Introduction
Ketosis is a normal physiological process during which the body utilizes fat to produce ketone bodies as its main fuel.1 Ketosis occurs when there is an absence or shortage of carbohydrates in the diet or glycogen storage in the body, such as during overnight fasting or prolonged fasting, during extended exercise, or when following a ketogenic diet.1 Ketogenic diets are very low in dietary carbohydrate (<50 g per day) and high in fat, and provide an adequate amount of protein.2 Adapting to a ketogenic diet has been shown to have benefits for weight management.1,2
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Mechanisms of action
The following metabolic adaptations (keto-adaptation) occur when consuming a ketogenic diet:10,11
- Glucose levels decrease as a result of reduced carbohydrate intake.
- Due to reduced glucose, circulating insulin is reduced.
- A reduction in circulating insulin levels helps reduce lipogenesis (fat accumulation) and increases lipolysis (release of fatty acids from adipose tissue), resulting in increased levels of free fatty acids (FFA).
- FFA are used by some tissues (e.g., skeletal muscle) directly as the source of energy in a keto-adapted state.
- FFA are also used by the body to generate ketone bodies (i.e., acetoacetate, β-hydroxybutyrate [βHB], and acetone), which act as the main source of energy in the keto-adapted state.
- Ketone bodies in circulation provide a stable source of fuel for the body and the brain, thereby sparing the need to convert protein into glucose for energy supply.
Research Highlights
- Ketosis is a normal physiological response during which the body utilizes fat to produce ketone bodies as its main fuel.1
- Ketone bodies may have effects on appetite-controlling hormones (e.g., ghrelin and leptin) or may have direct appetite-suppressing properties,3-5 and meta-analysis shows that individuals following a ketogenic diet are significantly less hungry.6
- Clinical intervention studies have demonstrated the effectiveness of ketogenic diets for weight loss and weight management.7-9
Composition and structure of the ketogenic diet
Studies of ketogenic diets that have demonstrated weight loss have included some energy restriction with a composition of ~10% of energy coming from carbohydrate, 20-30% of energy coming from protein, and 60-70% of energy coming from dietary fat.7-9 This macronutrient distribution is a general rule-of-thumb to help guide diet planning, and may vary depending on body size, physical activity, and caloric intake. The consumption of very low amounts of carbohydrate (<50 g per day) and adequate but not high protein intakes with remaining calories from fat, is key to achieving nutritional ketosis. Coaching on ketogenic meal planning and meeting dietary goals on a ketogenic diet weight-loss program is important to maintain ketosis.
Clinical evidence of the ketogenic diet for weight management
Ketogenic diets have been shown to be efficacious for weight
and fat mass loss:
- In 59 adults with BMI >30 kg/m2 who participated in a ketogenic dietary
intervention study, the mean reduction in body weight was 12.0 kg over
24 weeks, or a 12.9% change in body weight. Reductions in body fat mass
of 9.4 kg were reported, with 69% of participants losing >10% of initial body
weight at 24 weeks.7 - In 33 adults with abdominal obesity who completed a ketogenic dietary
intervention study, the mean reduction in body weight and body fat mass
after 12 months was 14.5 kg and 11.3 kg, respectively. Thirty out of 33 (91%)
of the participants lost ≥5% of body weight, and 25 out of 33 (76%) lost
>10% of body weight at 12 months.8 - In 153 adults with obesity participating in a ketogenic intervention,
the mean weight loss at 6, 12, and 24 months was 12.2 kg, 10.9 kg,
and 6.3 kg, respectively.12 - A meta-analysis of weight loss trials ≥1 year found that a ketogenic diet achieved greater reductions in body weight compared to a low-fat diet.9
Ketogenic diets may aid weight loss in the following ways:
- Ketone bodies generated while in a state of ketosis may have effects
on appetite-controlling hormones (e.g., ghrelin and leptin) or may have
direct appetite-suppressing properties.3-5 Although a reduction in satietypromoting gut peptides has been reported following weight loss,13 this
change in gut peptides was not seen following a ketogenic diet-induced
weight loss.4,14 Additionally, exogenous ketone supplements were shown
to suppress appetite in a clinical study.15 - Meta-analysis of ketogenic diets showed that individuals in ketogenic diet
groups were significantly less hungry and had significantly reduced desire
to eat compared with baseline measures, which may help facilitate
adherence to lower calorie intakes.6 - The reduction in fat accumulation and increase in fat oxidation during ketosis helps promote fat loss.16,17
- Individuals on a ketogenic diet are less hungry and have a reduced desire to eat.3,6
Safety and monitoring on the ketogenic diet
- Ketogenic diets are contraindicated for individuals with inborn metabolic
errors in fatty acid metabolism and mitochondrial enzymes.18,19 Some
individuals on ketogenic diets may encounter tolerance issues or mildto-
moderate adverse effects such as headache, asthenia, nausea and/or
vomiting, and muscle cramps.20 - Some individuals on ketogenic diets may experience increases in lowdensity
lipoprotein cholesterol (LDL-C) levels, creatinine clearance, and
urinary sodium and calcium excretion.21,22 - Ketones can be measured in the breath, blood, and urine. Circulating
levels of ketone bodies on a well-planned ketogenic diet range from
0.5-1.5 mmol/L. These levels are markedly lower than those identified
in diabetic ketoacidosis (>25 mmol/L) or other pathological states such
as alcoholic ketoacidosis, salicylate poisoning, and some inborn errors
of metabolism.
