Category: Medical Research & Technology

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Scientists Lift the Lid on The Secret Life of Manganese

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A new biosensor engineered by Penn State researchers offers scientists the first dynamic glimpses of the elusive – and vital – manganese ion. The researchers engineered the sensor from a natural protein called lanmodulin, which binds rare earth elements with high selectivity and was discovered five years ago by some of this study’s researchers. Their findings are published in the Proceedings of the National Academy of Sciences.

The researchers genetically reprogrammed the protein to favour manganese over other common transition metals like iron and copper, unlike most transition metal-binding molecules. The sensor could have broad applications in biotechnology to advance understanding of photosynthesis, host-pathogen interactions and neurobiology.

Like iron, copper and zinc, manganese is an essential metal for plants and animals. Its function is to activate enzymes. In humans, manganese is linked to neural development. Accumulation of excess manganese in the brain induces Parkinsonian-like motor disease, whereas reduced manganese levels have been observed in association with Huntington’s disease, the researchers explained.

“We believe that this is the first sensor that is selective enough for manganese for detailed studies of this metal in biological systems,” said Jennifer Park, a graduate student at Penn State and lead author on the paper. “We’ve used it – and seen the dynamics of how manganese comes and goes in a living system, which hasn’t been possible before.”

She explained that the team was able to monitor the behaviour of manganese within bacteria and are now working to engineer even tighter binding sensors to potentially study how the metal works in mammalian systems.

Scientific understanding of manganese has lagged behind that of other essential metals, in part because of a lack of techniques to visualise its concentration, localisation and movement within cells. The new sensor opens the door for all kinds of new research, explained Joseph Cotruvo, associate professor of chemistry at Penn State and senior author on the paper.

“There are so many potential applications for this sensor,” said Cotruvo. “Personally, I am particularly interested in seeing how manganese interacts with pathogens.”

He explained that the body works hard to restrict the iron that most bacterial pathogens need for survival, and so those pathogens instead turn to manganese.

“We know there is this tug-of-war for vital metals between the immune system and these invading pathogens, but we haven’t been able to fully understand these dynamics, because we couldn’t see them in real time,” he said, adding that with new capabilities to visualise the process, researchers have tools to potentially develop new drug targets for a range of infections for which resistance has emerged to common antibiotics, like staph (MRSA).

Designing proteins to bind to particular metals is an intrinsically difficult problem, Cotruvo explained, because there are so many similarities between the transition metals present in cells. As a result, there has been a lack of chemical biology tools with which to study manganese physiology in live cells.

“The question for us was, can we engineer a protein to only bind to one thing, a manganese ion, even in the presence of a huge excess of other very similar-looking things, like calcium, magnesium, iron, and zinc ions?” Cotruvo said. “What we had to do was create a binding site arranged in just the right way, so that this protein bond was more stable in manganese than any other metal.”

Having successfully demonstrated lanmodulin is capable of such a task, the team is now planning to use it as a scaffold from which to evolve other types of biological tools for sensing and recovering many different metal ions that have biological and technological importance.

“If you can figure out ways of discriminating between very similar metals, that’s really powerful,” said Cotruvo. “If we can take lanmodulin and turn it into a manganese-binding protein, then what else can we do?”

Source: Penn State

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ChatGPT can Now (Almost) Pass the US Medical Licensing Exam

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ChatGPT can score at or around the approximately 60% pass mark for the United States Medical Licensing Exam (USMLE), with responses that make coherent, internal sense and contain frequent insights, according to a study published in PLOS Digital Health by Tiffany Kung, Victor Tseng, and colleagues at AnsibleHealth.

ChatGPT is a new artificial intelligence (AI) system, known as a large language model (LLM), designed to generate human-like writing by predicting upcoming word sequences. Unlike most chatbots, ChatGPT cannot search the internet. Instead, it generates text using word relationships predicted by its internal processes.

Kung and colleagues tested ChatGPT’s performance on the USMLE, a highly standardised and regulated series of three exams (Steps 1, 2CK, and 3) required for medical licensure in the United States. Taken by medical students and physicians-in-training, the USMLE assesses knowledge spanning most medical disciplines, ranging from biochemistry, to diagnostic reasoning, to bioethics.

After screening to remove image-based questions, the authors tested the software on 350 of the 376 public questions available from the June 2022 USMLE release. 

After indeterminate responses were removed, ChatGPT scored between 52.4% and 75.0% across the three USMLE exams. The passing threshold each year is approximately 60%. ChatGPT also demonstrated 94.6% concordance across all its responses and produced at least one significant insight (something that was new, non-obvious, and clinically valid) for 88.9% of its responses. Notably, ChatGPT exceeded the performance of PubMedGPT, a counterpart model trained exclusively on biomedical domain literature, which scored 50.8% on an older dataset of USMLE-style questions.

While the relatively small input size restricted the depth and range of analyses, the authors note their findings provide a glimpse of ChatGPT’s potential to enhance medical education, and eventually, clinical practice. For example, they add, clinicians at AnsibleHealth already use ChatGPT to rewrite jargon-heavy reports for easier patient comprehension.

“Reaching the passing score for this notoriously difficult expert exam, and doing so without any human reinforcement, marks a notable milestone in clinical AI maturation,” say the authors.

Author Dr Tiffany Kung added that ChatGPT’s role in this research went beyond being the study subject: “ChatGPT contributed substantially to the writing of [our] manuscript… We interacted with ChatGPT much like a colleague, asking it to synthesise, simplify, and offer counterpoints to drafts in progress…All of the co-authors valued ChatGPT’s input.”

Source: EurekAlert!

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A New Possibility for Non-hormonal Male Contraceptives

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Thus far, very few contraceptive options being developed target the sperm cells. Researchers are now developing approaches that target testosterone or otherwise interrupt the sperm’s ability to fertilise an egg, yet these may not work for everyone. But now, researchers publishing in ACS’ Journal of Medicinal Chemistry have identified a new candidate molecule that could become an effective non-hormonal contraceptive for males.

Previously, Gunda I. Georg and colleagues investigated non-hormonal contraceptive options, as approaches targeting testosterone produced unwanted side effects. They developed a drug targeted at a specific vitamin A receptor and found that it worked as a highly effective contraceptive with no side effects. But numerous proteins are involved in forming sperm, and exploring multiple options would maximise chances for a drug that would eventually make it to market.

Another set of proteins involved in the cell cycle are the cyclin-dependent kinases, or CDKs, which play a role in sperm cell production and tumour development. Mice without the CDK2 receptor are sterile, so a drug that targets this protein could serve as an effective contraceptive. It also has potential as a cancer therapeutic because inhibiting the enzyme slowed tumour growth in previous studies. However, CDK2 has a very similar shape to other enzymes in its family, and currently available inhibitors tend to produce undesirable off-target effects by accidentally binding the others as well. So, Georg and her team wanted to develop a drug that could selectively inhibit CDK2 to serve as another contraceptive option.

The team previously discovered an unknown binding site in CDK2 and a commercially available dye molecule that successfully bound to it. Using the dye as a starting point, the researched screened tens of thousands of different compounds in their current work to find ones that also bound the pocket well. They narrowed the list down to just three, picking one to further optimize. The best version, named EF-4-177, demonstrated a long half-life and good diffusion into the testes of mice. After a 28-day exposure, the animals’ sperm counts decreased by about 45%. Additionally, EF-4-117 bound much more strongly to the CDK2 pocket than the dye, making it the highest affinity inhibitor for this site reported to date. The researchers say that this work proves the potential of this inhibitor for future therapeutic applications.

Source: Michigan State University

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New Mathematical Model for Potassium Homeostasis

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Blood samples
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Potassium is essential to normal cellular function, helping the cardiac muscle work correctly and aids in the transmission of electrical signals within cells. A new mathematical model published in PLOS Computational Biology sheds light on the often mysterious process of potassium homeostasis.

Using existing biological data, researchers at the University of Waterloo built a mathematical model that simulates how an average person’s body regulates potassium, both in times of potassium depletion and during potassium intake. Because so many foods contain abundant potassium, the body is continually storing, deploying, and disposing of potassium to keep it in a healthy range, ie the process of potassium homeostasis. Understanding potassium homeostasis is essential in helping diagnose the source of the problem when something goes wrong, for example, when kidney disease or medication leads to dysregulation.

“Too much potassium in the body, or hyperkalaemia, can be just as dangerous as hypokalaemia, or too little,” said study lead author Melissa M. Stadt, a PhD student in applied mathematics. “Dysregulation of potassium can lead to dangerous and potentially fatal consequences.”

The model could be used for a virtual patient trial, allowing researchers to generate dozens of patients and then predict which ones would have hyper- or hypokalaemia based on different controls.

“A lot of our models are pieces of a bigger picture,” said Anita Layton, professor of applied mathematics and Canada 150 Research Chair in mathematical biology and medicine. “This model is one new and exciting piece in helping us understand how our incredibly complex internal systems work.”

The model is especially exciting because it allows scientists to test the muscle-kidney cross-talk signal hypothesis. Scientists have hypothesised that skeletal muscles, which store most of the body’s potassium, can directly signal to the kidneys to dump potassium when there’s too much stores, and vice versa. When the mathematical researchers tested the hypothesis in their model, it more accurately reflected existing biological data regarding potassium homeostasis, suggesting that muscle-kidney cross talk might be an essential piece in the puzzle of potassium regulation.

Source: University of Waterloo

Categories : Medical Industry Medical Research & TechnologyTags :

A New Wave of Academia Spinouts is Shaking up Drug Development

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In recent times, new drug discoveries by independent large pharmaceutical companies have become increasingly rare, with almost 60% of new drugs discovered through mergers and acquisitions and drug licensing. Fortunately, an emerging trend of spinouts from academia and R&D investments heralds a promising shift in the industry’s interorganisational deal networks to improve research and development in the future. Researchers explore this new trend in Drug Discovery Today.

Launching a new drug in the market is risky, thanks to a low probability of success during the research and development (R&D) phase and the high costs involved. But through an improved understanding of disease biology, decision-making can be more streamlined through the effective use of scientific information.

With this in mind, researchers from Ritsumeikan University, Japan, led by Associate Professor Kota Kodama are uncovering how the trends in interorganisational deals in the pharmaceutical industry are changing to improve R&D productivity and drug discovery. “The network structure of innovation creation in the pharmaceutical industry has changed with the increasing emergence of start-up companies spinning out from academia and research institutions as players in the source of innovation,” explains Dr Kodama.

Their research suggests that the knowledge necessary for breakthrough innovation in drug discovery is more often than not obtained through alliance networks. Over the past decade, large research-based pharmaceutical companies have used research collaborations, innovation incubators, academic centres of excellence, public-private partnerships, mergers and acquisitions (M&As), drug licensing, and corporate venture capital funds as typical methods for external innovation. The researchers now aim to define the changes in the network structure and nature of such alliances that have occurred over the past decade to provide future strategic insights for industry and academic players involved in drug discovery.

Using data from the Cortellis Competitive Intelligence database, the researchers identified nearly 50 000 deals of various kinds related to pharmaceutical R&D across pharmaceutical, digital health software, animal drug, and medical device companies to uncover trends in the creation of new drugs for human use. They also studied the trends of 13 of the largest pharmaceutical companies with annual revenues of more than US$10 billion, who saw an improvement in their CAGR (compound annual growth rate) since 2015. The researchers noticed that the rising CAGR correlated to a significant change in M&A-related deals after 2015, indicating that M&A-related deals drive revenue growth for large pharmaceutical companies.

Furthermore, the number of organisations involved in interorganisational deals has been increasing yearly from 2012 to 2021. Although the number of organisations involved and the number of deals may be increasing, the density of the deal networks is decreasing annually, suggesting that networks are becoming more non-cohesive. The concentration of business relationships between organisations of certain areas in the network changed to dispersion around 2015, and new networks connecting different groups started to form after 2017. These trends are an important illustration of how the industry landscape is gradually evolving away from the traditional network in which large pharmaceutical companies drove drug discovery output. Now, interorganisational deals among more diverse players have become active and are driving R&D productivity for startups in biotechnology and pharmaceuticals.

A clear increase in the number of academia-owned spinouts of advanced technology and expansion of investment in start-ups is a positive sign. The emergence of new chemical modalities, such as biologics, oligonucleotides, and peptides that differ from traditional small molecule drug discovery indicate remarkable changes that have taken place over the past two decades. The trend of increased financing for start-up companies in personalised drug development is beneficial for patent creation and will positively impact innovation creation in the coming years.

“The presence of academia to support the technologies of these start-ups is becoming very important, and government and private support and investment in this area is boosting innovation. Our study shows that such medium- and long-term support may ultimately benefit the health and well-being of humankind,” concludes an optimistic Dr Kodama.

Source: Ritsumeikan University.

Categories : Medical Research & Technology NeurologyTags :

Newly Discovered Subarachnoidal Layer Protects the Brain

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Advances in neuro-imaging and molecular biology have unearthed a subtle, previously unknown layer in the brain. As described in the journal Science, the newly discovered layer forms a previously unknown component of brain anatomy that acts as both a protective barrier and platform from which immune cells monitor the brain for infection and inflammation.

“The discovery of a new anatomic structure that segregates and helps control the flow of cerebrospinal fluid (CSF) in and around the brain now provides us much greater appreciation of the sophisticated role that CSF plays not only in transporting and removing waste from the brain, but also in supporting its immune defenses,” said Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at University of Rochester and the University of Copenhagen. Nedergaard and her colleagues have made significant findings in the field of neuroscience, including detailing the many critical functions of previously overlooked cells in the brain called glia and the brain’s unique process of waste removal, which the lab named the glymphatic system.

The study focuses on the series of membranes that encase the brain, creating a barrier from the rest of the body and keeping the brain bathed in CSF.  The traditional understanding of what is collectively called the meningeal layer identifies the three individual layers as dura, arachnoid, and pia matter.

 This new layer discovered by the international research team further divides the space between the arachnoid and pia layers, the subarachnoid space, into two compartments, separated by the newly described layer, which the researchers name SLYM (Subarachnoidal LYmphatic-like Membrane).  While the paper mostly describes the function of SLYM in mice, it also reports its presence in the adult human brain as well.

SLYM is a type of membrane that lines other organs in the body, including the lungs and heart, called mesothelium. These membranes typically surround and protect organs, and harbour immune cells.

The new membrane is very thin and delicate, consisting of only a few cells in thickness.  Yet SLYM is a tight barrier, allowing only very small molecules to transit and it also seems to separate “clean” and “dirty” CSF.  This last observation hints at the likely role played by SLYM in the glymphatic system, which requires a controlled flow and exchange of CSF, allowing the influx of fresh CSF while flushing the toxic proteins associated with Alzheimer’s and other neurological diseases from the central nervous system.  This discovery will help researchers more precisely understand the mechanics of the glymphatic system.

Central nervous system immune cells (indicated here expressing CD45) use SLYM as a platform close to the brain’s surface to monitor cerebrospinal fluid for signs of infection and inflammation.

The SLYM also appears important to the brain’s defences.  The central nervous system has its own native population of immune cells, and the membrane’s integrity prevents outside immune cells from entering.  In addition, the membrane appears to host its own population of central nervous system immune cells that use SLYM as an observation point close to the surface of the brain from which to scan passing CSF for signs of infection or inflammation. 

Discovery of the SLYM opens the door for further study of its role in brain disease.  For example, the researchers note that larger and more diverse concentrations of immune cells congregate on the membrane during inflammation and aging.  Furthermore, when the membrane was ruptured during traumatic brain injury, the resulting disruption in the flow of CSF impaired the glymphatic system and allowed non-central nervous system immune cells to enter the brain. 

These and similar observations suggest that diseases as diverse as multiple sclerosis, central nervous system infections, and Alzheimer’s might be triggered or worsened by abnormalities in SLYM function. They also suggest that the delivery of drugs and gene therapeutics to the brain may be impacted by SLYM, which will need to be considered as new generations of biologic therapies are being developed.

Source: University of Rochester Medical Center

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A New Way to Measure Blood Pressure: A Digital Camera

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Male doctor with smartphone
Photo by Ivan Samkov on Unsplash

Engineers have designed a system that can remotely measure blood pressure from video of a person’s forehead and using artificial intelligence algorithms to extracting cardiac signals across a range of skin tones. They describe their new technology in a new paper published in Inventions.

Using the same remote-health technology they pioneered for non-contact monitoring of vital health signs, this new technology could replace the existing uncomfortable and cumbersome method of strapping an inflatable cuff to a patient’s arm or wrist, the researchers claim.

The researchers, from the University of South Australia and Baghdad’s Middle Technical University, describe the technique, which involves filming a person from a short distance for 10 seconds and then using AI to extract cardiac signals from two regions in the forehead.

Experiments were performed on 25 people with different skin tones and under changing light conditions, overcoming the limitations reported in previous studies. Compared to a digital sphygmomanometer (itself subject to errors), the systolic and diastolic readings were around 90% accurate.

“Monitoring blood pressure is essential to detect and manage cardiovascular diseases, the leading cause of global mortality, responsible for almost 18 million deaths in 2019,” says UniSA remote sensing engineer Professor Javaan Chahl. “Furthermore, in the past 30 years, the number of adults with hypertension has risen from 650 million to 1.28 billion worldwide.”

“The health sector needs a system that can accurately measure blood pressure and assess cardiovascular risks when physical contact with patients is unsafe or difficult, such as during the recent COVID outbreak,” Prof Chahl continues. “If we can perfect this technique, it will help manage one of the most serious health challenges facing the world today.”

The cutting-edge technology has come a long way since 2017, when the UniSA and Iraqi research team demonstrated image-processing algorithms that could extract a human’s heart rate from drone video.

In the past five years the researchers have developed algorithms to measure other vital signs, including breathing rates from 50 metres away, oxygen saturation, temperature, and jaundice in newborns.

Their non-contact technology was also deployed in the United States during the pandemic for non-contact monitoring of COVID signs.

Source: University of South Australia

Categories : Cancer Medical Research & TechnologyTags :

Removing Tumours – Without the Scalpel

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A novel technology described in the journal Nanoscale enables targeted destruction of cancerous tumours, via a combination of ultrasound and the injection of nanobubbles into the bloodstream. Unlike invasive treatment methods or the injection of microbubbles into the tumour itself, this latest technology enables the destruction of the tumour in a non-invasive manner.

Dr Tali Ilovitsh at Tel Aviv University said: “Our new technology makes it possible, in a relatively simple way, to inject nanobubbles into the bloodstream, which then congregate around ​​the cancerous tumour. After that, using a low-frequency ultrasound, we explode the nanobubbles, and thereby the tumour.”

At present, the usual cancer treatment is surgical removal of the tumour, in combination with complementary treatments such as chemotherapy and immunotherapy.

Therapeutic ultrasound to destroy the cancerous tumour is a non-invasive alternative to surgery, a method which comes with advantages and disadvantages. On the one hand, it allows for localised and focused treatment; the use of high-intensity ultrasound can produce thermal or mechanical effects by delivering powerful acoustic energy to a focal point with high spatial-temporal precision. This method has been used to effectively treat solid tumours deep within in the body. Moreover, it makes it possible to treat patients who are unfit for tumour resection surgery. The disadvantage is that the heat and high intensity of the ultrasound waves could cause damage to neighbouring healthy tissues.

Reducing off-target damage

In the current study, Dr Ilovitsh and her team sought to overcome this problem. In the experiment, which used an animal model, the researchers were able to destroy the tumour by injecting nanobubbles into the bloodstream (as opposed to what has been until now, which is the local injection of microbubbles into the tumour itself), in combination with low-frequency ultrasound waves, with minimal off-target effects.

“The combination of nanobubbles and low frequency ultrasound waves provides a more specific targeting of the area of the tumour, and reduces off-target toxicity,” explains Dr Ilovitsh.

“Applying the low frequency to the nanobubbles causes their extreme swelling and explosion, even at low pressures. This makes it possible to perform the mechanical destruction of the tumours at low-pressure thresholds.”

“Our method has the advantages of ultrasound, in that it is safe, cost-effective, and clinically available, and in addition, the use of nanobubbles facilitates the targeting of tumours because they can be observed with the help of ultrasound imaging.”

Dr Ilovitsh adds that the use of low-frequency ultrasound also increases the depth of penetration, minimises distortion and attenuation, and enlarges the focal point. “This can help in the treatment of tumours that are located deep with the body, and in addition facilitate the treatment of larger tumour volumes. The experiment was conducted in a breast cancer tumour lab model, but it is likely that the treatment will also be effective with other types of tumours, and in the future, also in humans.”

Source: Tel Aviv University

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Multiple Sclerosis Therapy also Improves Gut Flora Composition

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Gut microbiome. Credit: Darryl Leja, NIH

Dimethyl fumarate, a medication used to treat MS also has a beneficial effect on the composition of the intestinal flora, according to research published in Gut Microbes. Conversely, the gut flora also plays a role in which side effects occur during treatment with the medication.

Few previous studies have examined the effects of MS treatments on intestinal flora and on the role their composition plays with regard to efficacy and side effects. A team of researchers at the University of Basel and the University Hospital Basel has now examined these questions in a group of 20 MS patients being treated with dimethyl fumarate.

Dimethyl fumarate reduces the number of MS flare-ups by interfering with the metabolic processes of certain immune cells. However, the therapy is also associated with side effects, including hot flashes and gastrointestinal complaints, and in some cases lymphopenia, a lack of lymphocytes such as B cells and T cells in the blood. This can lead to severe complications.

More ‘good’ bacteria

In their study, the researchers led by Professor Anne-Katrin Pröbstel and Professor Adrian Egli, examined stool and blood samples from participants before and during the first twelve months of the treatment. Their focus was on the composition of the gut microbiome. Pröbstel and her team also measured the number of lymphocytes in the blood in order to identify patients who were experiencing lymphopenia as a side effect.

After only three months of treatment, the research team was already able to identify changes to the gut microbiome: “We were able to show that the gut bacteria of patients receiving the medication started to become more like the composition seen in healthy individuals,” Pröbstel explained. Treatment with dimethyl fumarate reduced the proportion of pro-inflammatory types of bacteria, which have been associated with MS, and supported the growth of “good” bacteria.

Furthermore, the researchers were able to draw a connection between the composition of the gut microbiome and the development of lymphopenia: The presence of Akkermansia muciniphila bacteria combined with the lack of Prevotella copri bacteria emerged as a risk factor for this side effect. The authors therefore suspect that P. copri may protect against lymphopenia.

Interaction between therapy and gut flora

“Our data suggest that immunomodulatory therapies affect not only immune cells, but also positively influence the gut microbiome,” Pröbstel explains. The connection between gut bacteria and clinical side effects of the treatment may eventually enable early identification of patients at risk of developing lymphopenia. Microbiologist Egli continues: “In the future, this relatively new field of microbiology may help us better understand the effects and side effects of many medications with regard to gut bacteria, and to personalise treatment accordingly.”

“What we have so far is only a pilot study with a relatively small number of participants,” she cautioned. Larger-scale studies are needed to confirm the results and explore the potential for supporting MS therapies via gut flora and for predicting side effects in advance.

Source: University of Basel

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Quantity of Water Needed by Humans Varies Greatly

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A large international study reveals a wide range in the amount of water people consume around the globe and over their lifespans, which pours cold water on the oft-repeated idea that the human body needs eight glasses a day. In the study, which appears in Science, some may need up to six litres a day while others get by with only one litre.

“The science has never supported the old eight glasses thing as an appropriate guideline, if only because it confused total water turnover with water from beverages and a lot of your water comes from the food you eat,” says Dale Schoeller, emeritus professor at University of Wisconsin-Madison. “But this work is the best we’ve done so far to measure how much water people actually consume on a daily basis — the turnover of water into and out of the body — and the major factors that drive water turnover.”

That’s not to say the new results settle on a new guideline. The study, measured the water turnover of more than 5600 people from 26 countries, ages ranging from 8 days to 96 years old, and found daily averages on a range between 1 and 6 litres per day.

“There are outliers, too, that are turning over as much as 10 litres a day,” says Schoeller, a co-author of the study. “The variation means pointing to one average doesn’t tell you much. The database we’ve put together shows us the big things that correlate with differences in water turnover.”

Previous studies of water turnover relied largely on volunteers to recall and self-report their water and food consumption, or were focused observations — of, say, a small group of young, male soldiers working outdoors in desert conditions — of questionable use as representative of most people.

The new research objectively measured the time it took water to move through the bodies of study participants by following the turnover of “labelled water”, which contains hydrogen and oxygen isotopes.

“If you measure the rate a person is eliminating those stable isotopes through their urine over the course of a week, the hydrogen isotope can tell you how much water they’re replacing and the elimination of the oxygen isotope can tell us how many calories they are burning,” says Schoeller, whose UW-Madison lab in the 1980s was the first to apply the labelled-water method to study people.

More than 90 researchers were involved in the study, which was led by a group that includes Yosuke Yamada, a former UW-Madison postdoctoral researcher in Schoeller’s lab and now section head of the National Institute of Biomedical Innovation, Health and Nutrition in Japan, and John Speakman, zoology professor at the University of Aberdeen in Scotland. They collected and analysed data from participants, comparing environmental factors – such as temperature, humidity and altitude of the participants’ hometowns – to measured water turnover, energy expenditure, body mass, sex, age and athlete status.

The researchers also incorporated the United Nations’ Human Development Index, a composite measure of a country that combines life expectancy, schooling and economic factors.

Water turnover volume peaked for men in the study during their 20s, while women held a plateau from 20 through 55 years of age. Newborns, however, turned over the largest proportion daily, replacing about 28% of the water in their bodies every day.

Physical activity level and athletic status explained the largest proportion of the differences in water turnover, followed by sex, the Human Development Index, and age.

All things equal, men and women differ by about half a litre of water turnover. As a baseline of sorts, the study’s findings expect a male non-athlete (but of otherwise average physical activity) who is 20 years old, weighs 70kg, lives at sea level in a well-developed country in a mean air temperature of 10°C and a relative humidity of 50%, would take in and lose about 3.2 litres of water every day. A woman of the same age and activity level, weighing 60kg and living in the same spot, would go through 2.7 litres.

Doubling the energy a person uses will push their expected daily water turnover up by about litre, the researchers found. Fifty kilograms more body weight adds 0.7 litres a day. A 50% increase in humidity pushes water use up by 0.3 litres. Athletes use about a litre more than non-athletes.

The researchers found “hunter-gatherers, mixed farmers, and subsistence agriculturalists” all had higher water turnover than people who live in industrialised economies. In all, the lower your home country’s Human Development Index, the more water you go through in a day.

“That’s representing the combination of several factors,” Schoeller says. “Those people in low HDI countries are more likely to live in areas with higher average temperatures, more likely to be performing physical labour, and less likely to be inside in a climate-controlled building during the day. That, plus being less likely to have access to a sip of clean water whenever they need it, makes their water turnover higher.”

The measurements will improve our ability to predict more specific and accurate future water needs, especially in dire circumstances, according to Schoeller.

Source: University of Wisconsin-Madison