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酮体代谢、β-羟丁酸信号转导与间歇性禁食的生物能量学
从 Randle 循环、表观遗传抑制到细胞自噬动力学的系统生物学及东方辟谷食气观考辨
Ketone Metabolism, β-Hydroxybutyrate Signalling and the Bioenergetics of Intermittent Fasting: From the Randle Cycle and Epigenetic Inhibition to Autophagy Kinetics, Read Beside Classical Chinese Fasting Texts
DOI10.5281/zenodo.23753263摘要
本书讨论进食与禁食之间的代谢切换，以及围绕它的流行说法哪些有证据、哪些没有。依次讨论：兰德尔循环与肝脏生酮的化学计量（按每分子氧计算，β-羟丁酸产生 4.78 个 ATP，高于脂肪酸的 4.61，低于葡萄糖的 5.33；经由酮体转手一次约损失 4% 的 ATP），以及肝糖原与血酮的两室模型；维奇关于酮体增大线粒体 NAD 与辅酶 Q 之间氧化还原跨度、提高 ATP 水解自由能的热力学假说，用能斯特方程计算，并说明它在离体心脏中有实验基础，在人体心脏中方向一致但机制未定，在运动表现中证据互相矛盾；β-羟丁酸作为 HCAR2 受体配体、组蛋白去乙酰化酶抑制剂（后续研究显示其细胞内作用远弱于丁酸）、NLRP3 炎症小体抑制剂与组蛋白 β-羟丁酰化来源的研究，以及按希尔方程计算的浓度–效应关系；AMPK–mTORC1 双负反馈开关的滞后性与细胞自噬，并指出小鼠的自噬时间线不能换算为人的小时数，人体中也没有简单无创的自噬计时标志物；癫痫、2 型糖尿病、代谢舱与限时进食随机试验的真实效应量（热量匹配时未见胰岛素模型预言的额外脂肪减少，限时进食也未见明确的额外减重），以及 LDL 胆固醇的个体差异风险；低碳水初期胰岛素下降引起的排钠利尿、细胞外液与钾的变化，以及糖原结合水。
八章与马王堆帛书《却谷食气》、葛洪《抱朴子内篇·杂应》（「断谷人止可息肴粮之费，不能独令人长生也」）、《素问》《灵枢》与《论语·乡党》并读，区分适度节制的饮食传统与危及生命的极端断食；最后给出个人代谢记录的四步核查表（含葡萄糖–酮体指数在低血酮时不稳定的计算），以及一项在提供餐食、热量与蛋白质相同条件下比较 16:8 早期限时进食与三餐分布的预注册随机交叉试验方案（主要结局为连续血糖监测的 MAGE，45 人完成、招募 57 人）。书中以标注框区分已发表的证据、可运行的 Python 计算（14 段程序，全部核对）、原典与作者的假说。本书不是医疗建议；1 型糖尿病、使用降糖药或 SGLT2 抑制剂、孕哺、进食障碍史、肝肾疾病等人群不应自行尝试禁食或生酮饮食。
关键词：酮体；β-羟丁酸；代谢切换；兰德尔循环；生酮作用；线粒体氧化还原状态；能斯特方程；组蛋白去乙酰化酶；HCAR2；NLRP3 炎症小体；AMPK；mTORC1；细胞自噬；克莱伯定律；限时进食；生酮饮食；排钠利尿；连续血糖监测；辟谷；抱朴子
Abstract
This book examines the metabolic switch between feeding and fasting, and which of the popular claims about it have evidence and which do not. It covers the Randle cycle and the stoichiometry of hepatic ketogenesis (per molecule of oxygen, β-hydroxybutyrate yields 4.78 ATP, more than fatty acid at 4.61 and less than glucose at 5.33; routing fat through ketones loses about 4 % of the ATP), with a two-compartment model of liver glycogen and blood ketones; Veech's thermodynamic hypothesis that ketones widen the mitochondrial redox span between NAD and coenzyme Q and raise the free energy of ATP hydrolysis, computed with the Nernst equation, with an experimental basis in the isolated heart, consistent direction but unsettled mechanism in the human heart, and conflicting evidence on exercise performance; research on β-hydroxybutyrate as an HCAR2 ligand, a histone deacetylase inhibitor (later work found its action in cells far weaker than butyrate's), an NLRP3 inflammasome inhibitor and a source of histone β-hydroxybutyrylation, with concentration–effect relations from the Hill equation; hysteresis in the AMPK–mTORC1 double-negative switch and autophagy, noting that mouse autophagy timelines cannot be converted into human hours and that humans lack a simple non-invasive marker that times autophagy; the real effect sizes of randomised trials in epilepsy, type 2 diabetes, metabolic wards and time-restricted eating (with calories matched, neither the extra fat loss predicted by the insulin model nor clear additional weight loss from time restriction), and the individual risk of rising LDL cholesterol; and the natriuresis, extracellular fluid and potassium changes caused by falling insulin in the first low-carbohydrate days, with glycogen-bound water.
The eight chapters are read beside the Mawangdui silk manuscript Quegu shiqi, Ge Hong's Baopuzi ("cutting off grain can only save the cost of food; it cannot by itself make a person live long"), the Suwen, the Lingshu and the Analects, distinguishing a tradition of moderate dietary restraint from life-threatening extreme fasting. They end with a four-step checklist for a personal metabolic log (including a calculation of how unstable the glucose–ketone index is at low ketone levels) and a pre-registered randomised crossover trial comparing 16:8 early time-restricted eating with three meals, with meals provided and calories and protein matched (primary outcome MAGE from continuous glucose monitoring; 45 completers, 57 recruited). Marked boxes separate published evidence, runnable Python calculations (14 programs, all checked), classical sources and the author's hypotheses. This book is not medical advice; people with type 1 diabetes, on glucose-lowering drugs or SGLT2 inhibitors, pregnant or breastfeeding, with a history of eating disorders or with liver or kidney disease, among others, should not try fasting or a ketogenic diet on their own.
Keywords: ketone bodies; beta-hydroxybutyrate; metabolic switching; Randle cycle; ketogenesis; mitochondrial redox state; Nernst equation; histone deacetylase; HCAR2; NLRP3 inflammasome; AMPK; mTORC1; autophagy; Kleiber's law; time-restricted eating; ketogenic diet; natriuresis; continuous glucose monitoring; bigu; Baopuzi
目录 · Contents
- 序：开关、燃料与信号English 中文Preface: A Switch, a Fuel and a Signal
- 第一章 代谢切换：从葡萄糖到酮体English 中文Chapter 1 The Metabolic Switch: from Glucose to Ketones
- 第二章 心脏与大脑为什么用酮体：维奇的热力学假说及其边界English 中文Chapter 2 Why the Heart and Brain Use Ketones: Veech's Thermodynamic Hypothesis and Its Limits
- 第三章 不只是燃料：β-羟丁酸的信号作用English 中文Chapter 3 More Than a Fuel: β-Hydroxybutyrate as a Signal
- 第四章 AMPK–mTORC1 开关与细胞自噬English 中文Chapter 4 The AMPK–mTORC1 Switch and Autophagy
- 第五章 人体随机试验说了什么English 中文Chapter 5 What Randomised Trials in People Show
- 第六章 生酮适应期：肾脏、钠与水English 中文Chapter 6 Keto-Adaptation: the Kidney, Sodium and Water
- 第七章 古典文献考辨：却谷、断谷与食养English 中文Chapter 7 Classical Texts Examined: Abstaining from Grain, Cutting Off Grain, and Nourishment by Food
- 第八章 实践与预注册试验English 中文Chapter 8 Practice and a Pre-registered Trial
How to cite · 引用
Fan, Y. (2026). Ketone Metabolism, β-Hydroxybutyrate Signalling and the Bioenergetics of Intermittent Fasting: From the Randle Cycle and Epigenetic Inhibition to Autophagy Kinetics, Read Beside Classical Chinese Fasting Texts [酮体代谢、β-羟丁酸信号转导与间歇性禁食的生物能量学] (Version 1.0.0). 5D Library. https://doi.org/10.5281/zenodo.23753263
BibTeX
@book{fan2026ketone,
title = {{Ketone Metabolism, β-Hydroxybutyrate Signalling and the Bioenergetics of Intermittent Fasting}: From the Randle Cycle and Epigenetic Inhibition to Autophagy Kinetics, Read Beside Classical Chinese Fasting Texts},
author = {Fan, Yafu},
year = {2026},
publisher = {5D Library},
edition = {Version 1.0.0},
doi = {10.5281/zenodo.23753263},
url = {https://doi.org/10.5281/zenodo.23753263},
note = {Chinese title: 酮体代谢、β-羟丁酸信号转导与间歇性禁食的生物能量学}
}
| DOI | https://doi.org/10.5281/zenodo.23753263 |
|---|---|
| DOI（全部版本 all versions） | https://doi.org/10.5281/zenodo.23753262 |
| ORCID | https://orcid.org/0009-0004-3519-1203 |
| 5D Library ID | 5DL-B-017 |
| 版本 Version | 1.0.0 · 中英双语版 Bilingual edition |
| 出版日期 Date | 2026-10-29 |
| 网址 Online | https://5dlibrary.com/books/ketone-metabolism-autophagy/ |
| SHA-256 · ketone-metabolism-autophagy_bilingual_v1.0.0.pdf | ab5b62a7d6cd12cae37e8aeada00c8ec20d74570844edc257787219ee7dadf68 |
| SHA-256 · ketone-metabolism-autophagy_en_v1.0.0.pdf | 542f407fd7f0dd948792a1ebeb8d5303bf95c6f1e428be502e7d1d17c1fdabb9 |
| SHA-256 · ketone-metabolism-autophagy_zh_v1.0.0.pdf | 85ae382909ebb2391abcdf5945eb8a313a5e5ddc39d04606d86c9d7222197a4c |
| Licence · 许可 | Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0). https://creativecommons.org/licenses/by-nc-nd/4.0/ |
Disclosure. The author runs two websites on ketogenic metabolism and NAD+, ketohackers.com and nadplusnadplus.com, and therefore has a direct commercial interest in the subject of this book. The book does not link to these sites and neither mentions nor recommends any product, supplement, testing device or course; the Chapter 8 trial is designed to be run and analysed by researchers independent of the author's business; all the code and the study protocol are published openly for anyone to check.