The restriction of carbohydrates is not necessary to lose weight, the restriction / exclusion of carbohydrates rich foods such as pasta, pizza, bread and sweets is a well-accepted strategy for patients because it avoids weighing foods and involves fast weight loss (resulting from cutting calories): it can be used by Certified Nutrition Specialists to increase adherence to treatment for short periods as long as it is followed by the prescription of a balanced diet and dietary education
The restriction of carbohydrates intended as the limitation of sugars and reduction of glycemic load has an impact on glycemic control and may be useful in the treatment of diabetes as part of an integrated dietary education program
The marked restriction of carbohydrates with physiological protein supplies is necessary to induce and maintain a metabolic state of therapeutic ketosis (plasma levels of beta-hydroxybutyrate between 2-5 mmol / L). This dietary therapy (called “classical ketogenic diet”) is a normocaloric, normoproteic, very-low carb and very high fat regimen prescribed for drug resistant epilepsy in developmental age and for some rare genetic diseases (in particular type 1 cerebral glucose transporter deficiency, GLUT1-DS, OMIM 606777): it must be prescribed and monitored by expert medical personnel.
References
Bolla AM, Caretto A, Laurenzi A, Scavini M and Piemonti L. Low-Carb and Ketogenic Diets in Type 1 and Type 2 Diabetes. Nutrients 2019, 11, 962; doi:10.3390/nu11050962
De Amicis R, Leone A, Lessa C, Foppiani A, Ravella S, Ravasenghi S, Trentani C, Ferraris C, Veggiotti P, De Giorgis V, Tagliabue A, Battezzati A, Bertoli A. Long-term effect of classic ketogenic diet on ghrelin and leptin concentration: a 12-months prospective study in a cohort of Italian children and adults with GLUT1-Deficiency Syndrome and drug resistant epilepsy. Nutrients 2019, 11(8), 1716 (DOI: https://doi.org/10.3390/nu11081716)
Dinu M, Pagliai G, Angelino D, Rosi A, Dall'Asta M, Bresciani L, Ferraris C, Guglielmetti M, Godos J, Del Bo' C, Nucci D, Meroni E, Landini L, Martini D, Sofi F. Effects of Popular Diets on Anthropometric and Cardiometabolic Parameters: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials. Adv Nutr. 2020 Jul 1;11(4):815-833. doi: 10.1093/advances/nmaa006
Feinman et al Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base. Nutrition 31 (2015) 1–13
Ferraris C, De Giorgis V, Brambilla I, Guglielmetti M, Trentani C, Manea L, Ferraro O, Bertoli S, Veggiotti P, Tagliabue A. Long-term effects of the ketogenic diet on growth in children with resistant drug epilepsy and Glucose Transporter Type 1 Deficiency Syndrome. Nutrients 2019, 29 (8), 884 DOI: https://doi.org/10.1016/j.numecd.2019.05.047)
Gibson AA, Seimon RV, Lee CMY, Ayre J, Franklin J, Markovic TP, Caterson ID and Sainsbury A. Do ketogenic diets really suppress appetite? In: A. A. Gibson et al. Obesity reviews 2015; 16, 64–76
Kirkpatrick CF, Bolick JP, Kris-Etherton PM, Sikand G, Aspry KE, Soffer DE, Willard K-E, Maki KC. Review of current evidence and clinical recommendations on the effects of low carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. Journal of Clinical Lipidology 2019; 13, 689–711
Larsen TM, Dalskov S-M, Marleen van Baak M, Jebb SA, Papadaki A, Pfeiffer AFH, Martinez JA, Handjieva-Darlenska T, Kunešová M, Pihlsgård T, Stender S, Holst C, Saris WHM and Arne Astrup for the Diet, Obesity, and Genes (Diogenes) Project. Diets with High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance. N Engl J Med. 2010; 363(22): 2102–2113. doi:10.1056/NEJMoa1007137.
Martin-McGill KJ, Jackson CF, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD001903. DOI: 10.1002/14651858.CD001903.pub4.
Pong, A.W.; Geary, B.R.; Engelstad, K.M.; Natarajan, A.; Yang, H.; De Vivo, D.C. Glucose transporter type I deficiency syndrome: Epilepsy phenotypes and outcomes. Epilepsia 2012, 53, 1503–1510.
Veggiotti P, Burlina A, Coppola G, Cusmai R, De Giorgis V, Guerrini R, Tagliabue A, and Dalla Bernardina B. The ketogenic diet for Dravet syndrome and other epileptic encephalopathies: an Italian consensus. Epilepsia 2011;52(Suppl. 2):83e9.
Westerterp-Plantenga MS. How are normal, high- or low-protein diets defined? Br J Nutr 2007; 97, 217–218
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):S105–12.
However, given the importance of identifying effective strategies for weight control, there is a growing scientific interest in evaluating the real effectiveness of different metabolic mixtures proposed as part of a low-calorie diet on short and long-term weight loss and their metabolic effects.
A first difficulty for the correct scientific evaluation of these approaches consists in the poor standardization, as there is no univocal definition of a high-protein diet. In fact, most studies consider "high-protein" a low-calorie diet with over 20% of the energy deriving from proteins but the intake of proteins in grams per kg of body weight, which would allow a more accurate definition, is rarely indicated (Westerterp et al 2007). As already described, most of the high-protein commercial regimens are also low-carb, therefore the metabolic mixture of the macronutrients can vary a lot, thus making a comparison difficult, in particular regarding the effects on the metabolic framework.
Even with these methodological limitations, the effects of "high-protein" diets on weight loss and cardiovascular risk are discussed in the very recent umbrella review carried out by the SINU Giovani Working Group (Dinu M et al, 2020). The authors considered all the meta-analyses published to date on the effects of diets of various kinds on anthropometric and metabolic risk parameters.
The analysis showed that the quality of the meta-analyses published on "high protein" diets (8 in all with protein percentages ranging from 25 to 35% of energy) is critically low and the number of participants relatively small. Little or no evidence is reported regarding the reduction in anthropometric parameters and blood pressure values while the data on the lipid and glycemic profile are discordant. The elevated intake of saturated fatty acids and the reduced fiber content may help explain the increases observed in LDL cholesterol, blood sugar and HbA1c levels and cast doubt on the health outcomes of this type of diet in the long term.
Regarding the maintenance of weight loss, the international Diogenes study concluded that a moderate increase in protein content and reduction in the glycemic index represent a useful tool to prevent weight re-gain following a low-calorie diet aimed at weight loss. (Larsen et al 2010). However, it is important to note that in this study, weight loss was achieved with the use of meal replacements and not with foods available on the market; the conclusions of the study therefore do not seem extensible to other dietary regimens. Subjects who are educated to the correct use of food products on the market may be able to achieve the goal of maintaining their weight even with a normoproteic diet. Finally, it is important to underline that the study did not take into account the long-term side effects that make diets with a moderate increase in protein intake contraindicated in overweight or obese subjects with comorbidities.
2) Low-carb-diets: is there the need to exclude carbohydrates from the diet for weight loss?
The study of the amount of carbohydrate intake in the diet is a different and complex topic. In the past the human brain was thought to be entirely dependent upon glucose, in the ‘60s circulating ketones were discovered to replace glucose as the brain’s major fuel during the marked hyperketonemia of prolonged fasting. Nowadays a hyperketonemic diet can allow growth and maintenance in subjects who lack the brain glucose transporter and, for these subjects, a very low- carb diet is a life-saving therapy (Pong et al 2012). However, low-carb diets are mainly known as weight loss diets used for this purpose since the ‘70s. As previously indicated, most commercial weight loss diets defined as "high protein" are actually also low-carb.
There has recently been a renewed scientific interest in assessing the impact of these diets on glycemic control and other cardiovascular risk factors in patients with prediabetes and type 2 diabetes, but little data on their long-term efficacy and safety is still available ( Kirkpatrick et al 2019; Bolla et al 2019).
Most reviews about the effects of low-carb diets on weight loss and metabolic parameters distinguish moderately low-carb diets, equivalent to 26–44% energy from CHO (130–225 grams per 2000 kcal reference intake), low-carb diets equal to 10-25% energy from CHO (50-130 grams) and very low-carb diets, less than 10% energy from CHO (<50 grams) (Feinman 2015, Kirkpatrick 2019). However, they do not distinguish the type of carbohydrates (starch or sugars) nor the quality of the nutrients that complete the metabolic mixture (type of fat? animal or vegetable protein?). For these reasons, many review conclusions based on this classification may be inappropriate. Limiting our attention to weight loss effects, we can refer again to the recent review (Dinu M et al, 2020) which shows greater short-term weight loss (6 months) with higher carbohydrate restriction diets, an outcome which fades as the duration of follow-up increases. Taking into account that obesity therapy is long-term, the usefulness of this approach therefore appears limited. Proponents of low-carb diets attribute the greater satiating effect of these regimens to the induction of ketosis. However, most commercial diets are not actually ketogenic. The restriction of carbohydrates is a necessary but not sufficient condition to induce a level of therapeutic ketosis (Kirkpatrick 2019): for this purpose, it is also necessary to maintain the protein intake in physiological quantities by supplementing the caloric share with lipids. The ketogenic potential of a diet can be expressed in a simplified way by the ratio (in grams) between ketogenic (fat) and non-ketogenic (proteins and carbohydrates) nutrients. This ratio must be at least equal to or greater than 2 to achieve a therapeutic level of ketosis. The highest levels of ketosis necessary for the treatment of some rare congenital diseases and for drug resistant epilepsy (Martin-McGill 2018, Pong et al 2012) are obtained with ratios of 3: 1 and 4: 1 (International Study Group on Ketogenic diet - International League Against Epilepsy https://www.ilae.org/patient-care/ketogenic-diets/international-centers)
The effects of ketosis on satiety are not completely elucidated (Gibson et al 2015). The long-term maintenance of a classic ketogenic diet (normocaloric, normoproteic, very low-carb and very high-fat ketogenic diet) does not alter ghrelin values and does not compromise weight and linear growth as demonstrated by recent studies conducted in children suffering from rare metabolic disease who require long-term ketogenc dietary treatment (Ferraris et al 2019; D'Amicis et al 2019).
In short:
High protein diets (not otherwise specified) are not necessary to lose weight, they often require expensive commercial products and have long-term side effects High-protein diets are not ketogenic (this is a publicity stunt from companies selling high-protein low-carb products for weight loss, based on the widespread concept that ketogenic = anorexant = slimming). The only ketogenic weight loss regimens are very low calorie ketogenic diet in which ketosis is induced by extreme calorie restriction .
The restriction of carbohydrates is not necessary to lose weight, the restriction / exclusion of carbohydrates rich foods such as pasta, pizza, bread and sweets is a well-accepted strategy for patients because it avoids weighing foods and involves fast weight loss (resulting from cutting calories): it can be used by Certified Nutrition Specialists to increase adherence to treatment for short periods as long as it is followed by the prescription of a balanced diet and dietary education
The restriction of carbohydrates intended as the limitation of sugars and reduction of glycemic load has an impact on glycemic control and may be useful in the treatment of diabetes as part of an integrated dietary education program
The marked restriction of carbohydrates with physiological protein supplies is necessary to induce and maintain a metabolic state of therapeutic ketosis (plasma levels of beta-hydroxybutyrate between 2-5 mmol / L). This dietary therapy (called “classical ketogenic diet”) is a normocaloric, normoproteic, very-low carb and very high fat regimen prescribed for drug resistant epilepsy in developmental age and for some rare genetic diseases (in particular type 1 cerebral glucose transporter deficiency, GLUT1-DS, OMIM 606777): it must be prescribed and monitored by expert medical personnel.
References
Bolla AM, Caretto A, Laurenzi A, Scavini M and Piemonti L. Low-Carb and Ketogenic Diets in Type 1 and Type 2 Diabetes. Nutrients 2019, 11, 962; doi:10.3390/nu11050962
De Amicis R, Leone A, Lessa C, Foppiani A, Ravella S, Ravasenghi S, Trentani C, Ferraris C, Veggiotti P, De Giorgis V, Tagliabue A, Battezzati A, Bertoli A. Long-term effect of classic ketogenic diet on ghrelin and leptin concentration: a 12-months prospective study in a cohort of Italian children and adults with GLUT1-Deficiency Syndrome and drug resistant epilepsy. Nutrients 2019, 11(8), 1716 (DOI: https://doi.org/10.3390/nu11081716)
Dinu M, Pagliai G, Angelino D, Rosi A, Dall'Asta M, Bresciani L, Ferraris C, Guglielmetti M, Godos J, Del Bo' C, Nucci D, Meroni E, Landini L, Martini D, Sofi F. Effects of Popular Diets on Anthropometric and Cardiometabolic Parameters: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials. Adv Nutr. 2020 Jul 1;11(4):815-833. doi: 10.1093/advances/nmaa006
Feinman et al Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base. Nutrition 31 (2015) 1–13
Ferraris C, De Giorgis V, Brambilla I, Guglielmetti M, Trentani C, Manea L, Ferraro O, Bertoli S, Veggiotti P, Tagliabue A. Long-term effects of the ketogenic diet on growth in children with resistant drug epilepsy and Glucose Transporter Type 1 Deficiency Syndrome. Nutrients 2019, 29 (8), 884 DOI: https://doi.org/10.1016/j.numecd.2019.05.047)
Gibson AA, Seimon RV, Lee CMY, Ayre J, Franklin J, Markovic TP, Caterson ID and Sainsbury A. Do ketogenic diets really suppress appetite? In: A. A. Gibson et al. Obesity reviews 2015; 16, 64–76
Kirkpatrick CF, Bolick JP, Kris-Etherton PM, Sikand G, Aspry KE, Soffer DE, Willard K-E, Maki KC. Review of current evidence and clinical recommendations on the effects of low carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. Journal of Clinical Lipidology 2019; 13, 689–711
Larsen TM, Dalskov S-M, Marleen van Baak M, Jebb SA, Papadaki A, Pfeiffer AFH, Martinez JA, Handjieva-Darlenska T, Kunešová M, Pihlsgård T, Stender S, Holst C, Saris WHM and Arne Astrup for the Diet, Obesity, and Genes (Diogenes) Project. Diets with High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance. N Engl J Med. 2010; 363(22): 2102–2113. doi:10.1056/NEJMoa1007137.
Martin-McGill KJ, Jackson CF, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD001903. DOI: 10.1002/14651858.CD001903.pub4.
Pong, A.W.; Geary, B.R.; Engelstad, K.M.; Natarajan, A.; Yang, H.; De Vivo, D.C. Glucose transporter type I deficiency syndrome: Epilepsy phenotypes and outcomes. Epilepsia 2012, 53, 1503–1510.
Veggiotti P, Burlina A, Coppola G, Cusmai R, De Giorgis V, Guerrini R, Tagliabue A, and Dalla Bernardina B. The ketogenic diet for Dravet syndrome and other epileptic encephalopathies: an Italian consensus. Epilepsia 2011;52(Suppl. 2):83e9.
Westerterp-Plantenga MS. How are normal, high- or low-protein diets defined? Br J Nutr 2007; 97, 217–218
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):S105–12.