Fact or fad: Ketogenic diets

In recent years, ketogenic diets (KD) have gained immense popularity as a dietary approach primarily because of their successful short-term effect on weight loss. They have also been implicated to be beneficial for metabolic and cardiovascular health and to treat conditions such as cancer. However, despite their quick rise in popularity and widespread use for weight management, there is limited evidence regarding their efficacy and risks which raises the question of how safe are they? This evidence-based article aims to dissect the science behind the ketogenic diet, exploring its mechanisms, health benefits, potential risks, and practical applications.

 What is the ketogenic diet?

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The ketogenic diet is characterised by its high-fat, moderate-protein, and low-carbohydrate composition. The macronutrient distribution typically ranges from approximately 55% to 60% fat, 30% to 35% protein, and 5% to 10% carbohydrates. For instance, in a 2000 kcal per day diet, the carbohydrate allowance would amount to approximately 20 to 50 grams daily (2). All variations of this diet, whether involving animal- or plant-based derivatives, are based on severely restricting overall intake of carbohydrates with a goal of bringing it down to less than 50 g/day. A well-formulated KD limits protein intake moderately to less than 1g-1.5/kg body weight, depending on the individual's activity levels. Additionally, the diet does not restrict fat intake while decreasing appetite and caloric intake, resulting in weight loss observed after the initiation of the diet (3).

How does it work?

The goal of the macronutrient ratios is to induce the metabolic state called ketosis. This is where the body shifts from using carbohydrates as its main fuel source to fat. The body has around 3 days’ worth of glycogen stores (from carbohydrates). Therefore, when deprived of carbohydrates for long enough (like when on a KD), additional energy sources are necessary to meet the metabolic requirements of the body and brain. In the absence of sufficient carbohydrates, ketone bodies are produced by breaking down fats in the liver (ketogenesis) which are used as the primary energy source in the body (3).

Potential health benefits and risks

Weight loss

Numerous studies have provided robust evidence supporting the efficacy of the ketogenic diet for short-term (<6  months) weight loss, body mass index, and abdominal circumference (4,5,3,6). It is often observed that individuals on a ketogenic diet often experience a rapid initial weight loss but it should be noted that this is a short-term result of body water loss that accompanies lower carbohydrate intake, not fat loss. However, perhaps most importantly, it appears that ketogenic diets can result in fat mass loss without inducing fat-free mass loss (4,5).

Long-term weight loss however is a different story. Ignoring the fact that the diet’s restrictive nature makes long-term adherence difficult, studies suggest that a KD is not more effective than any other weight loss approaches (7). Studies show that after 6 - 12 months and beyond, a ketogenic diet does not lead to significantly higher weight loss than other weight loss approaches. (1,3,8,9). Some authors even suggest that after one year there is a high likelihood of regaining the weight lost on a KD (3).

Cardiovascular health

Studies examining the effects of a ketogenic diet and various cardiovascular health markers have produced mixed results. Studies ranging from 3 to 36 months have found improvements in blood pressure, high lipoprotein cholesterol (HDL-C), triglycerides, and C-reactive protein (CRP) (10,11). Conversely, the same studies have also observed less favourable lipid profile changes; namely increases in LDL-C and total cholesterol (when compared to a low-fat control diet). (3,12,13). It is well documented that high LDL-C often leads to the development of atherosclerosis and increases the risks associated with cardiovascular disease (14).

Cancer

Emerging evidence suggests that ketogenic diets may hold promise in the complementary treatment of certain types of cancers. Cancer cells exhibit a heightened dependence on glucose for energy due to their preferential use of glycolysis, even in the presence of oxygen. Ketones serve as alternative fuel substrates for normal cells while impairing the metabolic flexibility of cancer cells, leading to reduced proliferation and increased apoptosis (15). Additionally, ketogenic diets have been shown to lower circulating insulin and insulin-like growth factor-1 levels, which are known to promote tumour growth and progression (16). In summary, the use of KD puts cancer cells in an unfavourable environment, which may enhance the antitumor effect. However, while some preclinical studies have demonstrated the efficacy of ketogenic diets in slowing tumour growth and improving treatment outcomes in animal models, KD may not be effective in treating all cancers. In one study, a ketogenic diet was shown to contribute to increased human melanoma growth in an animal model (15). There is still insufficient data to suggest that KD can be used as a primary anti-cancer therapy, but it may have a beneficial role as an adjuvant therapy.

Diabetes mellitus

Evidence suggests that ketogenic diets can be beneficial for individuals with type 1 (T1DM) and type 2 diabetes (T2DM) by decreasing glycemia, lowering levels of fasting insulin, decreasing insulin resistance, and potentiating decreasing requirements of insulin and/or oral glycaemic medications (3). 

Several studies indicate that adherence to KD in T1DM is associated with well-controlled HbA1c levels and minimal glycemic variability (17). However, the diet comes with increased risks of hypoglycaemic episodes. Hence, it is important to emphasise that insulin therapies, and any oral hypoglycaemic agents be closely monitored and adjusted in any diabetic patient following a ketogenic diet (17). Similarly, participants with T2DM experienced a decrease in their HbA1c levels after 16 weeks. This decrease was so marked that seven participants had their diabetic medications discontinued, and 10 participants had their medications decreased (18).  A KD showed more beneficial effects on reducing antidiabetic medications for up to 12 months (6).

Note: Individuals taking insulin or oral hypoglycaemic agents may experience severe hypoglycaemia if their medications are not appropriately adjusted before initiating a ketogenic diet (18). Additionally, individuals with diabetes often have other comorbid conditions such as dyslipidemia and CVD  which are contraindications of a KD (3). 

Important note about study strength

Researching this topic revealed that in general robust studies on ketogenic studies in a clinical setting are lacking. Most available studies lack generalisability and validity due to substantial limitations such as small sample sizes, short study duration, and high participant dropout rates (3). As mentioned, there are many smaller studies of short duration noting short-term positive outcomes, but there is limited long-term follow-up data available. This means information on any potential adverse effects, or if the observed positive effects are sustained, is just not available.

Fat and protein sources considerations

There is a well-established link between diets high in animal-derived fats and protein sources (particularly processed and red meats) and higher mortality rates. If embarking on a KD, it is recommended to prioritise consuming plant-based fats, fish, and plant proteins (19).

For more information on protein sources see: https://www.healthfullymyself.com/post/spotlight-on-protein-and-are-you-really-getting-enough

Risks and considerations

If contemplating starting a ketogenic diet, there are several risks and potentially negative side effects to consider. In the short term, transitioning into ketosis may lead to temporary side effects, often referred to as the "keto flu," characterised by fatigue, headache, dizziness, nausea, vomiting, constipation, and low exercise tolerance (18). These effects of the body adjusting to a new state can last for a few days to a few weeks. Long-term risks could include hepatic steatosis, hypoproteinaemia, hypocitraturia, hypercalciuria, kidney stones, and vitamin and mineral deficiencies (18).

There are several potentially serious contraindications for being on a ketogenic diet, so it is recommended that you consult with a healthcare professional before starting. As with any diet where whole food groups are excluded, there exists a high likelihood of developing nutrient deficiencies on a KD. Assistance from a nutrition professional may also be beneficial in creating a ketogenic diet that minimises nutrient deficiencies.

Sustainability

While ketogenic diets have demonstrated efficacy for short-term weight loss and metabolic improvements, long-term adherence to a KD is a major challenge. Aside from long-term safety concerns, its restrictive nature means that many studies have reported high participant dropout rates, even for short study periods (3). One review reported that over 50% of people failed to adhere to a ketogenic diet in many studies (20). The psychological and social implications of following a KD, such as social isolation and food-related anxiety, may impact long-term adherence. Imagine staying satisfied with the limited variety of foods available and being restricted from enjoying a piece of fruit or a slice of pizza; especially when going out to eat with friends. While some individuals may find success with ketogenic diets in the short term, research suggests that maintaining sustainable dietary changes over the long term often requires a more balanced and flexible approach than a KD, that aligns with individual preferences, cultural practices, and lifestyle factors.

Practical applications

Implementing the ketogenic diet requires careful planning and attention to dietary composition. Emphasising whole, nutrient-dense foods such as avocados, nuts, seeds, fatty fish, and non-starchy vegetables is the best strategy to help to avoid the outlined potential negative effects and to avoid nutrient deficiencies, while maintaining ketosis. Meal planning and tracking macronutrient intake can facilitate adherence to the ketogenic diet and optimise its efficacy for weight loss and metabolic health.

In summary

It cannot be definitively stated whether ketogenic diets are a fact or a fad due to the limited availability of robust studies and the lack of strong evidence supporting their short-term benefits or long-term effects. However, from a personal perspective, there is a lot of hype around a diet that is unproven and unsustainable for most people. Numerous meta-analyses have been conducted to assess the effects of ketogenic diet interventions on health-related outcomes, but various biases challenge the credibility of these associations. Future studies should prioritise rigorous research protocols to determine whether ketogenic diet interventions with longer intervention periods hold promise as a viable treatment option for various diseases. As the scientific community continues to explore the potential benefits and risks of ketogenic diets, individuals should approach these dietary interventions with caution and consult with healthcare providers before making significant dietary changes.

*Disclaimer*

The information presented in this article is for educational purposes only and is based on our interpretation of the current research. No content on this site should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.

References

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20. Kumar NK, Merrill JD, Carlson S, German J, Yancy WS Jr. Adherence to Low-Carbohydrate Diets in Patients with Diabetes: A Narrative Review. Diabetes Metab Syndr Obes. 2022;15:477-498. http://doi.org/10.2147/DMSO.S292742