Scientific research links many benefits to intermediate fasting. From improved blood pressure and resting heart rate to enhanced cognitive and physical performance.
In addition to increasing physical activity, a new diet is among the first things people think of when looking to improve their health. One of the main problems in searching for an appropriate diet is the lack of scientific evidence that supports claims made for a lot of these diets.
Neuroscientist Dr. Mark Mattson from Johns Hopkins University School of Medicine concludes that at least one diet has scientific evidence supporting its claims, and that is intermediate fasting. He studied intermittent fasting for 25 years and adopted it himself. His findings are published in the New England Journal of Medicine.
According to Dr. Mattson, intermediate fasting could be part of a healthy lifestyle. He states that intermittent fasting diets can be categorized into two types. One focuses on daily time-restricted feeding, which narrows eating times to 6 to 8 hours per day, and the other is named 5:2 intermittent fasting. In 5:2 intermittent fasting, people limit themselves to one moderate-sized meal two days per week
Animal and human studies have shown that alternating between times of fasting and eating boosts cellular health, presumably by triggering an age-old adaptation to periods of food scarcity called metabolic switching. (During a long period of our early existence as humans, we didn’t have a stable daily source of food intake). A switch like that occurs when cells use up their stocks of quickly available, sugar-based fuel, and start converting fat cells into energy paired with a slower metabolic process. According to Dr. Mattson, studies show that such a switch improves blood sugar regulation in addition to inhibiting inflammation and increasing our resistance to stress.
The benefits of intermittent fasting – Why doctors believe this method could lead to improved health –
Most people eat at least three times per day, in which case they don’t undergo the before mentioned switch causing them to miss the suggested benefits. In Dr. Mattson’s New England Journal of Medicine piece, he comments that in 4 studies of both animals and humans, intermittent fasting was found to decrease blood lipid levels, blood pressure as well as resting heart rates. In addition to that, evidence is growing that intermittent fasting is stated to be able to mitigate risk factors associated with obesity and diabetes.
Two studies done at the University Hospital of South Manchester of 100 overweight women revealed that those on the previously mentioned 5:2 intermittent fasting diet lost the same amount of weight as women that just restricted calorie intake, but did better when measured on insulin sensitivity and reduced belly fat.
More recent preliminary studies propose that intermittent fasting could benefit brain health as well. A multicenter clinical trial at the University of Toronto found that 220 healthy, nonobese adults that maintained a calorie-restricted diet for two years showed signs of improved memory.
It is important to note that a lot more research has to be done to conclusively prove any effects of intermittent fasting on memory and learning ability. Dr. Mattson stated that if such proof is found, the fasting (or a pharmaceutical equivalent that mimics it) might offer interventions that can stave off neurodegeneration and dementia.
According to Dr. Mattson, we are at a point of transition where we could soon think of adding information about intermittent fasting to medical school curricula in addition to the standard advice about healthy diets. He recognizes that scientists do not yet fully understand the specific mechanisms of metabolic switching and that some people are unable or unwilling to stick to the fasting regimens. But he maintains that with guidance and patience, most people can include them into their lives. It takes some time for the body to adjust to intermittent fasting, and to get beyond initial hunger pangs and irritability that accompany it.
Feeling starved and more irritable is typical for those that start with intermediate fasting. As specified by Dr. Mattson, these feelings typically go away after two to four weeks. The body and brain need to get familiar with new eating habits. Slowly increasing the duration and frequency of the fasting periods over the course of many months might alleviate the side effects a little.
While research needs to be done on the exact workings of metabolic switching as well as on the cognitive benefits of intermittent fasting, the health benefits that have already been presented to us are astounding.
Scientists at the USC Leonard Davis School of Gerontology have taken a closer look at the fasting-mimicking diet (FMD) and its potential benefits for human health.The study yielded interesting results revealing FMD’s potential not only to improve health markers but also to reduce biological ageing.
The team published their work in the peer-reviewed science journal Nature Communications. In this article, we will take a look at the findings.
FMD does not necessitate total abstention from food.
What is the fasting-mimicking diet?
The fasting-mimicking diet (FMD) is designed to replicate the benefits of a traditional fast without the need for complete food abstinence.
Over a five-day period, individuals consume meals high in unsaturated fats and low in calories, proteins, and carbohydrates. Developed by Professor Valter Longo and his team, the FMD is easy to follow and rich in nutrients, making the fasting experience both manageable and beneficial.
The study
The research looked at the impact of the fasting-mimicking diet (FMD) across two distinct clinical trial groups, consisting of individuals aged 18 to 70, inclusive of both genders.
Participants assigned to the FMD embarked on 3 to 4 cycles each month, following the diet strictly for 5 consecutive days before resuming their usual eating habits for the remaining 25 days of the month.
The FMD regimen featured a diet rich in plant-based soups, energy bars, drinks, chips, and tea, all portioned to last the 5-day period, complemented by a supplement packed with essential vitamins, minerals, and fatty acids. Meanwhile, individuals in the control group adhered to either a standard or Mediterranean diet.
Benefits of the Fasting-Mimicking Diet
Evaluations of blood samples from those on the FMD revealed notable health benefits, such as diminished factors contributing to diabetes risk, including reduced insulin resistance and lower HbA1c levels.
Magnetic resonance imaging (MRI) scans also indicated a significant reduction in both abdominal and liver fat, signalling a decreased likelihood of developing metabolic syndrome. Furthermore, undergoing the FMD was linked to an enhanced lymphoid-to-myeloid ratio, signifying a rejuvenation of the immune system.
Comprehensive statistical analyses from both trials highlighted that individuals adhering to the FMD managed to lower their biological age by an average of 2.5 years, suggesting an improvement in the functionality of their cells and tissues beyond mere changes in chronological age.
Should you consider the Fasting-Mimicking Diet?
The study adds to the growing body of evidence supporting the potential health benefits of fasting and fasting-mimicking diets. It suggests that periodic adherence to the FMD could offer a practical approach to improving health markers associated with ageing and chronic disease risk without the need for permanent lifestyle changes.
However, as with any dietary intervention, it’s important to approach the FMD with a nuanced understanding of its benefits and limitations. While the findings are promising, further research is needed to fully comprehend the long-term impacts and applicability to diverse populations.
Health decisions, especially those related to diet, should be made in consultation with healthcare professionals, taking into account individual health needs and conditions.
Scientists at Cambridge have found that fasting raises arachidonic acid levels in the blood, inhibiting inflammation and offering insights into the health benefits of fasting and the anti-inflammatory effects of drugs like aspirin on chronic diseases.
Scientists at Cambridge may have uncovered a novel mechanism by which fasting can reduce inflammation – a potentially harmful consequence of the immune system’s activity that is at the root of several chronic illnesses.
In research published in Cell Reports, the team describes how fasting raises levels of a chemical in the blood known as arachidonic acid, which inhibits inflammation. The researchers say it may also help explain some of the beneficial effects of drugs such as aspirin.
The Link Between Diet and Chronic Inflammation
Scientists have known for some time that our diet – particularly a high-calorie Western diet – can increase our risk of diseases including obesity, type 2 diabetes, and heart disease, which are linked to chronic inflammation in the body.
Inflammation is our body’s natural response to injury or infection, but this process can be triggered by other mechanisms, including by the so-called ‘inflammasome’, which acts like an alarm within our body’s cells, triggering inflammation to help protect our body when it senses damage. But the inflammasome can trigger inflammation in unintentional ways – one of its functions is to destroy unwanted cells, which can result in the release of the cell’s contents into the body, where they trigger inflammation.
Research Findings on Fasting and Arachidonic Acid
Professor Clare Bryant from the Department of Medicine at the University of Cambridge said: “We’re very interested in trying to understand the causes of chronic inflammation in the context of many human diseases, and in particular the role of the inflammasome.
“What’s become apparent over recent years is that one inflammasome in particular – the NLRP3 inflammasome – is very important in a number of major diseases such as obesity and atherosclerosis, but also in diseases like Alzheimer’s and Parkinson’s disease, many of the diseases of older age people, particularly in the Western world.”
Fasting can help reduce inflammation, but the reason why has not been clear. To help answer this question, a team led by Professor Bryant and colleagues at the University of Cambridge and the National Institute for Health in the USA studied blood samples from a group of 21 volunteers, who ate a 500kcal meal and then fasted for 24 hours before consuming a second 500kcal meal.
The team found that restricting calorie intake increased levels of a lipid known as arachidonic acid. Lipids are molecules that play important roles in our bodies, such as storing energy and transmitting information between cells. As soon as individuals ate a meal again, levels of arachidonic acid dropped.
When the researchers studied arachidonic acid’s effect in immune cells cultured in the lab, they found that it turns down the activity of the NLRP3 inflammasome. This surprised the team as arachidonic acid was previously thought to be linked with increased levels of inflammation, not decreased.
Implications and Future Directions
Professor Bryant, a Fellow of Queens’ College, Cambridge, added: “This provides a potential explanation for how changing our diet – in particular by fasting – protects us from inflammation, especially the damaging form that underpins many diseases related to a Western high-calorie diet.
“It’s too early to say whether fasting protects against diseases like Alzheimer’s and Parkinson’s disease as the effects of arachidonic acid are only short-lived, but our work adds to a growing amount of scientific literature that points to the health benefits of calorie restriction. It suggests that regular fasting over a long period could help reduce the chronic inflammation we associate with these conditions. It’s certainly an attractive idea.”
The findings also hint at one mechanism whereby a high-calorie diet might increase the risk of these diseases. Studies have shown that some patients that have a high-fat diet have increased levels of inflammasome activity.
“There could be a yin and yang effect going on here, whereby too much of the wrong thing is increasing your inflammasome activity and too little is decreasing it,” said Professor Bryant. “Arachidonic acid could be one way in which this is happening.”
The researchers say the discovery may also offer clues to an unexpected way in which so-called non-steroidal anti-inflammatory drugs such as aspirin work. Normally, arachidonic acid is rapidly broken down in the body, but aspirin stops this process, which can lead to an increase in levels of arachidonic acid, which in turn reduces inflammasome activity and hence inflammation.
Professor Bryant said: “It’s important to stress that aspirin should not be taken to reduce the risk of long-term diseases without medical guidance as it can have side-effects such as stomach bleeds if taken over a long period.”
Scientists at Cambridge have found that fasting raises arachidonic acid levels in the blood, inhibiting inflammation and offering insights into the health benefits of fasting and the anti-inflammatory effects of drugs like aspirin on chronic diseases.
Scientists at Cambridge may have uncovered a novel mechanism by which fasting can reduce inflammation – a potentially harmful consequence of the immune system’s activity that is at the root of several chronic illnesses.
In research published in Cell Reports, the team describes how fasting raises levels of a chemical in the blood known as arachidonic acid, which inhibits inflammation. The researchers say it may also help explain some of the beneficial effects of drugs such as aspirin.
The Link Between Diet and Chronic Inflammation
Scientists have known for some time that our diet – particularly a high-calorie Western diet – can increase our risk of diseases including obesity, type 2 diabetes, and heart disease, which are linked to chronic inflammation in the body.
Inflammation is our body’s natural response to injury or infection, but this process can be triggered by other mechanisms, including by the so-called ‘inflammasome’, which acts like an alarm within our body’s cells, triggering inflammation to help protect our body when it senses damage. But the inflammasome can trigger inflammation in unintentional ways – one of its functions is to destroy unwanted cells, which can result in the release of the cell’s contents into the body, where they trigger inflammation.
Research Findings on Fasting and Arachidonic Acid
Professor Clare Bryant from the Department of Medicine at the University of Cambridge said: “We’re very interested in trying to understand the causes of chronic inflammation in the context of many human diseases, and in particular the role of the inflammasome.
“What’s become apparent over recent years is that one inflammasome in particular – the NLRP3 inflammasome – is very important in a number of major diseases such as obesity and atherosclerosis, but also in diseases like Alzheimer’s and Parkinson’s disease, many of the diseases of older age people, particularly in the Western world.”
Fasting can help reduce inflammation, but the reason why has not been clear. To help answer this question, a team led by Professor Bryant and colleagues at the University of Cambridge and the National Institute for Health in the USA studied blood samples from a group of 21 volunteers, who ate a 500kcal meal and then fasted for 24 hours before consuming a second 500kcal meal.
The team found that restricting calorie intake increased levels of a lipid known as arachidonic acid. Lipids are molecules that play important roles in our bodies, such as storing energy and transmitting information between cells. As soon as individuals ate a meal again, levels of arachidonic acid dropped.
When the researchers studied arachidonic acid’s effect in immune cells cultured in the lab, they found that it turns down the activity of the NLRP3 inflammasome. This surprised the team as arachidonic acid was previously thought to be linked with increased levels of inflammation, not decreased.
Implications and Future Directions
Professor Bryant, a Fellow of Queens’ College, Cambridge, added: “This provides a potential explanation for how changing our diet – in particular by fasting – protects us from inflammation, especially the damaging form that underpins many diseases related to a Western high-calorie diet.
“It’s too early to say whether fasting protects against diseases like Alzheimer’s and Parkinson’s disease as the effects of arachidonic acid are only short-lived, but our work adds to a growing amount of scientific literature that points to the health benefits of calorie restriction. It suggests that regular fasting over a long period could help reduce the chronic inflammation we associate with these conditions. It’s certainly an attractive idea.”
The findings also hint at one mechanism whereby a high-calorie diet might increase the risk of these diseases. Studies have shown that some patients that have a high-fat diet have increased levels of inflammasome activity.
“There could be a yin and yang effect going on here, whereby too much of the wrong thing is increasing your inflammasome activity and too little is decreasing it,” said Professor Bryant. “Arachidonic acid could be one way in which this is happening.”
The researchers say the discovery may also offer clues to an unexpected way in which so-called non-steroidal anti-inflammatory drugs such as aspirin work. Normally, arachidonic acid is rapidly broken down in the body, but aspirin stops this process, which can lead to an increase in levels of arachidonic acid, which in turn reduces inflammasome activity and hence inflammation.
Professor Bryant said: “It’s important to stress that aspirin should not be taken to reduce the risk of long-term diseases without medical guidance as it can have side-effects such as stomach bleeds if taken over a long period.”
Summary: Researchers uncovered a new mechanism by which fasting reduces inflammation, a key factor in chronic diseases.
Their study reveals that fasting increases blood levels of arachidonic acid, which inhibits the NLRP3 inflammasome, thereby reducing inflammation. This discovery sheds light on the anti-inflammatory effects of fasting and offers insights into the benefits of calorie restriction for conditions like obesity, diabetes, heart disease, and neurodegenerative disorders.
The research also provides clues to how drugs like aspirin might function, further highlighting the intricate relationship between diet, inflammation, and disease prevention.
Key Facts:
Fasting elevates arachidonic acid levels in the blood, leading to reduced activity of the NLRP3 inflammasome and inflammation.
The findings offer a potential explanation for how fasting and calorie restriction can protect against chronic inflammation-related diseases.
This research may also explain the anti-inflammatory effects of non-steroidal anti-inflammatory drugs like aspirin, which increase arachidonic acid levels.
Source: University of Cambridge
Cambridge scientists may have discovered a new way that fasting helps reduce inflammation, a potentially damaging side-effect of the body’s immune system that underlies a number of chronic diseases.
In a paper titled “Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting,” published in Cell Reports, the team describes how fasting raises levels of a chemical in the blood known as arachidonic acid, which inhibits inflammation.
The researchers say it may also help explain some of the beneficial effects of drugs such as aspirin.
Scientists have known for some time that our diet—particularly a high-calorie Western diet—can increase our risk of diseases including obesity, type 2 diabetes and heart disease, which are linked to chronic inflammation in the body.
Studies have shown that some patients who have a high-fat diet have increased levels of inflammasome activity.
Inflammation is our body’s natural response to injury or infection, but this process can be triggered by other mechanisms, including by the so-called “inflammasome,” which acts like an alarm within our body’s cells, triggering inflammation to help protect our body when it senses damage.
But the inflammasome can trigger inflammation in unintentional ways—one of its functions is to destroy unwanted cells, which can result in the release of the cell’s contents into the body, where they trigger inflammation.
Professor Clare Bryant from the Department of Medicine at the University of Cambridge said, “We’re very interested in trying to understand the causes of chronic inflammation in the context of many human diseases, and in particular the role of the inflammasome.
“What’s become apparent over recent years is that one inflammasome in particular—the NLRP3 inflammasome—is very important in a number of major diseases such as obesity and atherosclerosis, but also in diseases like Alzheimer’s and Parkinson’s disease, many of the diseases of older age people, particularly in the Western world.”
Fasting can help reduce inflammation, but the reason why has not been clear. To help answer this question, a team led by Professor Bryant and colleagues at the University of Cambridge and National Institute for Health in the U.S. studied blood samples from a group of 21 volunteers, who ate a 500-kcal meal and then fasted for 24 hours before consuming a second 500-kcal meal.
The team found that restricting calorie intake increased levels of a lipid known as arachidonic acid. Lipids are molecules that play important roles in our bodies, such as storing energy and transmitting information between cells. As soon as individuals ate a meal again, levels of arachidonic acid dropped.
When the researchers studied arachidonic acid’s effect in immune cells cultured in the lab, they found that it turns down the activity of the NLRP3 inflammasome. This surprised the team, as arachidonic acid was previously thought to be linked with increased levels of inflammation, not decreased levels.
Professor Bryant, a Fellow of Queens’ College, Cambridge, added, “This provides a potential explanation for how changing our diet—in particular by fasting—protects us from inflammation, especially the damaging form that underpins many diseases related to a Western high-calorie diet.
“It’s too early to say whether fasting protects against diseases like Alzheimer’s and Parkinson’s disease, as the effects of arachidonic acid are only short-lived, but our work adds to a growing amount of scientific literature that points to the health benefits of calorie restriction. It suggests that regular fasting over a long period could help reduce the chronic inflammation we associate with these conditions. It’s certainly an attractive idea.”
The findings also hint at one mechanism whereby a high-calorie diet might increase the risk of these diseases. Studies have shown that some patients who have a high-fat diet have increased levels of inflammasome activity.
“There could be a yin and yang effect going on here, whereby too much of the wrong thing is increasing your inflammasome activity and too little is decreasing it,” said Professor Bryant. “Arachidonic acid could be one way in which this is happening.”
The researchers say the discovery may also offer clues to an unexpected way in which so-called non-steroidal anti-inflammatory drugs such as aspirin work. Normally, arachidonic acid is rapidly broken down in the body, but aspirin stops this process, which can lead to an increase in levels of arachidonic acid, which in turn reduce inflammasome activity and hence inflammation.
Professor Bryant said, “It’s important to stress that aspirin should not be taken to reduce risk of long terms diseases without medical guidance, as it can have side effects such as stomach bleeds if taken over a long period.”
Abstract
Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting
Highlights
In fasting compared to fed subjects, plasma IL-1β is lower and arachidonic acid (AA) is higher
Exogenous AA impairs NLRP3 inflammasome activity in human and mouse macrophages
AA inhibits phospholipase C and reduces JNK stimulation and hence NLRP3 activity
Summary
Elevated interleukin (IL)-1β levels, NLRP3 inflammasome activity, and systemic inflammation are hallmarks of chronic metabolic inflammatory syndromes, but the mechanistic basis for this is unclear.
Here, we show that levels of plasma IL-1β are lower in fasting compared to fed subjects, while the lipid arachidonic acid (AA) is elevated.
Lipid profiling of NLRP3-stimulated mouse macrophages shows enhanced AA production and an NLRP3-dependent eicosanoid signature.
Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs decreases eicosanoid, but not AA, production. It also reduces both IL-1β and IL-18 production in response to NLRP3 activation.
AA inhibits NLRP3 inflammasome activity in human and mouse macrophages. Mechanistically, AA inhibits phospholipase C activity to reduce JNK1 stimulation and hence NLRP3 activity.
These data show that AA is an important physiological regulator of the NLRP3 inflammasome and explains why fasting reduces systemic inflammation and also suggests a mechanism to explain how nonsteroidal anti-inflammatory drugs work.
Long periods of fasting between meals helped male mice live longer and healthier lives, regardless of the content of their diets.
More studies are needed to confirm these results and understand how different fasting periods may impact health.
Researchers are working to understand how fasting patterns affect health and lifespan.
Studies have suggested potential health benefits from long-term calorie restriction. In long-term calorie restriction, average daily caloric intake is kept below what is typical or habitual, but without malnutrition or deprivation of essential nutrients. Calorie restriction can be achieved through simply eating less overall, or through specific periods of fasting.
One decades-long study in rhesus monkeys found an extension of lifespan with calorie restriction. However, another did not. Differences between those two studies—including the type of food used—made comparisons difficult.
Researchers from NIH’s National Institute on Aging (NIA), led by Dr. Rafael de Cabo, wanted to better understand if the type of food eaten, and when it is eaten, alters how calorie restriction affects the body. They divided almost 300 male mice into two diet groups. One group was given a diet low in sugar and based more on whole foods. The other group’s diet was higher in sugar and more processed.
Within these two groups, the researchers divided the mice into three feeding regimens. One had access to a food dispenser at all hours of the day (ad libitum, AL). A calorie restricted (CR) group received 30% less food than the AL group, placed into their cage once a day at the same time. A meal fed, or MF, group was given the same amount of food as the AL mice on average, but were fed only once a day.
The mice were monitored over the course of their natural lives. Mice that died were examined for evidence of disease, including cancer and liver damage. The results were published on September 6, 2018, in Cell Metabolism.
The researchers had expected that mice eating the whole foods-based diet would have a survival advantage when calorie restricted. But this is not what they observed. Diet composition did not affect health and lifespans. However, the periods of fasting did.
Mice in the MF groups quickly learned that they would not have 24-hour access to food and developed the habit of eating quickly. Mice in the CR groups also finished their smaller meals rapidly. Therefore, the mice in these groups had extended periods of time without food.
Compared with mice in the AL groups, mice in the MF groups lived about 11% longer, even though their total food intake and body weights were similar. Mice in the CR group lived about 28% longer. Mice in the CR and MF groups also developed disease later than mice in the AL groups.
“Increasing daily fasting times, without a reduction of calories and regardless of the type of diet consumed, resulted in overall improvements in health and survival in male mice. Perhaps this extended daily fasting period enables repair and maintenance mechanisms [in the body] that would be absent in a continuous exposure to food,” Cabo says.
Studies in female mice, as well as in other animals, are needed to confirm these findings. More work will also be needed to explore how different lengths of fasting impact health. Finally, the impact of fasting on human health may differ in important ways.
Like all living things, cellular structures break down over time and must be recycled. In cells, this process is called autophagy. Most neurodegenerative diseases are related to the improper accumulation of cellular waste by-products. Now, for the first time, researchers at the Hospital for Sick Children (SickKids) have revealed a way to potentially reduce the amount of toxic cellular waste accumulating in patients with Zellweger Spectrum Disorder (ZSD). The researchers discovered that by genetically and pharmaceutically increasing a cell’s ability to recycle its own components it is possible to clear damaged cellular material, providing a new therapeutic target for treating ZSD. The new findings may also inform research in other neurodegenerative conditions such as Huntington’s disease and Parkinson’s disease.
The findings are published in Nature Communications in an article titled, “Upregulated pexophagy limits the capacity of selective autophagy,” and led by Peter Kim, PhD, a senior scientist in the cell biology program at SickKids, and Robert Bandsma, PhD, a scientist in the translational medicine program.
“Selective autophagy is an essential process to maintain cellular homeostasis through the constant recycling of damaged or superfluous components,” the researchers wrote. “Over a dozen selective autophagy pathways mediate the degradation of diverse cellular substrates, but whether these pathways can influence one another remains unknown. We address this question using pexophagy, the autophagic degradation of peroxisomes, as a model.”
ZSD is a group of rare, neurodegenerative genetic conditions caused by genetic variations that reduce the number of peroxisomes, which are the parts of cells that are responsible for, among other tasks, breaking down fats. ZSD varies in severity and is characterized by progressive neurodegeneration as well as symptoms that range from visual impairments, such as cataracts, to liver and kidney dysfunction.
Previous research from the Kim-Bandsma team found that the most common genetic variation that causes ZSD significantly increases pexophagy, causing healthy peroxisomes to get recycled alongside unhealthy ones. In the new study, Kyla Germain, PhD, a former graduate student in Kim’s and Bandsma’s labs, found that this increase in pexophagy can also prevent cells from degrading other cellular waste.
“Our work demonstrates for the first time that different cellular recycling pathways can influence one another,” Germain explained. “A cell’s recycling system has a maximum load capacity—an autophagic limit. When this limit is exceeded, toxic cellular waste will accumulate.”
After identifying this connection between different recycling pathways, researchers found they could improve the overall recycling process by increasing the autophagic limit. In doing so, they observed improved clearance of cellular waste, which opens new pathways to treat ZSD.
“These results are exciting as they show that through understanding a fundamental process that takes place in all our cells, we can potentially develop new and better treatments for a very serious condition,” said Bandsma, who is also a staff physician in the division of gastroenterology, hepatology, and nutrition at SickKids.
“We identified that protein aggregates involved in Huntington’s disease and Parkinson’s disease can also prevent the turnover of damaged peroxisomes, which means scientists may be able to target these components in patients outside the field of ZSD,” Kim said.
Looking toward the future, the Kim-Bandsma team’s next step is to take this research into a preclinical ZSD model to test various therapeutics that could either increase autophagy or inhibit pexophagy.
People with obesity and type 2 diabetes lost more weight using daily periods of fasting than by trying to restrict calories over a six-month period.
Blood sugar levels lowered in people in both groups, and no serious side effects were observed.
Time-restricted eating, also called intermittent fasting, may be an effective weight loss strategy. Katecat / Adobe Stock
Around 1 in 10 Americans live with type 2 diabetes, a disease in which levels of blood glucose, or blood sugar, are too high. Diabetes can lead to serious health issues such as heart disease, nerve damage, and eye problems.
Excess weight is a major risk factor for the development of type 2 diabetes, and weight loss is often recommended for those with excess weight and type 2 diabetes. Calorie restriction—reducing overall calorie intake—is a mainstay of most weight loss programs. But such regimens are very difficult to stick with over the long term.
Time-restricted eating, also called intermittent fasting, has emerged as an alternative weight loss paradigm. In this approach, the time of day during which food can be eaten is restricted, but the amount or types of food are not. Small studies have suggested that intermittent fasting is safe and promotes weight loss in people with type 2 diabetes. But these studies only tracked participants for a short period of time. They also didn’t compare the approach with traditional calorie restriction.
In a new clinical trial, an NIH-funded research team led by Dr. Krista Varady from the University of Illinois Chicago compared fasting and calorie restriction for weight loss and blood-sugar reduction. They recruited 75 people with obesity and type 2 diabetes. Of these, 70 were either Hispanic or non-Hispanic Black—two groups in the U.S. with an especially high prevalence of diabetes. The participants were randomly assigned to one of three diet groups for six months.
The fasting group could eat anything they wanted, but only between the hours of noon and 8 pm. The second group worked with a dietitian to reduce their calories by 25% of the amount needed to maintain their weight. A control group did not change their diet at all. All groups received education on healthy food choices and monitored their blood glucose closely during the study. The results were published on October 27, 2023, in JAMA Network Open.
After six months, participants in the fasting group lost an average of 3.6% percent of their body weight compared to those in the control group. In comparison, people in the calorie-restriction group did not lose a significant amount of weight compared to the control group.
Both groups had similarly healthy decreases in their average blood glucose levels. Both also had reductions in waist circumference. No serious side effects, including time outside of a safe blood glucose range, were seen in either treatment group. People in the fasting group reported that their diet was easier to adhere to than calorie restriction.
“Our study shows that time-restricted eating might be an effective alternative to traditional dieting for people who can’t do the traditional diet or are burned out on it,” Varady says. “For many people trying to lose weight, counting time is easier than counting calories.”
Some medications used to treat type 2 diabetes need adjustment for time-restricted eating. Therefore, people considering intermittent fasting should speak with a doctor before changing their eating pattern.
Intermittent fasting is a dietary pattern that has seen an increase in popularity in recent years, especially for weight management. But what actually is it, and is it right for you? This article aims to answer your questions, so you can feel ready for a conversation about weight management.
It may often seem like there is always a ‘new kid on the block’ when it comes to weight management methods, and intermittent fasting is one that has been slowly increasing in popularity in recent years, in particular the catchy 5:2 method. For those who have tried and tested several weight management approaches, it may be difficult to navigate the truth, and to try and understand what works best for you. The FAQs below are based on the science (albeit limited science so far!), so you can get a better understanding of the benefits and limitations of intermittent fasting.
It’s important to remember that people living with obesity are more likely to have micronutrient deficiencies, including an iron or vitamin D deficiency. Therefore, please speak to your healthcare provider before you start to restrict your diet, as they can perform the necessary assessments to support your health.
FAQs:
1. What is intermittent fasting, and how do you do it?
Intermittent fasting is a sweeping term that can be used when describing a program to restrict calorie-intake at certain times of the day, or week. This leads to periods of time known as extended fasting, where intake is typically around 25% of your energy needs.
One of the most popular and well known intermittent fasting methods is the 5:2 approach, where the extended fasting occurs on 2 non-consecutive days in the week. Another common approach is to follow ‘time-restricted eating’ where consumption is restricted to an 8-hour period within the day, and therefore the extended fast period is 16 hours daily.
It is important to understand that many people around the world also fast for religious reasons, and this should not be confused with intermittent fasting. For example, during the holy month of Ramadan, many complete a 12 hour fast each day, from sun rise to sunset.
2. How does intermittent fasting compare to popular diets?
It is important to remember that the scientific research for intermittent fasting is still evolving. Most recently, researchers who studied around 600 participants with overweight or obesity, have found that when following an intermittent fasting approach, people lost on average between 4-8% of their body weight over a six-month period. When compared to other diets that require a continuous restriction on energy intake, similar levels of weight loss were achieved.
When comparing weight management approaches, it is important to not just look at how much weight is possible to lose. The popular and well researched Mediterranean diet, where food intake can be characterised by a high level of plant-oriented food, and low levels of processed food, generally sees a similar level of weight loss, but has greater impact on your body’s cardiovascular system. A recent Spanish study found that an energy-unrestricted Mediterranean diet can reduce the risk of a major cardiovascular event by up to 30%. This study focussed specifically on people who lived in Mediterranean countries with an already high cardiovascular risk, so it’s important to understand your own body when comparing weight management approaches. You can find out more about the benefits of weight loss to your cardiovascular system here.
It is important to remember that when it comes to weight loss, changes to your diet are just one part of long-term management. Your healthcare provider will be able to recommend a weight management plan that is best for your lifestyle, as there is no ‘one size fits all’ method when it comes to managing your weight.
3. How does intermittent fasting affect your BMI?
Your Body Mass Index, often referred to as BMI, is a measurement of height compared with weight. It is the most common way to assess for overweight and obesity. For example, a BMI of 25 kg/m2 or ≥ 30 kg/m2, indicates overweight and obesity respectively.
For some people, intermittent fasting can lead to a reduction in BMI, although despite its widespread use in the medical community, BMI alone as an indicator for obesity has limitations that you should be aware of when using the indicator as a measurement of health.
4. Should you restrict your food intake if you are prescribed a weight management medication?
When talking to your healthcare provider about weight, they may prescribe you a weight management medication. There are several types of weight management medication, and they work with the chemistry in your brain that causes weight gain and prevents weight loss. Weight management medications are prescribed by healthcare professionals as a long-term approach to weight loss and can limit weight regain if continuously used.
Medications should always be taken alongside changes in nutrition and physical activity, rather than as an alternative.
As previously mentioned, for some, fasting is a religious practice rather than a tool for weight management. Studies into whether weight management medication is still effective during periods of fasting have so far shown that there is no change in how they work. However, some weight management medications can impact a person’s iron, vitamin D and other nutrient levels, so it is really important to consult your healthcare professional before you embark on periods of fasting when prescribed a weight management medication.
5. Do the outcomes of intermittent fasting differ between males and females?
As a common theme, the research into biological sex differences for intermittent fasting is limited, however there is no significant difference in how women respond to intermittent fasting versus men.
6. Should intermittent fasting be seen as a long-term approach to weight management?
It is important for your doctor to tailor a nutrition plan that meets your personal preferences, and treatment goals. This can take in a variety of factors that ensure safety, nutritionally sufficient, affordable and suitable changes for your lifestyle.For some, intermittent fasting may be appropriate, but there is limited evidence to show it can lead to weight reduction in the long-term.
Continuous calorie restriction may increase the chances of weight gain in the long-run, as this type of restriction can change the way your body signals hunger, satiety and body weight regulation.
In cases where behavioural interventions (diet and exercise) don’t work to manage your weight, psychological therapy, pharmacological therapy, or bariatric surgery can help you lose weight and prevent weight regain. For long-term weight management strategies, it is best to speak to your healthcare provider, who can assess your lifestyle to work out the best approach for you.
This approach can benefit individuals dealing with chronic insomnia and anxiety, too.
Intermittent fasting has become a go-to strategy for health and weight management for more and more people. Recent research suggests that avoiding eating for a minimum of 14 hours each night and restricting eating to a 10-hour window during the day (14:10) can enhance sleep, mood, and energy levels while reducing feelings of hunger.
This approach can benefit individuals dealing with chronic insomnia and anxiety, too. It can also be helpful for those facing issues such as fatigue and increased hunger resulting from dieting for weight loss.
The Different Forms of Fasting
There are various forms of intermittent fasting. In a 24-hour cycle, the most rigorous form is perhaps one-meal-a-day (23:1) fasting, while the more popular ones include 18:6 (essentially two meals a day, or eating only within a six-hour window) and 16:8 fasting. Intermittent fasting can also be structured on a weekly basis, such as the 5:2 (two days of light fasting each week whereby you eat less than 500 calories) and alternate-day fasting, whereby you eat less than 500 calories every other day.
Compared to these other intermittent fasting methods, the 14:10 fasting approach has a shorter fasting period and a longer eating window. It doesn’t significantly disrupt the usual three meals a day, making it relatively more flexible and easier to sustain. For example, if you start eating at 8 a.m., your last meal must be finished before 6 p.m., with no eating afterward.
What the Science Says
A research team from King’s College London conducted a study with 37,545 participants using the Zoe Health app. Results of the study were presented at the European Nutrition Conference on Nov. 14, 2023, in Belgrade, Serbia. In the first week of the study, participants were instructed to maintain their usual dietary habits, followed by two weeks during which they restricted their meals to a 10-hour window each day, referred to as the “eating window.” More than 36,231 participants chose to continue for additional weeks, with 27,371 considered “highly engaged.” Among this highly engaged group, 78 percent were female, with an average age of 60 and a body mass index (BMI) of 25.6 (normal range is between 18.5 and 24.9).
The study found that those who consistently ate within a fixed eating window had greater benefits than those with varying eating windows. Moreover, individuals who had the longest duration between their first and last bite each day before the intervention experienced greater improvements in their overall health.
Sarah Berry, associate professor at King’s College London and chief scientist at Zoe, said in a statement: “What’s really exciting is that the findings show that you don’t have to be very restrictive to see positive results.
“A ten-hour eating window, which was manageable for most people, improved mood, energy levels and hunger.”
However, she also emphasized the importance of consistency.
“We found for the first time that those who practiced time-restricted eating, but were not consistent day to day, did not have the same positive health effects as those who were dedicated every day,” she said.
Kate Bermingham from King’s College London and Zoe said that the study further demonstrates the importance of how we eat.
“The health impact of food is not just what you eat but the time at which you choose to consume your meals,” she said. “Findings show that we don’t need to be eating all the time. Many people will feel satiated and even lose weight if they restrict their food to a ten-hour window.”
A study published in Nature Medicine in April 2023 involving more than 200 participants and spanning 18 months found intermittent fasting more effective in reducing the risk of Type 2 diabetes than a calorie-restricted diet. In this experiment, intermittent fasting involved selecting three nonconsecutive days each week as fasting days, during which participants consumed two meals between 8 a.m. and 12 p.m., totaling only 30 percent of their daily energy requirements.
They refrained from eating anything for the remaining 20 hours and were free to eat ad libitum on the other four days of the week. After six months, participants practicing intermittent fasting showed a significant reduction in postprandial blood sugar, indicating enhanced glucose metabolism. This improvement was more pronounced than that of the group following a calorie-restricted diet.
A small-scale clinical trial published in Cell Metabolism in 2020 focusing on patients with metabolic syndrome found that following a 14:10 intermittent fasting plan for 12 weeks not only aided in weight loss but also resulted in reductions in waist circumference, body fat percentage, visceral fat, and improvements in blood pressure, atherogenic lipids, glycated hemoglobin (a blood sugar indicator), and sleep quality.
Exploring the Health Benefits of Intermittent Fasting
A review study published in The New England Journal of Medicine (NEJM) in 2020 summarized three intermittent fasting methods: alternate-day fasting, 5:2 fasting, and one-meal-a-day fasting, highlighting their numerous health benefits. These include improved glucose regulation, enhanced stress resistance, and suppression of inflammation. Intermittent fasting has demonstrated potent alleviating effects on various chronic diseases in animal models, such as effects on obesity, diabetes, cardiovascular diseases, cancer, and neurodegenerative brain disorders such as Alzheimer’s and Parkinson’s diseases.
Mark Mattson, a Johns Hopkins School of Medicine neuroscientist and one of the authors of the study, said in a statement that after several hours without eating, the body depletes its sugar stores and begins to burn fat. The purpose of intermittent fasting is to prolong the body’s fat-burning period.
The Key to Success in Intermittent Fasting
Regardless of the chosen intermittent fasting method, achieving optimal results relies on long-term consistency, as indicated by multiple studies. The body may take two to four weeks to adapt to intermittent fasting, during which you might experience hunger or irritability. After overcoming this initial phase, sustaining the practice in the long run becomes more manageable.
Therefore, it’s advisable to start intermittent fasting with the easiest method, such as 14:10. After adapting for a certain period, you can then progress to more rigorous fasting methods such as 16:8 or 18:6.
It’s worth noting that regular eating outside the fasting window doesn’t imply unrestrained indulgence, even though intermittent fasting doesn’t impose specific dietary restrictions. A study published in the Journal of the American Heart Association (JAHA) in January 2023 found that over a six-year follow-up period, the time interval between participants’ first and last meal each day wasn’t directly correlated with changes in body weight. Instead, reducing the frequency of large meals could be associated with weight control.
Additionally, longer fasting periods aren’t necessarily better. Extended durations of fasting, such as 24, 36, or 48 hours, pose risks and may not yield additional benefits. This is because prolonged periods without food might prompt your body to store more fat in response to hunger.
Is Intermittent Fasting Safe?
Intermittent fasting may lead to unpleasant side effects, including hunger, fatigue, insomnia, nausea, headaches, and more, but these symptoms usually subside within a month.
Intermittent fasting is generally safe for most people but may not suit everyone. Pregnant or breastfeeding women, children and adolescents under 18 years old, those with Type 1 diabetes taking insulin, and individuals with a history of eating disorders should avoid intermittent fasting. It’s advisable to consult a doctor before attempting an intermittent fasting regimen.
An animal study suggests fasting may negatively affect the immune system. Sergio Delle Vedove/EyeEm/Getty Images
Fasting has been linked to many health benefits, but a new study in mice suggests that there may be a cost in terms of reduced immunity.
The study found that immune cells migrated from the animals’ blood to their bone marrow during fasting and surged back when feeding re-started.
Hunger triggers a hormonal stress response in the brain, which may compel the immune system to conserve resources when food is scarce.
The research hints that regularly skipping breakfast could compromise immune defenses in humans, though this has yet to be established.
Breakfast is popularly known as “the most important meal of the day”, but scientific research into the health effects of skipping breakfast remains inconclusive.
Confusingly, a large number of studies have found that regular daytime fasting — such as limiting meals to a narrow window of time or “time-restricted feeding” — has several health benefits.
For example, studies showTrusted Source that fasting and calorie restriction are linked to reduced risk of age-related illnesses, such as hypertension, atherosclerosis, obesity, and diabetes.
But a new study in mice now suggests that fasting has a potential downside.
The research found that there was a rapid reduction in the number of circulating immune cells in animals that were not allowed to eat in the hours after they awoke.
“There is a growing awareness that fasting is healthy, and there is indeed abundant evidence for the benefits of fasting,” explains lead author Filip Swirski, Ph.D., director of the Cardiovascular Research Institute at the Icahn School of Medicine at Mount Sinai in New York, NY.
“Our study provides a word of caution as it suggests that there may also be a cost to fasting that carries a health risk,” he adds.
Mice are nocturnal, which means they are inactive during the day and forage for food at night.
The researchers compared mice that could eat whenever they wanted with mice that had no access to food in the hours after they became active.
After just four hours, the scientists recorded a 90% decrease in the numbers of monocytesTrusted Source — a type of immune cell — in the bloodstream of the mice that fasted.
Bone marrow generates monocytes, which normally patrol the body in search of pathogens. The cells also play a role in inflammation and tissue repair.
In further experiments, the scientists showed that during periods of fasting, the immune cells returned from the bloodstream to the bone marrow.
However, monocytes poured back into the bloodstream after feeding restarted, which resulted in unusually high concentrations of these immune cells, known as monocytosis.
“The study shows that, on the one hand, fasting reduces the number of circulating monocytes, which one might think is a good thing, as these cells are important components of inflammation,” says Dr. Swirski.
“On the other hand, reintroduction of food creates a surge of monocytes flooding back to the blood, which can be problematic,” he adds.
The scientists also gauged how fasting followed by feeding affects mice’s ability to fight off an infection.
After a 24-hour fast followed by 4 hours of feeding, they infected the mice with a bacterium called Pseudomonas aeruginosa, which is a common cause of pneumonia in hospitals.
Compared with mice that had free access to food throughout, the mice that fasted died sooner and in larger numbers, seemingly as a result of increased inflammation in their lungs.
Dr. Swirski explains that monocytes also play an important role in illnesses such as heart disease and cancer, so it will be important to understand exactly how fasting affects them.
In further experiments, the scientists showed that fasting led to changes in the brains of the mice, which in turn triggered the release of the stress hormone corticosterone.
The immune system responded to this stress signal by recalling the immune cells to the bone marrow. This may help the animals to conserve resources in times of scarcity.
“The study shows that there is a conversation between the nervous and immune systems,” says Dr. Swirski.
“We have plenty of evidence that there is a benefit to fasting,” Dr. Swirski told Medical News Today.
He said the new study demonstrates that there may also be a cost, however.
“It is the combination of cost and benefit that’s at stake here,” he said.
The key to balancing the costs and benefits may be more measured forms of fasting and controlled re-feeding, as opposed to feasting after fasting, he added.
It is too early to say whether studies like this one in mice have implications for people who skip breakfast, or who fast in order to lose weight.
However, Dr. Swirski pointed out that some research has found that fasting also reduces blood monocyte levels in humans.
“The broad implications of these studies to human health remain to be determined but it is worth saying that monocytes are critical cells involved in infections, cancer, cardiovascular disease, etc.,” he added.
In several of the experiments in the new study, mice fasted for 24 hours.
This may not reflect what happens in a human diet plan that involves fasting for much shorter periods, said Satchidananda Panda, Ph.D., who studies circadian rhythms at the Salk Institute for Biological Studies in La Jolla, CA.
A recent study co-authored by Dr. Panda — in which mice fasted for only 12–16 hours — found that the animals’ immunity actually improved.
The authors of the new research acknowledge that it may not apply very well to fasting in humans:
“Our study has limitations for translation into human physiology regarding the length of the fast and the related stress response. A [24-hour] fast in mice is different in humans, which makes our findings potentially more translatable to situations of severe food scarcity or eating disorders.”
“Human metabolism and immunity are not identical to that of mice,” pointed out Dr. Panda, who was not involved in the new study.
He added that research suggests that calorie reduction and fasting can help to control tumor growth in humans. “So, it will be important to test which form of immunity is improved and which ones are compromised in human fasting of various forms,” he told MNT.
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