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.

Current treatments mainly focus on easing symptoms and lowering inflammation, depending on the specific type of arthritis. Now, researchers at Aarhus University’s Department of Biomedicine have identified a possible new direction for future therapies involving GLP-1, the hormone targeted by popular weight loss medications such as Wegovy.

The findings were published in Lancet Rheumatology.

“Our study shows that the body’s own GLP-1 hormone is present only in very small amounts in the joints. This means that its natural effect in the joint is likely to be limited. However, it also suggests that GLP-1-based medication, which is administered in much higher doses, may be able to influence inflammation directly in the joints,” said Associate Professor Tue Wenzel Kragstrup, who led the research.

Because GLP-1 medications deliver much higher levels of the hormone than the body naturally produces in the joints, researchers believe these drugs could potentially affect inflammation in those tissues.

Possible Double Benefit From GLP-1 Drugs

Weight management is already recommended for many arthritis patients, especially those with osteoarthritis. According to the researchers, GLP-1 medications could eventually provide benefits beyond weight reduction alone.

“Weight loss is already part of the recommendations for many patients with arthritis, but our study may indicate that medication such as Wegovy could have a dual effect — both through weight loss and by increasing GLP-1 levels in the joints,” Kragstrup said.

The study analyzed blood samples and joint fluid taken from arthritis patients. The data work was led by medical doctor and PhD student Mads Brüner together with PhD student Amalie Broksø.

Researchers found that GLP-1 levels inside the joints closely matched levels circulating in the bloodstream.

“We can see that the levels of GLP-1 in joint fluid are closely linked to the levels in the blood. This suggests that it is primarily the amount of GLP-1 circulating in the body that determines how much reaches the joint,” Brüner explained.

First Detection of GLP-1 in Arthritic Joint Fluid

Earlier studies had suggested GLP-1 might have anti-inflammatory properties, but this marks the first time scientists have detected the hormone directly in the joint fluid of arthritis patients.

“Our findings provide a biological basis for investigating whether GLP-1-based medication may have direct effects in the joints — beyond the known effects on weight and metabolism. However, we have not demonstrated that the treatment works against arthritis. This will require a number of clinical studies,” Kragstrup said.

The researchers caution that patients should not expect GLP-1 drugs to become arthritis treatments anytime soon. Much more research is needed before doctors can determine whether these medications can actually reduce inflammation or relieve symptoms inside the joints.

“The next step is to investigate whether the medication reaches the joints in sufficient quantities and actually reduces inflammation in the joints.”

About the Study

The research was a translational clinical biomarker study that examined paired blood and joint fluid samples from patients with inflammatory arthritis, including rheumatoid arthritis and spondyloarthritis. The goal was to determine whether GLP-1 could be measured in joint fluid and how those levels compared with concentrations found in the blood.

The project involved researchers from Aarhus University’s Department of Biomedicine, the Department of Molecular Medicine (MOMA) at Aarhus University Hospital, the Clinic for Rheumatic and Connective Tissue Diseases at the Medical Diagnostic Centre at Hospitalsenhed Midt, the Novo Nordisk Foundation Center for Basic Metabolic Research, and the Department of Biomedical Sciences at the University of Copenhagen.

Funding came from Director Michael Hermann Nielsen’s Memorial Grant and the Risford Foundation. The authors reported no conflicts of interest related to the study.

The review was written by David Gems and Alexander Carver from University College London, along with Yuan Zhao from Queen Mary University of London. Their work combines ideas from evolutionary biology with findings from modern biomedical research to explain how early damage in the body may later contribute to diseases such as cancer, arthritis, and infections.

How Early-Life Damage May Shape Health Decades Later

According to the researchers, the first stage begins earlier in life when the body experiences various forms of disruption. These can include infections, physical injuries, or genetic mutations. While the body is often able to repair or contain much of this damage, some of it may remain hidden rather than being fully removed.

The second stage occurs later in life as normal genetic activity starts changing in ways that are no longer beneficial to the body. These late-life biological changes can weaken the body’s ability to keep earlier damage under control. As a result, previously contained problems may gradually develop into disease.

The scientists argue that this process helps explain why many illnesses appear mainly in older adults even though their origins may trace back much earlier.

Why Diseases Like Shingles and Arthritis Appear With Age

The review highlights aging as a multifactorial process, meaning it is driven by many interacting biological factors instead of a single cause. The proposed model suggests that the combination of earlier damage and later-life genetic changes plays a major role in age-related disease.

For example, dormant viruses that remain inactive for years can become active again when the immune system weakens with age, leading to conditions such as shingles. In a similar way, injuries sustained in youth may eventually contribute to osteoarthritis as aging tissues become less resilient over time.

Inherited genetic mutations may also stay silent for decades before increasing the risk of diseases such as cancer or fibrosis later in life.

Evolutionary Biology and Aging Research

The researchers say their model builds on long-standing evolutionary theories of aging. One influential idea is that natural selection becomes weaker later in life, allowing harmful biological processes to emerge with age because they have less impact on reproduction and survival earlier in life.

The review also references studies involving the roundworm Caenorhabditis elegans. In these experiments, early mechanical damage in the worms eventually led to fatal infections in old age. The scientists suggest similar patterns may also occur in humans.

A New Framework for Healthier Aging

Overall, the review presents aging as a process shaped by multiple interacting causes that unfold over time. By separating aging into two major stages, early-life damage and later-life genetic activity, the researchers believe their framework could help guide future strategies aimed at disease prevention and healthier aging.

The findings also raise the possibility that reducing damage earlier in life or targeting harmful late-life biological changes could help lower the risk of chronic disease in older adults.

We both work in languages education and recognize the real benefits that learning another language can bring. As well as myriad cognitive benefits, it brings with it cultural insights and empathetic awareness.

With that in mind, we’re here to dispel five myths about language learning that might be putting you off.

Myth one: it’s all about grammar and vocabulary

In fact, learning about people, history and culture is arguably the best part of learning a language. While grammar and vocabulary are undeniably important aspects of language learning, they don’t exist in isolation from how people communicate in everyday life.

Language learning can help us to have “intercultural agility”: the ability to engage empathically with people who have very different experiences from our own. To be able to do this means learning about people, history and culture.

Immersing yourself in a particular country or location, for example through studying or working, is a fantastic way to do this. But when this isn’t feasible, there are so many other options available. We can learn so much through music, books, films, musical theater and gaming.

Myth two: we should focus on avoiding mistakes – they’re embarrassing

One problem with formal language learning is that it encourages us to focus on accuracy at all costs. To pass exams, you need to get things “right”. And many of us feel nervous about getting things wrong.

But in real-life communication, even in our expert languages, we often make mistakes and get away with it. Think of the number of times you have misspelled something, or said the wrong word, and still been understood.

Less formal language learning can encourage us to think more about communication than accuracy.

One advocate of this approach is author Benny Lewis, who popularized a communicative learning approach he calls “language hacking” which focuses on the language skills needed for conversation. Language apps also encourage this, as does real-life travel and communication.

Myth three: it’s too much effort to start over with a new language

You can use languages in lots of ways, and the language you learn at school doesn’t have to be the only one you learn.

In England, most people learn one or more of French, Spanish or German at school. These languages can often serve as great apprenticeship languages, teaching us how to learn a language and about grammatical structures.

But they are not always the languages that we are most likely to use as adults, when family and work could take us anywhere. Our cultural interests might also lead us to want to know more about a new language.

Learning a language that you have a personal interest in can be very motivating and help you to keep going when things get a bit rocky.

Myth four: learning a language is an individual endeavor

You don’t have to learn alone. Learning with others, or having the support of others, can help motivate us to learn.

This might be through a multilingual marriage, joining a conversation group or chatting in a language learning forum online. Don’t feel that you have to have reached a certain proficiency before you start reaching out to others.

Language apps can also make language learning a collective endeavor. You can learn along with friends and family, and congratulate them on their language learning streaks.

This is something both of us do with multiple generations of our families, helping us engage with language learning in a lighthearted way.

Myth five: it’s a lot of hard graft

Learning a language in a systematic way can be challenging, whether in a classroom or from a self-study course. But some things make this easier. We have found that people are more motivated to engage when they have a personal reason to learn. This could be, for example, wanting to communicate with family or to travel to a particular country or region.

The growth in popularity and accessibility of language learning apps has made language learning possible from any location and at any time, often for free.

You can easily catch up on your Chinese from the comfort of your own armchair, at whatever time is most convenient for you. Apps can be fun and playful, and can help us maintain motivation, develop vocabulary and embed grammatical structures.

There are lots of reasons for learning a language, and lots of benefits. We encourage everyone to focus on these benefits, and give it a go.