How does a very low-calorie ketogenic diet affect metabolism?

Metabolic Effects of Very Low Calorie Ketogenic Diet

A very low-calorie ketogenic diet (VLCKD) fundamentally shifts the body's metabolism from primarily utilizing carbohydrates to predominantly using fat for energy production through a state of physiological ketosis, resulting in significant weight loss and metabolic improvements. The VLCKD induces a metabolic state called ketosis where the body primarily utilizes fat for energy production, leading to increased fat oxidation, reduced carbohydrate oxidation, and modest increases in protein oxidation. 1

Core Metabolic Changes

• VLCKD causes the body to transition from glucose-dependent metabolism to ketone body utilization, with ketone levels typically ranging from 0.3 to 4 mmol/L during physiological ketosis 1
• Ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone) are produced in the liver through ketogenesis from Acetyl-CoA when carbohydrate intake is restricted 1
• Carbohydrate oxidation decreases by approximately 65% while fat oxidation increases by about 11% after one month on VLCKD 2
• Energy expenditure decreases by approximately 10% after one month on VLCKD, reflecting metabolic adaptation to caloric restriction 2

Body Composition Effects

• VLCKD typically leads to rapid initial weight loss, with a significant portion being water weight due to glycogen depletion (glycogen is stored with water) 1
• After one month, body weight decreases by approximately 7%, reflecting an 8.8% reduction in fat mass and a 5.6% reduction in lean soft tissue 2
• The diet promotes preservation of skeletal muscle mass compared to simple fasting, acting as a "protein sparing modified fast" 1
• Monitoring changes in skeletal muscle mass is crucial to ensure weight loss comes predominantly from fat rather than muscle 1

Hormonal and Metabolic Regulation

• VLCKD reduces insulin levels while maintaining them within physiological ranges, which helps decrease fat storage and increase fat utilization 1
• According to the "Carbohydrate-Insulin-Model" of obesity, reducing carbohydrates decreases insulin secretion, reducing energy storage in adipose tissue 1
• Energy expenditure increases by approximately 52 kcal/day for every 10% decrease in carbohydrate contribution to total energy intake 1
• Ghrelin and leptin levels decrease significantly, contributing to reduced hunger, decreased fat deposition, and increased leptin sensitivity 1

Insulin Sensitivity and Glucose Metabolism

• VLCKD significantly improves insulin sensitivity, with studies showing a 57% decrease in insulin resistance 1
• Blood glucose levels and glycated hemoglobin decrease due to reduced carbohydrate intake and improved insulin sensitivity 3
• These improvements are particularly pronounced in individuals with pre-existing hyperinsulinemia 1
• The diet helps stabilize blood glucose levels by minimizing fluctuations in glycemia 4

Liver Metabolism

• VLCKD can reduce intrahepatic lipid content by approximately 31% in overweight individuals with non-alcoholic fatty liver disease 1
• The diet promotes increased ketogenesis in the liver and changes in gut microbiota that may contribute to improved liver health 1
• VLCKD shows stronger short-term reduction in intrahepatic lipid content compared to low-fat diets 1
• These liver benefits occur even with moderate weight loss, highlighting the metabolic advantages beyond simple caloric restriction 1

Gut Microbiota and Intestinal Effects

• VLCKD significantly alters gut microbiota composition, including an increase in the Firmicutes/Bacteroidetes ratio 5
• The diet reduces fecal short-chain fatty acids (butyrate, propionate, acetate) and may increase serum zonulin levels, potentially affecting intestinal permeability 5
• Some beneficial bacteria like Bifidobacter decrease while others like Akkermansia increase, with potential implications for long-term gut health 5
• These microbiome changes may contribute to both the beneficial metabolic effects and potential side effects of the diet 5

Potential Pitfalls and Caveats

• Initial rapid weight loss is primarily water weight and may create false expectations about the rate of fat loss 1
• The diet may lead to some loss of lean tissue (5.6%) alongside fat mass reduction 2
• Long-term adherence can be challenging due to the restrictive nature of the diet 4
• Potential side effects include digestive system disorders, headaches, irritability, fatigue, vitamin/mineral deficiencies, and possible worsening of lipid profiles in some individuals 4
• VLCKD should be implemented under medical supervision, especially for individuals with pre-existing health conditions 3, 4