Animal and plant‐based proteins have different postprandial effects on energy expenditure, glycemia, insulinemia, and lipemia: A review of controlled clinical trials

Abstract Dietary proteins have been shown to stimulate thermogenesis, increase satiety, and improve insulin sensitivity in the short and long term. Animal‐based proteins (AP) and plant‐based proteins (PP) have different amino acid profiles, bioavailability, and digestibility, so it seems to have various short‐ and long‐term effects on metabolic responses. This review aimed to compare the findings of controlled clinical trials on postprandial effects of dietary Aps versus PPs on energy expenditure (EE), lipemia, glycemia, and insulinemia. Data are inconclusive regarding the postprandial effects of APs and PPs. However, there is some evidence indicating that APs increase postprandial EE, DIT, and SO more than PPs. With lipemia and glycemia, most studies showed that APs reduce or delay postprandial glycemia and lipemia and increase insulinemia more than PPs. The difference in amino acid composition, digestion and absorption rate, and gastric emptying rate between APs and PPs explains this difference.

The possible biological mechanism for the high thermogenic effect of proteins is the lack of storage capacity for proteins in the body to cope with high-protein intakes, which lead to protein metabolization and thus increase thermogenesis (Gurr et al., 1980;Rothwell & Stock, 1987). The high thermogenic effect of protein may be attributed to (a) high Adenosine triphosphate (ATP) costs of peptide bonds (Garlick et al., 1991;Giordano & Castellino, 1997;Golden et al., 1977;Rennie et al., 1982), (b) the high-energy cost of the pathways that involve protein metabolism, including gluconeogenesis and urea production (Stryer, 1995), and (c) increased proton-pump activity in liver cell membrane following high-protein meal ingestion (Forslund et al., 1999).
The protein synthetic response largely depends on the availability of essential amino acids, especially; leucine (Atherton et al., 2010;Volpi et al., 2003). After ingestion of APs, protein synthesis increases more than PPs, which is due to the increase in plasma essential AAs (e.g., leucine; Gorissen et al., 2016Gorissen et al., , 2017Robinson et al., 2013;Yang et al., 2012).
Since APs and PPs have different amino acid compositions and different effects on protein synthesis, they may affect EE, DIT, and substrate oxidation (SO) differently in the postprandial period.
The findings of previous studies regarding the postprandial effects of APs and PPs on different markers of energy metabolism have been controversial (Table 1).
Some studies showed that APs increased postprandial EE and SO compared with PPs (Acheson et al., 2011;Mikkelsen et al., 2000;Tan et al., 2010). The higher EE and DIT due to AP ingestion may be due to the higher thermogenic response produced by a high biological value protein, consisting of a well-balanced amino acid mixture, than a lower biological value protein (soy; Nielsen et al., 1994;Pitkänen et al., 1994). Moreover, leucine, which is found in larger amounts in animal proteins, has the most thermogenic effect (Tsujinaka et al., 1996). APs also have lower protein oxidation than PPs, suggesting that APs, like meat, can produce a protein-sparing effect and might maintain lean body mass (Tan et al., 2010). On the other hand, some studies showed no significant difference in postprandial effects on EE, carbohydrate, and fat oxidation neither between APs and PPs nor between different AP proteins (Hawley et al., 2020;Melson et al., 2019).
In summary, although some studies declare that APs increase EE and SO more than PPs, the findings of controlled clinical trials are inconclusive, and there is a need for further studies to evaluate the effects of protein sources on postprandial EE and SO.

| Postprandial glycemia and insulinemia
The quality and quantity of dietary protein could affect glycemic response. Dietary proteins induce insulin secretion and influence glycemic response, both in the long and short term (Bowen et al., 2007;Layman et al., 2003;von Post-Skagegård et al., 2006). Therefore, high-protein meals with low or moderate carbohydrate content increase insulin secretion due to the synergistic effect of high-protein and low-carbohydrate intake on insulin sensitivity and glucose uptake (Frid et al., 2005;Gannon et al., 2003).
Animal-based proteins and PPs seem to affect insulin secretion and glucose uptake differently in the postprandial period (Frid et al., 2005). Some AAs, including BCAAs (valine, leucine, isoleucine), are known as insulinogenic amino acids and can increase insulin secretion in the short and long term (Schmid et al., 1992;von Post-Skagegård et al., 2006). On the other hand, the digestion and absorption rate of AP and PP is different, which alters the serum levels of the gastric inhibitory polypeptide as an insulinotropic peptide (Jakubowicz & Froy, 2013 of proteins, the faster the release of bioactive amino acids in the bloodstream and the higher stimulation of incretins secretion (Oliveira et al., 2011). Incretins, including Glucose-dependent insulinotropic polypeptide (GIP) and Glucagon-like Polypeptide-1 (GLP-1) stimulate insulin release and inhibit glucagon hormone secretion (Calbet & MacLean, 2002;Chacra, 2006;Johnston & Buller, 2005). The absorption and digestion rate of whey protein is faster than PPs. Whey protein contains higher concentrations of valine, leucine, isoleucine, and lysine, which have insulinotropic effects than PP. Therefore, whey protein can induce insulin secretion and improve insulin sensitivity and reduce glycemic response to a greater extent compared with PPs (Akhavan et al., 2010;Pal & Ellis, 2010;van Loon et al., 2000). In addition to digestion and absorption rate, the different gastric emptying rates may explain the differences in the glycemic response of AP and PPs (Lang et al., 1999). The concept of fast and slow proteins was first introduced by Boirie et al. (1997) (Boirie et al., 1997); hence, slow proteins reduce and delay glycemic responses due to gastric emptying ( Figure 1). Table 2  Furthermore, postprandial glycemia was more stable after whey protein consumption.
The absorption and digestion rate of whey protein is faster than PP. Whey protein contains higher concentrations of valine, leucine, isoleucine, and lysine, which have insulinotropic effects than PP. Therefore, whey protein can induce insulin secretion and improve insulin sensitivity, contributing to a lower glycemic response than PP (Akhavan et al., 2010;Pal & Ellis, 2010;van Loon et al., 2000). Hence, whey protein exerts a more significant effect on glycemic response. Dougkas and Östman (2018) compared the postprandial effects of breakfast meals containing PP (a blend of oat, pea, and potato), AP (milk), and a 50:50 mixture. The results showed that plasma glucose was higher after consuming the PP compared with the AP, possibly due to the higher insulin levels after ingestion of the AP meal.
However, this difference was not statistically significant.
In another randomized, crossover study by Crowder et al. (2016), the effects of AP versus PP on postprandial metabolic response, including postprandial glycemia, were compared (Crowder et al., 2016).
The authors showed that postprandial glucose was higher after PP meal ingestion than after AP meals. Moreover, the percent change F I G U R E 1 Schematic representation of postprandial glycemia, insulinemia, and lipemia modulated by dietary protein source.

TA B L E 2
Controlled clinical trials on the acute effects of protein source (AP vs. PP) on glycemia and insulinemia.

TA B L E 2 (Continued)
in glucose response from the postprandial peak was lower following the AP meal ingestion than a PP meal.
In summary, APs, especially whey protein, result in lower glycemic and higher insulin responses than PPs, including soy or peas. The amino acid composition, digestion and absorption rate, and gastric emptying rate between different protein sources may explain these differences.
Protein quantity and quality may also affect postprandial lipemia. It has been proven that consuming a high-protein diet enriched with AP leads to lower postprandial chylomicronemia than a low-protein diet (25% and 14%, respectively; Mamo et al., 2005).
APs and PPs have different effects on postprandial lipemia. The mechanism of the different effects of APs and PPs on postprandial lipemia is not clearly understood. However, some hypotheses have been proposed for these findings. One mechanism might be related to the formation and clearance of chylomicron (Mortensen et al., 2009). Another mechanism might be the different effects of protein sources on lipoprotein lipase (LPL) release (Acheson et al., 2011;Eckel, 1989). Lipoprotein lipase is the essential enzyme in regulating the metabolism of lipids and lipoproteins; it plays a vital role in the hydrolysis of the TG content of these lipoproteins (Eckel, 1989;Kersten, 2014). Another reason might be the difference in the insulinogenic amino acid content of different protein sources that results in different insulin stimulation (Acheson et al., 2011;Nilsson et al., 2004). Insulin is an essential stimulant for LPL and hormone-sensitive lipase, affecting TG lev- Some studies also showed that whey protein was associated with lower postprandial serum lipids and reduced TG content of chylomicron-rich supernatant (Acheson et al., 2011;Holmer-Jensen et al., 2013;Mortensen et al., 2009).
In contrast, Bjørnshave et al. (2019) reported no significant relationship between the type of ingested protein and postprandial lipemia (Bjørnshave et al., 2019).
The possible mechanisms for the greater effect on postprandial lipemia observed after whey protein ingestion might be as follow; whey protein induces insulin release, increases the activity of LPL, and leads to a lower postprandial lipemia compared with other proteins. On the other hand, increased insulin levels after consuming whey protein inhibits hormone-sensitive lipase and suppresses FFA release from adipose tissue.
Furthermore, some studies have mentioned that whey protein delays gastric emptying compared with casein (Acheson et al., 2011;Hall et al., 2003). Delayed gastric emptying may result in delayed and even slower postprandial peak levels of TG. However, the results of some previous studies regarding the difference in gastric transition were in contrast to the findings of the mentioned studies (Calbet & Holst, 2004;Mortensen et al., 2009) and SO more than PPs, which may be due to the higher thermogenic response produced by a high biological value protein consisting of a well-balanced amino acid mixture. APs also found to reduce or delay postprandial glycemia and lipemia and increase insulinemia more than PPs.
Knowing the differences in postprandial effects of APs and PPs may provide an opportunity for weight control programs and prevention and management of chronic diseases. However, further well-designed acute phase and long-term studies are needed to eval-