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In this episode of Longevity by Design, our hosts, Dr. Gil Blander and Ashley Reaver, MS, RD, CSSD, are joined by Dr. Krista Varady, Professor of Nutrition at the University of Illinois, Chicago. Research on intermittent fasting is largely conducted in cellular and animal models. Dr. Krista Varady is one of few scientists to conduct intermittent fasting clinical trials in humans. Tune in as Dr. Krista Varady discusses the latest science in the field.
*Please note, food restriction is not for everyone—individuals who are underweight, under 18 years old, pregnant or breastfeeding, have a history or currently struggle with eating disorders, and those with diabetes or on certain medications should refrain from intermittent fasting. Before beginning intermittent fasting, we recommend consulting with a doctor or dietitian to see if it’s appropriate for you.
Dr. Krista Varady, is a Professor of Nutrition at the University of Illinois, Chicago. Her research focuses on the efficacy of intermittent fasting for weight loss and metabolic disease reduction in people with obesity. Her work is funded by the NIH, American Heart Association, International Life Sciences Institute, and the University of Illinois. She has published over 100 publications on intermittent fasting and co-authors the book "The Every Other Day Diet."
To begin, Dr. Krista Varady compares intermittent fasting to daily caloric restriction. She mentions that in humans, there are currently no clear benefits to intermittent fasting over daily calorie restriction—rather, it is another method to consider if one's goal is to lose weight. "Intermittent fasting produces pretty much the same weight loss and health benefits as daily calorie restriction. Intermittent fasting is another option for people who prefer to watch the clock instead of tracking data in a food record." Dr. Varady drives home the message that the approach to weight loss is different for everyone. The most important point is to create healthy habits that are sustainable long-term.
One unique aspect of intermittent fasting that has potential health and longevity benefits is giving your body a break. "We are constantly bombarding our bodies with nutrients and food, and our bodies have to work to process the nutrients. With fasting, you're giving your system a rest and allowing it to look inward on itself to find dysfunctional cell components, break them down, and recycle them," says Dr. Varady. This process is commonly referred to as autophagy. And while animal and yeast models show promising results, Dr. Varady points out that autophagy cannot be measured in humans yet. Rather, Dr. Varady discusses the health benefits of resting your body from food.
Dr. Varady's research specializes in the clinical outcomes associated with intermittent fasting, which she elaborates on throughout the episode. She mentions that the clinical benefits of intermittent fasting tend to be related to weight loss. "We mostly see blood pressure reduction, cholesterol reduction, and reduction in inflammation, but it's due to weight loss and visceral fat mass loss," says Dr. Varady. She suggests that an individual will start to see changes in their biomarkers upon losing 5% of their body weight. Individuals with higher blood pressure or cholesterol baseline measurements tend to see the most significant reductions through intermittent fasting.
Interestingly, Dr. Varady recently conducted a literature review to study the effect of intermittent fasting on reproductive hormones. She briefly discusses the paper's major findings: a decrease in androgens in both men and women, making fasting potentially beneficial for women that have hyperandrogenism. They also found intermittent fasting to increase sex hormone-binding globulin (SHBG) levels in premenopausal females with obesity. Future studies will further quantify the effects of time-restricted eating on reproductive hormones.
Time-restricted eating (TRE) is one method of intermittent fasting that has gained popularity in recent years. When asked about the benefits of TRE, Dr. Varady explains that shorter eating windows are simply another way for people to reduce total calorie intake. She has found that eating within a four to six-hour window leads to about 550 fewer calories per day, compared to only 300 fewer calories during an eight-hour window. She points out that although people lose more weight when eating within shorter windows, this dietary pattern is much harder to stick to long-term.
Dr. Varady unpacks the clinical benefits of front-loading meals earlier in the day rather than eating at a later time. “I do think it is healthier for people to place the window earlier, in the sense that our bodies are a lot more insulin sensitive earlier in the day. As the day goes on, our ability to process nutrients gets worse,” says Dr. Varady. She says that morning eating compared to evening is associated with increased insulin sensitivity and decreased fasting insulin, which is beneficial. However, Dr. Varady points out that an earlier fasting window tends to be more challenging to adhere to long-term.
While there is exciting progress being made to understand how fasting can promote health, there is a caveat that Dr. Varady highlighted in her discussion—findings from cell or rodent models may not be generalizable to humans quite yet. In talking about intermittent fasting and biomarkers, she says, "Amazing benefits are seen with rodent studies because the animals have no choice but to adhere. There's a lot of backlash now when we publish studies in humans showing that very little has changed." Studying intermittent fasting in humans is far more challenging than animal models. As an example, Dr. Varady explains that there are social aspects to eating that are ignored when studying rodents, and unfortunately, some fasting diets are too restrictive for humans.
This discrepancy between human and animal studies also exists in processes like autophagy. Dr. Varady explains that we cannot yet measure autophagy in humans—we measure surrogate markers to assess gene expression. Based on where the research stands today, animal model data may not yet be generalized to humans at this point.
To close the episode, Dr. Varady gives practical advice to those interested in trying intermittent fasting.
Dr. Varady describes how to maintain muscle mass while practicing intermittent fasting. The distribution of weight loss from intermittent fasting mirrors that of calorie restriction. “Regardless of the method, about 75% of weight loss is fat mass, and 25% is lean mass. So, the best way to maintain lean mass is through resistance training and also consuming a higher protein diet.”
Few studies have researched intermittent fasting in older populations. Therefore, Dr. Varady says that at this time, it is not advisable for individuals over 65 to practice intermittent fasting. Likewise, there is no safety data on pregnant or breastfeeding women.
For her top tip, Dr. Varady recommends refraining from late-night snacking. “I try to follow an eight-hour window of eating. I typically eat from 10:00 AM to 6:00 PM, and then do not eat after dinner.”