Currently, the Covid‐19 pandemic forces almost every country to take drastic measures to stop the spread of the virus. These include the avoidance of close contact with other humans, staying at home whenever possible and the closure of gyms or sport clubs. Now that people are more or less bound to their home, it is even more important to stay physically active. The occasional walks between sofa and fridge are not enough to keep your body in shape. But why is exercise so important and is there anything one can take to get the most out of every single training session?

Regular exercise is essential for a healthy lifestyle. The widely known results are improved body composition, reduction of blood pressure, plasma cholesterol and body fat percentage.1-3 Furthermore, exercise leads to an improved whole body insulin sensitivity, by increasing the number of active glucose transporters and glycogen synthesis.4 It reduces the risk of several chronic diseases such as diabetes, cardiovascular diseases, dementia and depression.5 Exercise not only influences metabolism but also most certainly causes a gain in strength and muscle fibre size.6 In addition, the benefits are not only for the individuals themselves but may lead to a better epigenetic impact, regarding metabolic diseases, for their future offspring.7 Speaking of offspring—when using high doses of NSAIDs to ease the headache they can give you, muscle hypertrophy is impaired.8, 9 However, there are factors other than physical activity, which can influence the size of skeletal muscles, including genetics, environment and metabolism.10 The effects of exercise are more impressive in untrained compared to already trained persons.11 In other words, the relative progress due to training reduces with increased physical fitness. This may lead to a decrease in motivation in well‐trained subjects. As a result, people may resort to drugs or substances which support their training progress.

Performance‐enhancing substances (PES) have the ability or potential to alter the human body and biological functions, including the ability to considerably improve athletic performance.12 They are widely used by athletes in expectance of an increase in performance, strength and muscle mass. The international watchdog against use of illicit drugs among athletes, the World Anti‐Doping Agency (WADA), regularly updates the list of prohibited substances. This article, however, focuses on those which are legally accessible, specifically creatine, protein, beta‐hydroxy‐beta‐methylbutyrate and caffeine.

Creatine is an endogenic substance which is involved in energy metabolism, thus important in tissues with high metabolic demand.13 It is produced in two steps in the kidney and liver from the amino acids arginine and glycine. Up to 95% of formed creatine is stored in skeletal muscles, most of it as creatine phosphate.14 The creatine kinase transfers the phosphate group from phosphocreatine to ADP, forming ATP. After functioning as an energy substrate, creatine is degraded to creatinine, which is excreted by the kidney. Therefore, high serum creatinine levels can be an indicator for kidney damage. As a PES, creatine increases strength, performance in short‐duration and high‐intensity exercises, number of repetitions and total force.15 These effects may result from either increased availability of ATP leading to a greater energy reserve for exercise or a better adaption to a more intense training. It is also hypothesized that creatine enhances satellite cell (muscle stem cell) differentiation and mitotic activity.13 People who do not show an effect after creatine use are called non‐responders. It is said that their creatine level before supplementation was already high; thus, the extra creatine did not show great effects.14 Many studies indicate the safety of short‐term creatine use, but long‐term studies are limited.15 This is why creatine use for a long period should be avoided. Supplementation did not change serum creatinine levels in healthy individuals.15 There are theories that the osmotic activity of creatine, and the resulting flow of water into the muscle cells, can lead to dehydration, compartment syndrome, muscle cramps or heatstroke.15 But, none of these theories have been supported.

Protein supplementation is not only popular in sports but also it is also marketed to non‐athletes in different kinds of food, where the protein replaces carbohydrates or fat. These products, such as protein candy bars, protein bread, etc, supposedly offer a healthy alternative and help with weight management. The most common protein for athletes comes in the form of a powder, which is mixed with water or milk to make drinks. Additional protein supplementation, combined with resistance exercise, increases muscle mass and strength.16 It enhances protein synthesis rate and inhibits muscle protein breakdown.17 The effects are greater in trained and young individuals.16, 17 A protein intake of 1.6 g/kg BW/d is sufficient. An additional intake did not show any significant differences in gains of muscle mass or strength.16 However, a protein intake above 1.2 g/kg BW/d is considered a high‐protein diet and may cause alterations in renal function and health.18 The osmotic activity of amino acids leads to a higher glomerular filtration rate (GFR) at first, but a resulting kidney damage reduces the GFR in the long haul.18 People with normal kidney function are less likely to develop a reduced GFR through long‐term high‐protein intake than people with subnormal kidney function.18 Unfortunately, a decrease in GFR is normally diagnosed when the kidneys have already lost most of their functionality. Additional diagnostic tools for detection of early stage kidney injury are needed.19 Therefore, while protein supplementation may be beneficial for exercising, it should be used cautiously. Resistance exercise by itself has a greater effect on sports performance than the addition of protein supplements, so training should be the first priority.16

Beta‐hydroxy‐beta‐methylbutyrate (HMB) is an endogenous molecule and used as a PES. It is synthesized from leucine in two steps. First is the transamination of leucin to alpha‐ketoisocaproic acid, which occurs mainly in the skeletal muscles. Second, the ketoisocaproic acid is metabolized by KIC dioxygenase to HMB outside of the muscles.20 The half‐life of HMB is about 1‐3 hours in humans. It is excreted by the kidney, but most of the HMB will be used for HMG‐CoA synthesis, which is a direct precursor molecule for cholesterol synthesis.20 HMB enhances protein synthesis and reduces protein breakdown in skeletal muscles.14 The suggested mechanisms are the upregulation of mTOR and an influence on the growth hormone/IGF‐1 axis for protein synthesis and hypertrophy; and inhibition of ubiquitin proteasome and the autophagy‐lysosome systems for protein breakdown.14, 20 HMB increases muscle size, strength, aerobic performance, regenerative capacity and reduces muscle damage.20 In some studies, there was no positive effect of HMB supplementation in already strength trained athletes, for example, American football or rugby players. The positive effects only occur when combined with exercise.20 HMB does not show any adverse effects, which makes it a safe PES.14, 20

Caffeine is the most popular and most consumed stimulant all over the world. Many people claim to be tired or non‐productive without their daily caffeine. Maybe this is their way of whitewashing their addiction. Caffeine belongs to the group of xanthines and is found in various plants. Most people consume it in the form of coffee or tea, but there are also energy drinks or capsules/tablets which usually have a very high concentration. Caffeine is an adenosine receptor antagonist, whose effects include increased attentiveness, improved mood and cognitive processes; and in higher doses, it leads to an elevated heart rate and catecholamine levels.21 The catecholamines themselves also affect sympathetic activity. With regard to endurance exercise, strength and peak power, the performance is enhanced after caffeine ingestion of moderate to high doses.21 Caffeine stimulates the intracellular calcium release in striated muscles and stabilizes the ion concentration in the muscle cells. Both effects of caffeine may improve the muscular performance.22, 23 Low caffeine doses (<3 mg/kg BW) have small effects only in endurance exercises. This may be due to the influence on the nervous system, which is already activated in low doses compared to other tissues.21 The side effects of caffeine comprise gastrointestinal discomforts, nervousness, sleep disturbances and mental confusion.21 It is also debated if caffeine consumption can raise the risk of renal lithiasis, by increasing the amount of calcium in the tubules, or if it even helps against this matter, through its diuretic effect.24, 25

The majority of studies shows a beneficial effect of creatine, protein, HMB and caffeine on muscular growth and performance, when taken in an appropriate manner. However, it must be emphasized again, that exercise alone already has numerous benefits for body composition, metabolism and fitness level. Also, everyone capable of doing sports is trainable and physical training, in some way, is possible and necessary even under more difficult conditions.

目前，Covid-19大流行迫使几乎每个国家采取严厉措施来阻止病毒传播。这些措施包括避免与其他人紧密接触，尽可能呆在家里以及关闭体育馆或运动俱乐部。现在人们或多或少地被束缚在自己的家中，保持体育锻炼更加重要。偶尔在沙发和冰箱之间走动不足以保持身体健康。但是，为什么运动如此重要，并且有什么可以做以最大程度地利用每个培训课程的呢？

定期运动对于健康的生活方式至关重要。广为人知的结果是改善人体成分，降低血压，降低血浆胆固醇和人体脂肪百分比。1-3此外，通过增加活性葡萄糖转运蛋白和糖原合成的数量，运动可改善全身胰岛素敏感性。4它降低了几种慢性疾病的风险，例如糖尿病，心血管疾病，痴呆和抑郁。5运动不仅会影响新陈代谢，而且肯定会导致力量和肌纤维大小的增加。6此外，这些益处不仅对个人本身有利，而且可能对代谢疾病及其未来后代产生更好的表观遗传学影响。7说到后代，当使用大剂量的非甾体抗炎药缓解他们可能给您带来的头痛时，肌肉肥大就会受损。8，9但是，除了身体活动以外，还有其他一些因素会影响骨骼肌的大小，包括遗传，环境和新陈代谢。10与未经培训的人相比，未经培训的运动效果更显着。11换句话说，训练带来的相对进步会随着身体适应度的提高而降低。这可能会导致训练有素的受试者的动机下降。结果，人们可能求助于支持其训练进度的药物或物质。

增强表现的物质（PES）具有改变人体和生物学功能的能力或潜力，包括显着改善运动表现的能力。12它们被运动员广泛使用，期望提高性能，力量和肌肉质量。国际反对在运动员中使用非法药物的监督机构世界反兴奋剂机构（WADA）定期更新违禁药物清单。但是，本文重点介绍可合法获得的物质，尤其是肌酸，蛋白质，β-羟基-β-甲基丁酸酯和咖啡因。

肌酸是一种参与能量代谢的内源性物质，因此在具有高代谢需求的组织中很重要。13它是由氨基酸精氨酸和甘氨酸在肾脏和肝脏中分两步产生的。高达95％形成的肌酸储存在骨骼肌中，其中大部分为磷酸肌酸。14肌酸激酶将磷酸基团从磷酸肌酸转移到ADP，形成ATP。用作能量底物后，肌酸被降解为肌酸酐，并被肾脏排泄。因此，高血清肌酐水平可能是肾脏损害的指标。作为PES，肌酸可以增加力量，在短期和高强度锻炼中的表现，重复次数和总力量。15这些影响可能是由于ATP可用性的提高，从而导致更大的运动能量储备，或是更好地适应了更剧烈的训练。还假设肌酸增强卫星细胞（肌肉干细胞）的分化和有丝分裂活性。13服用肌酸后未见效果的人称为无反应者。据说补充前的肌酸水平已经很高；因此，多余的肌酸没有表现出很大的作用。14许多研究表明短期使用肌酸的安全性，但长期研究有限。15这就是为什么应避免长期使用肌酸的原因。补充剂不会改变健康个体的血清肌酐水平。15有理论认为，肌酸的渗透活性以及由此产生的水流入肌肉细胞会导致脱水，隔室综合征，肌肉痉挛或中暑。15但是，这些理论都没有得到支持。

补充蛋白质不仅在体育运动中很流行，而且还销售给非运动员使用不同种类的食物，其中的蛋白质代替碳水化合物或脂肪。这些产品，例如蛋白质直板棒，蛋白质面包等，据说可以提供健康的选择，并有助于减轻体重。对于运动员而言，最常见的蛋白质是粉末形式，将其与水或牛奶混合制成饮料。额外的蛋白质补充，加上抵抗运动，可以增加肌肉质量和力量。16它可以提高蛋白质合成速率并抑制肌肉蛋白质分解。17在训练有素的年轻人中影响更大。16、17每天摄入1.6 g / kg BW /天的蛋白质就足够了。额外的摄入量在肌肉质量或力量增加方面未显示任何显着差异。16但是，蛋白质摄入量超过1.2 g / kg BW / d被认为是高蛋白饮食，可能会导致肾脏功能和健康状况的改变。18氨基酸的渗透活性起初会导致较高的肾小球滤过率（GFR），但由此产生的肾脏损害会在长途中降低GFR。18肾功能正常的人比肾功能不正常的人通过长期高蛋白摄入而导致GFR降低的可能性较小。18不幸的是，通常在肾脏已经丧失大部分功能时才能诊断出GFR降低。需要用于检测早期肾脏损伤的其他诊断工具。19因此，尽管补充蛋白质可能有益于锻炼，但应谨慎使用。与添加蛋白质补充剂相比，抵抗运动本身对运动表现的影响更大，因此，训练应该是首要任务。16

β-羟基-β-甲基丁酸酯（HMB）是一种内源性分子，用作PES。它是由亮氨酸分两步合成的。首先是亮氨酸转氨为α-酮异己酸，主要发生在骨骼肌中。其次，酮异己酸被KIC双加氧酶代谢为肌肉外部的HMB。20 HMB在人类中的半衰期约为1-3小时。它通过肾脏排泄，但是大多数HMB将用于HMG-CoA合成，这是胆固醇合成的直接前体分子。20 HMB可增强蛋白质合成，并减少骨骼肌中的蛋白质分解。14建议的机制是mTOR的上调以及对蛋白质合成和肥大的生长激素/ IGF-1轴的影响；抑制泛素蛋白酶体和自噬溶酶体系统降解蛋白质。14,20 HMB增加肌肉大小，强度，有氧性能，再生能力和减少肌肉损伤。20在一些研究中，补充HMB对已经受过力量训练的运动员（例如美式橄榄球或橄榄球运动员）没有积极作用。只有与运动结合才能产生积极作用。20 HMB未显示任何不利影响，这使其成为安全的PES。14、20

咖啡因是全世界最受欢迎和最消耗的兴奋剂。许多人声称没有每日咖啡因会感到疲倦或无能为力。也许这是他们粉饰他们的瘾的方法。咖啡因属于黄嘌呤类，存在于多种植物中。大多数人以咖啡或茶的形式食用它，但也有能量饮料或胶囊/片剂，它们通常浓度很高。咖啡因是一种腺苷受体拮抗剂，其作用包括提高注意力，改善情绪和认知过程。高剂量会导致心率和儿茶酚胺水平升高。21儿茶酚胺本身也影响交感神经活动。关于耐力运动，力量和峰值力量，中度至高剂量摄入咖啡因后，性能会增强。21咖啡因刺激横纹肌中的细胞内钙释放，并稳定肌细胞中的离子浓度。咖啡因的两种作用均可改善肌肉性能。22，23低咖啡因剂量（<3 mg / kg体重）仅在耐力锻炼中有很小的作用。这可能是由于对神经系统的影响，与其他组织相比，神经系统已经以低剂量被激活。21咖啡因的副作用包括胃肠不适，神经质，睡眠障碍和精神错乱。21食用咖啡因是否会通过增加肾小管中钙的含量而增加肾结石的风险，或者是否通过利尿作用甚至有助于解决这一问题，也引起了争议。24、25

大多数研究表明，以适当的方式服用时，肌酸，蛋白质，HMB和咖啡因对肌肉生长和性能有有益作用。但是，必须再次强调，仅运动一项就已经对身体组成，新陈代谢和健身水平产生了许多好处。同样，每个有运动能力的人都是可以训练的，即使在更困难的条件下，以某种方式进行体育锻炼也是可能和必要的。