Alternate day fasting also demonstrates greater benefits compared with both calorie restriction and other intermittent fasting approaches, but the researchers say longer trials are needed to substantiate these findings.

According to the World Health Organization in 2022, approximately 2.5 billion adults, 43% of the global adult population, were overweight, and about 890 million (16%) lived with obesity. 

Weight loss can reduce cardiometabolic risk factors, such as high blood pressure, cholesterol and blood sugar levels, and consequently lower the burden of serious chronic conditions like type 2 diabetes and cardiovascular disease.

Intermittent fasting is an eating pattern that cycles between periods of eating and fasting on a regular schedule and is becoming a popular alternative to traditional calorie-restricted diets, which are often unsustainable in the long term.

While no clear definition exists for intermittent fasting, its various methods can fall under three broad categories: time restricted eating (eg, the 16:8 diet involving a 16 hour fasting period followed by an 8 hour eating window), alternate day fasting (a 24 hour fast on alternate days), and whole day fasting (eg, a 5:2 diet involving five days of unrestricted eating and two days of fasting).

But the health effects of intermittent fasting compared with continuous caloric restriction or an unrestricted (ad-libitum) diet remain unclear.

To address this, researchers analyzed the results of 99 randomized clinical trials involving 6,582 adults (average age 45; 66% female) to compare the effect of intermittent fasting diets with continuous energy restriction or unrestricted diets on body weight and cardiometabolic risk factors.

Participants had an average body mass index (BMI) of 31 and almost 90% had existing health conditions.

The trials ranged from 3-52 weeks (average 12 weeks) and were of varying quality, but the researchers were able to assess their risk of bias and the certainty of evidence using recognized tools.

All intermittent fasting strategies and continuous energy restriction diets may lead to small reductions in body weight when compared with an unrestricted diet. 

Alternate day fasting was the only intermittent fasting diet strategy to show a small benefit in body weight reduction compared with continuous energy restriction (mean difference -1.29 kg).

Alternate day fasting also showed a small reduction in body weight compared with both time restricted eating and whole day fasting (mean difference -1.69 kg and -1.05 kg respectively).

However, these differences did not reach the minimally important clinical threshold of at least 2 kg weight loss for individuals with obesity, as defined by the study authors.

Alternate day fasting was also linked to lower levels of total and “bad” cholesterol compared with time restricted eating. Compared with whole day fasting, however, time restricted eating resulted in a small increase in cholesterol levels. No benefit was found for blood sugar or "good" cholesterol levels in any diet strategy comparison.

Estimates were similar among trials with less than 24 weeks follow-up. But longer trials of 24 weeks or more only showed weight loss benefits in diet strategies compared with an unrestricted diet.

The researchers point to several limitations, such as high variation (heterogeneity) among the diet strategy comparisons, small sample sizes of many included trials, and low to moderate certainty of evidence in most of the investigated outcomes.

Even so, this is highlighted as one of the first systematic reviews to combine direct and indirect comparisons across all dietary strategies, allowing for more precise estimates.

As such, they conclude: “The current evidence provides some indication that intermittent fasting diets have similar benefits to continuous energy restriction for weight loss and cardiometabolic risk factors. Longer duration trials are needed to further substantiate these findings.”

The value of this study is not in establishing a universally superior strategy but in positioning alternate day fasting as an additional option within the therapeutic repertoire, say researchers from Colombia in a linked editorial.

They point out that any structured intervention - including continuous energy restriction - could show benefits derived not only from the dietary pattern but also from professional support, planning, and nutritional education, while diet quality during free eating days could also affect alternate day fasting outcomes.

The focus should be on fostering sustainable changes over time, they say. “Intermittent fasting does not aim to replace other dietary strategies but to integrate and complement them within a comprehensive, patient centred nutritional care model.”

Despite the high health risk posed by Pandoraea, their molecular properties were hardly known until now. "We only knew that these bacteria occur in nature and that they can be pathogenic because they have been found in the lung microbiome of patients with cystic fibrosis or sepsis," explains Herzog.

The race for iron

As for most living organisms, iron is also essential for bacteria. "Iron plays a central role in enzymes and the respiratory chain of living organisms, for example," explains Herzog. Particularly in iron-poor environments such as the human body, the conditions for sufficient absorption of the element are anything but ideal. Many microorganisms therefore produce so-called siderophores: small molecules that bind iron from the environment and transport it into the cell.

"However, there were no known virulence or niche factors in the Pandoraea bacteria that could help them survive," says Herzog. The research team therefore wanted to find out how Pandoraea strains can survive in such a competitive environment.

Using bioinformatic analyses, the team identified a previously unknown gene cluster called pan. It codes for a non-ribosomal peptide synthetase - a typical enzyme for the production of siderophores. "We started with a gene cluster analysis and specifically searched for genes that could be responsible for the production of siderophores," reports Herzog.

Through targeted inactivation of genes as well as culture-based methods and state-of-the-art analytical techniques - including mass spectrometry, NMR spectroscopy, chemical degradation and derivatization - the researchers from Jena succeeded in isolating two new natural products and elucidating their chemical structure: Pandorabactin A and B. Both are able to complex iron and could play an important role in how Pandoraea strains survive in difficult environments. "The molecules help the bacteria to take up iron when it is scarce in their environment," says Herzog.

Less iron, fewer competitors

Bioassays have also shown that pandorabactins inhibit the growth of other bacteria such as Pseudomonas, Mycobacterium and Stenotrophomonas by removing iron from these competitors.

Analyses of sputum samples from the lungs of cystic fibrosis patients further revealed that the detection of the pan gene cluster correlates with changes in the lung microbiome. Pandorabactins could therefore have a direct influence on microbial communities in diseased lungs.

"However, it is still too early to derive medical applications from these findings," emphasizes Herzog. Nevertheless, the discovery provides important information on the survival strategies of bacteria of the genus Pandoraea and on the complex competition for vital resources in the human body.

The study was carried out in close cooperation between the Leibniz-HKI and the universities of Jena, Heidelberg and Hong Kong. It was conducted as part of the "Balance of the Microverse" Cluster of Excellence and the ChemBioSys Collaborative Research Center and was funded by the German Research Foundation. The imaging mass spectrometer used for the analyses was funded by the Free State of Thuringia and co-financed by the European Union.