In a randomized clinical trial involving adults with overweight, participants who followed an ad libitum low-fat vegan diet substantially reduced the number of calories per gram of food they consumed. Researchers found that greater reductions in energy density were tied to lower calorie intake and greater weight loss, despite the absence of any instructions to eat less.

“This helps answer a question people often have about plant-based eating: How can you lose weight without counting calories or going hungry?” said Hana Kahleova, MD, PhD, director of clinical research at the Physicians Committee for Responsible Medicine and lead author. “The answer is energy density. Plant foods are rich in water and fiber, so you can fill your plate, feel full, and still take in fewer calories.”

How the Low-Fat Vegan Diet Was Tested

The findings come from an analysis of a 16-week randomized trial involving adults with overweight. Participants were assigned either to an ad libitum low-fat vegan diet centered on fruits, vegetables, grains, and legumes, or to a control group that continued eating as usual without making any dietary changes.

Neither group was given a calorie target or told to limit how much they ate. Researchers measured each participant’s dietary energy density by comparing total daily energy intake with the total weight of food consumed, expressed as total energy (kcal per day) divided by total food weight (grams per day).

The study produced several notable findings:

• The total weight of food consumed did not change significantly in either group, meaning those following the vegan diet continued eating about the same amount of food by weight.
• Calorie intake declined in both groups, but the decrease was larger among those following the vegan diet, at about 357 kcal/day.
• Energy density remained essentially unchanged in the control group but fell by about 30% in the vegan group.
• Larger reductions in energy density were associated with greater weight loss, and that relationship remained even after researchers accounted for changes in calorie intake.

Same Amount of Food, Fewer Calories

The difference came largely from changes in the types of foods participants were eating. The vegan diet removed calorie-dense animal foods including meat, dairy, and eggs while increasing consumption of foods that provide more volume for relatively few calories, particularly vegetables and legumes.

Because these plant foods generally contain fewer calories per gram, participants could continue eating generous portions while taking in less energy overall.

“This isn’t about willpower or smaller portions,” Dr. Kahleova said. “It’s about choosing foods that naturally deliver fewer calories in every bite. A 30% reduction in energy density is a substantial shift that would be very hard to achieve and sustain through portion control alone.”

Why Energy Density Can Affect Weight Loss

Energy density refers to the number of calories contained in each gram of food. Scientists have studied it for years because it can influence how much people eat and how satisfied they feel after a meal.

Controlled feeding studies have shown that reducing the energy density of meals can help people feel full while lowering the amount of energy they consume. Importantly, the physical volume of food can remain similar even when the calorie content drops.

“When the foods you eat are lower in energy density, your body’s natural appetite signals work in your favor,” Dr. Kahleova said. “You eat until you’re satisfied, and you simply end up with fewer calories. That’s a sustainable way to manage weight.”

A Different Approach to Weight Management

Weight-loss advice often emphasizes calorie restriction and smaller portions. These findings point to another possible strategy: changing the composition of the food on the plate rather than simply reducing the amount of food eaten.

Choosing more water-rich, high-fiber plant foods may help people lower their calorie intake while still eating enough to feel satisfied. That could make weight management easier for some people by reducing the sense of deprivation that can come with traditional calorie-cutting approaches.

“From a clinical standpoint, targeting energy density offers a realistic strategy for weight loss,” Dr. Kahleova said. “Instead of telling people to eat less, we can help them eat differently — and the results follow.”

The Bottom Line

The findings suggest that a low-fat vegan diet can substantially reduce dietary energy density, allowing people to consume fewer calories and lose weight without intentionally restricting their calorie intake.

“You don’t have to eat less,” Dr. Kahleova said. “You can eat more food, feel full, and still lose weight — by choosing foods that are naturally lower in energy density.”

That question matters because microbial organisms dominated Earth for roughly 90 percent of the planet’s history. Reconstructing the transition from a world populated almost entirely by microbes to one filled with plants, animals, and fungi could also help scientists understand whether complex life might develop elsewhere in the universe.

From Microbes to Complex Life

Life originated on Earth more than 3.5 billion years ago, according to Ross Anderson, a paleontologist at the University of Oxford in the U.K. Cyanobacteria and oxygen-producing photosynthesis were present by at least 2.3 billion years ago, while eukaryotes had appeared by at least 1.7 billion years ago.

Algae followed at least one billion years ago and probably emerged even earlier. Animals appeared at least 570 million years ago, and possibly somewhat before that.

To reach the common ancestor shared by the plant and animal kingdoms, Anderson says researchers must look back to around 1.6 billion years ago.

Crown eukaryotes, which are among the earliest eukaryotic forms scientists are trying to trace, played a crucial role in the emergence of complex life on Earth. Anderson considers eukaryotes to represent the planet’s first complex life.

What Makes Eukaryotes Different?

Eukaryotic cells contain a nucleus that encloses their DNA. They also contain organelles, which are specialized structures inside the cell. One example is the mitochondrion, which helps provide the energy needed to support more demanding forms of life.

Eukaryotes ultimately gave rise to complex multicellular organisms and large visible life forms. Every animal, plant, and fungus around us today is eukaryotic.

Finding their earliest ancestors, however, is extremely difficult.

Organisms older than 500 million years did not yet possess shells or skeletons. Because those hard structures had not evolved, paleontologists must rely on rare environments capable of preserving fragile cells and soft tissues.

That leaves scientists with relatively little information about how life changed during an enormous span covering about 90 percent of Earth’s history.

Searching for the Transition to Multicellular Life

Anderson’s research focuses on one of the biggest transitions in biological history: how Earth changed from a planet dominated by bacteria into one inhabited by complex multicellular organisms.

Because fossils of these early multicellular organisms are difficult to find, he studies the chemistry of ancient rocks to identify the environments most likely to have preserved them.

Another major obstacle is time itself. Eukaryotic microfossils have endured billions of years of geological alteration and degradation, making already tiny remains even harder to detect.

Scientists do know that the transition from single-celled life to multicellular organisms happened more than once in different parts of the world. Anderson is particularly interested in understanding how that process eventually produced the remarkable diversity seen among animals today.

Much of the foundation for modern animal diversity appeared around the Ediacaran/Cambrian transition roughly 540 million years ago. This period marked a major evolutionary shift from predominantly soft-bodied organisms toward the Cambrian explosion, when animals with greater mobility, shells, and skeletons became increasingly prominent.

Where Scientists Search for Ancient Microfossils

Finding fossils from much earlier periods requires searching in places where delicate biological material had an unusual chance of surviving.

Anderson and his colleagues are especially interested in a roughly 100sq. km region near Svalbard, Norway. About 80 degrees North, this remote island area was once covered by a shallow sea.

Australia has also produced important evidence. Just last year, researchers there discovered some of the oldest known eukaryotic microfossils, dating to roughly 1.75 billion years ago.

Ancient coastal environments are especially promising places to search. Eukaryotes living in these settings would have had access to abundant nutrients and organic material, conditions that could have supported greater diversity and the development of multicellularity.

Researchers often target pristine locations or regions that have received relatively little scientific sampling. Anderson specializes in studying areas where enormous deposits of clay may have helped preserve ancient eukaryotic remains.

Today, many of the best places to conduct this work are deserts or Arctic landscapes. With little or no vegetation covering the ground, ancient rocks remain exposed and accessible.

Why the Fossil Hunt Is So Difficult

Even in ideal locations, finding eukaryotic microfossils is an enormous challenge. The organisms were microscopic, lacked protective hard tissues, and have been exposed to billions of years of geological degradation.

According to Anderson, one of the greatest problems is simply that the fossil record from this period remains poorly sampled.

Researchers are nevertheless making progress. Scientists are becoming better at identifying the types of rocks most likely to contain early fossils, providing new evidence that can help reconstruct the history of Earth’s earliest life.

What Earth’s Earliest Life Could Tell Us About Alien Life

The search has implications far beyond understanding Earth’s biological past.

Anderson says much of his work involving clay deposits was originally motivated by the search for life on other planets. By learning which environments preserve ancient organisms on Earth, scientists may become better equipped to recognize possible signs of life elsewhere.

Understanding how life emerged and became increasingly complex on our own planet is therefore an important part of astrobiology. If scientists want to estimate how likely life is to arise and evolve elsewhere, they first need a clearer picture of how that process unfolded here on Earth.

The challenge has been finding a way to make biological DNA function effectively alongside electronic materials. Penn State researchers have now developed an approach designed to overcome that incompatibility.

The work, published in Advanced Functional Materials and the subject of a patent application, relies on two key components. One is synthetic DNA, made from commercially available, chemically engineered molecules arranged into short genetic sequences tailored for specific electronic requirements. The other is crystalline perovskite, a semiconductor already used in technologies including solar cells, lasers and data storage devices.

“Biology and electronics are different domains,” said Kavya S. Keremane, co-corresponding author and postdoctoral researcher in materials science and engineering at Penn State. “Bridging these two fields required developing an entirely new materials platform that allows them to function seamlessly together. By combining the information storage capabilities of DNA with the exceptional electronic properties of perovskite semiconductors, we created a bio-hybrid system that fundamentally changes how low-power memory devices can be designed.”

Building a Low Power Memory Device

Using these materials, the team created a memory resistor, known as a “memristor,” that operates with very little energy. Unlike ordinary resistors, which maintain a set resistance to electrical current in devices ranging from cell phones to space shuttles and lose their stored information when power disappears, memristors can preserve a record of previous electrical activity. They can remember the direction in which current previously flowed even after the power source is removed.

That ability allows information to be stored and processed in the same place, resembling the way neurons function in the brain. Such an arrangement could support more simultaneous and sophisticated forms of data processing. According to the researchers, however, practical commercial systems would still require enough storage capacity and electrical power to become costly and inefficient without DNA’s ability to pack enormous amounts of information into a very small space while consuming little energy.

“As the demand for artificial intelligence (AI) grows, we need a new strategy for low-power, high-storage devices,” said Bed Poudel, co-corresponding author and research professor of materials science and engineering at Penn State.

Poudel said AI and other emerging technologies are expected to depend increasingly on neuromorphic computing, which is designed to operate more like the human brain. Such systems can evaluate multiple inputs at once while making decisions informed by previous experiences and future priorities.

“Usually, it takes more power to store more information. Our device, however, consumes 100 times less power and the storage capacity is higher than traditional storage devices, like flash drives.”

Engineering DNA to Conduct Electricity

To construct the device, the researchers added silver nanoparticles to a layer of customized DNA sequences — specially designed to be of certain compositions and lengths — that was integrated with thin films of perovskite.

This technique, called “doping,” involves introducing a small amount of another material to produce specific properties. In this case, adding the silver nanoparticles allowed the DNA to conduct electricity while also helping its molecular units line up in a more orderly arrangement.

Synthetic DNA offered another important advantage over natural DNA. Unlike natural DNA — long, entangled strands that behave like wet spaghetti when handled — short and rigid pieces of synthetic DNA can be arranged with much greater precision at extremely small scales.

According to co-author Neela H. Yennawar, research professor and director of the Penn State Huck Institutes of the Life Sciences’ Biomolecular Interactions Core Facility, molecularly engineered DNA can provide structural organization, adjustable electrical conductivity and functional control that natural DNA cannot achieve when incorporated into thin films.

“We can computationally determine exactly which sequences we need and how long they should be, and then we can rationally design them with synthetic DNA,” Yennawar said. “These structures can be systematically doped with silver and other ions and engineered to interface seamlessly with perovskites — transforming DNA from a biological macromolecule into a programmable, multifunctional nanomaterials platform.”

DNA and Perovskite Work Better Together

When combined, the silver-doped DNA and perovskite formed bio-hybrid pathways that directed the flow of electrical current through the device.

The researchers found that electrons moved reliably when they applied less than 0.1 volt — for comparison, standard U.S. outlets have 120 volts — and the device responded predictably when the direction of the current was changed.

The carefully designed DNA structures, combined with the perovskite, also helped make the device unusually stable. According to the team, it continued operating consistently at temperatures approaching 250 degrees Fahrenheit and remained functional at room temperature for more than six weeks, substantially exceeding the performance standards of existing perovskite-based memory storage devices.

The researchers also reported that the new system could perform the same memory function as comparable technologies while consuming only one-tenth as much power. That level of efficiency could make the approach especially attractive for future electronics designed to handle large amounts of information with lower energy demands.

“Using just the DNA or just perovskite alone did not produce near as robust a result as the combination,” Keremane said. “It’s this combination that enables a very high memory storage density that requires very little power.”

A New Direction for Bio-Inspired Electronics

The team now plans to improve the technology further and explore additional uses for bio-inspired electronic systems.

“Nature has the solution — we just have to find it and apply it,” Poudel said. “This work of integrating DNA into electronics to do amazing things gives a glimpse into what is possible.”

In addition to Keremane, Yennawar and Poudel, other Penn State co-authors include co-corresponding author Luyao Zheng, postdoctoral research in materials science and engineering; Haodong Wu, doctoral student in materials science and engineering; Jiamao Zheng, who was a master’s student in materials science and engineering at the time of research and has since graduated from Penn State; Shashank Priya, who was a professor of materials science and engineering at the time of research; and Chiranth C. Ravi, who was a master’s student in the Huck Institutes of the Life Sciences at the time of research and has since graduated from Penn State. Abhinav Gorthy and co-corresponding author Rashmi Jha, chemical engineering and materials science, University of Minnesota, also contributed.

The U.S. National Science Foundation, the National Institutes of Health, Penn State and the University of Minnesota supported this research.

Heart failure is a serious and growing health problem. More than 500,000 people in the Netherlands are estimated to have the condition, and that number is expected to increase in the years ahead. In people with heart failure, the heart cannot pump blood as effectively as it should. This can lead to severe shortness of breath, fatigue, and repeated trips to the hospital.

Digoxin Could Join the ‘Fantastic Four’

Standard heart failure care currently relies on a combination of four medications, commonly known as the ‘Fantastic Four.’ Cardiologists have long investigated whether digoxin could provide additional benefits as a fifth treatment.

Three UMCG studies now provide evidence supporting that possibility. The findings were published in publications including Nature Medicine and the Journal of the American Medical Association (JAMA) and were also presented at the ESC Heart Failure Congress in Barcelona.

Heart Failure Hospitalizations Fell by 25%

One of the studies included 1,000 people with heart failure who were treated at 43 centers across the Netherlands. Half received a low dose of digoxin in addition to their usual treatment for an average of three years, while the other half received a placebo.

Among those taking digoxin, deaths from cardiovascular disease and worsening heart failure were reduced (by 19%). However, that individual result did not reach statistical significance.

The researchers then combined the findings with data from two earlier studies in a meta-analysis, creating a much larger group of patients. With the additional data, they found that digoxin produced a meaningful and statistically significant benefit, even when patients were already taking the four standard heart failure medications.

The clearest benefit was a reduction in hospital admissions for heart failure, which fell by an average of 25%. Low-dose digoxin was also found to be safe and relatively easy to use.

Problems Increased After Digoxin Was Stopped

A third study followed approximately 600 of the original 1,000 participants who had been assigned either digoxin or placebo.

Researchers found that people who had been taking digoxin and then had to stop experienced significantly more problems during the first six weeks compared with people who had never taken the drug. Among 288 patients, 14 were hospitalized or died.

According to the researchers, this finding does not directly prove that digoxin is effective. Still, they considered the size and timing of the effect both impressive and surprising.

A Heart Failure Drug That Costs Less Than Ten Cents a Day

The researchers believe the results of the three studies could eventually lead to changes in heart failure guidelines, potentially allowing many more patients to receive digoxin.

Its low price makes the findings especially notable. Digoxin has been used in medicine for centuries and costs less than ten cents per day. By comparison, many newer heart failure medications cost several euros each day.

Why a Low Dose of Digoxin Matters

Digoxin (digitalis) is the oldest and least expensive medicine used to treat heart failure. At a low dose, the drug primarily works by reducing several harmful compensatory responses that occur when the heart is struggling. For example, digoxin suppresses stress hormones (such as adrenaline) in the blood, which can benefit the heart.

Higher doses of digoxin were commonly prescribed in the past. Those doses caused heart muscle cells to contract more strongly, but that effect ultimately proved less helpful. For a weakened heart muscle, reducing strain is preferable to forcing it to work harder.

During the past 25 to 30 years, several effective new treatments for heart failure have become available. As a result, digoxin use has steadily declined, and only about 15 percent of heart failure patients now receive it.

Earlier research had already suggested that patients given low doses of digoxin did considerably better than those receiving higher doses. Until the new UMCG research, however, randomized, prospective studies had not directly investigated and confirmed this effect.

Funding Made the Digoxin Studies Possible

Research involving older and inexpensive medications can be difficult to fund, even when those drugs have the potential to improve patient care while lowering costs.

Hartstichting therefore provided 3 million euros for this research through its collaboration with ZonMw as part of the Good Use of Medicines program.