生酮飲食對(duì)體重管理、肌肉合成以及運(yùn)動(dòng)表現(xiàn)的影響

康杰（美），魏彤 譯

0 緒論

近年來(lái)，大量文獻(xiàn)報(bào)道極低碳水化合物生酮飲食在許多疾病起到治療作用，這類(lèi)飲食可以導(dǎo)致稱為酮癥的特殊代謝狀態(tài)。生酮飲食應(yīng)用在癲癇治療中已有數(shù)十年歷史[1]，而在20世紀(jì)70年代，這類(lèi)飲食因可以減輕體重而被廣泛知曉，特別是著名的“阿特金斯飲食法”[2]。最近，生酮飲食在治療其他

Introduction

During recent years,an increasing amount of evidence has accumulated in the literature,suggesting that very-low-carbohydrate ketogenic diets could have a therapeutic role in numerous diseases.These types of diets result in a metabolic state of ketosis.The use of ketogenic diets in treating epilepsy has been well estab-疾病的研究中也取得了較好的結(jié)果，鑒于目前美國(guó)每年的醫(yī)藥費(fèi)用達(dá)到7 500億美元[3]，如果飲食干預(yù)可以減少對(duì)藥物使用的依賴，它將帶來(lái)顯著的社會(huì)以及經(jīng)濟(jì)效益，這也將成為今后一個(gè)重要的研究方向。

最近生酮飲食療法也在許多運(yùn)動(dòng)項(xiàng)目中流行，希望通過(guò)生酮飲食療法減輕體重，獲得更好的運(yùn)動(dòng)表現(xiàn)。然而，生酮飲食對(duì)提高運(yùn)動(dòng)表現(xiàn)是否有功效并沒(méi)有得到一致的認(rèn)可。耐力運(yùn)動(dòng)員的主流營(yíng)養(yǎng)理念強(qiáng)調(diào)高碳水化合物、低脂肪的飲食方式。在這種飲食模式下，運(yùn)動(dòng)員主要依賴碳水化合物產(chǎn)能來(lái)完成大量的有氧運(yùn)動(dòng)[4]。生酮飲食對(duì)于耐力運(yùn)動(dòng)員的吸引力在于它改變了運(yùn)動(dòng)員利用能量的方式，從以利用碳水化合物為中心轉(zhuǎn)變?yōu)槔弥井a(chǎn)能為主。與有限的碳水化合物相比（如肌糖原），脂肪在體內(nèi)的儲(chǔ)存更豐富。經(jīng)過(guò)一段時(shí)間的飲食改變后，機(jī)體會(huì)產(chǎn)生代謝的變化。這種變化通常被稱為“脂肪適應(yīng)”。20世紀(jì)80年代以來(lái)這種代謝變化在研究中得到了充分的證實(shí)[5,6]。盡管在運(yùn)動(dòng)中利用脂肪作為能量來(lái)源具有生理上的優(yōu)勢(shì)，然而至今為止并沒(méi)有確鑿的證據(jù)表明這會(huì)提高運(yùn)動(dòng)能力[7]。

本文將討論生酮飲食的代謝效應(yīng)和潛在風(fēng)險(xiǎn)，以及近期關(guān)于生酮飲食對(duì)體重減輕、肌肉合成和運(yùn)動(dòng)表現(xiàn)影響的研究進(jìn)展。本文還將為那些有興趣嘗試這種飲食方法的人提供正確的飲食指導(dǎo)。lishedformanydecades[1]andthesedietshavebecome even more widely known,as they became popular in the 1970s for weight loss-especially as the ‘Atkins Diet’[2].More recently,the therapeutic use of ketogenic diets in other diseases has been studied with positive results-it is an important direction for research because,clearly,if nutritional intervention can reduce reliance on pharmaceutical treatments it would bring significant benefits from an economic as well as a social point of view given the current$750 billion annual cost of pharmaceuticals in United States[3].

Ketogenic diets have recently become popular dietary regimes for athletes who desire to reduce body mass and to obtain the extra performance edge.However,there is no consensus regarding the efficacy of ketogenic diets on sports performance.The overarching mainstream nutrition philosophy for endurance athletes is one that emphasizes a carbohydrate-dominant,low fat paradigm.Under these dietary conditions,athletes utilize carbohydrate as their predominant fuel source to fu el high volumes of aerobic exercise[4].The appeal of ketogenic diets for endurance athletes is likely due to the shift in fuel utilization,from a carbohydrate-centric model to one that utilizes fat predominantly,of which stores are unlimited compared to carbohydrate(i.e.,muscle glycogen).This metabolic shift,seen after a period of dietary alteration is often referred to as being‘fat-adapted’,which has been well-documented in studies since the 1980s[5,6].Despite the physiological advantage of utilizing fat as a fuel source during sub-maximal exercise,to date there is no conclusive evidence to suggest that this would result in subsequent performance enhancement[7].

This review will discuss metabolic consequences and potential risks of ketogenic diets as well as recent research progress with regard to the effects of ketogenic diets on weight loss,muscle mass development,and athletic performance.This article will also provide some practical guidelines for those who are interested to be able to carry out this dietary approach correctly.

1 什么是生酮飲食？

生酮飲食是指低碳水化合物 （通常小于20 g/d或低于每天總攝入能量的5%）而蛋白質(zhì)和脂肪相對(duì)增加的飲食[8]。碳水化合物的不足使得機(jī)體主要的能量來(lái)源為脂肪。最初的生酮飲食規(guī)定每天攝入脂肪與非脂肪的比例為4:1，80%的能量來(lái)源于脂肪，15%來(lái)源于蛋白質(zhì)，碳水化合物僅占5%。隨后生酮飲食也做了許多改進(jìn)，如減少脂肪與非脂肪的比例或不限制每天攝取的能量，隨意進(jìn)食蛋白質(zhì)和脂肪。

What Is the Ketogenic Diet?

Ketogenic diets are characterized by a reduction in carbohydrates (usually＜20 g/day or 5%of total daily energy intake)and a relative increase in the proportions

2 歷史背景

關(guān)于經(jīng)典生酮飲食的代謝效應(yīng)的知識(shí)，來(lái)源于Cahill等人在20世紀(jì)60年代在禁食方面的開(kāi)拓性工作[9,10]。 他們的研究發(fā)現(xiàn)在12 h至3周的時(shí)間內(nèi)禁食或僅攝取最少量的食物和含有熱量的飲料，可以誘導(dǎo)稱為酮癥的特殊代謝狀態(tài)。近年來(lái)，許多研究調(diào)查了在伊斯蘭教齋戒月期間每日禁食對(duì)機(jī)體的影響，在這1個(gè)月內(nèi)從日出到日落，需完全禁食禁水。盡管這種間歇性禁食對(duì)久坐人群的影響不大，但對(duì)于運(yùn)動(dòng)員的訓(xùn)練和表現(xiàn)，特別是在夏季日照時(shí)間長(zhǎng)的情況下會(huì)有重要的影響。齋戒月期間觀察到運(yùn)動(dòng)員體內(nèi)的血糖和組織水分從日出到日落逐漸降低。然而，如果運(yùn)動(dòng)員能夠保持足夠的能量、營(yíng)養(yǎng)物質(zhì)的攝入及良好的睡眠并調(diào)整訓(xùn)練負(fù)荷的時(shí)間，他們的整體表現(xiàn)不會(huì)受到影響[11,12]。

齋戒禁食是一種間歇性禁食模型，但禁食時(shí)間太短不能誘發(fā)酮癥。而因紐特人 （北美的愛(ài)斯基摩人）案例（Inuit Case）則是一個(gè)比較好的長(zhǎng)期的酮癥模型，這是由Schwatka探險(xiǎn)隊(duì)報(bào)道的第一個(gè)有據(jù)可查的禁食案例。Frederick Schwatka中尉是一支探險(xiǎn)隊(duì)的領(lǐng)隊(duì)，他在1879年至1880年前往尋找失蹤的皇家海軍“富蘭克林探險(xiǎn)隊(duì)”（Franklin Expedition）的過(guò)程中，與其他參與者包括12名極地土著人完成了超過(guò)5 000 km的雪橇旅程[13]。在最初攜帶的食物消耗完之后，探險(xiǎn)隊(duì)唯一的食物來(lái)源就是狩獵和捕魚(yú)，因?yàn)檠赝緵](méi)有其他的食物供應(yīng)來(lái)源。Schwatka中尉在他的日記中提到：當(dāng)?shù)谝淮瓮耆ㄟ^(guò)進(jìn)食馴鹿肉充饑時(shí)，整個(gè)機(jī)體似乎并沒(méi)有得到滿足，身體感到虛弱以致無(wú)法繼續(xù)艱苦而險(xiǎn)峻的旅程。但是這種感受在2到3周內(nèi)就會(huì)消失[14]。這是關(guān)于酮適應(yīng)的第一個(gè)有據(jù)可查的描述，這段文字被多次引用。

多年以后，一位名叫Vilhajalmur Stefansson的人類(lèi)學(xué)家前往北極學(xué)習(xí)因紐特人的語(yǔ)言和文化。在他的旅程中，體驗(yàn)了典型的因紐特人飲食，其中約80%～85%的能量來(lái)源于脂肪，15%～20%來(lái)自蛋白質(zhì)，他的身體沒(méi)有發(fā)現(xiàn)任何問(wèn)題[15]。隨后，因他的報(bào)道引起了爭(zhēng)議，Stefansson同意在貝爾維尤醫(yī)院的DuBois醫(yī)生的監(jiān)督下再次采用因紐特飲食，證實(shí)了之前的觀察，即采用脂肪/蛋白質(zhì)飲食對(duì)身體沒(méi)有任何損害，也不會(huì)導(dǎo)致?tīng)I(yíng)養(yǎng)缺乏。

在這些報(bào)道之后，生酮飲食的研究似乎就被人們所遺忘，直到20世紀(jì)20年代，它作為一種癲癇療法受到關(guān)注。然而隨著癲癇治療藥物的問(wèn)世，生酮飲食又受到冷落，而近年來(lái)因藥物療法具有嚴(yán)重的副作用，生酮飲食療法再次引起人們的興趣[16]。近幾年，有關(guān)生酮飲食的研究主要集中在減重或減脂方面。至今為止，僅有個(gè)別研究關(guān)注生酮飲食與運(yùn)動(dòng)表現(xiàn)之間的關(guān)系。生酮飲食在體育運(yùn)動(dòng)中具有兩種可能的應(yīng)用價(jià)值：第一，在有重量級(jí)別的體育項(xiàng)目中具有減輕體重的作用[17]；第二，在提高耐力方面具有潛在的作用[6]。of protein and fat[8].Such insufficient levels of carbohydrates can then force the body to use fat as a main fuel source.The original ketogenic diet was designed as a 4:1 lipid:nonlipid ratio,with 80%of daily energy intake from fat,15%protein,and 5%carbohydrate.Many modifications subsequently have been introduced to the original ketogenic diet,for example,lowering the lipid:nonlipid ratio or no restrictions in daily energy intake with ab libitum protein and fat.

Historical Background

The knowledge regarding the metabolic effects of classic ketogenic diets originates from the pioneering work of Cahill and colleagues in the 1960s on fasting[9,10].In these studies,ingesting no or minimal amounts of food and caloric beverages for periods that ranged from 12 h to 3 weeks has been found to induce a particular metabolic state called ketosis.In recent years,many studies have investigated the effects of the daily fasting used during Ramadan that requires a total abstention from food and drink from sunrise to sunset for 1 month.Although such ritual intermittent fasting has only minor effects on the sedentary population,it can have important consequences for the training and performance of the athlete especially during summer when daylight hours are long.In general,studies have found that,in athletes observing Ramadan,the glycemia and tissue hydration decrease progressively from sunrise to sunset.However,overall performance seems to be unaffected if athletes are able to maintain an adequate total energy and macronutrient intake and a sound sleep and to adjust the timing of the training load[11,12].

Ramadan fasting is an interesting model for intermittent fasting but is too short to induce ketosis;instead,a good model for prolonged ketosis is the Inuit case in which the first well-documented fasting was reported by theSchwatkaexpedition. Lt.Frederick Schwatka was the leader of an expedition that set out to find the missing Royal Navy “Franklin Expedition.”Lt.Schwatka and the other participants including 12 indigenous circumpolar people completed a more than 5000-km sled journey from 1879 to 1880[13].It is worth noting that,once they finished their initial provisions,the expedition’s only source of food was hunting and fishing because there were no other sources of supply a

3 生酮飲食的生理學(xué)基礎(chǔ)

經(jīng)過(guò)幾天的禁食或至少大幅減少膳食中碳水化合物含量 （即小于20 g/d或低于每天總能量攝入的5%），同時(shí)通過(guò)增加其他營(yíng)養(yǎng)物質(zhì)維持機(jī)體總的能量攝入，此時(shí)葡萄糖儲(chǔ)備不足使得三羧酸循環(huán)中的草酰乙酸供應(yīng)減少，不足以維持正常的脂肪氧化過(guò)程以及向中樞神經(jīng)系統(tǒng)供應(yīng)葡萄糖。在正常體溫下，草酰乙酸不穩(wěn)定，因此不能被積累和儲(chǔ)存，但三羧酸循環(huán)的持續(xù)運(yùn)作需要草酰乙酸，可通過(guò)葡萄糖轉(zhuǎn)化為丙酮酸，然后再生成草酰乙酸 （圖1）而不斷補(bǔ)充。由于生酮飲食導(dǎo)致草酰乙酸生成減少，通過(guò)三羧酸循環(huán)的脂肪氧化將大大減少，并伴隨一定程度的乙酰輔酶A的堆積。此外，中樞神經(jīng)系統(tǒng)需要葡萄糖作為能量來(lái)源，而在生酮飲食中過(guò)量乙酰輔酶A的生成使得酮體成為替代能源發(fā)揮作用。

圖1 葡萄糖對(duì)大腦供能和維持三羧酸循環(huán)正常運(yùn)作示意圖Figure 1 Glucose is essential as an energy supply for the brain and also for the production of oxaloacetate,the levels of which need to be maintained for the functioning of the Krebs cycle.

酮體由乙酰乙酸、β-羥基丁酸和丙酮組成。酮體生成主要在肝臟進(jìn)行（圖2）。在正常飲食條件下，體內(nèi)酮體濃度低于0.3 mmol/L，中樞神經(jīng)系統(tǒng)不利用酮體供能；而當(dāng)酮體濃度達(dá)到4 mmol/L，與葡萄糖濃度相似時(shí)，機(jī)體所有組織均可利用酮體供能。β-羥基丁酸轉(zhuǎn)化為乙酰輔酶A然后分解成2分子的乙酰輔酶A，可進(jìn)入三羧酸循環(huán)產(chǎn)生ATP。與葡萄糖相比，利用酮體可產(chǎn)生更多的線粒體ATP從而增加能量生成。例如，利用彈式熱量計(jì)計(jì)算，在相同碳單位的情況下，β-羥基丁酸燃燒產(chǎn)生的熱量較丙酮酸燃燒高31%[18]。生酮飲食后體內(nèi)酮體濃度最大可達(dá)到8 mmol/L[19]。long their route.Lt.Schwatka reported in his diary this often-cited sentence:When first thrown wholly on the diet of reindeer meat,it seems inadequate to properly nourish the system,and there is an apparent weakness and inability to perform severe,exertive,fatiguing journeys.But this soon passes away in the course of 2 to 3 weeks[14].This is the first documented description of the so-called keto-adaptation.

Years later,an anthropologist named Vilhajalmur Stefansson set out to travel throughout the Arctic mainland to study the Inuit language and culture.During his journeys,Stefansson experimented on himself with the typical Inuit’s diet,consisting of about 80-85%of energy from fat and 15%-20%from protein,and he reported noobservedproblems[15].Pressedbythe controversyraised from his reports,Stefansson agreed to recreate the Inuit diet under the scientific supervision of Dr.DuBois at the Bellavue Hospital,he confirmed his earlier observations that the adoption of a fat/protein diet was without any impairment or signs of nutrition deficiency.

After these earlier reports,however,the study of ketogenic diets seems to have sunk into oblivion until the 1920s when it experienced a “renaissance” as a therapy for epilepsy.Interest in this dietary therapy again waned with the introduction of pharmaceutical therapy for epilepsy,but it has been reawakened recently because of the severe side effects of pharmacological treatments[16].In more recent years,ketogenic diets mostly have been studied from a weight/fat loss point of view.Interestingly,up until now,only a few studies have investigated the relationship between ketogenic diets and sports performance.There are two main possible applications of ketogenic diets in sport:one is the more intuitive weight reduction for sports that involve weight classes[17]and the second is a potential for improving endurance performance[6].

A Closer Look at the Ketogenic Diet

After a few days of fasting or at least a drastically reduced dietary carbohydrate content(i.e.,＜20 g/day or 5%of daily energy intake)while maintaining usual energy intake through macronutrient redistribution,glucose reserves become insufficient both for normal fat oxidation via the supply of oxaloacetate in the Krebs cycle(which gave origin to the phrase‘fat burns in the

圖2 肝臟生酮生成路徑Figure 2.Ketone bodies production in the liver increases in response to low carbohydrates and/or high lipids in ketogenic diet

肝臟中生成的酮體主要是乙酰乙酸，但循環(huán)中的酮體以β-羥基丁酸為主。在正常富含碳水化合物的飲食中，游離乙酰乙酸的生成可忽略不計(jì)，且會(huì)被許多組織特別是骨骼肌和心肌快速代謝。而在乙酰乙酸過(guò)量生成時(shí)，乙酰乙酸富集并分解成其他兩種酮體，導(dǎo)致酮血癥和酮尿癥 （血液和尿液中存在酮體）。丙酮作為一種易揮發(fā)的化合物，可通過(guò)呼吸從肺內(nèi)排出，使得呼出的氣體有酮癥特征性的爛蘋(píng)果氣味。

盡管血液中的葡萄糖水平降低，但通過(guò)生糖氨基酸以及甘油三酯分解產(chǎn)生甘油的糖異生，血糖仍可維持在生理水平[20]。禁食以及極低碳水化合物飲食導(dǎo)致的“生理性酮癥”，盡管酮體水平可達(dá)到7～8 mmol/L，但機(jī)體PH水平不變。生理性酮癥是為應(yīng)對(duì)長(zhǎng)期食物缺乏所導(dǎo)致的營(yíng)養(yǎng)不足的一種進(jìn)化適應(yīng)。這些饑餓階段是生酮過(guò)程，使得血糖和胰島素水平降低，而為了維持生理性血糖水平，胰高血糖素增加。在病理性的糖尿病酮癥酸中毒中，酮體水平可超過(guò)20 mmol/L并伴有血液PH值降低。由于中樞神經(jīng)系統(tǒng)可有效利用酮體取代葡萄糖作為能量來(lái)源，正常人體內(nèi)酮體水平不會(huì)超過(guò)8 mmol/L。還有一點(diǎn)需要強(qiáng)調(diào)的是，盡管血糖水平降低，但仍維持在生理性水平，因?yàn)槠咸烟巧捎袃蓚€(gè)主要的來(lái)源：（1）生糖氨基酸 ；（2）甘油三酯水解釋放的甘油[21]。

4 生酮飲食與體重管理

自1980年以來(lái)，全世界肥胖人口迅速增加，幾乎翻了一番[22]。據(jù)統(tǒng)計(jì)，2016年，全世界18歲以上成年flame of carbohydrate’)and for the supply of glucose to the central nervous system.At normal body temperature,oxaloacetate is not stable and so cannot be accumulated and stored,but it is required for the continued functioning of the Krebs cycle and is replenished continually by the conversion of glucose to pyruvate and then to oxaloacetate(Figure 1).Due to the lack of production of oxaloacetate following ketogenic diets,fat oxidation through Krebs cycles will be reduced drastically.Moreover,the central nervous system requires glucose as an energy source and thus following a ketogenic diet will cause the need for an alternative energy source which is derived from the overproduction of acetyl-CoA namely ketone bodies.

Ketone bodies are made up of acetoacetate,3-hydroxybutric acid and acetone.This whole process occurs in the liver and is called ketogenesis (Figure 2).Under normal diet,the concentration of ketones bodies is less than 0.3 mmol/l and ketone bodies will not be used as an energy source by the central nervous system until this concentration reaches 4 mmol/l,similar to the glucose concentration.At that point,ketone bodies are then used as a source of energy by the all tissues.Specifically,3-hydroxybutric acid is transformed into acetoac etyl-coA which is then transformed into two molecules of acetyl-coA and acetyl-CoA are then used in Krebs cycle in generating ATP.Utilization of ketone bodies creates more energy than glucose because of greater mitochondrial ATP production.For example,the energy liberated by burning 3-hydroxybutric acid in a bomb calorimeter is 31%higher per two-carbon unit compared with the combustion of pyruvate[18].The maximum ketone bodies concentration in individuals following the ketogenic diet will reach up to～8 mmol/l[19].

The main ketone bodies produced in the liver is acetoacetate,but the primary circulating ketone is 3-hydroxybutyrate.Under normal conditions of adequate dietary carbohydrate,the production of free acetoacetic acid is negligible and it is rapidly metabolized by various tissues,especially the skeletal and heart muscles.In conditions of overproduction of acetoacetic acid,it accumulates above normal levels and part of it is converted to the other two ketone bodies leading to ketonemia and ketonuria(presence of KBs in the blood and urine).The characteristic ‘sweet’breath odor of keto sis is人有超過(guò)19億人超重，其中肥胖人口超過(guò)6.5億[23]。飲食作為一種肥胖的干預(yù)措施一直是一個(gè)富有爭(zhēng)議的話題，盡管目前許多類(lèi)型的飲食主張可以減輕體重，但并沒(méi)有科學(xué)依據(jù)表明其中某種飲食優(yōu)于其他飲食方法。目前最普遍接受的是一種高碳水化合物、低脂肪的飲食策略，但有研究表明，低脂肪飲食對(duì)于減輕體重效果甚微。另外，鑒于大多數(shù)肥胖人群偏愛(ài)高脂肪食物，他們對(duì)于高碳水化合物/低脂肪飲食的依從性也是一個(gè)問(wèn)題。實(shí)際上，低脂肪飲食可能導(dǎo)致糖以及碳水化合物的攝入增加，進(jìn)一步加劇體重問(wèn)題，同時(shí)低脂肪飲食也可能導(dǎo)致血脂異常，尤其是在胰島素抵抗的人群中[24]?？紤]到以上的問(wèn)題，近年來(lái)對(duì)于極低碳水化合物生酮飲食或單純的生酮飲食關(guān)注增加。

有強(qiáng)有力的證據(jù)表明生酮飲食是一種有效的減肥療法，但生酮飲食對(duì)減輕體重的作用機(jī)制仍待進(jìn)一步研究。阿特金斯起初認(rèn)為機(jī)體通過(guò)排泄酮體而失去能量供應(yīng)來(lái)減輕體重[2]，但最近有人提出了幾種不同的假設(shè)，其中一種認(rèn)為在生酮飲食中利用蛋白質(zhì)產(chǎn)能實(shí)際上是耗能過(guò)程，可導(dǎo)致卡路里丟失從而減輕體重[25]。在生酮飲食的最初階段，機(jī)體每天需要消耗60～65 g葡萄糖，16%的葡萄糖來(lái)源于甘油而大部分來(lái)源于飲食或組織蛋白的糖異生[26]。糖異生是一個(gè)耗能的過(guò)程，每天大約消耗400～600 kcal。但并沒(méi)有直接證據(jù)支持這個(gè)假設(shè)。相反的，最近有研究報(bào)道生酮飲食后靜息能量消耗沒(méi)有改變[27]。

也有研究者認(rèn)為生酮飲食導(dǎo)致的體重減輕可能歸因于蛋白質(zhì)的飽腹感效應(yīng)或酮體對(duì)食欲的抑制效應(yīng)，因?yàn)橥w也可作為一種飽食信號(hào)減少饑餓感[28,29]。已有文獻(xiàn)表明與基礎(chǔ)值相比，生酮飲食后個(gè)體的饑餓感減少，食欲下降[28]。有些研究發(fā)現(xiàn)，生酮飲食過(guò)程中主觀食欲測(cè)量的絕對(duì)改變雖然很小，但即使參與者攝入限制能量的飲食，他們的饑餓感也不會(huì)增加，從而導(dǎo)致顯著的體重減輕[30]。 因此，對(duì)于想要尋求一種方法既可以有效減肥而又不增加饑餓感的臨床醫(yī)生來(lái)說(shuō)，生酮飲食可以滿足這一需求。

目前很難確定生酮飲食導(dǎo)致的食欲下降是由酮癥引起還是由其他因素 （如飲食中蛋白質(zhì)或脂肪含量增加、碳水化合物含量減少）導(dǎo)致。這是因?yàn)樵诳偰芰坎蛔兊那闆r下，一種營(yíng)養(yǎng)物質(zhì)的膳食攝入量的改變必然會(huì)影響其他營(yíng)養(yǎng)物質(zhì)的攝入量。有研究認(rèn)為生酮飲食導(dǎo)致的食欲抑制歸因于飲食中高蛋白質(zhì)含量[31]。事實(shí)上，相對(duì)于正常飲食，生酮飲食中蛋白質(zhì)絕對(duì)含量只輕度增加或幾乎不增加。盡管生酮飲食中蛋白質(zhì)相對(duì)比例增加，但蛋白質(zhì)的絕對(duì)攝入量caused by acetone,which,being a very volatile compound,is eliminated mainly via respiration in the lungs.

It is important to note that,although the blood level of glucose drops,it still remains at a physiological level through gluconeogenesis involving glucogenic amino acids and also glycerol released from triglycerides[20].Fasting and very low carbohydrate diets lead to what is known as “physiological ketosis”where ketone body levels may rise to 7 to 8 mmol/l,but without any pH change.Physiological ketosis is an evolutionary adaptation to counter long periods of undernutrition because of unreliable food supplies.These periods of near starvation are ketogenic,leading to decreases in blood glucose and insulin,along with increases in glucagon as the body attempts to maintain physiological levels of glucose.In“pathological diabetic ketoacidosis”,on the other hand,ketonemia can exceed 20 mmol/l with a concomitant lowering of blood pH.In healthy people,the levels do not rise above 8 mmol/l because of the efficient use of ketone bodies instead of glucose for energy by the CNS.A further point to underline is that glycaemia,even though reduced,remains within physiological levels because of the fact that glucose is formed from two sources:1.glucogenic amino acids and 2.glycerol liberated via lipolysis from triglycerides[21].

Ketogenic Diet and Weight Management

Obesity is a rapidly growing epidemic worldwide that has nearly doubled since 1980[22].In 2016,more than 1.9 billion adults,18 years and older,were overweight and of these over 650 million were obese[23].Regarding obesity interventions,diet is one of the more controversial issues and many different types have been advocated for weight loss,but there is little scientific evidence to recommend one diet over another.The most commonly accepted dietary strategy is based on relatively high levels of carbohydrates and low fat content,but according to some studies these low fat diets yield only modest weight losses.In addition,adherence of obese individuals to high carbohydrate/low fat nutrition is often a problem because the majority have been shown to have dietary preferences for foods with a rich fat content.In fact,a low fat diet may actually encourage the consumption of sugars and refined carbo hydrates that can worsen weight problems and also facilitate dyslipi-僅為50～60 g/d。此外，蛋白質(zhì)攝入的增加并不能解釋饑餓或禁食狀態(tài)下饑餓感消失的現(xiàn)象[32,33]。進(jìn)一步研究發(fā)現(xiàn)，當(dāng)?shù)鞍踪|(zhì)攝入量相同時(shí)，不管在肥胖[28]或正常體重[34]的受試者中，生酮高蛋白飲食較非生酮高蛋白飲食抑制食欲作用更明顯，表明酮癥是主要的影響因素。

總的來(lái)說(shuō)，生酮飲食導(dǎo)致的體重減輕機(jī)制有以下幾點(diǎn)：（1）糖異生導(dǎo)致的代謝性消耗增加以及蛋白質(zhì)的熱效應(yīng)；（2）酮體導(dǎo)致的食欲抑制；（3）蛋白質(zhì)的飽腹感效應(yīng)和/或4）脂肪生成減少以及脂解或脂肪利用增加。

5 生酮飲食的潛在風(fēng)險(xiǎn)

有人也許會(huì)質(zhì)疑低碳水化合物、高蛋白、高脂肪飲食是一種不健康的飲食方式，因?yàn)樗赡軙?huì)增加體內(nèi)低密度脂蛋白膽固醇（LDL-C）和甘油三酯的含量，這個(gè)問(wèn)題在肥胖人群中尤其重要。然而，有證據(jù)表明，生酮飲食對(duì)心血管危險(xiǎn)因素具有保護(hù)作用。目前大多數(shù)研究均發(fā)現(xiàn)碳水化合物攝入減少有利于降低總膽固醇水平，提高高密度脂蛋白（HDL-C）含量，降低血甘油三酯水平[24,35]。 此外，生酮飲食可增加LDL-C顆粒的大小和體積[26]，由于LDL顆粒越小其致動(dòng)脈粥樣硬化作用越高，因此認(rèn)為這可降低心血管疾病風(fēng)險(xiǎn)。生酮飲食對(duì)內(nèi)源性膽固醇合成的影響具有生物化學(xué)基本原理支持。3-羥基-3甲基戊二酸單酰輔酶A（HMG-CoA）還原酶是膽固醇合成過(guò)程中的關(guān)鍵酶，可被胰島素活化。當(dāng)血液中葡萄糖水平增加時(shí)，胰島素分泌增加可促進(jìn)內(nèi)源性膽固醇合成。因此，膳食中碳水化合物減少并保證適量膽固醇攝入可抑制內(nèi)源性膽固醇合成。

另一個(gè)需要考慮的問(wèn)題是潛在的腎臟副作用。蛋白質(zhì)代謝過(guò)程中,氮排泄增多可增加腎小球壓力和超濾過(guò)[18]。在腎功能正常的受試者中，高蛋白飲食可導(dǎo)致腎臟功能以及形態(tài)的適應(yīng)性改變但沒(méi)有明顯的副作用[36]?？紤]到腎功能改變對(duì)血壓的影響，研究發(fā)現(xiàn)，在腎功能正常時(shí)，生酮飲食不會(huì)導(dǎo)致血壓升高[37]。關(guān)于生酮飲食中可能出現(xiàn)的酸中毒問(wèn)題，在胰島素功能正常的受試者中，由于酮體濃度不會(huì)超過(guò)8 mmol/L，這一風(fēng)險(xiǎn)幾乎不存在[38]。有關(guān)生酮飲食對(duì)健康的總體影響，目前也有許多不同意見(jiàn)。在最近的一篇基于有限觀察例數(shù)的研究中，Noto等人提出低碳水化合物/高蛋白質(zhì)飲食對(duì)健康可能有害：即全因死亡率風(fēng)險(xiǎn)增加，但對(duì)心血管疾病死亡率沒(méi)有影響[39]。而一項(xiàng)大型的歐洲研究表明，蛋白質(zhì)含量的增加和隨后血糖指數(shù)的下降可以更好地維持體重減輕且沒(méi)demia,especially in insulin resistance individuals[24].As a consequence of these concerns,there has been increased interest in recent years in very low carbohydrate ketogenic diets or simply ketogenic diets.

There is strong supportive evidence that the use of ketogenic diets in weight-loss therapy is effective;however,the mechanisms underlying the effects of ketogenic diets on weight loss is still a subject of debate.Atkins’original hypothesis suggested that weight loss was induced by losing energy through excretion of ketone bodies[2],but more recently different hypotheses have been proposed:one hypothesis is that the use of energy from protein in ketogenic is an “expensive” process for the body and so can lead to a “waste of calo ries”andthereforeincreasedweightloss[25].Duringthe first phase of a ketogenic diet,60-65 g of glucose per day are needed by the body,16%of this is obtained from glycerol while the major part is derived via gluconeogenesis from proteins of either dietary or tissue origin.Gluconeogenesis is an energy-demanding process calculatedatapproximately400-600kcal/day[26].Thereisthough no direct experimental evidence to support this intriguing hypothesis.On the contrary,a recent study reported that there were no changes in resting energy expenditure after a ketogenic diet[27].

Some authors claim instead that the weight loss obtained with ketogenic diets could be attributed to a reduction in appetite due to higher satiety effect of protein or the suppressant action of the ketone bodies because ketone bodies can also act as a satiety signal to reduce hunger[28,29].The existing literature demonstrated that individuals adhering to ketogenic diets are less hungry and have a reduced desire to eat compared with baseline measures.Although in some studies the absolute changes in subjective appetite measures during ketogenic diet were small and not significant,there was a clear lack of increase in hunger despite participants consuming an energy-restricted diet that resulted in a significant weight loss[30].Hence,for clinicians seeking an effective method of weight loss that does not increase hunger,ketogenic diets can achieve this target.

It is difficult to determine whether the appetite suppression seen with ketogenic diet is indeed due to ketosis or other factors such as an increased content of protein or fat in the diet or the restriction of carbohy有負(fù)面效應(yīng)[24]。

需要再次強(qiáng)調(diào)的是，嚴(yán)格來(lái)說(shuō)生酮飲食并不是低碳水化合物/高蛋白質(zhì)飲食。生酮飲食是指極低碳水化合物但蛋白質(zhì)含量正常的飲食，可產(chǎn)生特定的代謝狀態(tài)，而不應(yīng)等同于低碳水化合物/高蛋白質(zhì)飲食。

6 生酮飲食在體育運(yùn)動(dòng)中的應(yīng)用

與其他限制能量的飲食不同，生酮飲食是具有豐富蛋白質(zhì)（至少1.3～1.5 g/kg體重）且能量充足的飲食，不會(huì)導(dǎo)致必需營(yíng)養(yǎng)素（即維生素、礦物質(zhì)、必需脂肪酸和氨基酸等）以及幫助機(jī)體控制氧化應(yīng)激和炎癥過(guò)程的其他營(yíng)養(yǎng)物質(zhì)的缺失。因此，盡管碳水化合物含量非常低，但生酮飲食不會(huì)導(dǎo)致那些因長(zhǎng)期服用減肥飲食而引起的代謝失衡?；谏嬍硨?duì)身體產(chǎn)生極少副作用以及它的減肥效果，越來(lái)越多的研究旨在發(fā)現(xiàn)生酮飲食在體育運(yùn)動(dòng)中的潛在應(yīng)用，特別是摔跤、舉重、柔道等涉及重量級(jí)別的運(yùn)動(dòng)。

運(yùn)動(dòng)員渴望減肥的目的包括：（1）增加力量體重比；（2）在更有利的體重級(jí)別比賽；（3）與健身配合，達(dá)到審美上高度欣賞的極度瘦身狀態(tài)。然而目前運(yùn)動(dòng)員采用的許多常見(jiàn)的減肥方法會(huì)有許多副作用，進(jìn)而影響到他們的運(yùn)動(dòng)表現(xiàn)。這些快速減肥方法通常是在比賽前臨時(shí)進(jìn)行的，包括大幅減少能量攝入，通過(guò)桑拿浴、利尿劑或嘔吐造成脫水，或使用促進(jìn)體重減輕的藥物。這些減肥法會(huì)導(dǎo)致電解質(zhì)紊亂、脫水以及糖原貯存減少[17]。運(yùn)動(dòng)員對(duì)蛋白質(zhì)需求很高，嚴(yán)重的能量限制也意味著蛋白質(zhì)（以及其他必須營(yíng)養(yǎng)素）攝入的減少，使得運(yùn)動(dòng)員肌肉量下降，從而影響到體力、爆發(fā)力以及耐力。限制能量飲食[40]與利用桑拿浴或利尿劑導(dǎo)致脫水[41]的減肥方法對(duì)運(yùn)動(dòng)表現(xiàn)的影響類(lèi)似，除了會(huì)增加長(zhǎng)期的健康風(fēng)險(xiǎn)外，這些運(yùn)動(dòng)員到中年后體重增加以及肥胖的風(fēng)險(xiǎn)也會(huì)上升[42]。

快速減肥法在有體重要求的運(yùn)動(dòng)中的使用不容忽視。Franchini等最近的一項(xiàng)報(bào)道顯示，快速減肥在諸如摔跤運(yùn)動(dòng)員（60%～90%）和柔道運(yùn)動(dòng)（～90%）等對(duì)抗性運(yùn)動(dòng)中使用率很高[43]。Brito等人也發(fā)現(xiàn)其在柔道運(yùn)動(dòng)員（62.8%）、柔術(shù)（56.8%）、空手道 （70.8%）和跆拳道（63.3%）中的應(yīng)用有相似的比例[41]。在舉重方面，即使沒(méi)有確切的數(shù)據(jù)，快速的體重減輕也很常見(jiàn)。這些運(yùn)動(dòng)員通常采用大幅減少能量攝入并通過(guò)脫水來(lái)達(dá)到快速減肥的目標(biāo)，但他們的運(yùn)動(dòng)表現(xiàn)往往會(huì)受到負(fù)面影響。然而，生酮飲食，因能保證足夠drate.This is because the dietary intake of one particular macronutrient cannot be varied independently of the other macronutrients without affecting the total energy.For instance,the appetite suppression of ketogenic diets has been attributed to their high protein content[31].However,ketogenic diets involve only modest or no increases in absolute protein intake relative to normal diets.For example,while relatively high in protein,ketogenic diets typically provide absolute protein intakes of only～50-60 g/day.Additionally,increased protein intake cannot explain the observation of an ‘a(chǎn)bsence of hunger’during starvation or fasting regimes[32,33].Further,well-controlled studies have shown that when protein intake is matched,a ketogenic high-protein diet suppresses appetite more so than a nonketogenic high-protein diet in obese[28]and in lean subjects[34],highlighting ketosis as a plausible contributing factor.

In considering all literature,the weight-loss effect of ketogenic diets may be ascribed to 1.increased metabolic costs of gluconeogenesis and the thermic effect of proteins,2.appetite-suppressant action of the ketone bodies,3.reduced appetite due to higher satiety effect of proteins,and/or 4.decreased lipogenesis and increased lipolysis and fat utilization.

Potential Risks of Ketogenic Diets

One may argue that a low carbohydrate,high protein and fat diet is potentially unhealthy as it may cause a rise in LDL cholesterol and triglycerides and this issue is of special importance in obese individuals.However,there are evidence that point to beneficial effects of ketogenic diets on these cardiovascular risk factors.The majority of recent studies seem to demonstrate that the reduction of carbohydrate intake can actually lead to significant benefits in total cholesterol reduction,in creases in HDL and reduction of blood triglycerides[24,35].Furthermore,ketogenic diets have been reported to in crease the size and volume of LDL-C particles[26],which is considered to reduce cardiovascular disease risk since smaller LDL particles have a higher atherogenicity.There is a biochemical rationale behind the effects of ketogenic diets on endogenous cholesterol synthesis.A key enzyme in cholesterol biosynthesis is HMG-CoA reductase,which is activated by insulin.This means that an increase in blood glucose and consequently of的能量和蛋白質(zhì)攝取，可以避免因其他減肥方法所引起的負(fù)面效果。

7 生酮飲食對(duì)肌肉代謝的影響

與嚴(yán)格限制能量飲食不同，生酮飲食為運(yùn)動(dòng)員提供了足夠的能量和蛋白質(zhì)[25]，避免了蛋白質(zhì)的缺乏。與此同時(shí)，生酮飲食通過(guò)誘導(dǎo)空腹樣狀態(tài)導(dǎo)致代謝途徑、自噬和應(yīng)激抵抗等過(guò)程的改變。生酮飲食模擬限制能量效應(yīng)，通過(guò)磷酸化激活腺苷單磷酸激活蛋白激酶（Adenosine Monophosphate-activated Protein Kinase ，AMPK）、去乙?；?1（Sirtuin-1，SIRT-1）和過(guò)氧化物酶體增殖物激活受體γ輔激活物1-α（Peroxisome Proliferator-activated Receptor Gamma Coactivator 1-alpha ，PGC-1α）[44]。PGC-1α 轉(zhuǎn)移到細(xì)胞核內(nèi)，作為轉(zhuǎn)錄因子上調(diào)編碼脂肪酸轉(zhuǎn)運(yùn)、脂肪氧化以及氧化磷酸化等蛋白的基因的表達(dá)。AMPK一方面通過(guò)磷酸化激活PGC-1α，另一方面可促進(jìn)骨骼肌氧化代謝相關(guān)酶的表達(dá)。研究發(fā)現(xiàn)肥胖人群在禁食狀態(tài)下AMPK活性降低，同時(shí)伴有機(jī)體氧化能力下降[45]。

與禁食相似，生酮飲食削弱了胰島素樣生長(zhǎng)因子 1 （Insulin-like Growth Factor 1，IGF-1） 的作用。IGF-1是肌肉合成代謝中的主要介質(zhì)，在阻抗運(yùn)動(dòng)中機(jī)械應(yīng)力的增加可促進(jìn)局部肌組織IGF-1的釋放。雷帕霉素靶蛋白 （Mammalian Target of Rapamycin，mTOR）信號(hào)通路是正常細(xì)胞生長(zhǎng)和增殖過(guò)程的關(guān)鍵調(diào)節(jié)因子[46]，也參與了IGF-1促進(jìn)的合成代謝過(guò)程。因此，盡管生酮飲食能量攝入充足，但肌肉含量增加的可能性較小。

盡管生酮飲食對(duì)提高耐力表現(xiàn)有作用，但并不適合想要增加肌肉的運(yùn)動(dòng)員。鑒于生酮飲食抑制肌肉肥大的潛在作用，健身愛(ài)好者在增肌期間廣泛采用這種飲食似乎不妥，因?yàn)樗械纳约胺肿訖C(jī)制等數(shù)據(jù)均表明生酮飲食期間肌肉含量很難增加。

8 生酮飲食與肌肉力量

如前所述，對(duì)于在有體重級(jí)別的項(xiàng)目中參賽的運(yùn)動(dòng)員來(lái)說(shuō)，一種安全的且不影響其運(yùn)動(dòng)表現(xiàn)的減肥方法至關(guān)重要。遺憾的是，僅有一項(xiàng)研究報(bào)道了這一課題。在該研究中，Paoli等觀察到，與正常飲食相比，30 d的生酮飲食對(duì)一組高水平的體操運(yùn)動(dòng)員的爆發(fā)力和耐力表現(xiàn)沒(méi)有負(fù)面影響[47]。這一發(fā)現(xiàn)表明對(duì)于力量型運(yùn)動(dòng)員來(lái)說(shuō)，生酮飲食可以在維持力量水平的同時(shí)滿足相應(yīng)的體重級(jí)別。由于競(jìng)技運(yùn)動(dòng)員運(yùn)動(dòng)量大，對(duì)蛋白質(zhì)的需求較高，因此該研究采用的生酮飲食中蛋白質(zhì)含量達(dá)到2.8 g/kg/d[25]。insulin levels will lead to increased endogenous cholesterol synthesis.Thus,a reduction in dietary carbohydrate together with a correct intake of cholesterol will lead to a inhibition of cholesterol biosynthesis.

Another concern relates to potential negative renal effects.It is suggested that high levels of nitrogen excretion during protein metabolism can cause an increase in glomerular pressure and hyper-filtration[18].In subjects with intact renal function,nevertheless,higher dietary protein levels have caused some functional and morphological adaptations but without negative effects[36].It is important to also take into account the renal related ef fects on blood pressure[37].However,the potential hypertensive effect of this diet has not been evidenced in individuals with normal renal function.With regard to possible acidosis during ketogenic diet,since the concentration of ketone bodies never rises above 8 mmol/L,this risk is virtually non-existent in subjects with normal insulin function[38].Regarding the overall effects of ketogenic diet on health there are differences in opinion.In a recent systematic review based on limited observational studies,Noto et al.[39]suggested a possible harmful effect of low carbohydrate/high protein diet on health:i.e.,an increase of all-cause mortality risk whilst there was no effect on cardiovascular disease mortality.On the other hand,a large European study demonstrated that an increase in protein content and a subsequent reduction in the glycemic index led to better maintenance of weight loss without adverse effects[24].

It is important to underline once again that a ketogenic diet is not,strictly speaking,a low carbohydrate/high protein diet.A ketogenic diet is mainly a very low carbohydrate diet with a normal amount of protein that produce an unusual metabolic state that should not be assimilated to a low carbohydrate/high protein diet.

Utility of Ketogenic Diets in Sports

Unlike many other types of energy restricted diets,which can create situations of undernutrition for essential nutrients,i.e.,vitamins,minerals,essential fatty acids,and amino acids,as well as depriving the body of other macronutrients that help control oxidative stress and inflammatory processes,a ketogenic diet is energy-sufficient diet with an adequate amount of protein(minimum 1.3-1.5 g/kg of body weight).Thus,despite the fact that Davis和Phinney發(fā)現(xiàn)在3個(gè)月的生酮飲食期間，給予1.1 g/kg/d蛋白質(zhì)的受試者較給予1.5 g/kg/d蛋白質(zhì)的受試者的最大攝氧量（）顯著降低，表明蛋白質(zhì)含量降低可能會(huì)影響到運(yùn)動(dòng)表現(xiàn)[48]。

在禁食的早期階段，肌蛋白分解為氨基酸前體，參與糖異生過(guò)程，此時(shí)中樞神經(jīng)系統(tǒng)依賴于糖異生所產(chǎn)生的葡萄糖供能。但這只是暫時(shí)的過(guò)程，因?yàn)槔眉∪夥纸夤┠懿皇菣C(jī)體最佳選擇也不利于長(zhǎng)期生存。生酮飲食可通過(guò)來(lái)自大量脂肪的酮體抑制糖異生來(lái)保存肌肉量。生酮飲食不會(huì)增加肌肉含量，但它也不會(huì)導(dǎo)致肌肉損失以及肌力下降。在酮癥狀態(tài)下，利用酮體和游離脂肪酸供能可減緩肌蛋白的分解代謝，保留肌肉含量，而這種利用脂肪作為能量的“肌肉節(jié)約效應(yīng)”仍待進(jìn)一步研究。目前還不清楚長(zhǎng)期生酮飲食是否會(huì)阻礙肌肉形成，從而使得需要增加肌肉含量的運(yùn)動(dòng)員適得其反。

9 生酮飲食與耐力表現(xiàn)

生酮飲食在不經(jīng)常鍛煉或久坐者中的研究結(jié)果相互矛盾，有些報(bào)道表明生酮飲食可以改善體能[49]，而有些則認(rèn)為生酮飲食后體能降低[12]。例如，Phinney等指出，輕度肥胖且不鍛煉的受試者在60%的最大耗氧量下長(zhǎng)時(shí)間運(yùn)動(dòng)，即使6周內(nèi)飲食幾乎不含碳水化合物（小于10 g/d），他們依然能夠維持這一運(yùn)動(dòng)量。此外，在平均減重7.1 kg后，與基礎(chǔ)值（168～259 min）相比，他們的跑步時(shí)間提高了1.5倍[50]。 而White等[51]報(bào)道生酮飲食（碳水化合物提供5%的能量）增加了9 min行走的疲勞感。該研究?jī)H報(bào)道受試者主觀疲勞程度增加，但平均心率以及運(yùn)動(dòng)強(qiáng)度無(wú)明顯改變，并且和血乳酸水平也都沒(méi)有分析。最近研究發(fā)現(xiàn)，在肥胖人群中，與高碳水化合物飲食相比，8周的生酮飲食增加脂肪氧化，且對(duì)有氧運(yùn)動(dòng)表現(xiàn)以及肌肉力量等指標(biāo)沒(méi)有負(fù)面效應(yīng)[52]。

生酮飲食對(duì)耐力運(yùn)動(dòng)員影響的研究也很少，最早是由Phinney等人報(bào)道，他們發(fā)現(xiàn)4周的生酮飲食對(duì)于自行車(chē)運(yùn)動(dòng)員的耐力表現(xiàn)沒(méi)有負(fù)面作用[8]。最近Zajac等發(fā)現(xiàn)生酮飲食可增加山地自行車(chē)運(yùn)動(dòng)員的最大耗氧量以及乳酸閾值[53]。作者將該發(fā)現(xiàn)歸因于體重以及脂肪含量的減少和脂肪利用率的增加，同時(shí)生酮飲食也使得最大運(yùn)動(dòng)負(fù)荷以及達(dá)到乳酸閾值的運(yùn)動(dòng)負(fù)荷明顯提高。

盡管研究報(bào)道結(jié)果不一致，有幾個(gè)原因可以解釋這些矛盾。首先，生酮飲食不利于運(yùn)動(dòng)表現(xiàn)的研究只進(jìn)行不到兩周時(shí)間，這不足以使得酮適應(yīng)完全發(fā)揮作用。盡管Sawyer等的文章中表明7 d生酮飲食it entails very low carbohydrate levels,the diet does not lead to metabolic imbalances that can have irreversible effects if nutrient-deficient weight loss diets are repeated on a regular basis.In this context and based on weight loss effect of ketogenic diets,there has been growing research aimed to examine the potential application of ketogenic diets in sports,especially those involving weight classes such as wrestling,weight lifting,judo,etc.

Motivations that lead athletes to desire weight loss include 1.improving power-to-weight ratio,2.competing in a more favorable weight category,and 3.in case of an activity like bodybuilding,to achieve an extreme leanness that is highly desirable for aesthetic purposes.Unfortunately,many common methods that athletes use to reduce weight also may have some negative side effects that can be detrimental to actual sports performance.These methods that produce rapid weight loss are typically carried out immediately before competition.The weight loss is created through cutting energy intake drastically,creating dehydration by using saunas,diuretics,and spitting,or using medications that facilitate weight loss.This can lead to electrolyte imbalance,dehydration,and reduced glycogen stores[17].Severe energy restriction also means a reduction of protein intake(as well as other essential nutrients)that,considering the higher needs of athletes,could induce loss of skeletal muscle mass and,in consequence,impairment of strength,power and endurance performance.There are several generally harmful effects on performance resulting from such a very restricted energy intake[40]as well as harmful effects from methods such as dehydration using sauna or diuretics[41].Apart from increasing risks of long-term health problems,there also is an increased risk of weight gain and obesity in athletes who reach middle age[42].

The practice of rapid weight loss in weight dependent sports is not to be underestimated.A recent re view by Franchini and colleagues[43]showed that rapid weight loss has a high prevalence in combat sport practitioners such as wrestlers(60%-90%)and in judo(～90%).Brito et al.(41)reported a similar percentage in judo athletes(62.8%),jujitsu (56.8%),karate(70.8%),and taekwondo(63.3%).Also in weightlifting,rapid weight loss appears to be common even though no precise data are available.（5.4%碳水化合物，35.1%蛋白質(zhì)，53.6%脂肪）對(duì)31名訓(xùn)練者的力量沒(méi)有任何負(fù)面效應(yīng)，仍建議運(yùn)動(dòng)員在比賽前至少2周即開(kāi)始采用生酮飲食減重[54]。其次，受試者是否攝入足量電解質(zhì)尚不明確。在生酮飲食中，需要攝入鈉和鉀來(lái)維持組織功能及氮平衡[6]。最后，在生酮飲食期間，糖異生增加使得蛋白質(zhì)需求增加，因此蛋白質(zhì)攝入不足可能會(huì)影響到運(yùn)動(dòng)員的肌肉量。

10生酮飲食與心理問(wèn)題

除了會(huì)增加困倦、疲憊感以及抑郁等癥狀外，快速減肥還可能導(dǎo)致注意力不集中、短期記憶力減退以及自尊心降低[55]。所有這些改變均可能影響到運(yùn)動(dòng)員的表現(xiàn)。注意力不集中會(huì)影響到運(yùn)動(dòng)員的技術(shù)水平發(fā)揮。短期記憶障礙可能會(huì)造成技術(shù)或戰(zhàn)術(shù)缺陷。自尊心的降低可能會(huì)導(dǎo)致信心的喪失和消極的態(tài)度，這兩者都可能導(dǎo)致整體表現(xiàn)不佳。鑒于生酮飲食伴有足夠的能量攝入，與常見(jiàn)的快速減肥飲食有關(guān)的這些負(fù)面影響可能不會(huì)出現(xiàn)。與簡(jiǎn)單而極端的限制能量攝入的機(jī)制不同，生理性酮癥是一種特殊的代謝狀態(tài)。生酮飲食對(duì)情緒以及認(rèn)知影響的少數(shù)研究表明，對(duì)于心理健康的超重及肥胖人群，短期適度限制能量的低碳水化合物飲食與相同能量的傳統(tǒng)飲食具有相似的作用效果[52]。同時(shí)該研究小組也發(fā)現(xiàn)1年的低脂肪飲食較低碳水化合物飲食對(duì)超重和肥胖人群的情緒具有更有利的作用[56]。因此至少短期生酮飲食應(yīng)用可緩解運(yùn)動(dòng)員抑郁癥狀并減輕主觀疲勞感。

11實(shí)際應(yīng)用

近年來(lái)，對(duì)生酮飲食的研究逐漸增加。然而僅有個(gè)別研究報(bào)道生酮飲食對(duì)運(yùn)動(dòng)表現(xiàn)的影響，且結(jié)果不一致，有部分原因是由于未正確使用生酮飲食。以下是有關(guān)如何正確進(jìn)行生酮飲食的幾個(gè)關(guān)鍵點(diǎn)。

（1）為有效誘導(dǎo)生理性酮癥，生酮飲食中碳水化合物含量需低于每天攝入總能量的5%或小于20 g/d。

（2）為維持運(yùn)動(dòng)員的肌肉量，每天攝入蛋白質(zhì)含量需在1.2～1.7 g/kg范圍內(nèi)（不超過(guò)2.5 g/kg）。這一含量可以確保至少維持機(jī)體蛋白質(zhì)補(bǔ)充以及糖異生消耗量。而過(guò)量蛋白質(zhì)攝入（超過(guò)2.5 g/kg或每天消耗總能量的25%～30%）則可能抑制酮癥狀態(tài)。

（3）脂肪是達(dá)到每天總能量需求的基礎(chǔ)營(yíng)養(yǎng)物質(zhì)，因此，運(yùn)動(dòng)員可隨意攝取脂肪。

（4）應(yīng)確保受試者足夠的礦物質(zhì)以及每天3～5 g鈉和2～3 g鉀的攝入來(lái)維持組織功能和氮平衡。

Effect of Ketogenic Diets on Muscle Metabolism

Unlike sev ere energy restriction,ketogenic diets provide adequate amounts of energy and protein to ath letes[25],avoiding protein deficiency but,at the same time,the diet,by inducing a “fasting-like” state,leads to alterations in metabolic pathways and processes such as autophagy and stress resistance.Ketogenic diets “mimics”the energy restriction effect that is to activate adenosine monophosphate-activated protein kinase(AMPK),sirtuin-1(SIRT-1),and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)by phosphorylation[44].In this state,PGC-1α moves to the nucleus and acts as a transcription factor,increasing the expression of genes that code for proteins involved in fatty acid transport,fat oxidation,and oxidative phosphorylation.AMPK works in two ways,either by activating PGC-1α by phosphorylation or by promoting the expression of enzymes involved in skeletal muscle oxidative metabolism.It has been demonstrated that obese individuals have lower AMPK activation coupled with less oxidative capacity during fasting[45].

On the other hand,ketogenic diets,similar to fasting,blunts the action of insulin-like growth factor 1(IGF-1).IGF-1 is considered to be the primary mediator for the anabolic response in muscle and its release from local muscle tissue increases as muscle undergoes mechanical stresssuch asby resistanceexercises.IGF-1 accelerates anabolic process that involves mammalian target of rapamycin(mTOR)signaling pathway,which is a key regulator of normal cellular processes in volved in cell growth and proliferation[46].In this context,ketogenic diets can reduce the possibility of gaining muscle mass despite energy sufficiency.

So while ketogenic diets may be useful in endurance performance,it is an oxymoron when the athlete seeks muscle hypertrophy.Given the potential that ketogenic diets can suppress muscle hypertrophy,it appears somewhat contradictory that there is widespread use of this diet in bodybuilders also during “bulk up”periods,whilealldata regarding biochemicaland molecular mechanisms suggest that it is very difficult to increase muscle mass during a ketogenic diet.

Ketogenic Diets and Muscle Strength and Power

As previously mentioned,for athletes competing in

（5）受試者應(yīng)具有依從性，飲食計(jì)劃應(yīng)受專(zhuān)業(yè)營(yíng)養(yǎng)師或注冊(cè)營(yíng)養(yǎng)師監(jiān)督以確保堅(jiān)持生酮飲食。

（6）通過(guò)血液分析確保受試者處于酮癥狀態(tài)，血液檢查較尿液檢查效果更好，因?yàn)槟蛑型w缺乏并不一定意味著非酮癥狀態(tài)。

（7）受試者需記住在生酮飲食的前幾天，體重減輕的主要原因是糖原和水分的丟失，因?yàn)槊績(jī)?chǔ)存1 g糖原會(huì)附帶3 g水分。隨著時(shí)間延長(zhǎng)，脂肪的消耗逐漸增加，在5～7 d后，脂肪氧化顯著上升。

（8）如果在涉及體重級(jí)別的比賽中采用生酮飲食，為避免對(duì)運(yùn)動(dòng)表現(xiàn)產(chǎn)生副作用，建議至少提前兩周開(kāi)始。

（9）生酮飲食只適用于成年運(yùn)動(dòng)員，在青少年時(shí)期使用需謹(jǐn)慎。盡管有證據(jù)證明其在癲癇發(fā)作的兒童中的有效性和耐受性，但生酮飲食在青少年運(yùn)動(dòng)員中的應(yīng)用必須在醫(yī)療指導(dǎo)下進(jìn)行。

12結(jié)論

生酮飲食是指碳水化合物含量減少 （通常小于20 g/d或低于每天總能量攝入的5%）而蛋白質(zhì)和脂肪的比例相對(duì)增加的飲食。生酮飲食與其他類(lèi)型的減肥飲食不同，它的特點(diǎn)是能量充足但碳水化合物含量非常低，蛋白質(zhì)含量能夠滿足日常消耗且提供豐富的微量營(yíng)養(yǎng)素及必需營(yíng)養(yǎng)素。生酮飲食誘導(dǎo)的代謝性酮癥可抑制饑餓感并增加脂肪氧化，從而減輕體重。盡管有待進(jìn)一步研究，但短期生酮飲食不會(huì)引起任何重大的健康問(wèn)題。已有研究表明生酮飲食在某些運(yùn)動(dòng)，特別是在有體重級(jí)別，涉及審美以及耐力運(yùn)動(dòng)中具有重要作用，但訓(xùn)練者、體育醫(yī)生以及營(yíng)養(yǎng)師也必須充分了解采用這種飲食方法的正確步驟以及它的優(yōu)勢(shì)與不足之處。目前有關(guān)這種相對(duì)新的飲食方法的研究仍然有限，因此有關(guān)生酮飲食在治療肥胖及其并發(fā)癥中的潛在作用，以及在不影響運(yùn)動(dòng)員運(yùn)動(dòng)表現(xiàn)的情況下控制體重的特殊功效還尚待更多研究數(shù)據(jù)的積累。weight categ ory sports,a safe method of weight loss that does not impair performance can be a legitimate and important tool.Surprisingly,only one study has reported on this topic.In this study,Paoli et al.[47]demonstrated that,compared with a standard ad libitum diet,a 30-d ketogenic diet did not affect explosive and strength performance negatively in a group of high-level gymnasts.This finding suggests that ketogenic diets could be useful for power athletes to meet weight categories while maintaining power output.Because of the intense physical activity of competitive athletes,there is an increased demand for protein,and this was reflected in the ketogenic diet administered in the study,which provided approximately 2.8 g protein/kg/day[47].In fact,a lower quantity of protein may impair performance as demonstrated by Davis and Phinney[25]who showed that subjects consuming 1.1 g of protein/kgof body weight experienced a significant reduction in during a 3-month period during a ketogenic diet compared with subjects given 1.5 g/kg body weight.

In the earlyphase of fasting,the CNS is kept supplied with glucose for energy via gluconeogenesis,a process of breaking down muscle tissue to the amino acid precursors.Clearly,this is only a temporary measure as muscle wasting is compatible with neither optimal performance nor long-term survival.However,ketogenic diets are able to spare muscle mass by producing ketone bodies,a fat-based source of energy,at a high level.Ketogenic diets may not lead to a gain in muscle mass,but they normally don’t cause muscle loss nor decreased muscle performance either.It appears that during a ketotic state,the use of ketone bodies and free fatty acids for energy slows muscle protein catabolism,so lean body mass is generally conserved,although this “sparing effect” of the use of fats as an energy source remains to be evidenced.It is unclear if a long-term use of ketogenic diet can interfere with muscle development and thus be counterproductive especiallywhen the aim of the athlete is to gain muscle mass.

Ketogenic Diets and Endurance Performance

The available data on the use of ketogenic diets in untrained/sedentary subjects have shown contradictory results,with some reports of improvement[49]and others of reduction[12]in physical performance.For example,in mildly obese untrained individuals,Phinney et al.[50]noted that,while undergoing prolonged exercise at 60%they can sustain this even with almost no carbohydrate in the diet(＜10 g/day)across a period of 6 weeks.Furthermore,after a mean weight loss of 7.1 kg,there was a significant 155%increase compared with baseline in treadmill time (from 168 to 259 min).On the other hand,White et al.[51]reported that a ketogenic diet(5%of energy provided by carbohydrates)increased perception of fatigue during a 9-min walk.However,it was only the rating of perceived exertion that was significantly higher and there was no actual change in average heart rate or exercise intensity,whereas other measures of performance such asand blood lactate levels were not analyzed.Recent studies demonstrated that,in obese subjects,8 weeks of a ketogenic diet enhanced fat oxidation and had no detrimental effect on maximal or submaximal markers of aerobic exercise performance or muscle strength compared with a high-carbohydrate diet[52].

Very few studies have analyzed the effect of ketogenic diets in endurance athletes.The earliest is the study by Phinney et al.[8]who found that 4 weeks of ketogenic diet did not have any negative effects on endurance performance in cyclists.A more recent study by Zajac et al.[53]reported a significant increase inand improvement in the lactate threshold in off-road cyclists after a ketogenic diet.The authors attributed their findings to the reduction body mass and fat mass and increase in fat utilization even though the maximal workload and the workload at lactate threshold were both reduced significantly on the ketogenic diet.

Although these studies report divergent results,there are several factors that could explain the contradictory findings.First,studies showing a detrimental effect of a ketogenic diet on performance were performed for less than 2 weeks and this is not sufficient for the effects of full keto-adaptation to be seen.It is recommended that athletes should program a ketogenic diet for weight loss at least 2 weeks before competition,even though a recent article by Sawyer et al.[54]reported that power output was not affected negatively in 31 trained individuals after only 7 days of a ketogenic diet(5.4%carbohydrate,35.1%protein,and 53.6%fat).Second,it is unclear whether subjects consumed adequate amount of electrolytes.During a ketogenic diet,sodium and potassium need to be supplied to maintain tissue function and nitrogen balance[6].Finally,during a ketogenic diet,the need for protein is higher because of gluconeogenesis;thus,a low intake of protein may affect negatively the athlete’s muscle mass.

Ketogenic Diets and Psychological Issues

It must be noted that rapid weight loss may cause decreased concentration,short term memory loss,and lower self-esteem,as well as increasing confusion,fatigue,and depression traits[55].All these modifications can contribute to impaired performance in athletes.A lack of concentration could affect the ability of the athlete to focus on technique that would result in loss of performance.Impairment in short-term memory can cause a technical/tactical disadvantage.A reduction of self-esteem can result in a loss of confidence and negative attitudes,both of which can contribute to an overall subdued performance.Given that a ketogenic diet is accompanied by a sufficient energy intake,these negative observations associated with common rapid weight loss diets may not apply.This is because physiological ketosis is a specific metabolic state that is quite different from the mechanisms induced by simple but extreme energy restriction.The few studies available about the effects of a ketogenic diet on mood and cognition suggest that a short-term consumption of a moderately energy-reduced low-carbohydrate diet has similar effects on the psychological well-being of overweight and obese individuals compared with an isoenergetic conventional diet[52].This same research group also reported a more favorable effect on mood of low-fat diets compared with a low-carbohydrate diet after 1 year in overweight and obese individuals[56].It appears that ketogenic diets at least in the short-term such as that might be used by athletes can help alleviate depressive symptoms and also diminish perceptions of fatigue.

Practical Application

An increasing amount of research has been carried out on ketogenic diets during recent years.However,only a few studies are available on ketogenic diets and sport performance,and results are mixed in part because of an incorrect use of ketogenic diets.The fol lowing are the key points with regard to how ketogenic diets should be carried out adequately:

*A ketogenic diet shall contain less than 5%of total daily energy from carbohydrates or less than 20 g of carbohydrate daily in order to effectively induce physiological ketosis.

*In athletes,to preserve lean body mass,the daily requirement for protein should be in the range of 1.2 to 1.7 g/kg body weight (up to 2.5 g/kg body weight).This amount is needed to ensure the minimum quantity for body protein replacement and for gluconeogenesis.On the other hand,an excessive protein intake(＞2.5 g/kg body weight or more than 25-30%of daily energy expenditure)might suppress ketogenesis.

*Fats are fundamental to reach the total daily energy requirement;thus,for athletes,fat should be provided ad libitum.

*Subjects must insure an adequate mineral intake and supplementation with 3 to 5 g/day of sodium and 2 to 3 g/day total potassium can maintain tissue function and nitrogen balance.

*Subjects should be compliant,and the diet plan should be checked by an expert nutritionist or registered dietician to confirm adherence to a ketogenic diet.

*Blood analysis should be performed to confirm that subjects are in ketosis;blood examinations using a device that uses capillary blood are preferable to urine examinations because often a lack of ketone bodies in urine does not mean necessarily a nonketotic state.

*Subjects should keep in mind that during the first days of ketogenic diet,the main contributor to weight loss is muscle glycogen and,thus,water-it is well known that there are about 3 g of water stored with each gram of glycogen.In addition,the contribution of fat increases gradually overtime and it should be expected that a signifi cant increase in fat oxidation could be observed after 5-7 days.

*If a ketogenic diet is used for weight category sports,it is recommended that it begins early,at least 2 weeks prior to the competition in order to avoid any negative effects on performance.

*Ketogenic diets may only be applied to adult athletes and their use in youth needs caution.Even though there are convincing data about its efficacy and tolerability in children with seizures in epilepsy,the use of ketogenic diets in young athletes must require a medical supervision.

Conclusions

Ketogenic diets are characterized by a reduction in carbohydrates (usually＜20 g/day or 5%of total daily energy intake)and a relative increase in the proportions of protein and fat.The diet is fundamentally different from many other weight loss diets.The key feature of this diet is an energy sufficiency while with a very low carbohydrate intake and its compatibility with normal protein consumption and a rich nutrition that provides full complements of micronutrients and essential macronutrients.By inducing physiological ketosis,the diet can help control hunger and improve fat oxidative,thereby reducing body weight.Although more research is needed,the short term use of ketogenic diets has not been associated with any major health issues.There are some encouraging data that suggests a useful role of ketogenic diets in certain sports,especially those with weight categories and aesthetic and endurance sports,but it is necessary that trainers,sports physicians,and dieticians are awareof theproperprocedure and strengths and limitations associated with this nutritional strategy.As data are still quite limited with regard to this relatively “new”dietary approach,further studies are warranted to further investigate the potential role ketogenic diets play in treating obesity and its comorbidities and in helping athletes manage their body weight without sacrificing performance.

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