I'm Pam Taub. I'm a Cardiologist and Professor of Medicine and Director of Preventive Cardiology at UC San Diego in La Jolla, California.

What was the study design and patient population?

So I've been doing research on time-restricted eating, which is a type of intermittent fasting, for many years. Our first pilot study was published a few years ago in Cell Metabolism. And in that study, we took patients with metabolic syndrome and we asked them to fast for 14 hours and eat for 10 hours. And that was the only intervention that we did. And we found in patients with metabolic syndrome, there was improvement in glycemic parameters like hemoglobin A1C, atherogenic lipids, as well as weight loss. So that was a pilot study and we wanted to verify these findings in a larger study.

So we did a randomized control study in patients with metabolic syndrome, and we had 108 participants enrolled in this study and we randomized them to either time-restricted eating or standard of care. And this study was just published in the Annals of Internal Medicine in October of 2024. And in that study, similar to the pilot study, we found that there was a statistically significant reduction in hemoglobin A1C in this patient population with metabolic syndrome or prediabetes.

And some people might say that a decrease in the hemoglobin A1c of 0.1, which is what we saw, isn't that impressive. But when you look at the patient population, which is patients with metabolic syndrome, and you look at larger studies, a 0.1 decrease in hemoglobin A1C in the Diabetes Prevention study, which is a landmark clinical trial, showed that that resulted in a 58% reduction in new-onset type 2 diabetes.

So in our study, we showed that there was a 0.1 reduction in the hemoglobin A1C in the patients that were in the time-restricted eating group. We also saw a lot of other cardiometabolic benefits, including a decrease in LDL cholesterol. Also, we saw a decrease in body fat. So we looked at body composition in our study by having patients do DEXA scanning at the beginning and at the end of the study. And so we saw a decrease in total body fat and also in visceral fat.

Interestingly, we looked at skeletal muscle mass because there's a concern with weight loss, that there could be a decrease in skeletal muscle mass. And we didn't see any significant decrease in skeletal muscle mass, as has been seen in other studies with weight loss. And we also saw some improvements on certain parameters in continuous glucose monitoring, including glycemic variability.

So the overall message from our study is that a lifestyle intervention like time-restricted eating can have additional benefits on top of standard medical care for patients with metabolic syndrome.

What mechanistic pathways suggest time-restricted eating could improve cardiovascular risk markers?

So one of the mechanistic pathways that I find very intriguing that's been proposed as a potential reason for some of the benefits that we see with time restricted eating is a low-grade state of ketosis. So when you fast for more than 12 hours, your body shifts the way it utilises fuel, it goes from utilising glucose to free fatty acids. And there's generation of ketone bodies like beta-hydroxybutyrate. And these ketone bodies are thought to have numerous physiological benefits, including decreasing inflammation, improving endothelial function. And so we think that that is one of the underlying mechanisms that are responsible for the benefits of time-restricted eating.

How might this intervention complement existing pharmacological treatments for metabolic syndrome?

So it's really important to remember that pharmacology and lifestyle are very synergistic. And as a clinical cardiologist, this is something that I emphasise to all of my patients, is we need to do standard of care medications, whether it's for lipid management, whether it's for diabetes, whether it's for chronic kidney disease. But when you add lifestyle to pharmacotherapy, there is such an increased benefit. It's not just additive; it typically is synergistic.

And so in our studies, everyone was on standard of care medical therapy. So they were on statins for lipid lowering. Some people were on metformin for prediabetes. And so we are adding lifestyle therapy to standard of care. And what we find is that it is very beneficial. And of course, lifestyle therapy doesn't come with the cost that some medications have. And so it is also very accessible for a large portion of the population.

What implications does the study have for patient-specific personalised nutrition strategies?

I think that nutrition does need to be personalised for every patient depending on their current body composition and other comorbidities. There are certain patients, for instance, that might need more protein. Some patients with hypertension, we want to recommend lower salt. So there does need to be a very personalised aspect of nutrition.

But in addition to personalising what they're eating, time-restricted eating is a strategy of personalising when they eat. And so one of the things that I start with in my patients is I just inquire about when do they finish their last meal? Are they doing midnight snacks or nighttime snacks? And very interestingly, a huge number of my patients with metabolic syndrome, and it has been found in studies across the world, is people eat on average about 14 hours a day. So people are eating dinner typically later in the evening, and after dinner they're snacking. And many of these patients have poor sleep from things such as sleep apnea. And they're often waking up in the middle of the night and also snacking.

So they're basically eating for more than what's recommended, which is about 10 to 12 hours a day of eating. These people are eating constantly throughout the day. And so what we start with in our patients is just trying to eliminate the after dinner snacks and then moving up dinner to an earlier time. So people aren't finishing dinner at 9pm but maybe finishing dinner by 6 or 7pm. That's how I start, and then eventually with my patients I work up to a 14 hour fast, which is what we've seen in multiple studies has cardiometabolic benefits.

What potential broader cardiometabolic benefits warrant further investigation?

Well, I think this is where we need to focus on this concept of personalisation of diet. I think time-restricted eating is one aspect of that, but we also need to be thinking about other aspects of diet, including meal frequency. One thing that we don't have an answer to, is it better to eat multiple small meals or should we eat a couple of large meals? And so all of this really depends on someone's underlying metabolism. And using innovative tools such as continuous glucose monitoring and also looking at biomarkers can help us personalise better what an individual should be.

The other data gap that we have in the field is we need to know what are the long term consequences of a strategy like time-restricted eating. Most trials are looking at a three to six month duration of time-restricted eating. And I personally believe that the longer someone adheres to the strategy, that there will be more incremental benefit over time and that we will see an even further reduction in A1C and in LDL. And so those are studies that need to be done.

One other advantage of a lifestyle strategy like time-restricted eating: it's not all or none. And what I tell patients is if you can adhere to this six out of seven days a week, you are going to get benefit. And that's what we see in our trials. And so we also need to emphasise that lifestyle strategies are not stringent, that if you don't follow it every single day, that means you can't do it. That there is some flexibility to lifestyle strategies.

And I always tell patients about the 80:20 rule: that 80% of the time if you do things right, then 20% of the time when maybe you're eating outside of your eating window or you're eating things that are not typically recommended, that that 80% of time that you're doing things right will build your cardiometabolic resilience so that when you are doing non-recommended things that you don't develop type 2 diabetes, insulin resistance, but that you've built up that resilience to prevent adverse effects of certain lifestyle options.