Obesity has been strongly linked to a higher epigenetic age—changes to DNA that may contribute to chronic illness and, ultimately, a shorter lifespan. A new study suggests that a very low-calorie ketogenic diet (VLCKD) may support weight loss and reverse the epigenetic age of people living with obesity by up to six years, while also reducing their risk of type 2 diabetes and heart disease. But not all experts are on board with the restrictive approach.
The Spanish study, published in Nutrients, compared two groups—participants with obesity and those at a “normal” weight. Researchers measured biological age using epigenetic clocks, tools that analyse DNA from blood samples. Measurements were taken at the beginning of the study, after 30 days, and again after 180 days.
For at least the first 30 days, the group with obesity followed a VLCKD of 600 to 800 calories a day, based on the medically supervised commercial program known as the PronoKal Method. By day 180, food and calories had been gradually reintroduced, although the final calorie intake remained low—around 800 to 1500 calories per day.
This phase helped participants reach ketosis, a metabolic state where the body burns fat for fuel instead of carbohydrates. This process is believed to have contributed to the biological age reversal seen in the study. However, experts caution that VLCKDs are not suitable for general use.
“A very low-calorie ketogenic diet doesn’t provide enough energy to sustain the average person long term,” says triple board-certified in internal medicine, lifestyle medicine and obesity medicine Dr Meghan Garcia-Webb. “In my experience, patients struggle to maintain such a restrictive approach, and it can lead to a cycle of yo-yo dieting. In general, I don’t recommend it.”
What about the diet helped slow down ageing, exactly?
The study suggests several factors may have contributed to the reversal of epigenetic age in participants with obesity. Ketosis appeared to play a significant role, which “underscores the diet’s potential role in promoting overall health and longevity,” says registered dietitian Trista Best.
Researchers noted elevated levels of beta-hydroxybutyrate—a by-product of ketosis—may have supported these changes. This compound is known to improve antioxidant capacity, enhance insulin sensitivity and support brain health. Reduced body mass index from weight loss may also have played a role, as well as potential improvements to the gut microbiome.
Limitations to the study’s findings
Dr Garcia-Webb points out the study was small and that “findings are limited and do not assert direct causation or generalisability to a broader population.” That said, she finds the results “interesting” given that the VLCKD appeared to slow biological ageing more than what is often seen in patients after bariatric surgery. “This suggests the effect may be more related to nutritional ketosis and dietary factors than weight loss alone,” she says.
Best adds that “it’s essential to approach these findings with caution, considering individual variability and the need for personalised dietary interventions.” Extreme dietary restrictions can have negative impacts and participants in the study were closely monitored.
All participants were of European Caucasian background. People who were pregnant, had substance use concerns, or were on chronic medications (other than for diabetes) were excluded. It’s also unclear whether participants remained on a reduced-calorie diet after the study ended or if they regained any weight.
Dangers of a very low-calorie keto diet
Consuming between 600 and 800 calories a day is about as extreme as low-calorie diets get and comes with serious risks—including nutrient deficiencies, muscle loss, mental fog and gallstones. The ketogenic diet, which cuts back significantly on carbohydrates, can also trigger side effects like the “keto flu” (a collection of short-term flu-like symptoms that occur when starting keto), constipation, diarrhoea, dehydration, fatigue and potential challenges for kidney and heart health.
“Any dietary change patients make, I want them to be able to continue doing for decades,” says Dr Garcia-Webb. “If someone can’t see themselves following a low-calorie ketogenic diet at 80, then I wouldn’t advise starting now.” She adds that sticking to keto long-term can also significantly raise cholesterol levels, especially in those who consume high amounts of animal-based saturated fat. For most people, that level of restriction simply isn’t realistic or beneficial in the long run.
Put simply, there are other ways to lose weight and improve health that don’t carry the same risks as the protocol used in the study. “People can achieve a healthier body with less extreme measures that provide a more enjoyable, sustainable quality of life,” Dr Garcia-Webb says. “There’s not much point living longer if you’re miserable.”
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