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The impact of a ketogenic diet on weight loss, metabolism, body composition and quality of life [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. iScience. 2024 Oct 30;27(12):111291. doi: 10.1016/j.isci.2024.111291. eCollection 2024 Dec 20.
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- Summary
- Graphical abstract
- Highlights
- Introduction
- Results
- Discussion
- Resource availability
- Acknowledgments
- Author contributions
- Declaration of interests
- STAR★Methods
- Footnotes
- Supplemental information
- References
- Associated Data
Abstract
A ketogenic diet (KD) is increasingly debated as a countermeasure against nutrition-related modern diseases. While being immunologically beneficial, KD is still suspected of having severe metabolic side effects and negatively impacting general well-being, which prevents its widespread clinical use. We conducted a prospective pre-post interventional study investigating the effects of an eucaloric KD on metabolism, weight loss, body composition, diet adherence, and quality of life. The study had two stages: first, feasibility was tested in healthy, normal-weight participants over three weeks. After positive results, the KD period was expanded to three months, enrolling adults with overweight. Significant weight loss was observed in both groups, reducing body fat without affecting muscle or bone mass and without adverse metabolic changes. Quality of life improved, and fatigue symptoms in subjects with overweight decreased. These findings may help to overcome reservations about KD, encouraging its use as a medical tool for treating nutrition-related disorders.
Keywords: Diet; Human metabolism.
© 2024 The Authors.
Graphical abstract
Highlights
- Weight loss on ketogenic diet is due to visceral fat loss, preserving muscle mass
- Cholesterol levels remain stable during ketogenic diet
- Ketogenic diet enhances general and health-related quality of life
- Fatigue symptoms decrease in overweight individuals on a ketogenic diet
Human metabolism; Diet
Introduction
The production and mitochondrial utilization of ketones is an ancient, evolutionarily conserved metabolic strategy that enables humans to survive in times of food scarcity. In a ketogenic metabolic state, the stored body fat is converted hepatically into ketone bodies—mainly β-hydroxybutyrate (BHB)—which efficiently supply the non-hepatic organs with the required energy.1,2 In our modern world, this mechanism has been re-discovered. The reasons for this are of course not a lack of food but rather the opposite: The side effects of the typical carbohydrate-overemphasizing diet of modern societies, namely obesity and the associated systemic low-grade inflammatory state, are taking on pandemic proportions not only driving a plethora of metabolic and cardiovascular diseases but also cancer, neurodegenerative diseases, and depression.3,4 A ketogenic diet (KD), which metabolically mimics the fasting state by drastically reducing carbohydrates in favor of fat, is gaining attention as a potential countermeasure. KD is increasingly discussed as a tool for weight loss and as a potential health promoting intervention.5,6,7 This idea is based on the fact that KD interrupts the vicious circle of glucose intake and insulin production and enables the “trapped” body fat to be used for ketogenesis. Moreover, positive immunomodulatory properties have recently been found: ketones have been revealed as potent inhibitors of inflammatory processes while adaptive immunity is strengthened.8,9,10
In view of all these positive aspects, it is surprising that KD is not widely used to treat nutrition-related diseases. Doubts continue to persist, which particularly concern severe metabolic complications of KD, such as hyperlipidemia, unintended loss of fat-free mass, and insufficient dietary adherence due to an impairment of general well-being.11 Yet, scientific human studies to substantiate or refute these reservations are still scarce.
To shed new light on this ongoing controversy, we performed a prospective pre-post interventional study, investigating the effects of an eucaloric KD on metabolism, weight loss and body composition, dietary adherence, and quality of life. We monitored dietary success by regular point-of-care quantification of blood BHB. A two-stage study design was used: first, we tested the feasibility of this approach in healthy participants of normal weight over a time period of three weeks. Second, after obtaining positive results, we expanded our approach to a KD period of 3 months enrolling exclusively adults with overweight.
We found positive effects of KD in both intervention groups: significant weight loss was achieved by reducing body fat mass without affecting muscle or bone mass and without adverse metabolic changes. Surprisingly, we also could show that the quality of life of participants on a KD improved. These data may provide important new insights to overcome the reservations about KD and render it suitable as a routine medical tool for treating nutrition-related disorders.
Results
Effects of three weeks ketogenic diet
First, the effects of three weeks KD (3wKD) were assessed with focus on adherence of participants, impact on metabolism, body composition, and quality of life. 57 volunteers were screened for study eligibility. Of these, 51 were included, with 29 subjects assigned to the 3wKD group and 22 subjects assigned to the Western diet (WD) group. In the 3wKD group, three subjects dropped out during the intervention, and one subject was retrospectively excluded due to insufficient ketogenesis (Figure 1A). No adverse events were reported throughout the study period. The demographic characteristics of participants on a 3wKD as well as mean physical activity level (PAL) and mean caloric intake are depicted in Table 1.
Figure 1.
CONSORT recruitment flow diagram
(A) CONSORT diagram for dietary study period of three weeks.
(B) CONSORT diagram for dietwary study period of three months.
3wKD = three weeks ketogenic diet, 3mKD = three months ketogenic diet, WD = Western diet, KD = ketogenic diet.
Table 1.
Baseline characteristics of participants following a three-week KD
Three-week KD (3wKD) n 25 Age [years], mean ±SD 41.12 ± 13.28 Sex [%], male/female/diverse 25/75/0 BMI, [kg/m2], mean ± SD 22.83 ± 1.92 PAL, mean ±SD 1.82 ± 0.12 Calculated caloric intake [kcal/day], mean ±SD 2644 ± 271 Calculated carbohydrate intake [g/day], mean ±SD 33.06 ± 3.39 Participants on a KD successfully generated ketone bodies with mean blood BHB levels increasing from 0.24 ± 0.15 mmol/L at the start of the diet (T0) to 1.45 ± 0.95 mmol/L at the end of the diet (T1, p < 0.0001). The state of ketosis was achieved within three to five days with mean blood BHB concentrations exceeding 0.5 mmol/L (d3: 0.56 ± 0.40 mmol/L, d4: 0.86 ± 0.61 mmol/L, d5: 0.94 ± 0.59 mmol/L). Ketosis remained stable throughout the whole study period (Figure 2A). Fasting blood glucose remained within a normal range during the evaluation period (T0: 87.8 ± 8.2 mg/dL vs. T1: 85.1 ± 6.0 mg/dL, p = 0.1983; Figure 2B).
