Ketogenic diet in treating sepsis-related acquired weakness: is it friend or foe?

Abstract

Background: Sepsis is the body's extreme response to an infection leading to organ dysfunction. Sepsis-related acquired weakness (SAW), a critical illness closely related to metabolic disorders, is characterized by generalized sepsis-induced skeletal muscle weakness, mainly manifesting as symmetrical atrophy of respiratory and limb muscles. Muscle accounts for 40% of the body's total mass and is one of the major sites of glucose and energy absorption. Diet affects skeletal muscle metabolism, which further impacts physiology and signaling pathways. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that has shown benefits in patients with a variety of neuromuscular disorders. Patients with SAW are in a hypermetabolic state and can consume approximately 1% of total body muscle mass in a day. Due to the decreased total body energy expenditure secondary to starvation, skeletal muscles enter a low metabolic state, with reduced gluconeogenesis and protein consumption and elevated levels of ketone bodies. The latest research suggests that KD may be a new strategy for SAW prevention and treatment, but its mechanism is still unclear.

Objective: Our article aims to explore the effect and mechanism of KD on SAW. And we hope that our review will inspire further research on the KD and foster the exploration of novel strategies for combating SAW.

Methods: Search medical databases and related academic websites, using keywords such as "Sepsis-related acquired weakness," "ketogenic diet," and "skeletal muscle," and select representative literature. Using the method of induction and summary, analyze the effect and mechanism of KD on SAW.

Results: Compared with early nutrition, KD has a more protective effect on SAW, but its mechanism is complex. Firstly, KD can alter energy metabolism substrates to affect SAW's energy metabolism; Secondly, KD can directly act as a signaling molecule to improve mitochondrial function in skeletal muscle and stimulate skeletal muscle regeneration signaling molecules; Thirdly, KD can affect the gut microbiota to exert anti-inflammatory effects, enhance immunity, and thus protect SAW.

Conclusion: KD has a protective effect on SAW, which includes improving energy metabolism, stimulating muscle regeneration signals, optimizing gut microbiota composition, and reducing inflammation and oxidative stress.

Keywords: ICU-acquired weakness; gut microbiota; ketogenic diet; ketone bodies; sepsis-related acquired weakness.

Figure 1

The differences between the KD and a standard diet in energy production. In a standard diet, carbohydrates serve as the primary energy source post-consumption. In contrast, the KD mainly relies on KBs for energy production. These ingested KBs, alongside the ones produced by the liver, enter the tricarboxylic acid cycle to generate energy. Created with Figdraw.com.

Figure 2

The KD ameliorates SAW by changing the energy-supplying pattern. The KD ameliorates inflammation and hypoxia in muscles during sepsis. Fatty acids provide direct relief from SAW. KBs also have therapeutic effects on SAW by affecting the tricarboxylic acid cycle and subsequently enhancing mitochondrial function. Created with Figdraw.com.

Figure 3

The KD ameliorates SAW by maintaining gut microbiota homeostasis. The KD can maintain the homeostasis of the gut microbiota, the integrity of the intestinal barrier, and immune homeostasis, thereby inhibiting inflammation and ameliorating SAW. Created with Figdraw.com.