Tag: intermittent fasting

Categories : Diet and Nutrition Obstetrics & GynaecologyTags :

Study: Intermittent Fasting Positively Affects Female Hormones in PCOS 

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Polycystic ovary syndrome, or PCOS, affects as many as 18% of all childbearing-age women. The condition occurs when a woman’s body produces too androgens, chiefly testosterone. Menstrual irregularity, obesity and even infertility can result.

The first line of treatment is typically hormonal birth control, said UIC professor of nutrition Krista Varady. But there can be negative side effects to mood, libido and metabolism, plus an increased stroke risk in some people, Varady said.

“We’re looking for other ways of lowering testosterone levels in these women,” she said. “One way is through weight loss. If someone loses around 5% of their body weight, they can actually help lower testosterone levels and sidestep any kind of drug intervention.”

A new study led by Varady tested how one weight-loss method — intermittent fasting — affects hormones and symptoms in patients with PCOS. Published in Nature Medicine, the research shows that restricting eating to a six-hour daily window decreased testosterone without negatively affecting female hormones. The study also showed that weight loss through calorie counting decreased testosterone. 

However, some critics of intermittent fasting have posited that the diet disrupts female hormones, Varady said.

“There’s a particular sentiment that intermittent fasting is really bad for women.” This is untrue, she said. “This study and several other studies published by our lab and others show that intermittent fasting can actually improve female hormone levels, particularly in women with PCOS.” 

Varady and her colleagues studied a type of intermittent fasting called time-restricted eating. In this method, you eat only during a set six- or eight-hour period each day. During the remaining 18 or 16 hours, you fast with calorie-free beverages and water until the next day. 

Simply put, the strategy helps people eat less, Varady said. So does counting calories, a method Varady and her colleagues tested alongside intermittent fasting in the study. But intermittent fasting had some additional benefits.

“It’s a way of reducing energy intake without having to do really complicated calorie counting,” she said about intermittent fasting. Varady and others have shown in previous work that eating only during an eight-hour window can cut around 300 to 500 calories a day.

In addition to obesity and insulin resistance, which raise risks of diabetes and heart disease, PCOS can cause ovarian cysts, acne and facial hair growth.

In a group of 76 pre-menopausal women with PCOS, the researchers tested how outcomes differed after six months between time-restricted eating between 1 and 7 p.m. daily and calorie counting. Both diet schemes ended up cutting participants’ intake by about 200 calories per day, the team found, leading to average weight loss of about 10 pounds over the six months.

Both groups also experienced a decrease in testosterone concentrations. But only time-restricted eating reduced free androgen index, the ratio between testosterone and the protein that transports it through the blood, which is a marker of how much active testosterone is reaching a body’s tissues. It also improved A1C levels, a risk marker for diabetes, Varady said.

Though intermittent fasting did not lessen other PCOS symptoms, like menstrual period irregularity, Varady suggested those symptoms might improve with longer time on the diet and greater weight loss.

About 80% of the participants in the time-restricted eating group said they were going to continue the diet, Varady said.

Story by Tess Joosse

Source: EurekAlert!

Categories : Diet and NutritionTags :

Evidence Behind Intermittent Fasting for Weight Loss Fails to Match Hype

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Intermittent fasting is unlikely to lead to greater weight loss in overweight or obese adults than traditional dietary advice or doing nothing, a new Cochrane review finds. 

Obesity is a significant public health problem that has become a leading cause of death in high-income countries. Worldwide adult obesity has more than tripled since 1975, according to the WHO. In 2022, 2.5 billion adults were overweight. Of these, 890 million were living with obesity.

Intermittent fasting has surged in popularity in recent years, fuelled by social media, lifestyle influencers, and claims of rapid weight loss and metabolic benefits.

No meaningful difference in weight loss

Researchers analysed evidence from 22 randomised clinical trials involving 1995 adults across North America, Europe, China, Australia, and South America. Trials examined multiple forms of intermittent fasting, including alternate-day fasting, periodic fasting, and time-restricted feeding. Most studies followed participants for up to 12 months.

The review compared intermittent fasting with traditional dietary advice and with no intervention. Intermittent fasting did not appear to have a clinically meaningful effect on weight loss compared to standard dietary advice or doing nothing. 

Reporting of side effects was inconsistent across trials, making it difficult to draw firm conclusions. The evidence base remains limited, with only 22 trials, many with small sample sizes and inconsistent reporting. 

Hype outpaces the evidence

First author Luis Garegnani also cautioned against the hype surrounding fasting online. 

Intermittent fasting just doesn’t seem to work for overweight or obese adults trying to lose weight. It may be a reasonable option for some people, but the current evidence doesn’t justify the enthusiasm we see on social media.

— Luis Garegnani, Universidad Hospital Italiano de Buenos Aires Cochrane Associate Centre. 


Few trials have looked at the long-term results of intermittent fasting. The authors stressed that obesity is a chronic condition, and short-term trials make it difficult to guide long-term decision-making for patients and clinicians. 
 
The majority of the included studies enrolled predominantly white populations in high-income countries. As obesity is a rapidly growing crisis in low- and middle-income countries, further research is needed in these populations.

The authors therefore warn that these results may provide clues, but cannot be extrapolated to the entire population, as they may vary depending on sex, age, ethnic origin, disease status, or underlying eating disorders or behaviours.
 

With the current evidence available, it’s hard to make a general recommendation. Doctors will need to take a case-by-case approach when advising an overweight adult on losing weight.

— Eva Madrid, Cochrane Evidence Synthesis Unit Iberoamerica. 

By Mia Parkinson

Source: Cochrane Review

Categories : Diet and NutritionTags :

Two Hours’ Longer Fast Before Bed Improves Cardiometabolic Health

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Participants stopped meals three hours before bed, dimmed the lights and extended their overnight fast by two hours

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A new Northwestern Medicine study has personalised overnight fasting by aligning it with individuals’ circadian sleep-wake rhythm, an important regulator of cardiovascular and metabolic function, all without changing their caloric intake. 

The study found that among middle-age and older adults who are at higher risk for cardiometabolic disease, extending the participants’ overnight fast by about two hours, dimming the lights and not eating for three hours prior to bedtime improved measures of cardiovascular and metabolic health during sleep, as well as during the daytime. Nighttime blood pressure fell by 3.5mmHg while heart rate dipped by 5% compared to controls. while adherence was good – nearly 90%.

“Timing our fasting window to work with the body’s natural wake-sleep rhythms can improve the coordination between the heart, metabolism and sleep, all of which work together to protect cardiovascular health,” said first author Dr. Daniela Grimaldi, research associate professor of neurology in the division of sleep medicine at Northwestern University Feinberg School of Medicine.

The study was published Feb. 12 in the journal Arteriosclerosis, Thrombosis, and Vascular Biology, part of the American Heart Association.

“It’s not only how much and what you eat, but also when you eat relative to sleep that is important for the physiological benefits of time-restricted eating,” said corresponding author Dr Phyllis Zee, director of the Center for Circadian and Sleep Medicine and the chief of sleep medicine in the department of neurology at Feinberg.

Previous research has found only 6.8% of US adults had optimal cardiometabolic health in 2017 to 2018. Poor cardiometabolic health can lead to chronic illness, including type 2 diabetes, non-alcoholic fatty liver disease and cardiovascular diseases.

Time-restricted eating has continued to surge in popularity because research has shown it can improve cardiometabolic health and rival traditional calorie‑restricted diets, but most studies have focused on how long people fast, not how their fast lines up with their sleep schedule – a key factor in metabolic regulation.

Given the nearly 90% adherence rate in the study, the study’s novel approach of leveraging the sleep period as an anchor for the timing of time-restricted eating may be a more accessible non-pharmacological strategy for improving cardiometabolic health, particularly in middle-aged and older adults who are at higher risk for cardiometabolic disease, the study authors said.

The study authors said they plan refine the protocol from this study and take it to larger multi-centre trials. 

Improved blood pressure, heart rate, blood-sugar control

In the 7.5‑week study, people who finished eating at least three hours before going to bed saw meaningful improvements compared with those who kept their usual eating routines. They experienced:

  • Improved nighttime patterns in blood pressure (dipping by 3.5%) and heart rate (dipping by 5%): Their bodies showed a more natural drop in both measures during sleep, which is an important sign of cardiovascular health. Notably, their hearts beat faster during the day when they were active and slowed at night when they were resting. A stronger day-night pattern is linked to better cardiovascular health.
  • Better daytime blood‑sugar control: Their pancreas responded more efficiently when challenged with glucose, suggesting it could release insulin more effectively and keep blood sugar steadier.

In the study, 39 overweight/obese participants (36 to 75 years old) completed either an extended overnight fasting intervention (13 to 16 hours of fasting) or a control condition (habitual fast of 11 to 13 hours). Both groups dimmed the lights three hours before bedtime. The intervention group consisted of 80% women.

Source: Northwestern University

Categories : Diet and Nutrition Metabolic DisordersTags :

Intermittent Energy Restriction May Improve Outcomes in People with Obesity and Type 2 Diabetes

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Intermittent energy restriction, time-restricted eating and continuous energy restriction can all improve blood sugar levels and body weight in people with obesity and type 2 diabetes, according to a study being presented Sunday at ENDO 2025, the Endocrine Society’s annual meeting in San Francisco, Calif.

“This study is the first to compare the effects of three different dietary interventions intermittent energy restriction (IER), time-restricted eating (TRE) and continuous energy restriction (CER) in managing type 2 diabetes with obesity,” said Haohao Zhang, PhD, chief physician at The First Affiliated Hospital of Zhengzhou University in Zhengzhou, China.

Although researchers identified improved HbA1c levels, and adverse events were similar across the three groups, the IER group showed greater advantages in reducing fasting blood glucose, improving insulin sensitivity, lowering triglycerides, and strengthening adherence to the dietary interventions.

“The research fills a gap in directly comparing 5:2 intermittent energy restriction with a 10-hour time-restricted eating in patients with obesity and type 2 diabetes. The findings provide scientific evidence for clinicians to choose appropriate dietary strategies when treating such patients,” Zhang says.

Zhang and colleagues performed a single-centre, randomised, parallel-controlled trial at the First Affiliated Hospital of Zhengzhou University from November 19, 2021 to November 7, 2024.

Ninety patients were randomly assigned in a 1:1:1 ratio to the IER, TRE or CER group, with consistent weekly caloric intake across all groups. A team of nutritionists supervised the 16-week intervention.

Of those enrolled, 63 completed the study. There were 18 females and 45 males, with an average age of 36.8 years, a mean diabetes duration of 1.5 years, a baseline BMI of 31.7kg/m², and an HbA1c of 7.42%.

At the end of the study, there were no significant differences in HbA1c reduction and weight loss between the IER, TRE and CER groups. However, the absolute decrease in HbA1c and body weight was greatest in the IER group.

Compared to TRE and CER, IER significantly reduced fasting blood glucose and triglycerides and increased the Matsuda index, a measure of whole-body insulin sensitivity. Uric acid and liver enzyme levels exhibited no statistically significant changes from baseline in any study group.

Two patients in the IER group and the TRE group, and three patients in the CER group, experienced mild hypoglycemia.

The IER group had the highest adherence rate (85%), followed by the CER group at 84% and the TRE group at 78%. Both the IER and CER groups showed statistically significant differences compared with the TRE group.

Zhang said these findings highlight the feasibility and effectiveness of dietary interventions for people who have obesity and type 2 diabetes.

Source: The Endocrine Society

Categories : Diet and NutritionTags :

4:3 Intermittent Fasting Outperforms Daily Calorie Restriction in Weight-Loss Study

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The finding bucks a research trend that has shown little difference in weight lost between the two diet strategies

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Comparing intermittent fasting with traditional daily calorie restriction, researchers at the University of Colorado Anschutz Medical Campus found greater weight loss among the intermittent fasting group, a significant finding given that most previous studies reported no notable difference between the two diet strategies.

Singling out the 4:3 plan of the popular intermittent fasting (IMF) model – where dieters eat freely four days a week with three days a week of intense calorie restriction – the researchers found an average body weight loss of 7.6% among IMF participants at the one-year mark compared with 5% in the daily caloric restriction (DCR) group.

The study was published in the Annals of Internal Medicine and funded by the National Institutes of Health.

“It was surprising and exciting to me that it was better,” said Victoria Catenacci, MD, co-lead author and associate professor of endocrinology at the CU School of Medicine.

“The more important message to me is that this is a dietary strategy that is an evidence-based alternative, especially for people who have tried DCR and found it difficult,” Catenacci said, noting the weight-loss difference was modest.

An endocrinologist who specializes in obesity medicine, Catenacci’s work targets a decades-long health crisis in this country, with 40% of Americans 20 and older meeting the medical criteria for obesity. She works at the CU Anschutz Health and Wellness Center (AHWC), the study’s primary site.

She and co-lead author Danielle Ostendorf, PhD, who worked on the study as a post-doctoral fellow with Catenacci in 2018 and has since moved to the University of Tennessee Knoxville, share more about the research in the Q&A below.

Source: University of Colorado Anschutz Campus

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Intermittent Fasting: Is it the Calories or Carbs that Count?

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Adam Collins, University of Surrey

Intermittent fasting is not only a useful tool for weight loss, it’s also shown to have many benefits for metabolic health – independent of weight loss. Yet many people may find intermittent fasting to be a challenge, especially if following the 5:2 version of the diet where calories are severely restricted two days a week.

But my latest study shows that you don’t need to severely restrict your calories to get the metabolic benefits of intermittent fasting. Even just restricting the number of carbs you eat twice a week may be enough to improve your metabolic health.

Intermittent fasting appears to be so beneficial for health because of the way it alters our metabolism.

After a meal, our body enters the postprandial state. While in this state, our metabolism pushes our cells to use carbohydrates for immediate energy, while storing some of these carbs as well as fat for later use. But after several hours without food, in the postabsorptive “fasted” state, our metabolism switches to using some of our fat stores for energy.

In this regard, intermittent fasting ensures a better balance between the sources it uses for energy. This leads to improved metabolic flexibility, which is linked with better cardiometabolic health. In other words, this means lower risk of cardiovascular disease, insulin resistance and type 2 diabetes.

My colleagues and I previously ran a study to demonstrate the effects of a fast on the body. We observed that following a day of both total fasting or severe calorie restriction (eating around only 25% of each person’s daily calorie requirements), the body was better at clearing and burning the fat of a full English breakfast the next day. Fasting shifted the body from using carbs to using fat. This effect carried on both during the fast and the next day.

Our research has also compared the effects of intermittent fasting to a calorie-matched or calorie-restricted diet. Both groups followed the diet until they lost 5% of their body weight.

Despite both groups losing the same 5% of body weight, and at the same rate, the intermittent fasting group had greater improvements in their metabolic handling, similar to what we saw in the previous trial.

Other researchers who have compared the effects of the 5:2 variant of the intermittent fasting diet to a calorie-matched, calorie-restricted diet have also found fasting is beneficial for metabolic health.

Metabolic health benefits

But why exactly is intermittent fasting so beneficial for metabolic health? This is a question I sought to answer in my latest study.

For people who follow the 5:2 intermittent fasting diet, typical fasting days are, by their nature, very low in calories – equating to only a few hundred calories per day. Because people are consuming so few calories on fasting days, it also means they’re consuming very few carbohydrates. Given the postprandial state is governed by carbohydrate availability, this begged the question as to whether it’s the calorie restriction or the carbohydrate restriction that’s creating the metabolic effect when intermittent fasting.

We recruited 12 overweight and obese participants. Participants were first given a very low-carb diet one day. Another day, they were given a severely calorie-restricted diet (around 75% fewer calories than they’d normally eat). After each fasting day, we gave them a high-fat, high-sugar meal (similar to an English breakfast) to see how easily their bodies burned fat.

What we found was that the shift to fat burning and improved fat handling of the high-calorie meal were near identical following both the traditional calorie-restricted “fast” day and the low-carb day. In other words, restricting carbs can elicit the same favourable metabolic effects as fasting.

It will be important now for more studies to be conducted using a larger cohort of participants to confirm these findings.

Such findings may help us address some of the practical problems we face with intermittent fasting and traditional low-carb diets.

For intermittent fasting diets, severe calorie restriction on fasting days can increase the risk of nutritional deficiencies if not careful. It can similarly be a trigger for disordered eating.

Strict carb restriction can also be challenging to adhere to long-term, and may lead to an unhealthy fear of carbs.

The other limitation of both intermittent fasting and continuous carb restriction is that weight loss is a likely outcome. Hence these approaches are not universally beneficial for those who need to improve their health without losing weight or those looking to maintain their weight.

We are now testing the feasibility of an intermittent carb restriction diet, or a low-carb 5:2. So instead of restricting calories two days a week, you would restrict the number of carbs you consume twice a week. If this is proven to be beneficial, it would offer the benefits of fasting without restricting calories on “fast” days.

Adam Collins, Associate Professor of Nutrition, University of Surrey

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Intermittent Fasting could be Unsafe for Teenagers

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A recent study reveals that age plays a significant role in the outcomes of intermittent fasting. Researchers from Technical University of Munich (TUM), LMU Hospital Munich, and Helmholtz Munich discovered that chronic intermittent fasting disrupted the development of insulin-producing beta cells in young mice. The findings, published in Cell Reports, raise concerns about potential risks for humans, especially teenagers.

“Intermittent fasting is known to have benefits, including boosting metabolism and helping with weight loss and heart disease. But until now, its potential side effects weren’t well understood,” says Alexander Bartelt, the Else Kröner Fresenius Professor and Chair of Translational Nutritional Medicine at TUM. In a recently published study, the team shows that intermittent fasting during adolescence could have long-term negative effects on metabolism.

Fasting improves metabolism in older mice, but not in the young

The researchers studied three groups of mice: adolescent, adult, and older animals. The mice remained without food for one day and were fed normally on two days. After ten weeks, insulin sensitivity improved in both the adult and older mice, meaning that their metabolism responded better to insulin produced by the pancreas. This is key to regulating blood sugar levels and preventing conditions like type 2 diabetes.

However, the adolescent mice showed a troubling decline in their beta cell function, the insulin-producing cells of the pancreas. Insufficient insulin production is linked to diabetes and disrupted metabolism. “Intermittent fasting is usually thought to benefit beta cells, so we were surprised to find that young mice produced less insulin after the extended fasting,” explains Leonardo Matta from Helmholtz Munich, one of the study’s lead authors.

Defective beta cells resemble those of type 1 diabetes patients

The researchers used the latest single-cell sequencing to uncover the cause of the beta cell impairment. By examining the blueprint of the pancreas, the team found that the beta cells in the younger mice failed to mature properly. “At some point, the cells in the adolescent mice stopped developing and produced less insulin,” says Peter Weber from Helmholtz Munich, also a lead author. Older mice, whose beta cells were already mature before the fasting began, remained unaffected.

This shows an accumulation of beta cells from the pancreas of an older mouse.
Beta cells from an older mouse.

The team compared their mouse findings to data from human tissues. They found that patients with type 1 diabetes, where beta cells are destroyed by an autoimmune response, showed similar signs of impaired cell maturation. This suggests that the findings from the mouse study could also be relevant to humans.

“Our study confirms that intermittent fasting is beneficial for adults, but it might come with risks for children and teenagers,” says Stephan Herzig, a professor at TUM and director of the Institute for Diabetes and Cancer at Helmholtz Munich. “The next step is digging deeper into the molecular mechanisms underlying these observations. If we better understand how to promote healthy beta cell development, it will open new avenues for treating diabetes by restoring insulin production.”

Source: Technical University of Munich (TUM)

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Time to Debunk Four Persistent Myths about Intermittent Fasting

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In a new article published in Nature Reviews Endocrinology, researchers at the University of Illinois Chicago debunk four common myths about the safety of intermittent fasting. 

Intermittent fasting as a weight loss method has grown increasingly popular, with a large body of research demonstrating its safety. Despite this, several myths about fasting have spread among clinicians, journalists and the general public: that fasting can lead to a poor diet or loss of lean muscle mass, cause eating disorders, or decrease sex hormones. 

In a new commentary, UIC researchers debunk each of these. They base their conclusions on clinical studies, some of which they conducted and some done by others. 

“I’ve been studying intermittent fasting for 20 years, and I’m constantly asked if the diets are safe,” said lead author Krista Varady, professor of kinesiology and nutrition at UIC. “There is a lot of misinformation out there. However, those ideas are not based on science; they’re just based on personal opinion.”  

There are two main types of intermittent fasting. With alternate-day eating, people alternate between days of eating a very small number of calories and days of eating what they want. With time-restricted eating, people eat what they want during a four- to 10-hour window each day, then don’t eat during the rest of the day. The researchers conclude both types are safe despite the popular myths.

Their conclusions: 

Intermittent fasting does not lead to a poor diet: The researchers point to studies showing the intake of sugar, saturated fat, cholesterol, fibre, sodium and caffeine do not change during fasting compared with before a fast. And the percentage of energy consumed in carbohydrates, protein and fat doesn’t change, either.  

Intermittent fasting does not cause eating disorders: None of the studies show that fasting caused participants to develop an eating disorder. However, all the studies screened out participants who had a history of eating disorders, and the researchers say that those with a history of eating disorders should not try intermittent fasting. They also urge paediatricians to be cautious when monitoring obese adolescents if they start fasting, because this group has a high risk of developing eating disorders. 

Intermittent fasting does not cause excessive loss of lean muscle mass: The studies show that people lose the same amount of lean muscle mass whether they’re losing weight by fasting or with a different diet. In both cases, resistance training and increased protein intake can counteract the loss of lean muscle. 

Intermittent fasting does not affect sex hormones: Despite concerns about fertility and libido, neither oestrogen, testosterone nor other related hormones are affected by fasting, the researchers said. 

Source: University of Illinois Chicago

Categories : Cancer GastrointestinalTags :

Intermittent Fasting Protects against Liver Inflammation and Liver Cancer

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Fatty liver disease often leads to chronic liver inflammation and can even result in liver cancer. Scientists from the German Cancer Research Center (DKFZ) and the University of Tübingen have now shown in mice* that intermittent fasting on a five days on, two days off schedule can halt this development.

In mice with pre-existing liver inflammation, this fasting regime reduces the development of liver cancer . The researchers also identified two proteins in liver cells that are jointly responsible for the protective effect of fasting. An existing drug can partially mimic this effect.

The most common chronic liver condition is non-alcoholic fatty liver disease. If left untreated, it can lead to liver inflammation (metabolic dysfunction-associated steatohepatitis, MASH), liver cirrhosis and even liver cancer. Fatty liver disease is largely considered to be a direct consequence of obesity.

“The vicious circle of an unhealthy diet, obesity, liver inflammation and liver cancer is associated with major restrictions and suffering for those affected and also represents a considerable burden on healthcare systems,” says Mathias Heikenwälder, DKFZ and University of Tübingen. “We have therefore investigated whether simple dietary changes can specifically interrupt this fatal process.”

Intermittent fasting has already been shown in several studies to be an effective means of reducing weight and alleviating certain metabolic disorders. Heikenwälder’s team has now tested in mice whether this approach can also protect the liver from fatty degeneration and chronic inflammation. Their results are published in Cell Metabolism.

Resistance to liver inflammation is independent of calorie intake

The animals were fed with a high-sugar and high-fat diet corresponding to the typical Western diet. One group of mice had constant access to the food. As expected, these animals gained weight and body fat and developed chronic liver inflammation.

The mice in the other group were given nothing to eat on two days a week (5:2 intermittent fasting, or 5:2 IF for short), but were allowed to eat as much as they wished on the other days. Despite the high-calorie diet, these animals did not put on weight, showed fewer signs of liver disease and had lower levels of biomarkers that indicate liver damage. In short, they were resistant to the development of MASH.

Interestingly, resistance to the development of a fatty liver was independent of the total calorie intake, as the animals immediately made up for the lost rations after the end of the fasting periods.

When experimenting with different variants of intermittent fasting, it was found that several parameters determine protection against liver inflammation: The number and duration of fasting cycles play a role, as does the start of the fasting phase. A 5:2 dietary pattern works better than 6:1; 24-hour fasting phases better than 12-hour ones. A particularly unhealthy diet requires more frequent dieting cycles.

Heikenwälder’s team now wanted to find out the molecular background of the response to fasting. To this end, the researchers compared protein composition, metabolic pathways and gene activity in the liver of fasting and non-fasting mice. Two main players responsible for the protective fasting response emerged: the transcription factor PPARα and the enzyme PCK1. The two molecular players work together to increase the breakdown of fatty acids and gluconeogenesis and inhibit the build-up of fats.

“The fasting cycles lead to profound metabolic changes, which together act as beneficial detoxification mechanisms and help to combat MASH,” says Heikenwälder, summarizing the molecular details.

The fact that these correlations are not just a mouse phenomenon was shown when tissue samples from MASH patients were examined: Here, too, the researchers found the same molecular pattern with reduced PPAR α and PCK1. Are PPAR α and PCK1 actually responsible for the beneficial effects of fasting? When both proteins were genetically switched off simultaneously in the liver cells of the mice, intermittent fasting was unable to prevent either chronic inflammation or fibrosis.

The drug pemafibrate mimics the effects of PPARα in the cell. Can the substance also mimic the protective effect of fasting? The researchers investigated this question in mice. Pemafibrate induced some of the favourable metabolic changes that were observed with 5:2 fasting. However, it was only able to partially mimic the protective effects of fasting. “This is hardly surprising, as we can only influence one of the two key players with pemafibrate. Unfortunately, a drug that mimics the effects of PCK1 is not yet available,” explains Mathias Heikenwälder.

Intermittent fasting as liver therapy

While Heikenwälder and his team initially focused on the effects of intermittent fasting on MASH prevention, then investigated whether the 5:2 diet could also alleviate existing chronic liver inflammation.

To this end, the team examined mice that had developed MASH after months of being fed a high-sugar, high-fat diet. After a further four months of 5:2 intermittent fasting (on the same diet), these animals were compared with the non-fasting control group. The fasting mice had better blood values, less fatty liver and liver inflammation and above all: they developed less liver cancer and had fewer cancer foci in the liver.

“This shows us that 5:2 intermittent fasting has great potential – both in the prevention of MASH and liver cancer, as well as in the treatment of established chronic liver inflammation,” summarises principal investigator Heikenwälder. “The promising results justify studies in patients to find out whether intermittent fasting protects against chronic liver inflammation as well as in the mouse model.”

The 5:2 fasting regimen is popular. It is considered comparatively easy to integrate into everyday life, as the fasting days can be tailored to personal needs and no specific foods are prohibited. “Nevertheless, there will always be people who can’t stick to a strict diet in the long term,” says Heikenwälder. “That’s why we want to continue to investigate which combinations of drugs we can use to fully mimic the protective effects of fasting.”

Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

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Time-restricted Eating and High-intensity Exercise Might Work Together to Improve Health

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Combining time-restricted eating with high-intensity functional training may improve body composition and cardiometabolic parameters more than either alone, according to a study published May 1, 2024 in the open-access journal PLOS ONE by Ranya Ameur and Rami Maaloul from the University of Sfax, Tunisia, and colleagues.

Changes in diet and exercise are well-known ways to lose weight and improve cardiometabolic health. However, finding the right combination of lifestyle changes to produce sustainable results can be challenging. Prior studies indicate that time-restricted eating (which limits when, but not what, individuals eat) and high-intensity functional training (which combines intense aerobic and resistance exercise) may be beneficial and easier for individuals to commit to long term.

In a new study, researchers investigated the impact of time-restricted eating and high-intensity functional training on body composition and markers of cardiometabolic health such as cholesterol, blood glucose, and lipid levels. 64 women with obesity were assigned to one of three groups: time-restricted eating (diet only), high-intensity functional training (exercise only), or time-restricted eating plus high-intensity functional training (diet + exercise). Participants following the time-restricted eating regimen ate only between 8:00 am and 4:00 pm. Those in the functional training groups worked out three days per week with an instructor.

After 12 weeks, all three groups had significant weight loss and decreases in waist and hip circumference. Likewise, all groups showed favorable changes in lipid and glucose levels.

Some differences were seen between groups. For example, fat-free mass (a combination of lean mass and skeletal muscle mass) and blood pressure improved in the diet + exercise and exercise groups but did not change in the diet-only group.

Participants in the diet + exercise group generally experienced more profound changes in body composition and cardiometabolic parameters than either diet or exercise alone.

The researchers noted that this is a relatively small study, and it is difficult to tease out the contributions of specific exercise routines or of time-restricted eating and calorie reduction since both groups reduced their calorie intake. However, they note that combining time-restricted eating with high-intensity functional training might show promise in improving body composition and cardiometabolic health.

The authors add: “Combining time-restricted eating with High Intensity Functional Training is a promising strategy to improve body composition and cardiometabolic health.”

Provided by PLOS