Drugs that promise to help people lose weight have had a checkered past, such as the infamous fen-phen that was pulled from the market in 1997 after reports of heart valve damage. But now, drug company pipelines are filling up with new molecules that aim to help people safely shed extra pounds, according to a cover story in Chemical & Engineering News, an independent news outlet of the American Chemical Society.

About 42% of U.S. adults are considered clinically obese because they have a body mass index of 30 or higher, according to the U.S. Centers for Disease Control and Prevention. Being at a heavier weight is associated with an increased risk of other health conditions, such as diabetes, heart disease and high blood pressure. Because of these risks, and the tendency of people to cycle between weight loss and regain throughout their lives, many doctors now consider being fat a chronic disease called obesity, rather than a behavioral issue, as it was seen in the past, writes C&EN reporter Megha Satyanarayana. However, recent findings indicate that 29% of people who are fat are otherwise metabolically healthy, causing some to question whether calling many people’s normal state a disease is stigmatizing.

The legions of people who want to lose weight for health or aesthetic reasons promise large financial gains for pharmaceutical companies who can bring safe, effective weight-loss drugs to market. But the troubling history of the field has raised the U.S. Food and Drug Administration’s regulatory bar. Now, a new drug must not only show that it allows someone to maintain a loss of 5–10% of their starting weight for a year, but it also must have longer-term studies proving it is safe. Novo-Nordisk’s popular new weight-loss drug Wegovy (semaglutide), which mimics a hormone that helps regulate glucose, caused an average 15% weight loss when combined with lifestyle counseling, compared with a 2.5% loss for a placebo and counseling. Moreover, a different formulation of Wegovy’s active compound has been safely used to treat diabetes since 2017. Pharmaceutical companies are exploring other molecules that regulate hormone receptors involved in appetite and energy expenditure. If these drugs are being prescribed to treat a chronic condition, many people will need to keep taking the drugs for the rest of their lives to sustain their weight loss, and in the case of Wegovy and similar drugs, deal with long-lasting side effects of nausea, vomiting and constipation. Meanwhile, some people say that is too high a price to pay for society’s thin-at-all-costs obsession. 

The article, “New Weight-Loss Drugs Could Shift the Scales,” is freely available here.

Intermittent fasting can produce clinically significant weight loss as well as improve metabolic health in individuals with obesity, according to a new study review led by University of Illinois Chicago researchers. 

“We noted that intermittent fasting is not better than regular dieting; both produce the same amount of weight loss and similar changes in blood pressure, cholesterol and inflammation,” said Krista Varady, professor of nutrition at the UIC College of Applied Health Sciences and author of “Cardiometabolic Benefits of Intermittent Fasting.” 

According to the analysis published in the Annual Review of Nutrition, all forms of fasting reviewed produced mild to moderate weight loss, 1%-8% from baseline weight, which represents results that are similar to that of more traditional, calorie-restrictive diets. Intermittent fasting regimens may also benefit health by decreasing blood pressure and insulin resistance, and in some cases, cholesterol and triglyceride levels are also lowered. Other health benefits, such as improved appetite regulation and positive changes in the gut microbiome, have also been demonstrated. 

The review looked at over 25 research studies involving three types of intermittent fasting: 

• Alternate day fasting, which typically involves a feast day alternated with a fast day where 500 calories are consumed in one meal. 
• 5:2 diet, a modified version of alternate day fasting that involves five feast days and two fast days per week. 
• Time-restricted eating, which confines eating to a specified number of hours per day, usually four to 10 hours, with no calorie restrictions during the eating period. 

Various studies of time-restricted eating show participants with obesity losing an average of 3% of their body weight, regardless of the time of the eating window. 

Studies showed alternate day fasting resulted in weight loss of 3%-8% of body weight over three to eight weeks, with results peaking at 12 weeks. Individuals on alternate day fasting typically do not overeat or binge on feast days, which results in mild to moderate weight loss, according to the review. 

Studies for the 5:2 diet showed similar results to alternate day fasting, which surprised the study’s reviewers. The subjects who participate in the 5:2 diet fast much less frequently than alternate-day fasting participants do, but the results of weight loss results are similar.  

Weight loss in both the alternate day and 5:2 fasting are comparable to more traditional daily calorie-restrictive diets. And, both fasting diets showed individuals were able to maintain an average of 7% weight loss for a year. 

“You’re fooling your body into eating a little bit less and that’s why people are losing weight,” Varady said. 

Varady added the review set out to debunk some myths regarding intermittent fasting. Intermittent fasting does not negatively affect metabolism, nor does it cause disordered eating, according to the studies reviewed.  

“Fasting people are worried about feeling lethargic and not being able to concentrate. Even though you are not eating, it won’t affect your energy,” Varady said. “A lot of people experience a boost of energy on fasting days. Don’t worry, you won’t feel crappy. You may even feel better.” 

The study review includes a summary of practical considerations for those who may want to try intermittent fasting. Among the considerations are: 

• Adjustment time — Side effects such as headaches, dizziness and constipation subside after one to two weeks of fasting. Increased water intake can help alleviate headaches caused by dehydration during this time. 
• Exercise — Moderate to high-intensity endurance or resistance training during food abstention can be done, and some study participants reported having more energy on fast days. However, studies recommend those following alternate day fasting eat their fasting day meal after exercise. 
• Diet during fasting — There are no specific recommendations for food consumption during intermittent fasting, but eating fruits, vegetables and whole grains can help boost fiber intake and help relieve constipation that sometimes accompanies fasting. 
• Alcohol and caffeine — For those using an alternate day or 5:2 fasting plan, alcohol is not recommended on fast days as the limited calories should be used on healthy foods that provide nutrition. 

There are several groups who should not intermittent fast, according to the studies. Those individuals include: 

• Those who are pregnant or lactating. 
• Children under 12. 
• Those with a history of disordered eating. 
• Those with a body mass index, or BMI, less than 18.5.
• Shift workers. Studies have shown they may struggle with fasting regimens because of shifting work schedules. 
• Those who need to take medication with food at regimented times. 

“People love intermittent fasting because it’s easy. People need to find diets that they can stick to long term. It’s definitely effective for weight loss and it’s gained popularity because there are no special foods or apps necessary. You can also combine it with other diets, like Keto,” Varady said. 

New research published this week challenges a popular belief that intermittent fasting diets such as alternate day fasting or the ‘5:2’ are the most effective ways to lose weight.

Over recent years, diets which see people fast on a few days each week have increased in popularity, reinforced by images of people’s miraculous weight transformations, and backed by celebrity endorsements.

However, evidence to date about the effectiveness of fasting compared with more traditional diets which aim to reduce calorie intake over the course of a full week has been limited.

Published in the prestigious journal Science Translational Medicine, the new study from a team of physiologists at the University of Bath builds this evidence and indicates that there is ‘nothing special’ about fasting.

Participants in their randomised control trial lost less weight when fasting in comparison with those following a traditional diet – even when their calorie intake was the same overall.

The trial, organised by a team from the University’s Centre for Nutrition, Exercise & Metabolism (CNEM), saw participants allocated into one of three groups:

• Group 1 which fasted on alternate days with their fast day followed by a day of eating 50% more than usual.
• Group 2 which reduced calories across all meals everyday by 25%.
• Group 3 which fasted on alternate days (in the same way as Group 1) but followed their fast day with one day eating 100% more than usual.
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Participants across all three groups were consuming a typical diet of around 2000-2500 kcal per day on average at the start of the study. Over the course of the three-week monitoring period, the two energy restricted groups reduced this to be between 1500-2000 kcal on average. Whereas groups 1 and 2 reduced their calorie intake by the same amount in different ways, group 3’s diet saw them fast without reducing overall calories.

Their results found that the non-fasting dieting group (Group 2) lost 1.9 kg in just three weeks, and DEXA body scans revealed this weight loss was almost entirely due to a reduction in body fat content.

By contrast, the first fasting group (Group 1) who experienced the same reduced calorie intake by fasting on alternate days and eating 50% more on non-fasting days, lost almost as much body weight (1.6 kg) but only half this weight loss was from reduced body fat with the remainder from muscle mass.

Group 3, who fasted but increased their energy intake by 100% on non-fasting days, did not need to draw on their body’s fat stores for energy and therefore weight loss was negligible.

Professor James Betts, Director of the Centre for Nutrition, Exercise & Metabolism at the University of Bath who led the research explains: “Many people believe that diets based on fasting are especially effective for weight loss or that these diets have particular metabolic health benefits even if you don’t lose weight.

“But intermittent fasting is no magic bullet and the findings of our experiment suggest that there is nothing special about fasting when compared with more traditional, standard diets people might follow.

“Most significantly, if you are following a fasting diet it is worth thinking about whether prolonged fasting periods is actually making it harder to maintain muscle mass and physical activity levels, which are known to be very important factors for long-term health.”

These results focused on participants who were defined as ‘lean’ (i.e. body mass index 20-25 kg/m2). 36 people participated in the study which was conducted between 2018 – 2020 and funded by the University of Bath.