There are two forms of vitamin D supplements available: vitamin D2 and vitamin D3. Researchers have found that taking vitamin D2 supplements can lead to a drop in the body’s concentration of vitamin D3, which is the form our bodies naturally produce from sunlight and use most effectively to raise overall vitamin D levels.  

The study, published in Nutrition Reviews, analyzed data from randomized controlled trials and found that vitamin D2 supplementation resulted in a reduction in vitamin D3 levels compared to those not taking a vitamin D2 supplement. In many of the studies, the vitamin D3 levels went lower than in the control group. 

Emily Brown, PhD Research Fellow and Lead Researcher of the study from the University of Surrey’s Nutrition, Exercise, Chronobiology & Sleep Discipline, said: 

“Vitamin D supplements are important, especially between October and March, when our bodies cannot make vitamin D from sunlight in the UK.  However, we discovered that vitamin D2 supplements can actually decrease levels of vitamin D3 in the body, which is a previously unknown effect of taking these supplements. This study suggests that subject to personal considerations, vitamin D3 supplements may be more beneficial for most individuals over vitamin D2.”  

Professor Cathie Martin, Group Leader at the John Innes Centre, said:  

“This meta-analysis highlights the importance of ensuring plant-based vitamin D3 is accessible in the UK.” 

This research supports a previous study published in Frontiers in Immunology, led by Professor Colin Smith from the University of Surrey, which suggests that vitamin D2 and D3 do not have identical roles in supporting immune function. Vitamin D3 has a modifying effect on the immune system that could fortify the body against viral and bacterial diseases.   

Professor Colin Smith said: 

“We have shown that vitamin D3, but not vitamin D2, appears to stimulate the type I interferon signalling system in the body – a key part of the immune system that provides a first line of defence against bacteria and viruses. Thus, a healthy vitamin D3 status may help prevent viruses and bacteria from gaining a foothold in the body.” 

Further research into the different functionalities of vitamin D2 and D3 should be a priority in deciding whether vitamin D3 should be the first-line choice of vitamin D supplement, subject to individual requirements. 

Professor Martin Warren, Chief Scientific Officer at the Quadram Institute, said: 

 “Vitamin D deficiency represents a significant public health concern, especially during the winter months with significant deficiency across the UK population. This collaborative research effort aligns well with the Quadram Institute’s mission to deliver healthier lives through food innovation to enhance the nutrient density of the food we eat. Tackling this with the most effective form of vitamin D supplementation or fortification is of the utmost importance to the health of the nation.” 

The study also identified similar molecular patterns in human tissue, suggesting that important aspects of obesity-related nerve damage may occur in both mice and people. The findings were published in the journal Nature.

Obesity is known to affect much more than body weight and metabolism. It can alter immune activity, disrupt nerve structures, and reshape tissues throughout the body, increasing the risk of conditions such as type 2 diabetes, cardiovascular disease, stroke, neuropathy, and cancer. Despite these widespread effects, scientists have lacked tools capable of studying disease-related changes across an entire intact body in high detail.

To address that challenge, a research team led by Prof. Ali Ertürk, Director of the Institute for Biological Intelligence (iBIO) at Helmholtz Munich and Professor at LMU, developed MouseMapper. The AI framework uses foundation-model-based deep learning algorithms to analyze massive whole-body imaging datasets.

The system can automatically identify and segment 31 organs and tissue types while also mapping nerves and immune cells throughout the body. This allows researchers to examine how diseases affect multiple organ systems at the same time in intact mice.

“MouseMapper is built on a foundation model, which means it generalizes far beyond the data it was originally trained on,” says Ying Chen, co-first author of the study.

Transparent Mice and Whole-Body Imaging

To build the body maps, researchers first tagged nerves and immune cells in mice using fluorescent markers that glow under a microscope. They then used tissue-clearing methods to make the mice transparent while preserving the fluorescent signals, allowing scientists to see deep inside the body without cutting tissues apart.

Next, the team used advanced light-sheet microscopy to capture detailed three-dimensional images of entire mice. The process generated enormous datasets containing tens of millions of cellular structures from organs and tissues across the body.

MouseMapper then analyzed the images automatically, identifying anatomical regions, nerve networks, and immune-cell clusters throughout the animals.

This approach allowed the researchers to pinpoint exactly where inflammation and tissue damage appeared in organs such as fat tissue, muscle, liver, and peripheral nerves. Unlike earlier methods, scientists did not need to choose specific regions to study beforehand.

Obesity Linked to Facial Nerve Damage

To explore how obesity changes the body, the researchers fed mice a high-fat diet that produced obesity and metabolic problems similar to those seen in humans.

Using MouseMapper, the team found widespread alterations in immune-cell organization and nerve structures across the body. One of the most surprising discoveries involved the trigeminal nerve, a major facial nerve responsible for facial sensation and certain motor functions.

In obese mice, these sensory nerves showed a major reduction in branches and nerve endings, suggesting impaired nerve function. Behavioral tests supported that conclusion, showing that obese mice were less responsive to sensory stimulation compared to lean mice.

The researchers then focused on the trigeminal ganglion, which contains the cell bodies of facial sensory neurons. Through spatial proteomics analysis, they identified molecular changes linked to inflammation and nerve remodeling.

Importantly, many of the same molecular signatures were also found in trigeminal tissue from people with obesity. This suggests that the nerve-related changes observed in mice may also occur in humans.

“We revealed previously unknown structural and molecular changes in the trigeminal ganglion and its facial branches, and the same molecular signature was conserved in human tissue. This kind of finding simply cannot emerge from studying one organ at a time,” says Dr. Doris Kaltenecker, senior scientist at the Institute for Diabetes and Cancer (IDC) at Helmholtz Munich and first author of the study.

A New Tool for Studying Complex Diseases

The researchers believe MouseMapper could become an important tool for studying diseases that affect many organ systems simultaneously, including diabetes, cancer, neurodegenerative diseases, and autoimmune disorders.

Unlike earlier approaches focused on individual tissues or organs, MouseMapper provides an integrated whole-body analysis system that can identify disease hotspots throughout an organism.

The team has also made the whole-body datasets publicly available online so researchers around the world can explore obesity-related changes across organs and tissues.

“Our goal is to create a comprehensive framework for understanding how diseases affect the body as an interconnected system,” says Ali Ertürk. “Our long-term vision is to build truly realistic digital twins of mice in health and disease: cell-level atlases that we can query, perturb and screen in silico computationally. That would let us pinpoint the earliest changes a disease causes, design interventions to prevent them, and accelerate the discovery of new treatments while reducing the number of physical experiments we need to run.”

The work was supported by the European Research Council (Consolidator Grant CALVARIA to A. Ertürk; grant 949017 to M. Rohm), the German Research Foundation (DFG) under Germany’s Excellence Strategy within the Munich Cluster for Systems Neurology (SyNergy, ID 390857198, EXC 2145), DFG SFB 1052 (A9) and TR 296 (P03), the Collaborative Research Centre CRC 1744, the German Federal Ministry of Education and Research (NATON collaboration, 01KX2121, and HIVacToGC), the Vascular Dementia Research Foundation, the Nomis Heart Atlas Project Grant (Nomis Foundation), the Else-Kröner-Fresenius-Stiftung, the Edith-Haberland-Wagner Stiftung, the Helmut Horten Foundation, the EFSD and Novo Nordisk A/S Programme for Diabetes Research in Europe (to D. Kaltenecker), and the China Scholarship Council (to Y. Chen).

Among the compounds of concern are polycyclic aromatic hydrocarbons, or PAHs (hydrophobic organic compounds comprising multiple fused aromatic rings). Some PAHs are known for their cancer causing potential, which makes reliable food testing an important part of protecting public health.

A Hidden Food Safety Challenge

Detecting PAHs in food is not simple. Conventional extraction methods, such as solid phase extraction, liquid liquid extraction, and accelerated solvent extraction, can be affordable, but they often require lengthy preparation, heavy hands on labor, and chemical intensive procedures that are not ideal for workers or the environment.

To solve these problems, scientists have been turning to a streamlined method known as QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe). The approach is designed to speed up sample preparation, reduce chemical use, improve recovery rates, and make food contaminant testing more practical for routine safety checks.

In a 2025 study, researchers from the Department of Food Science and Biotechnology at Seoul National University of Science and Technology, led by Professor Joon-Goo Lee, used QuEChERS to measure eight PAHs (Benzo[a]anthracene, Chrysene, Benzo[b]fluoranthene, Benzo[k]fluoranthene, Benzo[a]pyrene, Indeno[1,2,3-cd]pyrene, Dibenz[a,h]anthracene, and Benzo[g,h,i]perylene in food. The findings were published in the journal Food Science and Biotechnology.

Faster Testing With Strong Accuracy

The team used acetonitrile to extract PAHs from food samples, then tested several purification strategies involving different combinations of sorbents. The method was validated across multiple food matrices, showing strong performance. Calibration curves for all eight PAHs had R2 values above 0.99, indicating a highly linear and reliable measurement system.

Further analysis using gas chromatography and mass spectrometry showed that the limits of detection ranged from 0.006 to 0.035 µg/kg, while the limits of quantification ranged from 0.019 to 0.133 µg/kg. Recovery rates were also strong, ranging from 86.3 to 109.6% at 5 µg/kg, 87.7 to 100.1% at 10 µg/kg, and 89.6 to 102.9% at 20 µg/kg. Precision values stayed between 0.4 and 6.9% across all tested food matrices.

The study also reported that, among the foods tested, the highest PAH levels were found in soybean oil, followed by duck meat and canola oil.

Prof. Lee explains, “This method not only simplifies the analytical process but also demonstrates high efficiency in detection compared to conventional methods. It can be applied to a wide range of food matrices.”

Why PAHs Matter

PAHs can form when food is exposed to high temperatures or smoke. According to the National Cancer Institute, PAHs can develop when fat and juices from meat drip onto a hot surface or open flame, creating smoke that deposits these compounds onto the food. PAHs can also form during smoking and may be found in sources such as cigarette smoke and car exhaust fumes.

The NCI notes that PAHs and related high temperature cooking compounds have caused cancer in animal studies, although human population studies have not established a definitive link between exposure from cooked meats and cancer. This uncertainty is one reason more accurate measurement tools are valuable. Better testing can help regulators, researchers, and food companies understand where contamination is occurring and how it can be reduced.

Newer Research Points to Broader Use

Since the SeoulTech study, other researchers have continued refining QuEChERS based methods for PAH detection. A 2025 study in Foods developed a modified QuEChERS method with a freeze out step and applied it to 302 retail food samples. That work found the highest concentration of four priority PAHs in Kezuribushi, a smoked and dried fish product, and identified grilled chicken feet as a possible health concern based on the European Food Safety Authority margin of exposure approach.

Another 2025 study focused on cereals and cereal based products. Researchers developed a modified QuEChERS method using Z Sep⁺ clean up and gas chromatography with tandem mass spectrometry. In 96 cereal samples and 18 cereal based products from the Romanian market, only chrysene was quantified in 17% of cereal samples, while no PAHs were quantified in the derived products.

Together, these newer findings suggest that QuEChERS based approaches are becoming increasingly useful for different food categories, from oils and meats to smoked products and cereals. They also show why food specific testing matters, since PAH levels can vary widely depending on ingredients, processing, cooking methods, and environmental exposure.

Safer Food Testing and Cleaner Labs

For the food industry, a faster and more efficient PAH testing method could improve safety management by making it easier to inspect products before they reach consumers. The approach may also reduce costs and improve working conditions by cutting down on time consuming procedures and limiting the use of hazardous chemicals.

“Our research can improve public health by providing safe food. It also reduces the use and emission of hazardous chemicals in laboratory testing,” concludes Prof. Lee.

The broader takeaway is clear: food safety testing is becoming faster, cleaner, and more precise. By improving how scientists detect PAHs, methods like QuEChERS could help identify hidden contaminants, support safer food production, and reduce chemical waste in the lab.

About Professor Joon Goo Lee

Joon Goo Lee is a Professor at the Department of Food Science and Biotechnology, Seoul National University of Science and Technology. He is an expert in food regulation and safety assessment. He served as a scientific officer at Korea’s Ministry of Food and Drug Safety and as a visiting researcher at FSANZ. He is a member of the National Food Sanitation Committee and an expert for the FAO/WHO JECFA. He also serves as the executive director of the Korean food safety societies. His research focuses on risk assessment and the reduction of contaminants in food, contributing to science based policies and improved public health.

A UCSF led study found that healthy older people with lower vitamin B12 levels, even when those levels still fell within the accepted normal range, showed signs of subtle neurological and cognitive problems. The findings raise a provocative possibility: some people may be told their B12 status is fine while their brains are already showing early signs of strain.

“Normal” B12 May Not Always Mean Optimal

The study, published in Annals of Neurology, looked at older adults who did not have dementia or mild cognitive impairment. Even in this relatively healthy group, lower levels of active B12 were linked to slower thinking, slower visual processing, and more visible injury in the brain’s white matter. White matter is made up of the nerve fibers that allow different parts of the brain to communicate.

The work was led by senior author Ari J. Green, MD, of the UCSF Departments of Neurology and Ophthalmology and the Weill Institute for Neurosciences. Green and his colleagues said the results call attention to a possible weakness in current B12 guidelines. The minimum threshold used to define deficiency may not capture early functional changes in the nervous system.

“Previous studies that defined healthy amounts of B12 may have missed subtle functional manifestations of high or low levels that can affect people without causing overt symptoms,” said Green, noting that clear deficiencies of the vitamin are commonly associated with a type of anemia. “Revisiting the definition of B12 deficiency to incorporate functional biomarkers could lead to earlier intervention and prevention of cognitive decline.”

Brain Scans Revealed a Troubling Pattern

Researchers enrolled 231 healthy participants through the Brain Aging Network for Cognitive Health (BrANCH) study at UCSF. The participants had an average age of 71, and none had dementia or mild cognitive impairment.

Their average blood B12 level was 414.8 pmol/L, far above the U.S. minimum cutoff of 148 pmol/L. Instead of relying only on total B12, the researchers focused on the biologically active form of the vitamin, which may better reflect how much B12 the body can actually use.

After adjusting for age, sex, education, and cardiovascular risk factors, the team found that participants with lower active B12 had slower processing speed on cognitive tests. The effect was stronger with older age. They also had delayed responses to visual stimuli, pointing to slower visual processing and reduced brain signaling efficiency.

MRI scans added another warning sign. Participants with lower active B12 had a higher volume of white matter lesions, which are areas of brain injury that have been linked to cognitive decline, dementia, and stroke risk.

Why Older Adults May Be More Vulnerable

The study focused on older adults, a group that may be especially sensitive to lower B12 because absorption can become less efficient with age. Some medications, digestive conditions, and diets low in animal based foods can also increase the risk of low B12.

Co-first author Alexandra Beaudry-Richard, MSc, said the findings suggest that low but technically normal B12 could have broader effects than previously recognized. These levels could “impact cognition to a greater extent than what we previously thought, and may affect a much larger proportion of the population than we realize.” Beaudry-Richard is currently completing her doctorate in research and medicine at the UCSF Department of Neurology and the Department of Microbiology and Immunology at the University of Ottawa.

“In addition to redefining B12 deficiency, clinicians should consider supplementation in older patients with neurological symptoms even if their levels are within normal limits,” she said. “Ultimately, we need to invest in more research about the underlying biology of B12 insufficiency, since it may be a preventable cause of cognitive decline.”

Newer Evidence Adds Important Context

Research published after and around the UCSF study has added nuance rather than a simple answer. A 2025 comprehensive review concluded that B12 deficiency remains a modifiable risk factor for neurological and cognitive problems, especially in high risk groups such as older adults and vegetarians. The review also highlighted the growing importance of better biomarkers and brain imaging for detecting problems earlier.

A 2025 systematic review and meta analysis of randomized trials found that supplementation with B vitamins, including B6, B9, or B12, produced a very small benefit in global cognitive function among older adults. The authors rated the cleaned analysis as high certainty, but the effect was small, suggesting that supplementation is not a dramatic brain boost for everyone.

Another 2025 study using Mendelian randomization found no clear evidence that genetically higher total serum B12 levels protect the general population from psychiatric disorders or cognitive impairment. However, the authors noted an important limitation: their analysis used total serum B12, not the bioactive form measured in the UCSF work.

Together, the newer evidence supports a more careful message. B12 is clearly essential for the nervous system, and deficiency should not be ignored. But simply raising B12 for everyone may not be the answer. The more urgent question is whether current testing misses people whose brains are already affected despite “normal” results.

A Preventable Risk Worth Taking Seriously

The UCSF findings do not prove that lower active B12 directly causes cognitive decline, and they do not mean every older adult should begin taking supplements without medical guidance. They do, however, suggest that the current definition of B12 deficiency may be too blunt for brain health.

For clinicians, the study points to the possible value of looking beyond total B12, especially when older patients have neurological symptoms. For patients, it highlights a practical message: a “normal” lab result may not always tell the full story, particularly when subtle changes in memory, thinking speed, or vision are already appearing.

Authors: Co first author is Ahmed Abdelhak, MD, PhD, of the UCSF Department of Neurology and the Weill Institute for Neurosciences.

Funding and Disclosures: Westridge Foundation and the Canadian Institutes of Health and Research. There are no conflicts of interest to report.

A clinical trial from researchers at the University of Utah, New York University, and Stanford University points to a different possibility: changing the way a person walks.

A Personalized Shift in Foot Angle

In the yearlong randomized controlled trial, people with knee osteoarthritis were trained to make a small, personalized change in the angle of their foot while walking. The result was striking. Participants who received the real gait retraining reported pain relief comparable to medication, and MRI scans suggested they had less knee cartilage deterioration than people in the placebo group.

The study, published in The Lancet Rheumatology, was co led by Scott Uhlrich of the University of Utah’s John and Marcia Price College of Engineering. According to the researchers, it was the first placebo controlled study to show that a biomechanical intervention could help treat osteoarthritis symptoms and potentially slow joint damage.

“We’ve known that for people with osteoarthritis, higher loads in their knee accelerate progression, and that changing the foot angle can reduce knee load,” said Uhlrich, an assistant professor of mechanical engineering. “So the idea of a biomechanical intervention is not new, but there have not been randomized, placebo-controlled studies to show that they’re effective.”

Why the Treatment Had To Be Customized

The study focused on people with mild to moderate osteoarthritis in the medial compartment of the knee, which is the inner side of the joint. This area usually carries more weight than the outer side, making it a common site for knee osteoarthritis.

But there is a key challenge: the best walking adjustment is not the same for everyone. Some people reduce knee loading by turning their toes slightly inward. Others benefit more from pointing them outward. For some, the wrong change can fail to help or even increase stress on the painful part of the knee.

“Previous trials prescribed the same intervention to all individuals, resulting in some individuals not reducing, or even increasing, their joint loading,” Uhlrich said. “We used a personalized approach to selecting each individual’s new walking pattern, which improved how much individuals could offload their knee and likely contributed to the positive effect on pain and cartilage that we saw.”

That point has become even more important as related research continues to show that foot angle changes can affect knee forces differently depending on the person, the joint, and the walking pattern. A 2024 study in Bioengineering, for example, found that inward and outward foot rotation affected different peaks of knee loading, while not significantly increasing ankle joint moments in the group studied. Other research has also shown that foot progression angle can be measured outside the lab with wearable sensors, supporting the idea that future versions of this approach could be easier to deliver in real life.

How the Trial Worked

During their first two visits, participants received a baseline MRI and walked on a pressure sensitive treadmill while motion capture cameras measured the mechanics of their gait. The researchers used those data to determine whether each person would benefit more from turning the toes inward or outward, and whether a 5° or 10° adjustment would be best.

This screening also identified people who were unlikely to benefit because none of the tested foot angle changes reduced loading in their knees. Those participants were excluded from the trial. The researchers noted that including such people in earlier studies may have helped explain why previous results on pain were less clear.

Of the 68 participants enrolled, half were assigned to the real gait retraining group. The other half received a sham treatment designed to control for the placebo effect. In the sham group, participants were assigned foot angles that matched their natural walking pattern. In the intervention group, each participant received the foot angle change that produced the greatest reduction in knee loading.

Training the New Walking Pattern

Both groups returned to the lab for six weekly training sessions. During these sessions, participants walked on a treadmill while wearing a device on the shin that provided vibration feedback. The vibrations helped them keep their assigned foot angle while walking.

After the six week training period, participants were encouraged to practice the walking pattern for at least 20 minutes each day. The goal was for the movement to become automatic. Follow up visits showed that, on average, participants stayed within one degree of their prescribed foot angle.

After one year, participants reported their knee pain levels and underwent a second MRI so researchers could measure changes in cartilage health.

“The reported decrease in pain over the placebo group was somewhere between what you’d expect from an over-the-counter medication, like ibuprofen, and a narcotic, like oxycontin,” Uhlrich said. “With the MRIs, we also saw slower degradation of a marker of cartilage health in the intervention group, which was quite exciting.”

A Drug Free Option for a Long Treatment Gap

For some participants, one of the most appealing parts of the approach was that it did not require pills, surgery, braces, or a device worn all day. One participant said: “I don’t have to take a drug or wear a device…it’s just a part of my body now that will be with me for the rest of my days, so that I’m thrilled with.”

That long term adherence could be one of the intervention’s biggest strengths. Many people develop osteoarthritis decades before they are candidates for joint replacement. During that time, they may rely heavily on pain medications and other symptom management strategies.

“Especially for people in their 30’s, 40’s, or 50’s, osteoarthritis could mean decades of pain management before they’re recommended for a joint replacement,” Uhrlich said. “This intervention could help fill that large treatment gap.”

A 2026 conference abstract in Osteoarthritis and Cartilage also highlighted continued interest in placebo controlled trials of foot progression angle retraining, underscoring that researchers are still trying to determine which gait strategies work best and for whom. However, this area remains under active study, and the 2025 Lancet Rheumatology trial is still one of the strongest clinical demonstrations of a personalized approach.

Why Patients Should Not Try This Alone

Although the findings are promising, the researchers emphasized that this is not a simple “turn your toes in” or “turn your toes out” recommendation. The benefit depended on careful measurement and personalization. For some people, the wrong adjustment could increase stress on the knee rather than reduce it.

That is why the process still needs to be simplified before it can be used widely in clinics. The motion capture system used to prescribe each person’s walking change is expensive and time consuming. The research team envisions a future version that could be delivered through physical therapy, with retraining taking place during normal walks rather than only inside a lab.

“We and others have developed technology that could be used to both personalize and deliver this intervention in a clinical setting using mobile sensors, like smartphone video and a ‘smart shoe’,” Uhlrich said. Future studies of this approach are needed before the intervention can be made widely available to the public.

Those interested in participating in future studies can contact Uhlrich’s Movement Bioengineering Lab by filling out this web form.

The study, titled “Personalised gait retraining for medial compartment knee osteoarthritis: a randomised controlled trial,” was published in The Lancet Rheumatology. Co lead authors are Valentina Mazzoli of NYU’s Department of Radiology and Julie Kolesar of Stanford’s Human Performance Lab. Coauthors include Amy Silder, Andrea Finlay, Feliks Kogan, Garry Gold, Scott Delp and Gary Beaupre of Stanford and the VA Palo Alto Medical Center. The research was supported by federal research grants from the Department of Veterans Affairs, National Institutes of Health and National Science Foundation.