Vitamin deficiency linked to chronic pain in new study

 Lower levels of certain vitamins and minerals were found to be associated with chronic pain in a recently completed study led by researchers at the University of Arizona Health Sciences and published in Pain Practice. 

Lower levels of vitamin D, vitamin B12, folate and magnesium  were seen in people with severe chronic pain.

This is the first study to take a precision medicine approach to chronic pain on a large scale by broadly examining micronutrient levels of people with and without chronic pain and exploring the incidence of chronic pain in people with or without micronutrient deficiencies. The findings could inform personalized nutritional strategies to help manage chronic pain.

“I treat chronic pain patients, and oftentimes we don’t come up with a diagnosis. But just because there isn’t a surgery that will help you doesn’t mean you’re not in pain. It's just means that our understanding of pain is limited to date,” said senior author Julie Pilitsis, MD, PhD, head of the U of A College of Medicine – Tucson Department of Neurosurgery and member of the Comprehensive Center for Pain & Addiction. “This study is a novel way to approach chronic pain treatment, where you are looking at the patient holistically to see what could be going on systemically that is easily modifiable – changes in diet as opposed to medications or other things.”

The research team focused on five micronutrients commonly associated with chronic pain: vitamins D, B12, and C, folate and magnesium. They examined the micronutrient status of three groups: people without pain, people with mild-to-moderate chronic pain and people with severe chronic pain.

“The finding that surprised us the most was that Asian females had higher vitamin B12 levels than expected,” said co-author Deborah Morris, PhD, a research laboratory manager in the Department of Neurosurgery, explaining that B12 deficiencies were seen in other gender, race and ethnicity groups. “Asian females with severe chronic pain had the highest vitamin B12 levels overall. We were expecting it to be lower.”

The results varied for vitamin C, where males with mild-to-moderate and severe chronic pain were more likely to have low and borderline low levels of vitamin C than males without chronic pain. Men with borderline and severe vitamin C deficiency were also more likely to have chronic pain.

Participant data came from the National Institutes of Health’s All of Us Research Database, where the largest enrollment has come from the University of Arizona-Banner Health program.

“The findings that are coming from complex demographic studies such as this one show that we can’t just make assumptions for every patient that walks in the office,” said Pilitsis, who is a member of the BIO5 Institute.

“Our study across various chronic pain conditions in a large, diverse population found that certain vitamins and mineral deficiencies are more frequent in people with chronic pain, and particularly in some in specific racial and ethnic groups,” Morris added. “Our goal is to improve the quality of life for people with chronic pain and reduce opioid usage, and these findings have the potential to do that as part of a holistic approach to pain management.”

A November 2024 data brief from the Centers for Disease Control and Prevention stated that nearly 25% of U.S. adults are living with chronic pain, which is associated with decreased quality of life, opioid misuse, increased anxiety and depression, and unmet mental health needs.

Yoga, Tai Chi, walking and jogging may be best forms of exercise for insomnia

 

Findings back use of exercise as primary treatment strategy for poor sleep, say researchers

Yoga, Tai Chi, walking and jogging may be the best forms of exercise to improve sleep quality and ease insomnia, suggest the findings of a comparative pooled data analysis published in the online journal BMJ Evidence Based Medicine.

The findings back the use of exercise as a primary treatment strategy for poor sleep patterns, say the researchers.

Characterised by difficulties falling and staying asleep, and early morning awakening, the prevalence of insomnia ranges from 4-22%, note the researchers. It is associated with heightened risks of various mental and physical health conditions, including dementia and cardiovascular disease.

Drug treatments for insomnia are not without their side effects, and cognitive behavioural therapy (CBT), while effective, isn’t always available due to the shortage of trained therapists, explain the researchers.

An emerging body of research suggests that exercise is helpful, but current guidelines don’t specify which types of exercise might be most beneficial. The researchers therefore set out to plug this knowledge gap, with a view to informing clinical practice and helping patients choose the most appropriate exercise for managing their insomnia.

They scoured research databases looking for relevant randomised clinical trials published up to April 2025 and included 22 in a network meta analysis—a statistical technique used to simultaneously compare multiple interventions.

The trials involved 1348 participants and 13 different treatment approaches to ease insomnia, seven of which were exercise based: yoga; Tai Chi; walking or jogging; aerobic plus strength exercise; strength training alone; aerobic exercise combined with therapy; and mixed aerobic exercises. These programmes ranged from 4 up to 26 weeks in length.

The other approaches included CBT; sleep hygiene; Ayurveda; acupuncture/massage; nothing; and existing treatment, such as usual care and/or lifestyle changes, the durations of which ranged from 6 to 26 weeks. 

Validated scoring systems for sleep quality and insomnia severity —PSQI and the ISI45—as well as subjective and objective measures of total sleep time, sleep efficiency (percentage of time spent asleep while in bed), number of awakenings after going to sleep, and time taken to fall asleep (sleep latency) were used to assess sleep patterns.

Compared with existing treatment, CBT is likely to result in a large increase in total sleep time based on subjective sleep diary data. It may also improve sleep efficiency, and shorten the amount of time spent awake after falling asleep as well as sleep latency, with sustained improvements, the findings suggest.

But some of the exercise-based interventions also seemed to be effective, when compared with existing treatment. 

Yoga likely results in a large increase in total sleep time of nearly 2 hours and may improve sleep efficiency by nearly 15%. It may also reduce the amount of time spent awake after falling asleep by nearly an hour, and shorten sleep latency by around half an hour. 

Walking or jogging may result in a large reduction in insomnia severity of nearly 10 points, while Tai Chi may reduce poor sleep quality scores by more than 4 points, increase total sleep time by more than 50 minutes, and reduce time spent awake after falling asleep by over half an hour. It may also shorten sleep latency by around 25 minutes.

Further in-depth analyses revealed that Tai Chi performed significantly better on all subjectively and objectively assessed outcomes than existing treatments for up to 2 years. 

There are potentially plausible biological explanations for the findings, say the researchers.

With its focus on body awareness, controlled breathing, and attentional training, yoga may alter brain activity, thereby alleviating anxiety and depressive symptoms which often interfere with a good night’s sleep, they suggest.

Tai Chi emphasises breath control and physical relaxation and has been shown to decrease  sympathetic nervous system activity, dampening down hyperarousal, they add. And its combination of meditative movement and mindfulness may promote emotional regulation, deactivate ‘mental chatter’, and reduce anxiety. It may also help to curb the production of inflammatory chemicals over longer periods, they suggest.

Walking or jogging may improve sleep by increasing energy expenditure, curbing cortisol production, improving emotional regulation, boosting secretion of the sleep hormone melatonin, and enhancing the amount of deep sleep, they continue. 

The researchers acknowledge that 15 (68%) of the included trials contained design and methodological flaws. And there were no standardised, quantifiable metrics for the frequency or intensity of exercise interventions, while the sample sizes of some of the studies were small.

Nevertheless, they conclude: “The findings of this study further underscore the therapeutic potential of exercise interventions in the treatment of insomnia, suggesting that their role may extend beyond adjunctive support to serve as viable primary treatment options. 

“Although current clinical guidelines make only limited mention of exercise, this study provides relatively comprehensive comparative evidence that may inform the development of more specific and actionable clinical recommendations. 

“Given the advantages of exercise modalities such as yoga, Tai Chi, and walking or jogging—including low cost, minimal side effects, and high accessibility—these interventions are well-suited for integration into primary care and community health programmes.”

And there may well be one type of exercise that is best suited to easing a particular symptom of insomnia, they suggest, which further research may clarify.

---

Journal

BMJ Evidence-Based Medicine

DOI

10.1136/bmjebm-2024-113512 

Common sugar substitute shown to impair brain cells, boost stroke risk

 From low-carb ice cream to keto protein bars to “sugar-free” soda, the decades-old sweetener erythritol is everywhere.

But new University of Colorado Boulder research shows the popular sugar substitute and specialty food additive comes with serious downsides, impacting brain cells in numerous ways that can boost risk of stroke.

The study was published in the Journal of Applied Physiology.

“Our study adds to the evidence suggesting that non-nutritive sweeteners that have generally been purported to be safe, may not come without negative health consequences,” said senior author Christopher DeSouza, professor of integrative physiology and director of the Integrative Vascular Biology Lab.

First approved by the Food and Drug Administration in 2001, erythritol is a sugar alcohol, often produced by fermenting corn and found in hundreds of products. It has almost no calories, is about 80% as sweet as table sugar, and has negligible impact on insulin levels, making it a favorite for people trying to lose weight, keep their blood sugar in check or avoid carbohydrates. 

But recent research has begun to shed light on its risks.

One recent study involving 4,000 people in the U.S. and Europe found that men and women with higher circulating levels of erythritol were significantly more likely to have a heart attack or stroke within the next three years.

DeSouza and first author Auburn Berry, a graduate student in his lab, set out to understand what might be driving that increased risk.

Researchers in the lab treated human cells that line blood vessels in the brain for three hours with about the same amount of erythritol contained in a typical sugar-free beverage.

They observed that the treated cells were altered in numerous ways: They expressed significantly less nitric oxide, a molecule that relaxes and widens blood vessels, and more endothelin-1, a protein that constricts blood vessels. Meanwhile, when challenged with a clot-forming compound called thrombin, cellular production of the natural clot-busting compound t-PA was “markedly blunted.” The erythritol-treated cells also produced more reactive oxygen species (ROS), a.k.a. “free radicals,” metabolic byproducts which can age and damage cells and inflame tissue.

“Big picture, if your vessels are more constricted and your ability to break down blood clots is lowered, your risk of stroke goes up,” said Berry. “Our research demonstrates not only that, but how erythritol has the potential to increase stroke risk.”

DeSouza notes that their study used only a serving-size worth of the sugar substitute.  For those who consume multiple servings per day, the impact, presumably, could be worse.

The authors caution that their study was a laboratory study, conducted on cells, and larger studies in people are needed.

That said, De Souza encourages consumers to read labels, looking for erythritol or “sugar alcohol” on the label. 

“Given the epidemiological study that inspired our work, and now our cellular findings, we believe it would be prudent for people to monitor their consumption of non-nutrient-sweeteners such as this one,” he said.

 

---

Journal

Journal of Applied Physiology

DOI

10.1152/japplphysiol.00276.2025 

How useful are over-the-counter herbal products and dietary supplements used for depression?

In a new report published in Frontiers in Pharmacology researchers found 64 different over-the-counter (OTC) products that have been evaluated for depression – but with differing levels of evidence for each.  

Why look at this topic? 

Depression is increasingly common, to the extent that it is sometimes described as an epidemic. In the UK, 11.3% of people report mild depressive symptoms, 4.2% moderate depressive symptoms, and 3.3% severe depressive symptoms. Many of us know someone who struggles with minor or moderate levels of depression, or we may struggle from depressive symptoms ourselves. Often, we will try many things to help, such as antidepressants, talking therapies, meditation, or exercise. One common treatment people try is OTC products which are widely available and accessible from supermarkets, pharmacies, health food shops, and online.  

Once you start looking into which OTC product might be helpful, the list becomes endless. This is particularly the case if you read online blogs or look at social media promotion of various products. How do we know what is evidence-based? What products are effective? Are they safe?  

Given my background, I was naturally interested in understanding which products might be helpful and where research should focus next.  

What did we do? 

As a team we reviewed 23,933 study records and 1,367 papers. Overall, we found 209 clinical trials that assessed 64 OTC products for depression where the product was taken for more than one week. We focussed on the most rigorous way of evaluating the effectiveness and safety – clinical trials. Studies in adults aged 18-60 years with depression symptoms or a diagnosis were included. We also checked if there was an age bias by reviewing trials in older people separately and found there is. This project is part of a larger series of studies, also looking into products for anxiety and insomnia. 

It can be challenging to classify OTC products – different countries have different regulations, and some products are commonly used in some places but not in others. Two volunteers from the public helped us to narrow our choices, which helped us exclude some very obscure products, such as eels’ head powder!   

So what did we find?  

We anticipated a lot of studies, but over 200 was more than we expected! We had to recruit an intern to help us to sort through the findings. Studies were not always straightforward – some tested multiple doses or products, some were in addition to antidepressants and in some trials people had a range of physical conditions in addition to depression. We grouped our findings into products with substantive evidence (more than 10 trials), emerging evidence (between two and nine trials), and single trials only.  

The products with substantive evidence are those that are well known – omega-3s (39 trials), St John’s Wort (38), probiotics (18) and vitamin D (14) – as well as saffron (18), which is important in the Middle East and parts of Asia.   

Compared to placebo, fewer omega-3 trials found effects for depression than those that found no effects. However, St John’s Wort and saffron more often showed effects compared to placebo, and similar results to prescription antidepressants. Probiotics and vitamin D were more likely to reduce depressive symptoms than placebo.  

Out of the 18 products with emerging evidence, folic acid, lavender, zinc, tryptophan, rhodiola, and lemon balm were the most promising. Bitter orange, Persian lavender, and chamomile tea also showed positive effects in two trials each. Some products that are gaining in popularity, such as melatonin, magnesium, and curcumin, showed mixed effects upon depression across multiple clinical trials. Mixed results were also found for cinnamon, echium, vitamin C, and a combination of vitamin D plus calcium. Prebiotics, which support the good bacteria in our gut, and a supplement called SAMe did not seem to be better than placebo. 41 products had only a single trial available. This is helpful as a starting point, but does not give us conclusive evidence.  

It’s good news that very few safety concerns arose from any of these products, whether they were taken alone or in combination with antidepressants. However, a healthcare professional should always be consulted on whether a product might interact with something else you are taking. A higher standard of safety reporting in trials is essential – only 145 (69%) of the examined studies fully reported any side effects from the products.  

What do we recommend for the future? 

Whilst 89 trials tested products in combination with antidepressants, few looked at whether taking OTC products whilst having talking therapies has an additional effect. There was also only one study that looked at whether taking an OTC product (folic acid) saved the health service money – it was not more effective than placebo and did not lead to savings – but knowing more about this would be useful in future. Some evidence is also available for often overlooked OTC products.

So, what we have is relatively conclusive evidence for some products. When we looked at surveys of what people commonly take, chamomile, lavender, lemon balm, and echium emerged as commonly consumed products with an emerging evidence base, which we recommend be studied further. Other commonly used herbal medicines for depressive symptoms are ginseng, gingko, lime flowers, orange blossom, and peppermint, but no studies have evaluated these products. Thus, our study has pioneered an exploration into what research is needed to further assess such widely used health care products.  

Being consistently physically active in adulthood is linked to a 30–40% lower risk of death

 Being consistently physically active in adulthood is linked to a 30–40% lower risk of death from any cause in later life, while upping levels from below those recommended for health is still associated with a 20–25% lower risk, finds a pooled data analysis of the available evidence, published online in the British Journal of Sports Medicine.

The findings prompt the researchers to conclude that switching to a more active lifestyle at any point in adult life may extend the lifespan, and that it’s never too late to start.

Currently, it’s recommended that adults should aim for 150-300 weekly minutes of moderate intensity physical activity, or 75-150 weekly minutes of vigorous intensity physical activity, or a combination of the two, note the researchers.

But while these recommendations were based on the best evidence available, most of it captured measurements of physical activity at only one point in time, which might hide the potential impact of changing patterns during adulthood, they add.

The researchers therefore wanted to find out if differing patterns of physical activity, as well as its cumulative impact during adulthood, might be associated with a lower risk of death from all causes, and specifically from cardiovascular disease and cancer. 

They scoured research databases for relevant studies that assessed physical activity at two or more points in time, and included in their review 85 studies published in English up to April 2024, with sample sizes ranging from 357 to 6,572,984 participants. 

Fifty nine of the studies looked at long term patterns of physical activity across adulthood; 16 looked at the average benefits of different physical activity levels; and 11 explored the potential impact of cumulative physical activity on risk of death.

To overcome the challenges posed by different analytical methods used, the researchers carried out separate analyses for each of them.

Pooled data analysis of the study results showed that, overall, a higher level of physical activity was associated with lower risks of all the included outcomes. 

Consistently active people (32 studies) had around a 30–40% lower risk of dying from any cause, while those who increased their levels of physical activity (21 studies) from below those recommended had a 20-25% lower risk of death from any cause. 

Specifically, participants who switched from being physically inactive to being active were 22% less likely to die from any cause than those who remained inactive, while those who increased their leisure time physical activity levels were 27% less likely to do so.

On the other hand, swapping an active lifestyle for an inactive one wasn’t associated with a lower risk of death from any cause.

Generally, the associations observed between a high level of physical activity and a lower risk of death were more evident for cardiovascular disease than for cancer. 

Compared with participants who were consistently inactive over time, those who were consistently active, overall, or only in their leisure time, were around 40% and 25% less likely to die from cardiovascular disease and cancer, respectively. 

But in general, the evidence for the associations between physical activity patterns and death from a specific cause remained inconclusive, especially for death from cancer.

The pooled data suggested that people who were consistently active or who became active had lower risks of death from any cause, and specifically from cardiovascular disease, when meeting the recommended weekly physical activity levels.

But being consistently physically active and clocking up more than the recommended maximum weekly amount of moderate to vigorous intensity exercise was associated with only a small additional reduction in risk.

Maintaining or increasing physical activity at levels below the recommended weekly amount, however, was associated with appreciable health benefits, indicating that some physical activity is always better than none, say the researchers.  

And an average volume of physical activity that met the recommended weekly amount was also associated with a 30–40% lower risk of death from all causes. But more research is needed to confirm this, they add.

The researchers acknowledge some limitations to their findings, including that most of the studies included in the pooled data analyses relied on subjective assessments of physical activity, which may not always have been accurate. 

And there were only a few studies that looked at cumulative amounts of physical activity, or cancer deaths.

Nevertheless, the findings have important public health implications, insist the researchers.

“First, our results emphasised the importance of [physical activity] across adulthood, indicating that initiating [it] at any point in adulthood may provide survival benefits.” 

They add: “As being consistently active provides greater health benefits than being previously active (ie, no longer maintaining activity), this highlights the importance of sustained [physical activity] over time. 

“Future [physical activity] interventions may not only target inactive people, but also support active people to maintain their activity.”

Eating a healthy plant-based diet helps protect against inflammatory bowel disease

 

A large prospective study published in Molecular Nutrition and Food Research reveals that a healthy plant-based diet is linked with a reduced risk of inflammatory bowel disease.

For the study, 143,434 individuals in the UK reported on their dietary intake. During an average follow-up of 14.5 years, 1,117 participants developed inflammatory bowel disease—795 cases of ulcerative colitis and 322 cases of Crohn’s disease.

A healthy plant-based diet was associated with an 8% lower risk of ulcerative colitis, and a 14% lower risk of Crohn’s disease. An unhealthy plant-based diet was associated with a 15% higher risk of Crohn’s disease, with results suggesting that this was in part due to higher intake of vegetable oils and animal fats. Fruits and vegetables were identified as protective factors against inflammatory bowel disease.

Blood analyses suggested that the benefits seen in this study might be explained by the anti-inflammatory properties of plant-based foods.

“Our research indicates that a healthy plant-based diet may protect against inflammatory bowel disease, with its anti-inflammatory properties playing a key role,” said corresponding author Zhe Shen, MD, of the Zhejiang University School of Medicine, in China.

In menopause, sleep is vitally important for women’s long-term heart health

During the menopause transition, only 1 in 5 women have optimal scores using the American Heart Association’s health-assessment tool, known as Life’s Essential 8 (LE8). Among the tool’s eight components, four of them — blood glucose, blood pressure, sleep quality and nicotine use — are key in driving future cardiovascular risks, with sleep being particularly crucial for long-term cardiovascular health.

The findings – published today in Menopause – were made by researchers at the University of Pittsburgh, Albert Einstein College of Medicine and Baylor University.

“Previously we’ve shown that the menopause transition is a time of accelerating cardiovascular risk,” said senior author Samar R. El Khoudary, Ph.D., M.P.H., professor of epidemiology at Pitt’s School of Public Health. “This study underscores that it’s also an opportunity for women to take the reins on their heart health.”

The team analyzed health data collected from about 3,000 women who participated in the Study of Women’s Health Across the Nation (SWAN), an ongoing, longitudinal, multi-site, multi-ethnic study of midlife women that began in 1996. The researchers compared the women’s LE8 scores at baseline, around age 46, to their evolving health trajectories over time, from subclinical cardiovascular disease measures, such as increased carotid-artery thickness, to cardiovascular events, including heart attacks and strokes, to mortality of all causes. The team also examined impacts of each of the individual LE8 components: nutrition, physical activity, smoking abstinence, sleep, body mass index, blood lipids, blood sugar and blood pressure.

The analysis showed that four LE8 components — blood glucose, blood pressure, sleep quality and nicotine use — were the most important factors driving the study participants’ future cardiovascular risks.

Above all, sleep emerged as a potential predictor for long-term effects of cardiovascular disease events and all-cause mortality, though it was not linked to the shorter-term effects of carotid-artery thickening. The team found that at midlife, meeting the bar for healthy sleep, defined in Life’s Essential 8 as seven to nine hours on average for most adults, may contribute to women’s heart health and longevity, a hypothesis that should be tested in a future clinical trial, said Ziyuan Wang, Ph.D. candidate at Pitt Public Health and first author.

Low total LE8 scores correlated with increased cardiovascular risk, as expected—however, only 21% of the midlife women studied had an ideal LE8 score.

“With heart disease being the leading cause of death in women, these findings point to the need for lifestyle and medical interventions to improve heart health during and after menopause among midlife women,” said El Khoudary.