Ketogenic diet (but not sugar restriction) alters glucose tolerance, lipid metabolism, peripheral tissue phenotype and the gut microbiome: an RCT.

Restricted sugar and ketogenic diets can both alter energy balance and metabolism, but any resultant decrease in energy intake may be counteracted by compensatory reductions in energy expenditure. In healthy adults, randomization to restriction of free-sugars or overall carbohydrates (ketogenic diet) for 12 weeks reduced fat mass without changes in physical activity or resting metabolic rate, compared to a control diet. Free-sugar restriction had minimal effect on metabolism or gut microbiome other than decreased serum low-density lipoprotein cholesterol concentrations. In contrast, ketogenic diet-induced weight loss decreased glucose tolerance, coinciding with increased PDK4 and reduced AMPK and GLUT4 levels in skeletal muscle. In the first 4 weeks, the ketogenic diet reduced fasting glucose, increased apolipoprotein B, C-reactive protein and postprandial glycerol concentrations. However, despite sustained ketosis, these effects were no longer apparent by week 12, when gut microbial beta diversity was altered, possibly reflective of longer-term ketotic adaptation and/or new energy balance status. These data demonstrate that restricting either free-sugars or overall carbohydrates can reduce energy intake without altering physical activity, but with divergent effects on glucose tolerance, lipoprotein profiles and gut microbial composition.

限糖饮食与生酮饮食（ketogenic diet）均可改变机体能量平衡与代谢状态，但由此引发的能量摄入减少，可能会通过能量消耗的代偿性降低得到抵消。与对照饮食相比，对健康成人随机分配至为期12周的游离糖（free-sugars）限制或总碳水化合物限制（即生酮饮食，ketogenic diet）干预后，受试者的脂肪量出现减少，且身体活动水平与静息代谢率（resting metabolic rate）均未发生变化。游离糖限制仅对血清低密度脂蛋白胆固醇（low-density lipoprotein cholesterol）浓度产生了降低作用，对代谢或肠道微生物组（gut microbiome）几乎无其他影响。与之形成对比的是，生酮饮食诱导的体重减轻会降低葡萄糖耐量，该变化与骨骼肌内PDK4、AMPK及GLUT4的水平变化相一致——其中PDK4表达上调，AMPK与GLUT4水平降低。在干预的前4周，生酮饮食可降低空腹血糖水平，同时升高载脂蛋白B、C反应蛋白与餐后甘油浓度。然而，尽管受试者持续处于酮症状态，但至第12周时，上述效应已不再显著，此时受试者的肠道微生物β多样性已发生改变，这或许反映了长期酮症适应及/或新的能量平衡状态。本研究数据表明，限制游离糖或总碳水化合物摄入均可在不改变身体活动水平的前提下减少能量摄入，但二者对葡萄糖耐量、脂蛋白谱及肠道微生物组成的影响存在显著差异。