Metabolic and hormonal responses to nutritional ketosis differ by sex and metabolic phenotype in adults
This study demonstrates that while a 60-day ketogenic diet successfully induces nutritional ketosis and reduces body fat in adults, the resulting metabolic, hormonal, and appetite responses are heterogeneous and significantly shaped by both sex and metabolic phenotype.
Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer
For decades, doctors and public health officials have relied on a simple ruler to measure the risk of weight-related illness: the body mass index, or BMI. This calculation, which divides a person's weight by their height, sorts people into neat categories like normal weight, overweight, or obese. Yet, two people with the exact same BMI can look and feel completely different. One might carry most of their weight in muscle, while another carries it as fat around their organs; one might have blood sugar that spikes dangerously after a meal, while another's remains steady. This hidden variation means that a single number on a chart often fails to capture the true metabolic reality of a human body. Furthermore, men and women process food and store fat in distinct ways, adding another layer of complexity to how our bodies react to change. Because of this, researchers are increasingly asking whether a diet that works for one person might work differently for another, depending on their specific body composition and biological sex.
A recent study set out to test this idea using a ketogenic diet, a way of eating that drastically reduces carbohydrates and replaces them with fat. When the body runs low on sugar, it switches its fuel source, burning fat instead and producing molecules called ketones. This state, known as nutritional ketosis, is the goal of the diet and is often used to manage weight and improve metabolic health. However, it has remained unclear whether the body's reaction to this switch is the same for everyone. To find out, a team of researchers in Poland followed thirty-four adults over a period of sixty days. They did not treat all participants as a single group. Instead, they carefully sorted them into six distinct categories based on whether they were male or female and whether their bodies were lean, carried extra weight, or had obesity. This allowed the scientists to watch how different types of bodies adapted to the same dietary rules over time.
The researchers confirmed that the diet worked as intended for everyone who stayed in the study. Within two weeks, all participants had successfully entered nutritional ketosis, with their bodies producing higher levels of ketones. But while the starting point was the same, the journey looked very different depending on who was walking it. The most dramatic changes in ketone levels occurred in men with obesity, whose bodies seemed to ramp up production more aggressively and consistently than any other group. In contrast, the response of free fatty acids—tiny particles of fat released into the blood to be used as fuel—was chaotic and varied wildly. For some women, these fat levels stayed steady, while for others they rose and then fell sharply. For men, the levels tended to drop later in the study. This suggests that simply being in ketosis does not mean the body is handling fat in a uniform way; the internal machinery of metabolism is tuned differently for each person.
The diet also had a clear impact on how the body managed sugar and insulin, the hormone that helps cells absorb sugar. Blood sugar levels dropped for everyone shortly after the diet began. However, the improvement in insulin function was not equal across the board. The participants who started with the most difficulty regulating their sugar—specifically those who were overweight or had obesity—saw the most significant benefits. Their bodies became much better at handling insulin, while those who were already lean saw smaller, less consistent changes. This indicates that the diet acts as a powerful reset for those with metabolic struggles, but its effect is less pronounced for those whose systems are already functioning well.
Beyond the blood chemistry, the study looked at how the diet affected hunger and stress. The researchers found that feelings of hunger were not the same for everyone. People with obesity reported feeling less hungry or more full compared to those who were lean or overweight, who actually reported feeling hungrier as the weeks went on. This difference was linked to leptin, a hormone that signals fullness. As participants lost body fat, their leptin levels dropped, but the connection between fat loss and hunger signals depended heavily on whether the person was male or female and what their starting weight was. Interestingly, another hunger hormone, ghrelin, did not change much for anyone, suggesting that the diet's effect on appetite is driven more by fat stores than by immediate hunger signals.
The emotional side of the diet also revealed surprising differences. While some people felt more stressed as they began the strict eating plan, others felt less stressed. Women with lean bodies and men with obesity reported higher stress levels as the study progressed, whereas lean men actually felt less stressed by the end. The body's stress hormone, cortisol, showed a temporary spike in the first two weeks for most groups before settling down, suggesting that the initial shift to this new way of eating is a physiological shock that the body eventually adapts to.
Physically, the diet led to weight loss for everyone, but the composition of that loss told a nuanced story. All groups lost body mass, but men tended to lose more fat than women over the same period. The diet also reduced dangerous fat stored around the internal organs, known as visceral fat, which is a major risk factor for heart disease and diabetes. Liver enzymes, which can indicate stress on the liver, improved significantly for men who started with higher levels, suggesting the diet helped clear out fat from the liver in those who needed it most.
The study concludes that while a ketogenic diet can successfully induce a state of fat-burning in almost anyone, the body's response is far from a one-size-fits-all experience. The changes in hormones, hunger, stress, and body composition are deeply shaped by a person's starting metabolic health and their sex. This means that the diet is not a uniform biological event but a highly individualized adaptation. For those considering such a dietary change, the findings suggest that the outcome will depend heavily on their unique biological starting point, and that what works best for one person may look very different for another.
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