Misdiagnosed with acid reflux and anxiety, her heart's arteries were blocked
Fasting-like Diet May Help Reverse Biological Aging By 2.5 Years
Three cycles of a so-called fasting-mimicking diet (FMD) was shown to reduce biomarkers associated with insulin resistance, liver fat in humans, and other markers associated with aging.
USC Leonard Davis School Professor Valter Longo, the senior author of the new study, designed the FMD. This five-day diet is high in unsaturated fats and low in protein, carbohydrates, and calories.
The study examined the diet's impact in two clinical studies, which included men and women between the ages of 18 and 70. Participants who followed the fasting-mimicking diet went through 3-4 monthly cycles, following the FMD for 5 days and adhering to a normal diet for the other 25 days.
Results showed that patients in the FMD group had less insulin resistance, lower HbA1c results, and better fasting glucose results. They also had less abdominal fat and liver fat, along with improved immune system markers suggesting lower inflammation.
In addition, both clinical studies showed that those who followed the FMD had lowered markers associated with biological aging by 2.5 years on average.
The study was published in Nature.
This clinical study, involving 100 participants, indicated that a plant-based fasting-mimicking diet done for 5 days a month could reduce the biological age of people after only three monthly cycles and without changing their lifestyle.
The researchers provided participants with food that had been formulated to contain certain proportions of macro- and micro-nutrients, such as soups, energy bars, snacks, and teas, for days 1-5. These were provided by the company L-Nutra Inc., a company that sells ready-packaged meals for people who are fasting. Two of the authors 'have equity interest in L-Nutra', the study read.
The first study carried out by these researchers was published in Metabolic Health and Disease in 2023, and showed similar results.
"The results are particularly convincing because both studies, one done in Los Angeles and one in Tennessee, showed similar effects on the reduction of biological age by 2.5 years as measured by the biome method developed by Morgan Levine at Yale but also showed parallel evidence of rejuvenation or improved function/health of multiple system including the immune system, the liver and the endocrine system as measured by standard methods," Prof. Longo told Medical News Today.
"The next step is to continue to allow many universities to perform clinical trials to test how cycles of this standardized plant-based FMD, which comes in a box like medicine, can help people stay younger but also prevent or treat diseases like diabetes, CVD, cancer, and Alzheimer's considering that biological age and multi-system dysfunction are the major risk factors for these diseases."— Professor Valter Longo
"We also hope that these studies will convince doctors to add the FMD to their toolkit for disease prevention and possibly treatment," he added.
There are numerous ways this diet can improve overall health.
Reducing inflammation"The FMD does exactly what it is named after- mimics fasting," said Dr. Nicole Avena, nutrition consultant, assistant professor of neuroscience at Mount Sinai School of Medicine, visiting professor of health psychology at Princeton University, and author of Sugarless.
"This diet is beneficial to balancing blood sugar, improving insulin resistance, and reducing overall inflammation throughout the body. By giving your body time to rest, rather than digest, it allows us to heal inflammation and put energy towards more pressing internal 'issues,'" she explained.
Lowering biological age and risk factors for diseaseMany lifestyle diseases, such as diabetes or cardiovascular disease are associated with shortened lifespan.
"These diseases raise inflammation within the body and allow for reactive oxygen species (ROS) to multiply," Avena explained. "ROS in excess cause disease, therefore aiming for a low-inflammatory lifestyle like FMD is beneficial for aging."
"Biological age, in particular, is interesting because it is genuinely what age we feel versus what age we really are. The more inflammation and disease we have determines our abilities to perform acts of daily living," she added.
While the clinical consensus is that the FMD is generally safe, there are some people who should not follow this diet.
"If you are pregnant or trying to conceive, and if you are considered an older adult, the FMD is not for you," Avena said.
"During pregnancy, we have higher metabolic demand, and in old age, we do not have as fast of a metabolism as we do when we are younger," she added.
During pregnancy, getting enough nutrients is essential for the health of the baby and parent.
For seniors, fasting is usually not recommended, especially if they already have chronic health issues.
Usually, the FMD consists of higher-fat foods while staying relatively lower in protein.
"This is a great time to try a Mediterranean-style diet, which includes beans, olive oils, fatty fish, and whole grains," said Avena.
"Remember, you are trying to eat under your estimated calorie needs for 5 days while drinking plenty of water. Doing this once a month is the way it is planned, but you should continue to incorporate healthy foods like those included [in] a Mediterranean diet throughout the month," she explained.
Fasting-like Diet Lowers Risk Factors For Disease, Reduces Biological Age In Humans
Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat in humans, resulting in a lower biological age, according to a new USC Leonard Davis School of Gerontology-led study.
The study, which appears in Nature Communications on Feb. 20, adds to the body of evidence supporting the beneficial effects of the fasting-mimicking diet (FMD).
The FMD is a five-day diet high in unsaturated fats and low in overall calories, protein, and carbohydrates and is designed to mimic the effects of a water-only fast while still providing necessary nutrients and making it much easier for people to complete the fast. The diet was developed by the laboratory of USC Leonard Davis School Professor Valter Longo, the senior author of the new study.
"This is the first study to show that a food-based intervention that does not require chronic dietary or other lifestyle changes can make people biologically younger, based on both changes in risk factors for aging and disease and on a validated method developed by the Levine group to assess biological age," Longo said.
Previous research led by Longo has indicated that brief, periodic FMD cycles are associated with a range of beneficial effects. They can:
In addition, the FMD cycles can lower the risk factors for cancer, diabetes, heart disease and other age-related diseases in humans.
The Longo lab also had previously shown that one or two cycles of the FMD for five days a month increased the healthspan and lifespan of mice on either a normal or Western diet, but the effects of the FMD on aging and biological age, liver fat, and immune system aging in humans were unknown until now.
Lower disease risks & more youthful cells
The study analyzed the diet's effects in two clinical trial populations, each with men and women between the ages of 18 and 70. Patients who were randomized to the fasting-mimicking diet underwent 3-4 monthly cycles, adhering to the FMD for 5 days, then ate a normal diet for 25 days.
The FMD is comprised of plant-based soups, energy bars, energy drinks, chip snacks, and tea portioned out for 5 days as well as a supplement providing high levels of minerals, vitamins, and essential fatty acids. Patients in the control groups were instructed to eat either a normal or Mediterranean-style diet.
An analysis of blood samples from trial participants showed that patients in the FMD group had lower diabetes risk factors, including less insulin resistance and lower HbA1c results. Magnetic resonance imaging also revealed a decrease in abdominal fat as well as fat within the liver, improvements associated with a reduced risk of metabolic syndrome. In addition, the FMD cycles appeared to increase the lymphoid-to-myeloid ratio -- an indicator of a more youthful immune system.
Further statistical analysis of the results from both clinical studies showed that FMD participants had reduced their biological age -- a measure of how well one's cells and tissues are functioning, as opposed to chronological age -- by 2.5 years on average.
"This study shows for the first time evidence for biological age reduction from two different clinical trials, accompanied by evidence of rejuvenation of metabolic and immune function," Longo said.
The study, conducted by first authors Sebastian Brandhorst, USC Leonard Davis research associate professor, and Morgan E. Levine, founding principal investigator of Altos Labs and USC Leonard Davis PhD alumna, lends more support to the FMD's potential as a short-term periodic, achievable dietary intervention that can help people lessen their disease risk and improve their health without extensive lifestyle changes, Longo said.
"Although many doctors are already recommending the FMD in the United States and Europe, these findings should encourage many more healthcare professionals to recommend FMD cycles to patients with higher than desired levels of disease risk factors as well as to the general population that may be interested in increased function and younger age," Longo said.
High-Protein Diet Could Drive Heart Disease
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When I get home from my morning gym session, the first thing I reach for is my protein shaker – determined to get ahead of my recovery before I do it all over again tomorrow. According to a survey of the average American diet, I'm not alone in this cycle. Nearly 25% of the American population receive over 22% of all daily calories from protein alone, mostly from animal sources. But what if this ritual isn't the best thing for our bodies?
A new study published in Nature Metabolism investigated the potentially adverse effects of a high protein diet, which is often promoted as a "healthy lifestyle".
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Subscribe for FREE Protein is an essential macronutrientWhile protein is a vital nutrient for human health, many people in Western societies consume around more protein than the recommended daily allowance on average. Driven by the idea that a high-protein diet is the key to unlocking greater health, we might overlook the potential dangers this could cause, said Dr. Babak Razani, professor of cardiology at the University of Pittsburgh School of Medicine, and corresponding author: "You can read a lot of things on the internet and not only is much of it untrue, it is not based on clinical evidence or efficacy."
Razani and team previously discovered that excess dietary protein increases the risk of atherosclerosis in mice. The researchers partnered with Dr. Bettina Mittendorfer a metabolism expert at the University of Missouri, Columbia, to further investigate the potential mechanism behind this association, and its relevance in humans.
High-protein diets trigger immune cell activationThe researchers employed a combination of cell, animal and small human studies to explore the pathway underlying the link between a high-protein diet and atherosclerosis shown in mice. Using their previous results, Razani and team investigated the effects of varying protein intake in humans, by comparing the effects of liquid meals, which contained either 10% or 50% of energy as protein, on monocyte mTORC1 activation. They also compared the same outcomes in participants who consumed either a standard-protein mixed meal or a mixed meal with modestly increased protein content (15% kcal versus 22% kcal). Blood samples were collected before and one hour and two hours after consuming the meals to assess plasma amino acid concentrations and monocyte mTORC1 signalling.
The team demonstrated that consuming more than 22% of daily dietary calories through protein negatively impacts human macrophages, which leads to the accumulation of cellular debris inside vessel walls, resulting in the worsening of atherosclerotic plaques.
"When one eats higher amounts of protein, it leads to activation of their macrophages, an immune cell that is a key driver of atherosclerosis, and we identified an important protein in the macrophages called mTOR that mediates this process," said Razani.
To determine which of the seven amino acids contributed to mTORC1 signalling in monocytes/macrophages, the researchers used cultured human monocyte-derived macrophages (HMDMs) to study the macrophage-specific mTORC1 response to each amino acid. These results were also confirmed in mice.
"We then discovered that only leucine – an amino acid highly enriched in animal-based proteins – is the main activator of the mTOR pathway in macrophages and in turn atherosclerosis risk. Amino acids are the building blocks of proteins, and there are 20 of them that make up any protein we ingest. But it is only leucine that is the bad actor in worsening the heart artery disease," Razani said.
"We hope that this study starts a conversation about the false notion that dialing up dietary protein consumption is a panacea for improving all aspects of metabolic health. It is much more complex than that," added Razani.
Finding the protein "sweet spot"The data also suggest that differences in leucine levels between plant-based and animal diets may explain the differences in their effect on cardiovascular and metabolic health. "We are working on follow-up studies to determine whether consuming mostly plant-based protein (which can lead to lower leucine elevations than animal-based protein) can diminish the risk of cardiovascular disease," Razani said. "There is a lot of talk about the benefits of plant- vs animal-based proteins and my group has the opportunity to study it mechanistically and with a level of detail that is rarely done."
Razani outlined several additional questions that need to be addressed in this line of research. First, what happens when someone consumes between the recommended 15% of daily dietary protein to 22% of their daily calories? Could there be a potential number that allows for muscle growth while still avoiding the immune cell cascade that increases atherosclerosis risk?
Further studies are needed to investigate the effects of varying amounts and types of dietary proteins that lead to the increased risk of atherosclerosis, and how these may evolve the current dietary guidelines concerning protein intake.
"We hope that this study raises awareness that increasing dietary protein consumption is not a cure-all for your metabolic health but may put you at a higher risk of heart disease," said Razani.
Dr. Babak Razani was speaking to Rhianna-lily Smith, Junior Science Editor for Technology Networks.
Reference: Zhang et al. Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk. Nature Metabolism. 2024. Doi: 10.1038/s4 2255-024-00984-2
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