Metabolic Syndrome

Michael J. Wilkinson, MD, on Whether Time-Restricted Eating Could Play a Role in Treating Metabolic Syndrome

Time-restricted eating may help improve cardiometabolic health among patients with metabolic syndrome receiving standard medical care, including those who are treated with statins and anti-hypertensive medications, according to new findings published in Cell Metabolism.1

“[Time-restricted eating] is a potentially powerful lifestyle intervention that can be added to standard medical practice to treat metabolic syndrome,” the authors of the study said.1

They arrived at their conclusion after performing a single-arm, paired-sample trial of 19 participants with metabolic syndrome and a baseline mean daily eating window of at least 14 hours.1 Most participants were receiving statin and/or antihypertensive therapy. During the trial, participants underwent a 10-hour time-restricted eating intervention, defined as all dietary intake within a consistent self-selected 10-hour window, for 12 weeks.1

Consultant360 discussed the findings from the trial further with first study author Michael J. Wilkinson, MD, cardiologist at the University of California, San Diego.

Consultant360: What is known about the impact of eating habits, timing, and circadian rhythms on endocrine function and the prevention or reversal of metabolic diseases?

Dr Wilkinson: There is a growing body of evidence that eating habits, timing of dietary intake, and disruption of these patterns, such as travel, time zone changes, and shift work, are associated with increased risk of metabolic diseases. It has been observed that frequent changes in the timing of daily activities are associated with a disruption in normal metabolism as well. The metabolism in animals including humans follows a circadian rhythm, which is followed initially by exposure to light. The central clock in the brain senses the presence of light vs dark and triggers downstream gene expression and regulation of metabolism in peripheral organs. The central clock responds to light, and peripheral organs respond to the central clock, as well as other environmental factors.

One prime example of this is the influence of dietary intake on the activity of the peripheral clocks and organs, such as the liver. The liver follows cues from the central clock, and metabolism will shift from a healthy, active daytime metabolism that is primed to quickly and efficiently metabolize foods, to a state of fasting once the central clock cues that day has become night. Organs like the liver also respond to input from diet. Food that is consumed after the liver has started to shift towards a fasting state will interrupt this process, and the liver will subsequently change its metabolism to respond to the food that has been consumed. In turn, this will ramp up other metabolic processes that might have begun to shift into a fasting state. The hypothesis is that, by interrupting this normal pattern of metabolism that is coordinated between the central and peripheral clocks, more strain is placed on the body and on organs like the liver.

The work of investigators like Satchidananda Panda, PhD, who was one of the key investigators and senior authors of our study, has been pioneering in terms of determining how the interruption of this normal pattern of metabolism can increase predisposition to metabolic diseases. In animal models, including mouse models from Dr Panda’s lab, consumption of a high-fat diet at any time during the day and night has been associated with an increase in body weight, disruption in normal glucose and cholesterol metabolism, and accumulation of fat in the liver. All of these observations mirror what has been seen clinically in human patients with metabolic diseases ranging from insulin resistance and prediabetes to type-2-diabetes­–related conditions. However, in studies where mice are placed on time-restricted feeding paradigms, the mice appear to experience protection against the development of these metabolic derangements. Mice that consume all dietary intake within a 9- to 12-hour window appear to be protected against weight gain, abnormal glucose and insulin levels, and the accumulation of liver fat, even when consuming a high-fat diet.

Consultant360: With the findings from your study in mind, when might clinicians want to consider recommending time-restricted eating to a patient?

Dr Wilkinson: Our study specifically included patients who have metabolic syndrome, many of whom were already being treated with medications to lower their low-density lipoprotein cholesterol (LDL-C) levels and blood pressure. This study serves as an example of using time-restricted eating to promote cardiometabolic health in patients who have established cardiovascular risk factors. However, our study is a pilot study, so I would encourage any patients with metabolic syndrome or conditions like type 2 diabetes to discuss time-restricted eating with their health care provider before adopting this on their own because it could necessitate medication adjustment.

For healthy people and for people without prediabetes, diabetes, or a high risk for cardiovascular disease (CVD), the existing research suggests that time-restricted is something that can be considered.

Consultant360: Is time-restricted eating an eating pattern that patients can easily adhere to? If not, what are some adherence strategies that clinicians can use with patients?

Dr Wilkinson: In our study, we used a smartphone app to allow participants to actively log their daily dietary intake in real time. I think this aspect of the study helped with adherence. Participants were allowed to self-select their 10-hour window that they would use for the 12 weeks of the trial, which I also think improved adherence. Our hypothesis was that, if participants are allowed to choose their own 10-hour window, that their personal choice may be more conducive with their daily routine, thus promoting adherence.

The results of our study showed that, during the intervention period, more than 80% of people were adherent with logging their daily dietary intake for 12 weeks. Furthermore, logging food intake by more than an hour outside participants’ 10-hour window only occurred during about 7% of days during the intervention. Most of the time, participants were very adherent to their self-selected 10-hour window.

We also measured the rate of long-term adherence to time-restricted eating, which we assessed by contacting participants an average of 16 months after the end of the study. After the end of the 12-week intervention period, we had not asked any participants to continue time-restricted eating. When we followed up with participants at 16 months, we were impressed to see that 63% of patients still practiced some amount of time-restricted eating on their own. This suggests that the initial intervention had a lasting effect.

Another important note is that studies of time-restricted eating in animal models have shown that missing a day or two of time-restricted eating does not reduce the benefits of this intervention. I think this finding is important and encouraging for patients. Even if there is a day or a weekend where time-restricted eating is not compatible with a patient’s schedule, that patient is still likely to benefit from time-restricted eating if they adhere to it most of the time. One specific mouse model that placed mice on time-restricted eating 5 days a week and gave them the ability to eat when they wanted for 2 days showed that those mice still experienced the benefits of time-restricted eating as long as they adhered to it at least 5 days of the week.2 I think allowing that flexibility also helps with adherence.

Consultant360: What are the next steps in terms of future research on time-restricted eating?

Dr Wilkinson: There are still many areas to explore with time-restricted eating and translating findings from animal models to humans, particularly those with metabolic diseases and CVD, as well as those with a high risk of these conditions. Our group is building off of the pilot studies reported in this paper by examining time-restricted eating in a much larger group of patients with metabolic syndrome, and we are using a control arm so that we can compare a standard-of-care group with individuals undergoing time-restricted eating for 3 months.

I think an important next step in exploring the effects of time-restricted eating is assessing this intervention in patients with other diseases, such as metabolic diseases, other risk factors for CVD, and certain types of cancers, as well as in patients receiving different forms of medical treatment for these conditions. There is also interest in determining whether time-restricted eating affects the efficacy of medications. These are all areas where researchers can continue to translate promising studies in animal models into clinical care. There is still much work to be done, but it is an exciting area of research. I expect many more studies and large randomized controlled trials to be performed within the next 1 to 2 years.

—Christina Vogt

References:

  1. Wilkinson MJ, Manoogian ENC, Zadourian A, et al. Ten-hour time-restricted eating reduces weight, blood pressure, and atherogenic lipids in patients with metabolic syndrome [Published online December 5, 2019]. Cell Metab. https://doi.org/10.1016/j.cmet.2019.1004.
  2. Chaix A, Zarrinpar A, Miu P, Panda S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab. 2014; 20(6):991-1005. http://dx.doi.org/10.1016/j.cmet.2014.11.001.

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