For more than a century the ketogenic diet, a very high-fat, very low-carbohydrate eating plan has been a trusted therapy for epilepsy that doesn’t respond to medication(1).
In that setting, its benefits are clear and well documented.
In recent years, however, the diet has been promoted far beyond its medical origins, touted as a solution for everything from obesity and diabetes to cancer and Alzheimer’s disease(2).
So what does the science actually say and where should we be cautious?
Under typical conditions, the body’s main fuel source is carbohydrates, which are broken down into glucose to power muscles and the brain. When carbohydrate intake drops sharply, the body switches to fat for energy, producing ketone bodies in the process, small molecules that can substitute for glucose. This metabolic shift is called ketosis.
In essence, the body changes its energy system: still functional but operating in a different mode. While that shift can be therapeutic in epilepsy, it may not be equally beneficial or sustainable for other conditions.
By the mid-20th century, researchers began exploring whether ketosis might also improve metabolic health by lowering insulin and blood sugar levels(3). This idea helped launch the modern keto movement, which now markets the diet as a tool for weight loss and disease prevention.
Many people report short-term benefits, such as rapid weight loss or improved blood sugar control. Yet, the scientific evidence for long-term safety and effectiveness remains inconsistent. Some studies suggest potential downsides, including metabolic stress and accelerated aging in animal models that deserve closer scrutiny.
As one medical journal aptly summarized, 'enthusiasm outpaces evidence(4).'
Recent animal studies are starting to clarify how the ketogenic diet affects metabolism, and the findings are more nuanced than keto advocates might expect.
Both males and females were studied to examine sex-related differences in response(5).
Mice fed the ketogenic diet gained less weight than those on the Western diet, but more than those on a low-fat plan. In other words, keto prevented extreme weight gain but was not a metabolic miracle.
When obese mice switched to a ketogenic diet, they lost weight initially but regained it once the diet ended. This pattern mirrors human studies showing that keto can support short-term weight loss yet offers little evidence of lasting success once normal eating resumes.
In simple terms, the mice were burning fat for energy but generating more metabolic “exhaust” in the process, a kind of internal wear and tear that could damage organs over time.
Insulin acts as the body’s molecular key, unlocking cells so glucose can enter and be used for energy. While high insulin levels are harmful in type 2 diabetes, too little insulin is equally problematic.
Mice on the ketogenic diet had unusually low insulin levels, which initially appeared favorable. But deeper examination showed that the beta cells in their pancreas that produce insulin were under stress. Inside these cells, researchers found evidence of protein traffic jams in the endoplasmic reticulum (ER) and Golgi apparatus, the cell’s packaging and delivery centers.
This congestion disrupted insulin production and release, leading to erratic blood sugar control. Over time, these changes could resemble early diabetic processes, even if blood sugar appears normal at first glance.
Although animal studies don’t always translate directly to humans, they raise important questions about long-term keto use, especially when diets are high in saturated fats. Clinical data show that many people struggle to maintain strict carbohydrate restriction, even in medical settings.
For instance, fewer than half of children prescribed the ketogenic diet for epilepsy remain on it after one year.
When used temporarily and under medical supervision, keto can be both safe and effective for controlling seizures. But as a long-term lifestyle plan for weight management or 'metabolic optimization,' the evidence suggests caution. What works as a potent medical therapy may become physiologically stressful when extended indefinitely.
A ketogenic diet changes the way your body makes energy. It can help in certain medical situations, but staying on it too long can put extra strain on your system. This research indicates that keto’s metabolic impact may worsen over time, highlighting potential long-term health risks that short-term studies overlook.
Like any strong intervention, keto is not a cure-all but a targeted tool.
Used wisely and with medical guidance, it can serve an important purpose. Used indiscriminately, it may do more harm than good.
Until long-term human studies provide clearer answers, the most responsible approach is to treat the ketogenic diet not as a lifestyle, but as a specialized therapy that is powerful, promising, and deserving of respect.
Another popular intervention that has a lot of misconceptions often combined with the ketogenic diet is intermittent fasting. If you want to learn more about the benefits of intermittent fasting and how to get the most out of it, you can learn about 10 intermittent fasting rules that are critical to success here.
References:
1. Paoli A, Rubini A, Volek JS, et al: Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr 67:789-96, 2013
2. McDonald TJW, Cervenka MC: Lessons learned from recent clinical trials of ketogenic diet therapies in adults. Curr Opin Clin Nutr Metab Care 22:418-424, 2019
3. Paoli A: Ketogenic diet for obesity: friend or foe? Int J Environ Res Public Health 11:2092-107, 2014
4. Joshi S, Ostfeld RJ, McMacken M: The Ketogenic Diet for Obesity and Diabetes-Enthusiasm Outpaces Evidence. JAMA Intern Med 179:1163-1164, 2019
5. Gallop MR, Vieira RFL, Mower PD, et al: A long-term ketogenic diet causes hyperlipidemia, liver dysfunction, and glucose intolerance from impaired insulin secretion in mice. Science Advances 11:eadx2752, 2025
