The Impact of the Keto Diet on Weight Loss and Metabolic Health

1. Introduction

The ketogenic diet (keto diet) is a high-fat, low-carb diet that has been shown to boost fat and weight loss. The keto diet works by radically reducing the amount of carbohydrates (CHO) allowed for consumption, consequently preventing the body from relying on CHO as its primary fuel source, as is usual in Western diets.

This turns the body into a state of ketosis. Ketosis is when the body is practically’starved’ of carbohydrates and forces the body to effectively burn fat for energy when glucose (mainly derived from carbohydrates) is lacking. The keto diet claims to achieve numerous health benefits that exceed weight loss and is significant because it can improve metabolic conditions such as type 2 diabetes and metabolic syndrome.

Metabolic syndrome (MetS) is a cluster of risk factors, including obesity, hyperglycemia, dyslipidaemia, hypertension, and inflammation. A major contributor to these health problems is generally viewed in the first place as lipid accumulation and the increase of fat in the form of triglycerides in the liver (mainly in the form of VLDL) and the adipose tissue (in the form of fatty acids and circulating glycerol).

This increases both adipocytes quantitatively and the number of small insulin-resistant, dysfunctional fat cells that release the classical pro-inflammatory and labor mediators. Thus, immune disregard is increasing, which amplifies metabolic disorders. Despite the increase in healthcare costs, numerous attempts, and endless undertakings to organise and execute proposals for new treatments and guidelines, the worldwide prevalence of obesity and type 2 diabetes continues to rise.

2. Understanding the Ketogenic Diet

Although the ketogenic diet became popular in the 19th century as an adjunct treatment for epilepsy, recently it has become a weight loss diet of choice for millions of people worldwide. The diet, high in healthy fats and low in carbohydrates, is believed to control the levels of glucose in the blood and to force human bodies to reach a state of metabolism called ketosis.

As a result of such an altered metabolism, fatty acids get turned into ketones and replace glucose as the body’s main source of energy. Since glucose comes from the carbohydrates consumed or is formed in the body via the process of gluconeogenesis, the idea is that drastically reducing carbohydrate intake is a means to again reduce blood glucose levels and control them.

Although in principle rather simple, the reactions and processes of the ketogenic diet occurring in the human body are complex and not fully explained and understood.

It is important initially to recognise that there are different types of ketogenic diets, which may vary according to the desired outcomes and goals. It has been known for some time that the therapeutic ketogenic diet for epilepsy is not an ideal weight loss programme. Therefore, if considering the ketogenic diet to lose weight, it is important to have a carbohydrate intake of more than 25 g.

It is mainly the glucose from the carbohydrates that modulates the insulin, and thus, by increasing the fat intake just slightly, the body can reach a state of ketosis suitable to start breaking down the stored fat.

2.1. Principles and Mechanisms

The ketogenic, or keto, diet is characterised primarily by a lower intake of carbohydrates and an increased intake of fats and non-starchy vegetables. “Users” of the diet hope to lose weight, lose body fat, improve systemic metabolism, improve lipid metabolism, and improve insulin action by following the dietary recommendations.

The benefits of the keto diet for the aforementioned aspects of health can very likely be assumed from a wide range of data derived from animal studies and with the majority of data available in study models in which non-pregnant, obese adults adopt the diet over a range of periods which represents the majority of the adult lifespan in the western world.

For those consumers adopting a keto diet, a lower intake of carbohydrates results in a lower rate of hepatic glycolysis and glycogen storage, a decrease in the use of glucose as a primary fuel source, and an associated decrease in the rhythmic release of the hormone insulin. One of the short-term features of a keto diet is the metabolism of FFA derived from adipose tissue: fat tissue.

Our liver converts FFA to the molecules acetyl-coenzyme A (acetyl CoA) and produces a family of molecules defined as ketones, two of which are beta-hydroxybutyrate (3-hydroxybut position). The flow of 2 molecules of acetyl-CoA is altered from the oxidative pathways to a non-oxidative pathway, of which the primary products are ketones.

Petite ketones are released into the circulation and are used in multiple tissues as fuel. The uptake of OA emitted generated by ketones by muscle tissue causes the synthesis of a molecule named acetoacetate. We will return to the metabolic production of ketones later in this section.

2.2. Types of Ketogenic Diets

One feature that may make low-carbohydrate and high-fat diets more effective than energy-matched high-carbohydrate and low-fat diets is their ability to raise circulating levels of the hormone β-hydroxybutyrate. This is the major circulating ketone body, and the state of raised levels of circulating ketone bodies is known as ketosis.

Our focus in this thesis is on the modulation of fatty acid metabolism in the liver by a popular intermittent fasting intervention (in which food is consumed only between the hours of midday and 8 pm; 16:8) compared to the standard three-meal-a-day control condition (where food is eaten at 8 am, midday, and 8 pm).

We sought to investigate whether a 16:8 diet of keto-type foods or a high-fat diet that included many of the same foods, but spaced into three meals throughout the day introduced many of the other negative impacts of the 16:8 KD. The results showed that the 6-8 entirely counteracted the other negative metabolic impacts of the 16:8 KD, and a 3-meal very high-fat diet induced minimal impairments.

Given that the cKD is unsustainable in the long term, due to the side effects many individuals experience, including headaches, constipation, bad breath, and fatigue, as stated, as well as elevations in LDL-cholesterol, the development of a dietary approach that can safely achieve the multiple benefits of the cKD, without the detriments, is highly warranted.

Specification of a dietary strategy that eliminates the plethora of negative side effects of the cKD, while maintaining the MRKDs various beneficial mechanisms of action, has the potential to considerably improve population nutrition and public health policy. We have detailed the likely causes of, and causal roles for, the many side effects of the cKD elsewhere. From this knowledge, in principle, one can develop a novel dietary strategy that primarily overcomes these potentially energy-depressing adaptations.

3. Evidence Supporting the Keto Diet for Weight Loss

The fact that the ketogenic diet restricts carbohydrates in order to switch the body’s primary fuel source from glucose to fatty acids and ketone bodies brings up the question of why a person should pick the ketogenic diet over other low-carbohydrate strategies. While it is marketed for weight loss benefits, there is no clear answer.

Since both the ketogenic and low-fat diets appear to be equally effective at improving weight as well as metabolic outcomes, the right choice might be to liken dietary strategies to disease treatments in that a person should try another approach if one is ineffective. It is true that all low-carbohydrate strategies assist with weight, while the ketogenic diet appears to facilitate weight loss in particular.

There is a plethora of clinical studies on the ketogenic diet, many of which are well-designed and carry a high level of scientific strength. Meta-analyses find superior weight loss following one to two years of ketogenic dietary advice, including a persistent reduction in body mass index (BMI) and waist circumference.

Morphometric parameters also confirm weight loss in users of the diet. The diet may possibly be as effective as bariatric surgery in the short term, seeing a comparable rate of weight reduction. Patients’ diabetes also enters remission after using the ketogenic diet, even in the absence of weight loss. Ketonuria is a sign of adherence to and efficacy of the ketogenic diet.

The more time spent in ketosis, the less body weight is carried, particularly in individuals already affected by obesity. When asked about the appetite suppressing power of the diet, participants of the ketogenic diet generally report an improvement.

3.1. Clinical Studies and Research Findings

Our understanding of the metabolic impact of the ketogenic diet has generally been derived from smaller clinical studies. The reduction in carbohydrate content in the diet leads to a decreased stimulation of insulin production, which is modulated by β-cell suppression and inhibition of incretin (a peptide released by the intestine in response to food, causing an increase in the amount of insulin released from the pancreas) secretion.

This is largely due to the cytokine IL-1β, which is released from the inactive form within the β-cell after recognising an increase in metabolic intermediates such as B-OH butyrate. These metabolic outcomes appear to be replicated in both rodents, the most popular study species, and humans.

Although a number of retrospective analyses of low carbohydrate diets (≤60g carbohydrates per day) have been performed for periods of up to four years demonstrating reductions in body weight (in both the overweight and obese) and improving cardiovascular risks, this metabolic outcome is comparable with those seen with low fat/energy-restricted diet interventions (but with large variability in regression models), and therefore the changes in risk factors do not appear to be driven by the specific reduction in morphokinetics with the ketogenic dietary carbohydrate restriction.

A direct evaluation of the ketogenic diet in a weight management trial demonstrated a significant difference between the two arms of the trial. There was a mean reduction in body weight of 9.7% in the ketogenic group at one year, compared to a 5.3% reduction for those receiving usual care.

4. Effects of the Keto Diet on Metabolic Health

Many of us have heard of the ketogenic (keto) diet for weight loss, but fewer know that there is consistent evidence showing that following a keto diet leads to improvements in blood sugar and metabolic health independent of weight loss. When we burn mostly sugar for energy, as is the case when we follow a more standard American diet, we increase our risk for weight gain, diabetes, heart disease, and many other chronic diseases.

But when we primarily burn fat for energy, as is the case when we follow a well-formulated keto diet, we can improve our metabolic health dramatically. This blog summarises some of the research on the effects of the keto diet on metabolic health discovered by our team.

The keto diet results in lower fasting insulin in people who are prediabetic, along with improvements in other aspects of insulin sensitivity. Other research has shown that this dramatic improvement in diabetes risk is also evident after meals, not just at fasting. In just two weeks of following the keto diet, young adults experienced increased insulin sensitivity.

The drop in fasting insulin associated with the keto diet has also been shown to be independent of weight loss. The keto diet has also been shown to lead to a decrease in the glucose produced by the liver and released into circulation. These metabolic benefits also occur in children who experience significant improvements in fasting insulin and insulin sensitivity following the diet.

While a keto diet has long been used to treat epilepsy in children, our team has shown that following a keto diet for just 2 weeks leads to dramatic improvements in metabolic health in young adults, decreasing the risk of chronic disease by 25-40%.

4.1. Impact on Insulin Sensitivity

A ketogenic diet can lead to an overall increased level of energy expenditure. However, more recent work is beginning to suggest that the degree of response may not be consistent between people. In some long-term studies, resting energy expenditure has been shown to decrease following weight loss with a ketogenic diet.

At least part of the decrease in energy expenditure over time can be attributed to the loss of body mass and the metabolic adaptation that follows. In the most metabolically flexible, the decrease in resting energy expenditure does not change the advantages of a ketogenic diet. The ketogenic diet is the most successful diet for those who can stick to it.

Insulin sensitivity, or the lowering of insulin in response to a given amount of glucose, is a key part of metabolic health. Typically, a diet low in carbohydrates provides a greater degree of insulin sensitivity. In general, diets high in carbohydrates lead to more oscillations in glucose levels. During states of overfeeding, if tissue is already ‘full’ of glucose, excess dietary glucose might be stored as ‘unwanted’ fat.

A ketogenic diet is lower in carbohydrates, meaning less time spent with increased glucose. Typically associated with weight loss, even in the absence of weight loss, the metabolic condition can improve insulin sensitivity. Additionally, ketones can reduce insulin levels themselves. Some research even hypothesises an insulinotropic effect of ketosis.

More research is needed. The diet also provides therapeutic benefits in reducing glucose variability. The lower insulin levels seen during a ketogenic diet could be explained partly by reduced body fat, a known cause of insulin resistance.

4.2. Influence on Blood Lipids

The ketogenic diet principally produces a reduction in the concentration of triacylglycerol-rich lipoproteins in the blood and a decrease in the production of very low-density lipoproteins, largely due to the positive effects of insulin.

The gradual decrease in blood lipid levels observed during the ketogenic diet occurs for several reasons: (i) the stored glycogen becomes depleted, increasing the conversion of insulin over the organism to glucagon, causing an increased rate of free fatty acid liberation and subsequent hepatic ketogenesis; and (ii) the increased fat intake favours either increased hepatic synthesis of ketone bodies and/or reduced peripheral utilisation of the same by the extra-hepatic tissues.

Low carbohydrate diets may produce undesirable changes to the lipid profiles, i.e., a reduction in the concentration of high-density lipoprotein cholesterol (HDL-C). It is thought that the low carbohydrate intake of the study participants was the primary factor causing the heart disease risks to rise, along with the low glycaemic index of the carbohydrate diet.

Nevertheless, leveling the unconditional reduction in HDL-C with the lowest glycaemic index seems to imply that it is carbohydrate restriction per se, and not a low glycaemic index diet, that causes the unconditional reduction in HDL-C levels. Metabolic effects of ketogenic diets also involve a significant reduction of blood glucose and a negative condition named low ‘physiological insulin resistance’, i.e., a reduced insulin function in mediating glucose disposal into muscles together with an increase in the blood insulin tropism.

5. Practical Recommendations and Considerations

To study diet and the ways people can learn the best approach to diet for themselves, there are many questions to be asked. Many of these are outside the expertise of human metabolic scientists but are crucial to success. We tried to explore one set of approaches that could help open up this question.

Regular monitoring of prior diets among adherents of ketogenic diets is a good start, but it is clear that even among those continuing to eat ketogenic diets, many fail to maintain ketosis after their earliest experiences with the diet. Future, properly researched ketogenic diet trials might shed a different light on the implementation of this now-popular eating strategy.

From a practical perspective, it is not simply measuring ketones that provides information about how best to design and follow a ketogenic dietary plan. The pressure was used to develop and confirm the relevance of a new set of nutritional targets and benchmarks. Such efforts typically await scientific consensus about the relevance and robustness of the targets in question.

Once available, these benchmarks can then become KPIs and guidelines. With this in mind, it is important that scientists attempting to validate or develop KPIs, EEs, and guidelines be aware of how dietary practice in the field might differ from and be important with respect to protocol-based practices.

Short of serum or urine tests, how might a person best interpret these signs of active ketosis and thus best evaluate whether a ketogenic dietary strategy is being followed in practice? Knowing when a person might have the best chance of achieving healthy active ketosis would require further robust study, yet the signs of ketosis and the timing of their appearance warrant more detailed review and discussion as an aid to interest in, adherence to, and the application of ketogenic dietary plans.

Also read: The Ultimate Diet Log: A Unique Food and Exercise Diary That Fits Any Weight-Loss Plan

 

6. Conclusion

In conclusion, and in agreement with the latest research, the ketogenic diet seems to be a promising tool to promote weight loss and improve metabolic measures in the short term, particularly for severely obese individuals. Rapid weight loss during the first weeks of a ketogenic dietary intervention can be a valuable source of motivation for continuity and compliance with treatment for many volunteers, as it has been shown to be effective in both free-living subjects and prospective trial settings.

Therefore, the strategic design of the initial phase of a dietary intervention to promote relatively large weight loss can potentially help with the management of the dropout rate. A very low-carbohydrate diet such as the ketogenic diet can offer an advantage in weight loss compared to standard low-calorie diets, particularly in insulin-resistant individuals or in those with high levels of circulating insulin.

Weight regain at follow-up is frequent regardless of the diet prescribed, although epidemiologic and laboratory evidence shows that the acquisition of the ability to fuel movement and the brain with fat, instead of glucose, can protect against weight regain in some individuals.

While the long-term implications of ketogenic diets among well-motivated adults are unknown, we should consider short-term treatments as an opportunity to gather efficacy and safety data that can then also help to inform long-term discussions. Independent of the ethical and review board considerations behind the decision to include a control group, there is a need for retreatment studies, which would allow all eligible participants to test a ketogenic diet for a shorter term as an investigation of weight regain.

As with post-regain results, it is equally important to consider physiological relevance and learning potential over implications for weight loss per se.