Longer-Term Effects of the Glycaemic Index on Substrate Metabolism and Performance in Endurance Athletes

rition has a decisive in uence on athletic performance. However, it is not only the nutrient intake during exercise that is important, but the daily diet must also be adapted to the requirements of physical activity in order to optimally promote training adaptations. The goal of prolonged endurance training is to enhance fat oxidation, to maintain aerobic performance at a higher intensity while sparing limited carbohydrate stores. The targeted modi cation of macronutrient intake is a common method of in uencing substrate metabolism, fuel selection, and performance. However, it is not well established whether the glycaemic index of carbohydrates in our daily diet can improve endurance performance by in uencing carbohydrate or fat oxidation during training. Therefore, the aim of the following review is to elucidate the possible in uence of the glycaemic index on substrate utilization during exercise and to clarify whether the consumption of a long-term high- carbohydrate diet with different glycaemic indices may have an in uence on substrate metabolism and endurance performance. Keywords: glycaemic index; long-term effects; sport nutrition; endurance performance; substrate metabolism 1. Introduction Endurance athletes should not only pay attention to

possible in uence of the glycaemic index on substrate utilization during exercise and to clarify whether the consumption of a long-term high- carbohydrate diet with different glycaemic indices may have an in uence on substrate metabolism and endurance performance. Keywords: glycaemic index; long-term effects; sport nutrition; endurance performance; substrate metabolism 1. Introduction Endurance athletes should not only pay attention to suf cient carbohydrate intake during exercise, but also to the carbohydrate content of their daily diet, in order to optimally replenish glycogen stores. The recommended amount of daily CHO intake depends on several factors, including training frequency, duration, and intensity. Therefore, the recommendation for CHO intake varies from 3 to 12 g kg body weight 1 day 1 . Depending on which metabolic or structural adaptation is to be the focus of the current training load, it must be decided whether more or less carbohydrates should be supplied [1,2]. Furthermore, it is important for athletes to be mindful of the nutritional and physio- logical effects associated with their dietary intake. The quality of carbohydrates, and in particular the glycaemic index, can signi cantly in uence the metabolic processes after ingestion. The glycaemic index (GI) categorizes carbohydrates according to their impact on blood glucose concentration and the extent to which they stimulate insulin secretion, usually compared to glucose (GI = 100) or white bread (GI = 70) [3,4]. Therefore, the GI re ects the availability of the consumed CHO in the blood. So, for the same amount of carbohydrates, a low-GI food (GI 55) will not raise blood glucose to the same extent as a high-GI food (GI 70). Low-GI foods are therefore digested and absorbed more slowly compared to high-GI foods [5,6]. Among other factors, the relative ratio of carbohydrate to fat oxidation is decisively co-regulated by the level of insulin concentration in the blood. The higher the GI, the faster the blood glucose rises, the higher the insulin secretion, and Nutrients2023,15, 3028.

to fat oxidation is decisively co-regulated by the level of insulin concentration in the blood. The higher the GI, the faster the blood glucose rises, the higher the insulin secretion, and Nutrients2023,15, 3028.

Nutrients2023,15, 3028 2 of 15 the lower the fat oxidation. This relationship has already been demonstrated in athletes during endurance activity [7,8]. For improving performance, an athlete needs a combination of adequate fuel stores to provide enough ATP for muscle work and metabolic exibility. Metabolic exibility refers to the capacity to effectively utilize various pathways to optimize ATP regeneration, while also enabling the utilization of all muscle fuel sources to meet the speci c demands of exercise at different intensities [9]. So far, it has been believed that a low-carbohydrate diet has bene cial effects on fat oxidation. However, the disadvantage of these so-called low- carbohydrate diets is that performance at higher intensities deteriorates because metabolic exibility is worsened by the absence of carbohydrates [10]. In theory, with the help of the GI and its in uence on postprandial insulin secretion and fat oxidation, it should be possible to improve metabolic exibility by improving fat oxidation and having suf cient carbohydrates for energy provision at high intensities. The present review aims to investigate whether the glycaemic index plays a role in en- durance sports and if the consumption of long-term carbohydrate-rich diets with different glycaemic indices can have an in uence on substrate metabolism and endurance performance. 1.1. Mechanism of Substrate Oxidation during Endurance Exercise and In uencing Factors During prolonged endurance exercise, the main source of ATP fuel for muscle work is derived from the oxidative phosphorylation of both fat and carbohydrates (CHO). The primary substrates utilized by the muscles, include muscle and liver glycogen, blood glucose, and fatty acids derived from muscle and adipose tissue triglyceride stores [11,12]. The oxidation of proteins for energy production is less important compared to the primary sources—carbohydrates and fats—and they contribute only about 5% to ATP supply [12]. As the intensity of exercise increases, there is a greater reliance on glucose and glycogen as fuel sources, surpassing the oxidation of fat. This shift occurs because carbohydrates provide a greater energy output per unit of time, leading to an increased reliance on glucose and glycogen [13–15]. In healthy individuals, maximal rates of fat

about 5% to ATP supply [12]. As the intensity of exercise increases, there is a greater reliance on glucose and glycogen as fuel sources, surpassing the oxidation of fat. This shift occurs because carbohydrates provide a greater energy output per unit of time, leading to an increased reliance on glucose and glycogen [13–15]. In healthy individuals, maximal rates of fat oxidation can be expected at intensities of 60–65% of maximal oxygen uptake (VO2max) [16] and vary from 0.18 to 1.01 g min 1 [17]. With glycogen stores in the muscles and liver limited to approximately 2000 kcal, they represent one of the most important limiting factors for prolonged endurance exercise at higher intensities. Research over recent decades has shown that the most effective diet is the one that is able to augment and preserve CHO fuel stores (i.e., muscle and liver glycogen) for the decisive phases of a race [18]. Fat stores, on the other hand, are normally present in the body in suf cient quantities to theoretically supply the body with fuel for several days [12]. Half a kilogram of fat provides around 4500 kcal and the high storage capacity makes fat the energy source of choice for low to moderate intensities when enough oxygen is available [19–21]. Combined with exercise, a high rate of fat oxidation modulates insulin sensitivity and glucose tolerance. Hence, enhanced fat oxidation is not only a goal for athletes but also for the general population as it might improve performance at rst glance and health in the longer-term speaking [22,23]. Substrate utilization can be in uenced through the intake of exogenous carbohydrates during exercise. Since the beginning of the 20th century, the effects of CHO intake during prolonged endurance exercise have been of interest for researchers [24–26]. Dill, et al. [27] for example, found as early as 1932 that the blood sugar level in dogs could be kept con- stant during prolonged exercise by administering 20 g of carbohydrates per hour and, furthermore, the dogs could maintain a certain speed for a longer time-period compared to when consuming water. Moreover, it was found that

for researchers [24–26]. Dill, et al. [27] for example, found as early as 1932 that the blood sugar level in dogs could be kept con- stant during prolonged exercise by administering 20 g of carbohydrates per hour and, furthermore, the dogs could maintain a certain speed for a longer time-period compared to when consuming water. Moreover, it was found that by supplying carbohydrates be- fore and during exercise, symptoms of hypoglycaemia could be avoided and endogenous carbohydrate stores were spared [28–30]. Controlled studies have shown that carbohy- drate supplementation can prolong performance during endurance exercise because CHO oxidation can be maintained for a longer period of time compared to placebo administra- tion [31–34]. The understanding that carbohydrates exert an in uence on performance was

Nutrients2023,15, 3028 3 of 15 established many years ago. Since then, numerous studies have been conducted to nd the optimal amount, type, and timing of carbohydrate intake during exercise [35]. The current recommendations suggest ingesting up to 60 g h 1 of rapidly available carbohy- drates such as glucose or glucose-fructose mixes for activities that are not longer than 2.5 h. When mixtures of glucose and fructose are ingested, this amount could be increased up to 90 g h 1 for prolonged exercise, because of different intestinal transport pathways [1,2,36]. As shown in Figure, both CHO via glycolysis and fat via beta-oxidation can supply acetyl CoA for the tricarboxylic acid cycle (TCA, also known as the Krebs cycle or citric acid cycle) [37,38]. Therefore, these two mechanisms are closely related. Thus, the mnemonic that fat burns in the re of carbohydrates was presented. On the one hand, it has been observed that the complete oxidation of fatty acids is facilitated by the simultaneous oxidation of carbohydrates. Early studies have shown that the intermediates from the TCA have an igniting effect on fat oxidation by accumulating adenosine diphosphate (ADP) and forming an acetyl-acceptor in the form of oxaloacetate [38]. On the other hand, however, research with isotopes has shown that carbohydrate metabolism can limit the oxidation of fatty acids by limiting the production of ketone bodies [39]. Early studies conducted on isolated cells have shown that acetyl CoA derived from carbohydrates is accessible for forming acylcarnitine, while acetyl CoA from beta-oxidation is more readily available for the TCA cycle. However, the rate of fatty acid oxidation is in uenced by the acetyl CoA derived from the pyruvate metabolism [40]. Because of the steps in the metabolism of carbohydrates and lipids that occur before the TCA cycle, it is dif cult to draw conclusions from studies with isolated cells or where only the isolated substrate was added to start the TCA cycle.Nutrients 2023, 15, x FOR PEER REVIEW 3 of 16 understanding that carbohydrates exert an influence on performance was established many years ago. Since then, numerous studies have been conducted to

occur before the TCA cycle, it is dif cult to draw conclusions from studies with isolated cells or where only the isolated substrate was added to start the TCA cycle.Nutrients 2023, 15, x FOR PEER REVIEW 3 of 16 understanding that carbohydrates exert an influence on performance was established many years ago. Since then, numerous studies have been conducted to find the optimal amount, type, and timing of carbohydrate intake during exercise [35]. The current recommendations suggest ingesting up to 60 g·h −1 of rapidly available carbohydrates such as glucose or glu- cose-fructose mixes for activities that are not longer than 2.5 h. When mixtures of glucose and fructose are ingested, this amount could be increased up to 90 g·h −1 for prolonged exer- cise, because of different intestinal transport pathways [1,2,36]. As shown in Figure 1, both CHO via glycolysis and fat via beta-oxidation can supply acetyl CoA for the tricarboxylic acid cycle (TCA, also known as the Krebs cycle or citric acid cycle) [37,38]. Therefore, these two mechanisms are closely related. Thus, the mne- monic that fat burns in the fire of carbohydrates was presented. On the one hand, it has been observed that the complete oxidation of fatty acids is facilitated by the simultaneous oxidation of carbohydrates. Early studies have shown that the intermediates from the TCA have an igniting effect on fat oxidation by accumulating adenosine diphosphate (ADP) and forming an acetyl-acceptor in the form of oxaloacetate [38]. On the other hand, however, research with isotopes has shown that carbohydrate metabolism can limit the oxidation of fatty acids by limiting the production of ketone bodies [39]. Early studies conducted on isolated cells have shown that acetyl CoA derived from carbohydrates is accessible for forming acylcarnitine, while acetyl CoA from beta-oxidation is more readily available for the TCA cycle. However, the rate of fatty acid oxidation is influenced by the acetyl CoA derived from the pyruvate metabolism [40]. Because of the steps in the metab- olism of carbohydrates and lipids that occur before the TCA cycle, it is difficult to draw conclusions from studies with isolated cells

acetyl CoA from beta-oxidation is more readily available for the TCA cycle. However, the rate of fatty acid oxidation is influenced by the acetyl CoA derived from the pyruvate metabolism [40]. Because of the steps in the metab- olism of carbohydrates and lipids that occur before the TCA cycle, it is difficult to draw conclusions from studies with isolated cells or where only the isolated substrate was added to start the TCA cycle. Figure 1. The TCA cycle with all intermediates (black), energy providing products (green), and en- zymes (italic). The formation of acetyl CoA is carried out either by glycolysis or beta-oxidation. NADH = nicotinamide adenine dinucleotide; FADH 2 = flavin adenine dinucleotide; GDP = guano- sine diphosphate; GTP = guanosine triphosphate. When both carbohydrates and fats are present for fuel, the muscle tends to prioritize the oxidation of carbohydrates. This preference for carbohydrates is due to their higher gly- colytic flux and the resulting increased production of acetyl CoA. Consequently, carbohy- drates hinder the oxidation of fats by inhibiting the production of acetyl CoA from fat and impeding the transport of long-chain fatty acids into the mitochondria [41]. However, the Figure 1. The TCA cycle with all intermediates (black), energy providing products (green), and enzymes (italic). The formation of acetyl CoA is carried out either by glycolysis or beta-oxidation. NADH = nicotinamide adenine dinucleotide; FADH 2= avin adenine dinucleotide; GDP = guanosine diphosphate; GTP = guanosine triphosphate. When both carbohydrates and fats are present for fuel, the muscle tends to prioritize the oxidation of carbohydrates. This preference for carbohydrates is due to their higher glycolytic ux and the resulting increased production of acetyl CoA. Consequently, carbo- hydrates hinder the oxidation of fats by inhibiting the production of acetyl CoA from fat and impeding the transport of long-chain fatty acids into the mitochondria [41]. However, the oxidation of fatty acids also regulates the rate and fate of glucose metabolism in the

CoA from fat and impeding the transport of long-chain fatty acids into the mitochondria [41]. However, the oxidation of fatty acids also regulates the rate and fate of glucose metabolism in the

Nutrients2023,15, 3028 4 of 15 muscle. This reciprocal relationship between the oxidation of the two fuels is known as the glucose/fatty acid cycle [42]. Insulin counts as a key regulator in this complex interplay. It is known as an anabolic hormone, which regulates the storage of energy in the form of glycogen and fat [43]. During the process of energy production, insulin has various effects on fat oxidation. Firstly, insulin stimulates the activity of acetyl-CoA carboxylase (ACC), an enzyme responsible for the conversion of acetyl CoA into malonyl-CoA. Malonyl-CoA, in turn, hinders the function of carnitine palmitoyltransferase (CPT), which is responsible for transporting fatty acids into the mitochondria for energy generation. Monitoring the concentration of malonyl-CoA can provide insights into the availability of carbohydrates as a substrate. When carbohydrates are oxidized (CHO oxidation), there is an increase in glycolytic ow and a greater production of pyruvate. Consequently, the concentration of acetyl CoA, and hence malonyl-CoA, rises, leading to a decrease in fatty acid oxidation. This decrease occurs as CPT's activity is inhibited, reducing the transportation of long-chain fatty acids into the mitochondria [44,45]. Secondly, insulin is a potent inhibitor of lipolysis, working by reducing non-esteri ed free fatty acid (NEFA) availability. During the process of fatty acid release from adipose tissue, insulin hinders the activity of hormone-sensitive lipase in adipose tissue. This inhibition leads to a decrease in the levels of non-esteri ed fatty acids (NEFAs) in the bloodstream. Consequently, the muscle is compelled to utilize glucose to a greater extent. When plasma insulin increases, after the administration of carbohydrates [46,47], a reduction in total fat oxidation could be observed [41,48–50]. During periods of low CHO availability, insulin secretion is suffocated and the organism relies on fat as a fuel [43]. Overall, insulin has two signi cant effects on substrate oxidation, ultimately resulting in the inhibition of fat oxidation and the promotion of glucose utilization: (1) increasing malonyl-CoA concentration through activated ACC and thereby decreasing the rate of fatty acid oxidation via inhibited CPT activity; and (2) reducing NEFA availability via the effect on adipose tissue lipolysis. In the fed

[43]. Overall, insulin has two signi cant effects on substrate oxidation, ultimately resulting in the inhibition of fat oxidation and the promotion of glucose utilization: (1) increasing malonyl-CoA concentration through activated ACC and thereby decreasing the rate of fatty acid oxidation via inhibited CPT activity; and (2) reducing NEFA availability via the effect on adipose tissue lipolysis. In the fed state (i.e., when insulin secretion is stimulated), insulin regulates energy storage and limits fat oxidation, whilst in the fasted state, fat oxidation is promoted. In summary, since the GI re ects the insulinemic response of a CHO, low-GI foods can attenuate the suppression of fat oxidation compared to high-GI foods. A low-GI CHO results in a lower postprandial increase in blood glucose and insulin and consequently a mitigated inhibition of fat oxidation. Modifying substrate metabolism through dietary and exercise interventions has been a subject of interest for several years. For prolonged low-intensity endurance exercise, it is bene cial to promote high fat oxidation as it helps to reduce lactate concentrations and conserve limited carbohydrate stores. Various approaches and dietary plans, such as ketogenic or low-carbohydrate, high-fat diets (LCHF), have been suggested to alter substrate metabolism and, consequently, enhance endurance performance. During a low- carbohydrate, high-fat (LCHF) diet, the intake of carbohydrates (<20 E-% carbohydrates per day, >50 E-% fat per day) is drastically reduced. These metabolic changes facilitate an increase in the availability of free fatty acids, resulting in a reduced utilization of muscle glycogen and a reduction in CHO oxidation during physical activity [16,47,51]. After two to three weeks on a LCHF diet, the body enters a ketogenic state, which is thought to enhance performance during prolonged exercise by improving substrate utilization in favor of fat and conserving muscle glycogen [52,53]. The process of oxidizing non-esteri ed fatty acids in the liver produces ketone bodies (such as acetoacetate, acetone, etc.), leading to ketosis. In situations when carbohydrate availability is limited, muscles oxidize ketone bodies to generate energy [16,54]. Volek, et al. [55] demonstrated that a long-term LCHF diet can increase maximal fat oxidation to 1.5 g/min and the intensity

This review investigates the impact of glycaemic index on endurance performance.