Context: A recent study published in the journal Nutrients sheds light on the dynamics of fasting-induced ketosis, emphasizing its potential as a non-pharmacological intervention for chronic disease prevention and management.
Long-term fasting has been shown to normalize glucose and lipid metabolism, reduce oxidative stress, restore gut microbiota balance, and exert anti-inflammatory effects. Despite its benefits, fasting-induced ketosis is often misinterpreted as akin to diabetic ketoacidosis. The metabolic transition to utilizing endogenous energy sources is a hallmark of the fasting process.
When food intake is halted, glucose and insulin levels decline, prompting glucagon secretion and the breakdown of glycogen into glucose. Once glycogen reserves are depleted, lipolysis occurs, releasing fatty acids into the bloodstream for energy. The liver then converts these fatty acids into ketone bodies, which are energy-rich, water-soluble molecules that can be transported to peripheral tissues for ATP synthesis.
About the Study: The study, titled “Long-Term Fasting-Induced Ketosis in 1610 Subjects: Metabolic Regulation and Safety,” involved participants aged 18 to 91 from a fasting clinic. Individuals with type 1 diabetes, cachexia, dementia, anorexia nervosa, cerebrovascular insufficiency, or cognitive diseases were excluded to ensure a healthy cohort.
Before the fasting period, participants underwent medical examinations. A day prior to fasting, they were provided with a 600-kcal vegetarian diet. A laxative was administered on the first fasting day, during which participants consumed fresh fruit juice (250 ml), vegetable soup (250 ml), and honey (20 g). Daily hydration included two to three liters of herbal tea or non-caloric water.
Caloric intake during fasting ranged from 75 to 250 kcal, complemented by daily physical activity and rest. An ovo-lacto-vegetarian diet was reintroduced on the last day of fasting. Blood samples were collected to measure ketonemia as β-hydroxybutyrate levels, while urinary acetoacetate excretion was assessed using sodium nitroprusside tests. Ketostix strips were utilized to evaluate ketosis, alongside assessments of emotional and physical well-being, lipid profiles, glycemic indicators, and other health parameters.
Findings: The study included 1,610 participants. Researchers first examined the correlation between ketonuria (urinary acetoacetate levels) and ketonemia (blood β-hydroxybutyrate levels) in 32 subjects. They found that semi-quantitative urinary acetoacetate measurement is a convenient, non-invasive method to accurately reflect ketosis induced by long-term fasting.
Cumulative calorie loss during fasting among these individuals ranged from 124 to 1,468 kcal, with an average loss of 56.2 kcal/day from ketone bodies. Notably, those who engaged in higher physical activity during the fasting program experienced a more rapid increase in ketonemia. While some participants excreted minimal ketones, others exhibited significantly higher levels, with increased ketonuria observed in those who refrained from consuming fruit juice and honey.
Among a subgroup of 179 participants, those in the lowest quartile of calorie intake (averaging 98 kcal) had a higher incidence of high ketonuria (31 individuals) compared to low ketonuria (14 individuals), primarily due to consuming only soup. Conversely, individuals in the highest intake quartile (averaging 228 kcal) showed mixed results in ketonuria levels.
Factors influencing ketonuria included age, gender, physiological status, and physical activity. Participants with high ketonuria were generally younger, male, with lower levels of high-density lipoprotein and urea, but higher body weight. The reduction in glycated hemoglobin and glucose levels due to fasting was less pronounced in those with low ketonuria.
Changes in body weight and waist circumference were more significant in high ketonuric participants. Uric acid levels increased by 206 µmol/L in high ketonuric individuals compared to 97 µmol/L in low ketonuric participants, with a strong correlation between ketonuria and uric acid levels. However, no significant differences were found in blood pressure, well-being, cholesterol, and triglyceride levels between the two groups.
Conclusions: This study highlights that long-term fasting-induced ketosis remains within healthy physiological limits. Factors such as gender, age, physiological status, and physical activity significantly influence ketosis levels. Notably, carbohydrate intake modulated but did not suppress ketosis. These findings suggest that individual characteristics can predict the outcomes of long-term fasting, paving the way for personalized fasting strategies.
Source:By Tarun Sai Lomte Reviewed by Susha Cheriyedath, M.Sc
