How intermittent fasting changes liver enzymes and helps prevent disease
Research on mice reveals surprising impact on fat metabolism
March 10, 2020
Science Daily/University of Sydney
Researchers in Australia have used state-of-the-art analytical tools to understand how intermittent fasting works on the liver to help prevent disease. The findings will help medical scientists working in cancer, cardiovascular and diabetes research develop new interventions to lower disease risk and discover the optimum intervals for fasting.
In experiments with mice, researchers led by Dr Mark Larance at the University of Sydney identified how every-other-day fasting affected proteins in the liver, showing unexpected impact on fatty acid metabolism and the surprising role played by a master regulator protein that controls many biological pathways in the liver and other organs.
"We know that fasting can be an effective intervention to treat disease and improve liver health. But we haven't known how fasting reprograms liver proteins, which perform a diverse array of essential metabolic functions," said Dr Larance, a Cancer Institute of NSW Future Research Fellow in the Charles Perkins Centre and School of Life and Environmental Sciences at the University of Sydney.
"By studying the impact on proteins in the livers of mice, which are suitable human biological models, we now have a much better understanding of how this happens."
In particular, the researchers found that the HNF4-(alpha) protein, which regulates a large number of liver genes, plays a previously unknown role during intermittent fasting.
"For the first time we showed that HNF4-(alpha) is inhibited during intermittent fasting. This has downstream consequences, such as lowering the abundance of blood proteins in inflammation or affecting bile synthesis. This helps explain some of the previously known facts about intermittent fasting," Dr Larance said.
The researchers also found that every-other-day-fasting -- where no food was consumed on alternate days -- changed the metabolism of fatty acids in the liver, knowledge that could be applied to improvements in glucose tolerance and the regulation of diabetes.
"What's really exciting is that this new knowledge about the role of HNF4-(alpha) means it could be possible to mimic some of the effects of intermittent fasting through the development of liver-specific HNF4-(alpha) regulators," Dr Larance said.
The research, published today in Cell Reports, was done in collaboration with the Heart Research Institute and Dr John O'Sullivan at Royal Prince Alfred Hospital. Dr O'Sullivan is an Adjunct Professor in the Faculty of Medicine & Health and a Senior Lecturer at the Sydney Medical School.
A technique known as multi-Omics, which considers multiple data sets such as the total collection of proteins and genes, was used in the study, allowing for the integration of large amounts of information to discover new associations within biological systems.
Dr O'Sullivan said: "These multi-Omics approaches give us unprecedented insight into biological systems. We are able to build very sophisticated models by bringing together all the moving parts."
The multi-Omics data was obtained at Sydney Mass Spectrometry, part of the University of Sydney's Core Research Facilities.
Dr Larance said that the information can now be used in future studies to determine optimum fasting periods to regulate protein response in the liver.
"Last year we published research into the impact of every-other-day-fasting on humans. Using these mouse data, we can now build up improved models of fasting for better human health."
https://www.sciencedaily.com/releases/2020/03/200310164737.htm
Weight loss and health improvements with Mediterranean, fasting & Paleo diets
January 23, 2020
Science Daily/University of Otago
There were some weight loss and health benefits for overweight adults who followed the Mediterranean, Intermittent Fasting and Paleo diets, though adherence to the diets dropped off considerably during the one-year study, new University of Otago research shows.
Intermittent fasting -- whereby participants limit their energy intake to about 25 per cent of their usual diet (500kcal for women and 600kcal for men) on two self-selected days per week, led to slightly more weight loss than the other diets. The Mediterranean diet also improved blood sugar levels.
Co-lead author Dr Melyssa Roy, a Research Fellow in the Department of Medicine, says the amount of weight loss was modest -- on average two to four kilograms for the 250 participants, but for those choosing the fasting or Mediterranean diets, clinically significant improvements in blood pressure were also seen.
The aim of the research was to examine how effective all three diets were in a "real world" setting, where participants self-selected which diet they wished to follow, without any ongoing support from a dietitian.
Dr Roy says the evidence shows that for some people the Mediterranean, fasting or paleo (Paleolithic) diets can be "healthful, beneficial ways to eat."
"This work supports the idea that there isn't a single 'right' diet -- there are a range of options that may suit different people and be effective. In this study, people were given dietary guidelines at the start and then continued with their diets in the real world while living normally. About half of the participants were still following their diets after a year and had experienced improvements in markers of health.
"Like the Mediterranean diet, intermittent fasting and paleo diets can also be valid healthy eating approaches -- the best diet is the one that includes healthy foods and suits the individual."
The Mediterranean diet encouraged consumption of fruit, vegetables, whole-grain breads and cereals, legumes, nuts, seeds and olive oil with moderate amounts of fish, chicken, eggs and diary and red meat once a week or less.
The paleo diet consists of mostly less-processed foods with an emphasis on eating fruit and vegetables, animal proteins, nuts, coconut products and extra-virgin olive oil. While "original" Paleo diets strictly exclude all legumes, dairy and grains, this study used a modified version including some dairy as well as up to one serving daily of legumes and grain-based food.
Co-lead author Dr Michelle Jospe, a Postdoctoral Fellow in the Department of Medicine, says the results showed people found the Mediterranean diet to be the easiest to adhere to.
"Our participants could follow the diet's guidelines more closely than the fasting and paleo diets and were more likely to stay with it after the year, as our retention rates showed."
Most of the 250 participants (54 per cent) chose the fasting diet, while 27 per cent chose the Mediterranean and 18 per cent the paleo. After 12 months, the Mediterranean diet had the best retention rate with 57 per cent of participants continuing, with 54 per cent still fasting and 35 per cent still on the paleo diet.
After 12 months, the average weight loss was 4.0kg for those choosing the fasting diet, 2.8kg on the Mediterranean diet and 1.8kg on the paleo diet.
Reduced systolic blood pressure was observed among those participating in the fasting and Mediterranean diets, together with reduced blood sugar levels in the Mediterranean diet.
Dr Jospe explains participants who said they were still following their diet at 12 months lost even more weight, showing the importance of choosing a diet that is sustainable.
She believes the results of this study are relevant to the thousands of people following self-chosen diets with little supervision and indicates more realistic outcomes.
https://www.sciencedaily.com/releases/2020/01/200123170721.htm
Meal timing strategies appear to lower appetite, improve fat burning
July 24, 2019
Science Daily/The Obesity Society
Researchers have discovered that meal timing strategies such as intermittent fasting or eating earlier in the daytime appear to help people lose weight by lowering appetite rather than burning more calories, according to a report published online today in the journal Obesity, the flagship journal of The Obesity Society. The study is the first to show how meal timing affects 24-hour energy metabolism when food intake and meal frequency are matched.
"Coordinating meals with circadian rhythms, or your body's internal clock, may be a powerful strategy for reducing appetite and improving metabolic health," said Eric Ravussin, PhD, one of the study's authors and associate executive director for clinical science at Louisiana State University's Pennington Biomedical Research Center in Baton Rouge.
"We suspect that a majority of people may find meal timing strategies helpful for losing weight or to maintain their weight since these strategies naturally appear to curb appetite, which may help people eat less," said Courtney M. Peterson, PhD, lead author of the study and an assistant professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham.
Peterson and her colleagues also report that meal timing strategies may help people burn more fat on average during a 24-hour period. Early Time-Restricted Feeding (eTRF) -- a form of daily intermittent fasting where dinner is eaten in the afternoon -- helped to improve people's ability to switch between burning carbohydrates for energy to burning fat for energy, an aspect of metabolism known as metabolic flexibility. The study's authors said, however, that the results on fat-burning are preliminary. "Whether these strategies help people lose body fat need to be tested and confirmed in a much longer study," said Peterson.
For the study, researchers enrolled 11 adult men and women who had excess weight. Participants were recruited between November 2014 and August 2016. Adults, in general good health, aged 20-to-45-years old were eligible to participate if they had a body mass index between 25 and 35 kg/m2 (inclusive), body weight between 68 and 100 kg, a regular bedtime between 9:30 p.m. and 12 a.m., and for women, a regular menstrual cycle.
Participants tried two different meal timing strategies in random order: a control schedule where participants ate three meals during a 12-hour period with breakfast at 8:00 a.m. and dinner at 8:00 p.m. and an eTRF schedule where participants ate three meals over a six-hour period with breakfast at 8:00 a.m. and dinner at 2:00 p.m. The same amounts and types of foods were consumed on both schedules. Fasting periods for the control schedule included 12 hours per day, while the eTRF schedule involved fasting for 18 hours per day.
Study participants followed the different schedules for four days in a row. On the fourth day, researchers measured the metabolism of participants by placing them in a respiratory chamber -- a room-like device -- where researchers measured how many calories, carbohydrates, fat and protein were burned. Researchers also measured the appetite levels of participants every three hours while they were awake, as well as hunger hormones in the morning and evening.
Although eTRF did not significantly affect how many calories participants burned, the researchers found that eTRF did lower levels of the hunger hormone ghrelin and improved some aspects of appetite. It also increased fat-burning over the 24-hour day.
"By testing eTRF, we were able to kill two birds with one stone," said Peterson, adding that the researchers were able to gain some insight into daily intermittent fasting (time restricted-feeding), as well as meal timing strategies that involve eating earlier in the daytime to be in sync with circadian rhythms. The researchers believe that these two broader classes of meal timing strategies may have similar benefits to eTRF.
Hollie Raynor, PhD, RD, LDN, who was not associated with the research, said "this study helps provide more information about how patterns of eating, and not just what you eat, may be important for achieving a healthy weight." Raynor is a professor and interim dean of research in the Department of Nutrition, College of Education, Health, and Human Sciences at The University of Tennessee, Knoxville.
Peterson and colleagues said prior research was conflicted on whether meal timing strategies help with weight loss by helping people burn more calories or by lowering appetite. Studies in rodents suggest such strategies burn more calories, but data from human studies were conflicting -- some studies suggested meal timing strategies increase calories burned, but other reports showed no difference. The study's authors said, however, that previous studies did not directly measure how many calories people burned or were imperfect in other ways.
https://www.sciencedaily.com/releases/2019/07/190724103702.htm
Intermittent fasting could improve obese women's health
January 8, 2019
Science Daily/University of Adelaide
Research shows that obese women lost more weight and improved their health by fasting intermittently while following a strictly controlled diet.
The study, published in the journal Obesity, involved a sample of 88 women following carefully controlled diets over 10 weeks.
"Continuously restricting their diet is the main way that obese women try to tackle their weight," says Dr Amy Hutchison, lead author from the University of Adelaide and the South Australian Health and Medical Research Institute (SAHMRI).
"Unfortunately, studies have shown that long-term adherence to a restricted diet is very challenging for people to follow, so this study looked at the impact of intermittent fasting on weight loss.
"Obese women who followed a diet in which they ate 70% of their required energy intake and fasted intermittently lost the most weight.
"Other women in the study who either fasted intermittently without reducing their food intake, who reduced their food intake but did not fast, or did not restrict their diet at all, were not as successful in losing weight," says Dr Hutchison.
The study also checked the effect of the different diets on the women's health. Women who fasted intermittently as well as restricting their food improved their health more than those who only restricted their diet or only fasted intermittently.
"By adhering to a strict pattern of intermittent fasting and dieting, obese women have achieved significant weight loss and improvements in their health such as decreased markers for heart disease," says Dr Hutchison.
Participants who fasted intermittently ate breakfast and then refrained from eating for 24 hours followed by 24 hours of eating. The following day they fasted again.
All participants of the study were women who were overweight or obese with a Body Mass Index (BMI) in the 25-40 range and aged between 35 and 70 years. They followed a typical Australian diet consisting of 35% fat, 15% protein and 50% carbohydrate.
"The most successful participants lost approximately 0.5 to 1 kg per week for each week of the study," says Dr Hutchison.
"This study is adding to evidence that intermittent fasting, at least in the short term, may provide better outcomes than daily continuous diet restriction for health and potentially for weight loss," says Associate Professor Leonie Heilbronn from the University of Adelaide and SAHMRI.
"While the study confirms that intermittent fasting is more effective than continuous diet restriction, the underlying signal for limiting people's appetite, which could hold the key to triggering effective weight loss, requires further research."
New trials now being undertaken will examine the effectiveness of long-term fasting on both men and women.
https://www.sciencedaily.com/releases/2019/01/190108125526.htm