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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. Dudley Lamming, an Associate Professor at the University of Wisconsin-Madison School of Medicine in the Division of Endocrinology, Diabetes, and Metabolism. Tune in as Dr. Lamming discusses his research on protein restriction and fasting. As the principal investigator of his lab, Dr. Lamming has extensive knowledge of nutrient signaling pathways and how dietary patterns promote health. Tune in as Dr. Lamming 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.
Meet Longevity by Design’s podcast guest, Dr. Dudley Lamming
Dr. Dudley Lamming is an Associate Professor at the University of Wisconsin-Madison School of Medicine in the Division of Endocrinology, Diabetes, and Metabolism. He received his PhD in Experimental Pathology from Harvard University and pursued Postdoc research at the Whitehead Institute for Biomedical Research. Dr. Lamming is also the principal investigator at the Dr. Lamming laboratory for the Molecular Physiology of Aging. His research focuses on nutrient-responsive signaling pathways that can promote health and longevity.
Does caloric restriction alone impact health?
Dr. Lamming begins by discussing a recent breakthrough experiment in his lab when his team compared the health benefits of traditional caloric restriction to caloric restriction with fasting in mice.
This feeding experiment yielded a surprising finding—caloric restriction in combination with fasting resulted in an extended lifespan in mice. But, interestingly, caloric restriction alone was associated with a shorter lifespan. “Normally, calorie restriction with fasting results is associated with improved insulin sensitivity, less frailty with age, and beneficial effects on memory. However, in this study, none of these benefits were seen without fasting,” explains Dr. Lamming.
It turns out that fasting alone had health benefits in mice, even without calorie restriction. Dr. Lamming explains that when you give mice their daily caloric intake but only let them eat in a two-hour window, they experience the same health benefits as mice that are fasted with calorie restriction. “At the gene-transcription level, about 90 or 95% of the genes are pretty much the same between fasted and calorie-restricted animals,” says Dr. lamming.
The major takeaway from this study? Fasting periods were beneficial for multiple health outcomes in mice. When asked if these findings are generalizable to humans, Dr. Lamming speculates, “If these lessons apply to humans—which remains to be seen—it would seem like calorie restriction should definitely include some sort of fasting component,” says Dr. Lamming.
What happens when dietary protein is restricted?
The optimal macronutrient ratio for health has been controversial for decades. Sometimes fat is vilified, and other times it is carbohydrates. While fat and carbohydrates are often the macronutrients restricted in nutrition studies—it left Dr. Lamming wondering, what about protein?
To this end, Dr. Lamming’s lab studies the effects of protein restriction on health. Dr. Lamming recalls one of his studies that examined the metabolic effects of restricting protein intake in men who are overweight and have prostate cancer.
Study participants who restricted protein experienced substantial weight loss and restrictions in fasting blood glucose. “Dietary protein promotes satiety, making you feel more full and eat less. Due to the absence of protein, the participants had about a 10% increase in their calorie intake. They were eating more but gaining less weight,” says Dr. Lamming.
Reproducing protein restriction studies in mice generated similar results. “Mice and rats that eat low protein diets tend to gain less weight; they tend to be leaner, improve their glucose tolerance, and sometimes improve insulin sensitivity. Protein-restricted male mice experienced a lifespan extension of up to 30%,” he states.
While his studies find that protein restriction is correlated with a longer lifespan, Dr. Lamming clarifies that protein is essential for life—especially in those who regularly exercise or are in a skeletal muscle-building phase.
Genetics influences the health impact of diet
Scientists are able to control nearly every factor about a mice’s behavior in mice studies—which isn’t true of human subject trials. One example is the homogeneity of mice compared to the heterogeneity of humans. The subjects in mice studies are typically Black 6 mice, which are genetically identical to each other. But we know that humans are genetically heterogeneous.
To address this discrepancy in his laboratory, Dr. Lamming runs studies on different strains of mice. “Looking across strains and sexes of mice, a lot of strains benefit from protein restriction, but some don't. When we restrict protein, some strains lose weight, while others gain more fat mass,” says Dr. Lamming. This finding supports the notion that humans respond to diets differently.
To that end, Dr. Lamming is interested in using an individual's genome to determine their optimal diet. He notes that the field of personalized nutrition has grown in recent years and is excited to see what the future holds.
Examining the amino acid isoleucine
There are nine essential amino acids in humans and mice, meaning they are essential to consume in the diet because the body doesn’t produce them on its own. Three essential amino acids—leucine, isoleucine, and valine—are categorized as branched-chain amino acids based on their chemical structure.
Branched-chain amino acids (BCAAs) are significant to health in multiple ways. Studies show that BCAA levels tend to be elevated in those with diabetes who are overweight or obese. BCAA levels are also correlated with blood sugar and hemoglobin levels.
Dr. Lamming’s lab finds that isoleucine is the most impactful BCAA. Restricting isoleucine led to dramatic improvements in glucose tolerance and even blocked fat mass secretion. He proposes that restricting isoleucine causes the browning of white adipose tissue, a process in which white adipose tissue changes from a storage depot to a tissue that burns fat and creates additional energy.
Isoleucine’s differences from other BCAAs are not mTOR-mediated. Rather, Dr. Lamming hypothesizes that isoleucine is catabolized differently than other BCAAs.
Populations that should not restrict protein intake
Dr. Lamming cautions that protein restriction is not suitable for everyone—and there are two groups of people who shouldn't restrict protein.
First, Dr. Lamming notes that protein restriction likely won't benefit those that regularly exercise. Dietary protein is necessary to build skeletal muscle. "After exercising, you're essentially pulling all that extra protein out of your blood, and it's going into your muscle. That muscle uses glucose, making you more insulin-sensitive." Excess protein intake needs somewhere to be stored; it's either broken down for energy or stored as fat.
Protein restriction is also not advised for anyone over the age of 65. In fact, research supports the longevity benefits of protein consumption in those over the age of 65. For example, sarcopenia, the age-related decline in muscle mass, is a major health concern in the older population. For this reason, Dr. Lamming says he would be very cautious about protein restriction in the elderly.
