Category: 8. Health

What’s good for your aging gut may also be good for your aging brain. The first study of its kind in twins found that taking daily protein and prebiotic supplements can improve scores on memory tests in people over the age of 60.

Published early last year, the findings are food for thought, especially as the same visual memory and learning test is used to detect early signs of Alzheimer’s disease.

The double-blinded trial involved two cheap plant fiber prebiotics that are available over the counter in numerous nations around the world.

Watch the video below for a summary on the research:

Prebiotics are non-digestible consumables that help stimulate our gut microbes. One of the supplements was inulin; a dietary fiber in the fructan class. The other, a fructooligosaccharide (FOS), is a plant carbohydrate often used as a natural low calorie sweetener.

To test the effect of these supplements on the aging brain, researchers at King’s College London enrolled 36 pairs of twins over the age of 60.

Each duo was randomly split so that one twin was assigned a daily prebiotic in a protein powder and the other was assigned a daily placebo in a protein powder.

The twin who unknowingly took inulin or FOS generally scored higher on a cognitive test three months later.

Related: Can This Blue Chemical Really Boost Your Brain? Here’s What We Know.

What’s more, the daily fiber supplements were linked to slight changes in the gut microbiome between twins. The beneficial Bifidobacterium, for instance, were more plentiful in twins taking inulin or FOS.

Studies on mice suggest Bifidobacterium reduces cognitive deficits by regulating gut-brain connections.

“We are excited to see these changes in just 12 weeks. This holds huge promise for enhancing brain health and memory in our aging population,” said Mary Ni Lochlainn, a geriatric medicine researcher at King’s College London, when the findings were published in March 2024.

“Unlocking the secrets of the gut-brain axis could offer new approaches for living more healthily for longer.”

King’s College is home to the United Kingdom’s largest adult twin registry, and twin studies are highly valuable when it comes to differentiating between the effect of genetics and the environment on human health.

Past studies on rodents suggest that high-fiber supplements, like inulin and FOS, can ‘feed’ the colon’s microbiome, allowing ‘good’ bacteria to thrive.

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Some of these bacterial players are also linked to improved cognitive function in both mice and humans.

Evidence for the close relationship between the gut and the brain is growing year after year. Some experts are now so convinced by the results, they refer to the gut as the body’s ‘second brain’.

But the way these two nervous systems work together remains a mystery.

The recent twin study at KCL suggests that consuming certain ‘brain foods’ may be a promising way to treat cognitive decline.

But while prebiotics might improve some aspects of cognitive function in an aging brain, like memory and processing times, there don’t appear to be significant physical benefits.

Muscle loss didn’t improve among aging twins taking high-fiber supplements, despite the fact that inulin and FOS are important factors in musculoskeletal maintenance.

“These plant fibers, which are cheap and available over the counter, could benefit a wide group of people in these cash-strapped times. They are safe and acceptable too,” said geriatrician Claire Steves at KCL.

“Our next task is to see whether these effects are sustained over longer periods and in larger groups of people.”

The twins that participated in the current trial were mostly female, and even though the researchers adjusted for sex differences in their findings, they acknowledge that there may be some selection bias amongst KCL’s twin cohort.

That said, females are more susceptible to Alzheimer’s disease, and studies like the current one support the emerging idea that cognitive decline is not always a disease of the brain, but may involve external factors, too.

The gut has its fingers in many bodily ‘pies’, including the immune system and the central nervous system. Feeding its microbiome certain prebiotics and probiotics could open the door to treating a plethora of illnesses and diseases.

The study was published in Nature Communications.

An earlier version of this article was published in March 2024.

In a bid to better understand how cancer cells power their explosive growth and spread, scientists at Johns Hopkins Medicine say they have shed new light on the location and function of power-generating waves on the covering, or membrane, of these cells. The scientists say the waves, generated by rhythmic propagation of enzymes that produce energy from glucose, could potentially be used to better stage cancers, and as targets of drugs designed to slow down or halt the spread of cancer.

In experiments with human cancer cells grown in the laboratory, the researchers also suggest that measuring the energy-producing waves could help to stage cancers in a more universal and standardized way, regardless of subtypes and genetic mutations.

A report of the findings, funded in part by the National Institutes of Health, was published July 1 in the journal Nature Communications. 

Our findings suggest a correlation between higher levels of the energy-producing waves and a greater severity of the cancer, or the cancer’s potential to spread to other organs.”

Peter Devreotes, Ph.D., the Isaac Morris and Lucille Elizabeth Hay Professor of Cell Biology at the Johns Hopkins University School of Medicine

In cancer biology, scientists have long known of the Warburg effect, a process in which cancer cells utilize more energy from a less efficient pathway – glycolysis – rather than the more efficient mechanism, oxidative phosphorylation.

“That appears to be a paradox for cancer because cancer cells need much more energy to grow than normal cells,” says David Zhan, Ph.D., postdoctoral researcher in Devreotes’ lab. 

The researchers say it was taught in biochemistry class for many decades that glycolysis occurred uniformly in the cytosol, or the fluid matrix of the cell. 

But when the Johns Hopkins team examined cancer cells grown in the lab, they found that energy-generating enzymes gather and move as waves on the cell membrane, suggesting a more fine-tuned energy production process.

“This finding may challenge the canonical textbook knowledge that we all learn from the biochemistry course,” Zhan says.

Zhan and colleagues began the study by comparing samples of normal cells from the lining of human breast ducts with the same type of cells from people with breast cancer. The scientists used genetic engineering to tag fluorescent molecules to these glycolytic enzymes, enabling visibility and accurate measurement of these energy-producing enzymes under a high-powered microscope.

In breast cancer cells, the scientists found an abundant amount of glycolytic enzymes on the cells’ membrane, and that the molecules moved in organized waves. In normal cells, the scientists observed almost no glycolytic enzymes in the cell surface or waves.

“The more aggressive the cancer, the more waves we found on the cell surface,” says Devreotes. This discovery stems from earlier research from Zhan and Devreotes, published in 2020 in Developmental Cell, which suggests that cancer stages are linked to glycolytic wave activity.

In the most recent study, the scientists measured the level of ATP, the energy “currency” within breast cancer and normal cells, and found that more aggressive breast cancer subtypes were associated with higher levels of ATP produced from these waves.

Using other cancer cell types, including lab-grown cell lines of human pancreatic, lung, breast, colon and liver cancers, the researchers found similar results: increases in wave activity and levels of ATP in subtypes of cancer considered to be more aggressive when compared with less aggressive types of cancer cells.

“The increased presence of these glycolytic waves drives more ATP production from glycolysis in cancer cells, and that leads to enhanced reliance on glycolysis for energy,” Zhan says.

In search of a way to slow down the cancer cell energy wave activity, they used a small molecule, Latrunculin A (LatA), that disrupts the assembly of the glycolytic waves in cancer cell lines. The scientists then found a 25% decrease in ATP, suggesting that cancer cells largely depend on these waves to fuel and execute their daily energy-intensive activities.

“When we inhibit the activity of these waves, we may be able to stop these cancer cells from being able to consume nutrients and grow,” says Zhan. “Cancer cells require a lot of energy to drive cancer malignancy, so disrupting this process might be able to slow or stop its spread.”

Next, Devreotes says his team plans to investigate exactly how the energy-producing waves occur in the cell membrane.

Funding support for this research was provided by the National Institutes of Health (GM118177, FA95501610052, R01GM136711, S10 OD016374), the Multidisciplinary Research Program of the University Research Initiative of the Air Force Research Laboratory, the Defense Advanced Research Projects Agency, a Cervical Cancer SPORE Pilot Project Award (P50CA098252), the Sol Goldman Pancreatic Cancer Research Center, a Johns Hopkins Discovery Award and the W.W. Smith Charitable Trust Award.

In addition to Devreotes and Zhan, other scientists who contributed to this work are Dhiman Sankar Pal, Jane Borleis, Yu Deng, Yu Long and additional corresponding authors Chris Janetopoulos and Chuan-Hsiang Huang of Johns Hopkins.

Cannabis use for medical purposes is on the rise, especially for the management of chronic pain. Marco Ternelli, MSc Pharm, a compounding pharmacist in Bibbiano, Italy, fields a steady stream of about 1000 such prescription requests every month, he told Medscape Medical News.

Yet despite the surge in demand, the scientific evidence supporting their use for pain management remains a complex and often contradictory picture, making it difficult for clinicians to know how to advise their patients.

“There is strong evidence from preclinical research that supports the hypothesis of cannabinoid-induced analgesia,” David Finn, PhD, professor of pharmacology and therapeutics at the University of Galway, Galway, Ireland, told Medscape Medical News. “But the clinical evidence is weaker, in large part due to low quality studies with low sample size or short duration of treatment and sometimes patient population not well-defined.”

Medical Cannabis in Europe

The regulatory landscape for medical cannabis is undergoing a significant transformation in Europe.

In Italy, authorized cannabis-based medicines can be prescribed to patients using a special form approved by the Ministry of Health.

Two cannabis-based medicines have received UK marketing authorization and can be prescribed there by specialist doctors.

Germany legalized recreational cannabis in 2024, a move that also broadened access to medical cannabis.

Other countries like France, Spain, and Denmark are in the process of establishing or expanding their medical cannabis programs.

Slovenia has also moved to regulate medical cannabis, and the Netherlands is set to break its state monopoly on its production.

Figures of medical cannabis use in Europe are difficult to find, but a recent Prohibition Partners European Cannabis Report suggested that almost half a million people had obtained it through legal routes by the end of 2024.

In 2019, the European Parliament and the European Medicinal Cannabis Association, a Brussels-based industry body representing the interests of European medicinal cannabis suppliers and manufacturers, called for unified rules and more research. Since then, more countries have regulated cannabis use for medical purposes, but gray areas remain and the regulatory landscape remains fragmented.

What Is Medical Cannabis and How Does It Work?

The Cannabis sativa plant contains more than 100 cannabinoids that interact with the body’s endocannabinoid system (ECS). The two most well-known and studied cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Minor cannabinoids include cannabigerol), cannabichromene, and cannabinol. Additionally, other compounds, such as terpenes like limonene, pinene, and beta-caryophyllene, as well as flavonoids, may have a role in the overall efficacy of medical cannabis.

THC is a partial agonist of CB1 receptors, which are highly concentrated throughout the central nervous system in areas related to pain modulation. This interaction is responsible for not only the main analgesic effects but also psychotomimetic properties of cannabis.

CBD acts as a negative allosteric modulator of CB1 and CB2 receptors, dampening their response to agonists like THC and natural endocannabinoids. Unlike THC, CBD is not psychotomimetic, so it does not give the “high” and it can help reduce THC’s psychotomimetic properties when used in combination. Its therapeutic potential is likely due to its influence on a broad range of molecular targets, including serotonin 1A receptor and peroxisome proliferator-activated receptor gamma. It also exhibits antioxidant properties and can reduce proinflammatory cytokines, such as interleukin (IL)-6, IL-1, and TNF-alpha.

Minor cannabinoids are non-psychotomimetic and bind to multiple receptors. “These are not selective compounds. They are very promiscuous. But many of these receptors are implicated in pain,” Kent Vrana, PhD, a professor in pharmacology at the Center for Cannabis and Natural Product Pharmaceutics at Penn State Neuroscience Institute, Pennsylvania, told Medscape Medical News.

The varying ratios of THC, CBD, and minor compounds in different products factor in their therapeutic effects and side effect profiles. Products with a higher percentage of THC are generally considered more effective for pain relief but carry a higher risk for psychotomimetic side effects. Products containing mainly or solely CBD are often favored for inflammatory conditions and are generally better tolerated.

What Does the Evidence Say About Cannabinoids for Chronic Pain?

In 2021, the International Association for the Study of Pain gathered 20 international pain researchers to systematically analyze the available evidence on the use of cannabis in pain management. They found that, overall, numerous knowledge gaps exist and that the quality of the research is flawed.

Other reviews published in 2021 found the evidence was inconsistent, with some studies showing a slight improvement in pain relief compared with placebo and side effects that included dizziness, drowsiness, nausea, vomiting, cognitive impairment, and impaired attention.

Two recent reviews, both published in February this year, have suggested that cannabis may be a promising alternative or adjunct to opioids, with some studies showing that its use can lead to a reduction or cessation of opioid prescriptions.

In the journal Medical Cannabis and Cannabinoids, researchers found convincing evidence that cannabinoids are often beneficial. Sativex, a spray with equal parts THC and CBD, for example, has been shown to reduce neuropathic pain. It is approved in Canada and Europe for cancer-related pain, often used as an adjuvant to manage pain caused by cancer or its treatments. “That is probably the one product for which we have good data,” said Emily M. Lindley, PhD, an associate professor in the Department of Orthopedics at the University of Colorado Anschutz Medical Campus. “Aside from that, I would be hard-pressed to find probably more than one, maybe two studies using the exact same product in trials.”

Another group of researchers reported in the journal Biomedicines that the evidence for cannabinoids is mixed across conditions. Some randomized controlled trials showed moderate evidence of cannabinoid efficacy in relieving neuropathic pain and reasonable evidence for symptom relief in multiple sclerosis. Weaker evidence was found for the relief of headache and migraine. The evidence remains inconsistent for pain relief in fibromyalgia, cancer-related pain, and musculoskeletal pain. The main risks and side effects linked to the use of cannabinoids are addiction and tolerance, especially with THC. Some patients report increased levels of anxiety, psychosis, and cognitive impairment. Other risks include drug interactions, particularly with medications metabolized by cytochromes P450, a family of enzymes involved in the oxidation and reduction of lipid-soluble compounds.

Some studies included in the Biomedicines review showed that many patients view cannabis to be safer than opioids and report subjective improvement in quality of life despite the level of their pain remaining the same. “Are we conflating the euphoria with the analgesia?” Vrana asked. Or maybe cannabinoids have a holistic effect, said Rachael Rzasa Lynn, MD, an anesthesiologist and pain management expert at UCHealth Pain Management Clinic at Anschutz Medical Campus.

This potential holistic effect was examined in a small study published in 2023 in Journal of Cannabis Research. That study compared the holistic effects of medical cannabis with those of opioids on the pain experience of Finnish patients with chronic pain. It found that both substances were perceived as equally effective in reducing pain intensity, but cannabinoids were associated with more positive emotional and holistic effects and an overall sense of well-being. The authors suggested that the psychoactive effects of medical cannabis, rather than being solely negative, may be a part of its therapeutic mechanism.

Lindley and Rzasa Lynn have also compared the short-term acute effects of a THC and minimal CBD vaporized combination with those of placebo and oxycodone. The study, which is yet to be published, showed that cannabis provided a significant relief in chronic back pain, more than both placebo and oxycodone.

Why Is It Hard to Find Agreement?

C sativa has been used as a remedy for millennia. But the classification of cannabis as a narcotic drug has severely hampered research into its therapeutic potential, explained Rzasa Lynn. Beyond the regulatory hurdles, there are several inherent challenges in conducting high-quality clinical trials on medical cannabis, particularly for chronic pain, she said.

Cannabis is not a single compound but a complex plant. Treatments are nuanced, with significant variations in routes of administration such as oils, flowers, and edibles. Different growth conditions produce different cannabinoid profiles, and there can be high batch-to-batch inconsistency. This makes it difficult to standardize interventions and compare results across studies. “It’s not like a single pill at a couple of doses. It’s so much more complicated,” Lindley said.

The plant extract contains hundreds of pharmacologically active molecules, explained Finn. This complexity makes pharmacokinetics challenging. He added that different people might respond differently to the same extract. “To some extent, cannabis is used by patients as a personalized medicine. They’re choosing the THC and CBD concentrations that work for them. They’re titrating those to suit their needs. But randomized controlled trials often aren’t configured in that sort of a way,” he said.

Synthetic products might solve this problem, but the experts agreed that it is likely the combination of the wide range of compounds in the plant working together that enhances the overall therapeutic impact. “We don’t know what we might be losing if we use a pure product,” Rzasa Lynn said.

Also, pain is a complex and subjective experience that varies widely between patients and even within the same patient over time. “Chronic pain is distinct from what most people experience day to day with acute pain. It behaves a little bit differently in the face of treatment over prolonged periods,” said Rzasa Lynn. “This creates limitations for measuring outcomes.”

Another challenge is to find a “good patient population,” she said. “When you’re running a clinical trial, you want the human equivalent of a lab rat, but pain can be really difficult to narrow in a way that you can easily compare one patient to another, not only because it’s subjective but also because there are so many different physiological pathologies that can lead to pain as the outcome, and they all may respond very differently to different types of treatment.”

What Should Clinicians Know?

Lindley said clinicians should create an environment where patients feel comfortable discussing their interest in the use of cannabis. Many patients are exploring cannabis on their own, and even if a clinician is not an expert, expressing a willingness to learn with the patient can be a productive approach, she said. “Too often it’s just swept under the rug.”

Rzasa Lynn said it is important to evaluate if cannabis is truly providing a functional benefit. “We got so focused on pain as this unidimensional number, 0-10, and that is our success,” she said. “But the goal of any pain-reducing treatment is to improve global function. And that’s not just physical function, but that’s social engagement, and that’s work around the house, and that’s sleeping well, and everything that goes into quality of life.”

If a patient is using high doses of cannabis but still reports inadequate pain control and poor function, the use of these products should be questioned, she explained. This conversation should be framed around the patient’s goals and their perception of how cannabis helps achieve them. “Is it really making you better? Because if it was that effective, I think you probably wouldn’t be here right now.”

Ternelli, Finn, Lindley, and Rzasa Lynn reported having no relevant financial relationships. Vrana reported receiving an unrestricted research grant from Pennsylvania Options for Wellness. 

Manuela Callari is a freelance science journalist specializing in human and planetary health. Her work has been published in The Medical Republic, Rare Disease Advisor, The Guardian, MIT Technology Review, and others.

When Nikki Myers found the lump in her neck last fall, she visited an urgent care clinic. Doctors suspected Myers had a chest infection that caused an inflamed lymph node and performed a CT scan. But the scan offered unclear results.

“They were confused because they were like, ‘Usually these areas on a CT scan would determine some sort of infection,’” Myers, 33, of Long Beach, Texas, tells TODAY.com. “They were like, ‘Here try this antibiotic, and then if it doesn’t get better, come back and we can do additional testing.’”

Over the next two weeks, the lump remained, and doctors sent her for more testing. Eventually, she learned what was wrong — she had Stage 4 ovarian cancer.

“The red flag was there. I hadn’t been sick prior. I had no previous colds,” she says. “Cancer was totally random in my eyes.”

A Lump Suddenly Appears

In September 2023, Myers gave birth to her third child via Cesarean section and appeared to be healthy then.

“During that time, I had multiple scans, ultrasounds and blood work and nothing was detected,” she recalls.

In the summer of 2024, she noticed that she had some bloating often around the time of her period, which she didn’t think was unusual.

“Bloating was not uncommon for me,” she says. “(I was) trying to lose some weight … the first place I would lose weight was my stomach (but) it didn’t go anywhere.”

In September, she noticed the lump and visited an urgent care facility. After, she took the medication as directed.

“On the last day of (taking) my antibiotic, I woke up and my shoulder felt a little stiff,” she says. “I was never in pain. I had always pressed on the lump. It never got bigger.”

Myers visited urgent care again because the lump remained, and doctors gave her another antibiotic and performed a chest X-ray. They noticed more masses.

“They started throwing around ‘an oncologist,’” she says. “They threw that word out there like, ‘Let’s send a referral to the oncologist.’”

They referred her to an otolaryngologist for a biopsy, and recommended she get a mammogram because the doctor felt something in her right armpit. The biopsy and bloodwork revealed that Myers had ovarian cancer that had spread to her neck, making it Stage 4 ovarian adenocarcinoma, which had spread throughout her lymphatic system.

“They knew that I had quite a lot of tumors,” she says. “It was quite far away from the origin, which was down below my pelvic region.”

She visited a gynecological oncologist in Dallas and learned about the next steps. She underwent a PET scan to determine “how invasive it was,” and started chemotherapy, which was four rounds of chemotherapy every three weeks.

“I’m getting blasted with chemo,” she says.

Genetic testing revealed that she was positive for BRCA1, a genetic mutation that increases one’s risk of breast and ovarian cancers, especially at an earlier age. Following chemotherapy, doctors performed another CT scan and more bloodwork to see if her tumor markers decreased. Then they performed surgery.

“They wanted to remove the bulk of (the cancer),” she says. “They did a total hysterectomy.”

Doctors removed her uterus, cervix, fallopian tubes and lymph nodes and “anything that looked questionable.”

Following surgery, she underwent three more rounds of chemotherapy and is now on a PARP inhibitor, a medication that treats cancers from genetic mutations, such as BRCA, that restricts DNA repair in cancer cells, says MD Anderson Cancer Center.

“I can take that up to two years in the hopes of not getting a recurrence,” she says.

Ovarian Cancer

Most ovarian cancers — about 85% to 90% — are carcinomas, the American Cancer Society notes. In 2025, about 20, 890 women will learn they have ovarian cancer with about 12, 730 dying from ovarian cancer, the organization says.

While it often occurs in women in their 60s or older, having a BRCA mutation increases the chances of developing ovarian cancer the National Cancer Institute says. About 39% to 58% with a BRCA1 mutation will be diagnosed with ovarian cancer and 13% to 29% of people with the BRCA2 mutation will develop it.

Diagnosing ovarian cancer can be difficult because it has few symptoms. If symptoms do occur, they can be confused with other conditions, past TODAY.com reporting says. Signs can include:

“A lot of the time there are no symptoms, and even when it’s Stage 3 or 4, symptoms are very vague,” Dr. Zaid Al-Wahab, a gynecological oncologist at Corewell Hospital in Royal Oak, Michigan told TODAY.com previously. “There’s always this perception that it happens in certain types of patients … it can happen in much younger women so more awareness of ovarian cancer (is needed).”

‘Terrifying’ and ‘Wonderful Moments’

As a mom of three children under 10, Myers feels grateful that her “wonderful support group” helped her navigate a cancer diagnosis and treatment.

“My entire family, the moment they found out I had cancer, flew in and drove in for me,” she says. “Helping whenever, especially with my children, and my kids have been wonderful through all of this.”

Myers’ identical twin sister is also BRCA1 positive, and doctors removed her fallopian tubes and uterus after a difficult delivery. Luckily, she had no signs of cancer at that time. For now, Myers’ condition is stable, and she’ll see her doctor every three months to make sure she remains healthy.

“I have been very fortunate to have a very positive reaction to everything,” she says. “I haven’t been in pain, except for obviously the pain chemo inflicted on me.”

She shares her story on TikTok so other young people with cancer don’t feel as alone and that has helped her navigate some of the challenges of having cancer.

“Cancer is scary. It’s all-consuming. But it doesn’t have to be that way,” Myers says. “There are terrifying moments and there are wonderful moments.”

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease, expressing its inflammatory manifestations within the synovial joints, provoking pain, swelling, and, if untreated, destroying the joints.^1,2 Despite significant progress in the cessation of its physiopathology and the designing of tailored therapies, RA remains difficult for patients and healthcare providers to cope with.^3,4

The complicated interrelation of not only different immune mediators but also of numerous signaling pathways ensures that inflammation is self-maintained in RA.⁵ Of these mediators, IL-8 is the most powerful cytokine that plays the most important role during the inflammatory process in the synovial cavity.⁶ IL-8 is mainly released upon being activated by macrophages, fibroblasts, and endothelial cells in response to the inflammation trigger, and it acts through the production of neutrophils and their activation at sites of inflammation.^7,8

Patients with RA have been found to have elevated levels of IL-8 in joint synovial fluid and the blood was assessed for the disease and joint damage severity.⁹ Along with a wide variety of immune mediators that have been found to be involved in RA, IL-8 and vitamin D have come to light as crucial with the prospects of influencing inflammation responses and dysregulated immunity. IL-8, representing the family of cytokines with a proven pro-inflammatory potency, exhibits its effects by mediating the recruitment and activation of neutrophils in the synovial fluid, whereby inflammation is only amplified in RA patients.^10,11 Besides its aggressive joint damaging effect, the prolonged inflammatory state plays a role in impairing overall health which makes RA chronic disability.¹²

However, vitamin D, which was once known as a bone health and calcium homeostasis regulator, has got the interest of researchers because of its immunomodulatory capacities.¹⁰ Besides the classical functions, apart from its anti-inflammatory effects, vitamin D is one of the factors that modulate the activities of various immune cells, including T lymphocytes, macrophages, and dendritic cells.¹³ The results of a number of epidemiological studies have shown how low levels of vitamin D in the serum correspond with an increased possibility that a person will relapse or progress into rheumatoid arthritis.¹⁴ Though the activities of IL-8 and vitamin D in inflammation and immune functioning are quite clear, the exact processes through which they interact in RA are yet to be fully understood. Discovering the interplay between IL-8 and vitamin D concentrations in RA patients might help us to recognize in more depth the complicated immunological interactions that lead to sickness development and progression.

The primary objective of this study is to investigate the correlation between IL-8 and 25-hydroxyvitamin D levels in patients diagnosed with rheumatoid arthritis. To the best of our knowledge, this is the first study to explore the interplay between these biomarkers in Jordanian RA patients.

Therefore, this study aims to compare serum levels of IL-8 and vitamin D between RA patients and healthy controls and assess the relationships between these biomarkers and other inflammatory indicators such as RF, anti-CCP antibodies, CRP, ESR, and WBC count. Understanding these associations may help clarify the roles of IL-8 and vitamin D in RA pathogenesis and guide future diagnostic or therapeutic strategies.

Subjects and Methods

Design and Study Population

The current study was carried out between February and April 2024 on 123 participants divided into two groups, 63 patients with RA fulfilling the American Rheumatism Association 1987 revised criteria for the classification of RA and 60 normal healthy age-and sex-matched controls. The study was conducted in a private medical laboratory (Smart Labs, Amman, Jordan). Participants were selected from subjects referred to in the laboratory for routine checkups. This study was conducted in accordance with the principles of the Declaration of Helsinki. Zarqa University approved the study protocol (IRB /ZU/2024/15). The objective of the study was explained, and information sheets and consent forms were distributed to participants before data and blood collection.

Subjects were divided into two groups based on levels of RF. Subjects with RF >14.0 IU/mL were classified as patients, while subjects with lower than these cut-off values were considered controls. History and clinical examinations were conducted. Age, gender, intake of medication, and supplements were assessed as appropriate.

Participants were excluded from the study if they had any of the following conditions: other autoimmune diseases, chronic infections, malignancies, liver or kidney disorders, recent Vitamin D supplementation (within the past three months), corticosteroid or immunosuppressive therapy unrelated to RA, or pregnancy. These criteria were applied to ensure that the observed changes in Vitamin D and IL-8 levels were specifically related to RA and not influenced by other confounding conditions.

Biochemical Investigations

Ten milliliters of peripheral venous blood was collected from each subject via venipuncture and divided into two parts. The first part was left without an anticoagulant for serum separation, while the second part was collected into sterile EDTA vacutainers for complete blood count and ESR measurements. ESR was recorded in millimeters per hour. CRP, mg/L and RF, IU/mL were analyzed using immunoturbidimetry on a cobas 6000 (Roche) CCP, U/mL was checked using an ELISA assay on a Chorus Trio 2013 system (Italy). Vitamin D (ng/mL) 25-OH vitamin D was evaluated using an enzyme-linked immunosorbent assay in serum samples from patients, on a cobas 6000 (Roche) system.

Total concentrations of IL-8 in serum samples were measured using a commercial Enzyme-linked Immunosorbent Assay (ELISA) Kit (My BioSource, according to manufacturer’s instructions.

Statistical Analysis

Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp). Qualitative data were described using numbers and percentages. The Kolmogorov–Smirnov test was used to verify the normality of distribution. Quantitative data were described using ranges (minimum and maximum), mean, standard deviation, median, and interquartile range (IQR). The significance of the results obtained was judged at the 5% level.

Results

Characteristics of Patients Population

Sixty-three patients with confirmed RA were enrolled in this study. Sixty individuals served as a control group. The details of age and gender of the individual are presented in Table 1. Patients did not receive any treatment. Most of the patients were females (47 females versus 16 males). In controls, there were 35 males versus 25 females. Mean age of RA patients was 44.42 ± 10.01 while that of controls was 36.6 ± 12.9 years.

Serum Levels of IL-8

A statistically significant higher levels of IL-8 (P < 0.001) in RA patients compared to healthy controls, 33.0 (176.5 ± 546.9) versus 2.8 (3.1 ± 2.7) was demonstrated (Table 2).

Table 2 Comparison Between the Two Study Groups According to IL-8 and Vitamin D

Serum Level of Vit D

A statistically significant lower levels of Vitamin D (P < 0.001) in RA patients compared to healthy controls, 34.0 (25.0–47.6) versus 48.0 (37.0–55.0) was demonstrated (Table 2).

In Table 3, all inflammatory markers (RF, CCP, CRP, ESR, and WBC) showed significantly higher levels in the patients’ group compared to normal subjects (p= <0.001 for all parameters).

Table 3 Comparison Between the Two Study Groups According to Inflammatory Parameters

Among the patients’ group, Table 4 showed no correlation between IL-8 and vitamin D with p = 0.737. In addition, Table 5 illustrates that there is no correlation between IL-8 and vitamin D with other inflammatory markers (RF, CCP, CRP, ESR, and WBC) with IL-8 (P= 0.061, 0.387, 0.375, 0.661, and 0.281; respectively), and vitamin D (P= 0.114, 0.416, 0.769, 0.663, and 0.777; respectively).

Table 4 Correlation Between IL-8 and Vitamin D in Patients’ Group (n = 63)

Table 5 Correlation Between IL-8 and Vitamin D with Different Parameters in Patient Group

Discussion

The current study intended to determine the Plasma Rheumatoid Factor (RF), inflammatory markers, and cytokines among the patient and normal control subjects emphasizing Vitamin D and interleukin-8 (IL-8). This study involved 123 participants divided into two groups: 63 patients and 60 normal subjects, out of each group 15 males and 15 females. To give a clearer perspective on the magnitudes and directions of these outcomes, the results of this study were benchmarked against the results of prior research.

The present study showed that the female patient group had a higher percentage (74. 6%) than the normal group (41.7%). This has been consistent with another study which indicates that autoimmune diseases such as rheumatoid arthritis are more prevalent in the female population compared to the male population (Kvien et al, 2010; Tobón et al, 2010; Cincinelli et al, 2018) showed that female patients account for some 57% of rheumatoid arthritis cases, which is 1.5 times the number of male patients, and this study agreed with that, too. On hormonal differences, especially estrogen, it has been proposed that they contribute to gender differences in autoimmune disease susceptibility.^15–17

The comparison of the mean vitamin D levels between the patient and the normal group revealed that the patient had lower vitamin D levels than the normal group. As for the patient group the mean Vitamin D level was established to be 41.4 ± 25.2 < w = 46 > 5 ± 12.4. Analyzing the relationship between Vitamin D and autoimmune diseases¹⁸ identified low levels of the Vitamin as present in individuals with autoimmune diseases and discussed how Vitamin D plays an important role in immune regulation and that deficiency in it increases vulnerability to autoimmune diseases. These findings of a significant difference re-emphasize that Vitamin D supplementation may be effective in the management of rheumatoid arthritis and other inflammatory diseases as an additional therapy.¹⁸

Vitamin D levels were significantly lower in the RA patient group compared to the controls (p = 0.002). This finding supports previous studies that highlighted the role of Vitamin D deficiency in the pathogenesis and progression of RA. For instance, Rossini et al, 2010; Meena et al, 2018 found that Vitamin D deficiency is common in RA patients and is associated with increased disease activity and severity. Low levels of Vitamin D may contribute to the immunological dysregulation observed in RA, as Vitamin D has immunomodulatory effects that are crucial in maintaining immune homeostasis.^19,20

The levels of IL-8 were significantly higher in the patient group compared to the normal group (MD = 176,95% CI: 121–230; WMD = 0.33,95% CI: 0.21–0.45; p < 0.001). 5 ± 546.9 pg/mL and 3.1 ± 2.7 pg/mL, respectively. Russo et al, 2014 reported that IL-8 exhibits pro-inflammatory properties and has been linked to rheumatoid arthritis due to its contribution to inflammation.⁸ Research has established that IL-8 has a significant role in inflammation, which is associated with rheumatoid arthritis. Physiologically, a rise in the level of IL-8 indicates that there is increased inflammatory activity in the body of patients with rheumatoid arthritis, as established Gremese et al, 2023 who noted that higher levels of IL-8 were found in patients with active rheumatoid arthritis and are associated with disease activity.⁹ The levels of IL-8 were significantly higher in the RA patient group compared to the control group (p < 0.001). The levels of IL-8 were significantly higher in the RA patient group compared to the control group (p < 0.001). IL-8 is a pro-inflammatory cytokine that plays a critical role in the inflammatory process associated with RA. Elevated levels of IL-8 in RA patients have been reported in studies,²¹ indicating its role in promoting the recruitment and activation of neutrophils and other immune cells in the synovial fluid and tissues of RA patients. This study’s findings corroborate these reports, suggesting that IL-8 is a key player in the inflammatory milieu of RA. Both RF and anti-CCP were significantly higher in the patient group or 49 ±13 versus 17±5, p < 0.001, and 32 ±11 versus 8 ± 2, p < 0.001, respectively. This was expected given the persistently elevated inflammatory marker evident in these patients. These findings are also consistent with the data of Nishimura et al, 2007 who observed that high titers of circulating RF and CCP antibodies correlate with rapid disease progression in patients with RA.²² CRP and ESR are proven biomarkers of inhabitants and are pragmatic tools in clinical medicine to assess the level of inflammation and response to various treatments.

A cross-sectional comparison of the variables showed no positive relationship between IL-8 and vitamin D in the patient group with a correlation coefficient of 0.737. Additionally, it is worth underlining that there was no graded relationship between IL-8 and other markers of inflammation: RF, CCP, CRP, ESR, and WBC with p-values ranging from 0.061 to 0.661. In the same manner, results on Vitamin D were not different from these inflammatory indicators with corresponding p-values of 0.114 to 0.777. Based on these observations, IL-8 and Vitamin D, have a relationship exclusively with the inflammation process and disease states, but they are unlikely to combine in a way that is reflected in the parameters that were measured in this study. The lack of correlation is in line with Cutolo et al, 2011 where the authors noted that Vitamin D deficiency and inflammatory cytokine levels contribute to disease severity in RA but do not interact with each other.²³ However, RF and CCP are specific markers for RA, and elevated levels of these markers are associated with more severe disease with an ability to predict disease progression. This study’s results align with previous findings that both RF and CCP are significantly higher in RA patients, underscoring their diagnostic and prognostic value.

Elevated levels of the systemic inflammation markers CRP and ESR in RA patients, as observed in this study, indicate ongoing inflammation and are commonly used to monitor disease activity and response to treatment.

An increased WBC count in RA patients reflects the inflammatory response and is a common finding in active RA. This study’s results are in line with the general observation that RA is associated with leukocytosis due to chronic inflammation. The results of the present study are in almost complete concordance with the earlier findings pointing towards the generally accepted understanding of the disease causation and the following clinical progression of RA and other autoimmune disorders. Several elements have supported the findings such as, the patient group predominantly consisting of females, lower levels of Vitamin D, higher levels of IL-8, and higher significant inflammatory markers have all been documented in the previous literature. Nonetheless, the observed relationship between IL 8 and RA did not show any significant association with Vitamin D or other inflammatory biomolecules; this points to the conclusion that both factors have independent roles to play in the progress of the disease.

The present study has several limitations. Firstly, the number of patient samples is small, which may affect the generalizability of the findings. Secondly, the patients were taking various medications, which could potentially influence the results. Lastly, the use of anti-inflammatory medications among the participants may have affected the inflammatory markers, thereby impacting the study’s outcomes.

Conclusion

In this study, we found that people with rheumatoid arthritis had higher levels of IL-8 and lower levels of vitamin D compared to healthy individuals. However, these two markers did not show a clear link to each other or to other signs of inflammation. This suggests that IL-8 and vitamin D may affect the disease in different ways. Our findings highlight the importance of checking vitamin D levels in RA patients and suggest that IL-8 could be a useful marker for tracking inflammation. More research is needed to better understand how these factors contribute to the disease.

Data Sharing Statement

Derived data supporting the findings of this study are available from the corresponding author on request.

Ethics Approval Statement

This study was conducted in accordance with the principles of the Declaration of Helsinki. The study was examined and given approval by the Zarqa University’s Ethics Committee for Scientific Research (ECSR), with approval number IRB/ZU//2024/15.

Consent to Participate and Publication

Informed consent was taken from all participants.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This research was supported by Zarqa university. (Grant No: 74/33/1/1).

Disclosure

The authors declare that they have no competing interests.

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Spirituality is becoming an area of growing interest in cardiovascular medicine as evidence mounts linking it to improved physiological outcomes and treatment adherence. Emerging research suggests that qualities such as purpose in life, gratitude, and hope — even when not tied to religious practice — may positively influence cardiovascular health.

At the 45th Congress of the Cardiology Society of the State of São Paulo, experts explored how this subjective dimension may contribute to fewer hospitalizations, better blood pressure control, and improved clinical outcomes in patients with heart disease.

Opening the discussion, cardiologist and hypertension specialist Fernando Nobre, MD, PhD, emphasized the important distinction between spirituality and religiosity. While often used interchangeably, the two are not synonymous. Religiosity refers to structured beliefs, practices, and rituals associated with faith and community life. In contrast, spirituality encompasses moral, emotional, and mental values that shape an individual’s behavior and decision-making. These can be assessed using scientific frameworks.

“Religiosity is about how connected someone is to their religion — attendance at services, observance of rituals. That can be part of spirituality, but spirituality goes further. It cuts across and transcends a person’s life, shaping their choices and way of living,” said Nobre, who is also a professor at the University of São Paulo, São Paulo, Brazil.

Patients with a stronger sense of spiritual engagement tend to have lower blood pressure and are less likely to develop hypertension. Studies suggest these effects may be linked to lower peripheral vascular resistance, improved cardiac output, and better adherence to prescribed treatment — particularly among women.

One recent example is the Brazilian Feel study, led by cardiologist Maria Emília Figueiredo Teixeira, MD, PhD, at the Brazilian Federal University of Goiás, Goiânia, Brazil. Cited by Nobre, the study was published in 2024 and followed 100 individuals with hypertension over 12 weeks. The intervention group received short, non-religious videos and messages promoting spiritual reflection — delivered via WhatsApp — and were encouraged to write about gratitude, forgiveness, life purpose, and optimism.

The group receiving the intervention showed a more significant drop in blood pressure and notable improvement in endothelial function, measured through flow-mediated dilation.

“If spirituality appears to influence both key components of blood pressure, that alone is reason enough for us to understand it better,” said Nobre.

Heart Failure: Fewer Hospitalizations, Better Quality of Life

In patients with heart failure, spirituality may influence not only psychological resilience but also the underlying pathophysiology of the disease. Studies have found that individuals with greater spiritual engagement show reduced sympathetic nervous system activity, lower levels of stress hormones, and decreased inflammatory cytokines. Clinically, these changes are associated with fewer symptoms, fewer hospitalizations, and an improved quality of life.

At the session, cardio-oncologist Rafael Nunes, MD, PhD, of the Oswaldo Cruz German Hospital, São Paulo, highlighted a 2022 review published in JACC: Heart Failure. The review analyzed 47 studies examining spirituality in heart failure patients. Despite differences in methodology, the evidence consistently linked higher spirituality levels with lower rates of anxiety and depression, improved adherence to treatment, fewer hospital admissions, and, in some cases, reduced mortality.

A follow-up review published in 2023 reinforced these findings and added an important distinction: Participation in religious organizations alone was not sufficient to deliver clinical benefit. “It’s the spiritual experience — the meaning a person assigns to their life, beliefs, and motivations — that is associated with positive outcomes,” explained Nunes.

Another study underscored this point. Titled Is Belonging to a Religious Organization Enough?, the study separately assessed the effects of religiosity and spirituality. The results showed that spirituality was linked to lower levels of anger, anxiety, and emotional exhaustion. In contrast, religiosity alone — without deeper personal engagement — did not significantly impact emotional well-being.

Coronary Artery Disease: Stress and Acute Cardiac Events

While coronary artery disease can remain stable for years, its progression into acute myocardial infarction — one of the leading global causes of death — can be sudden and unpredictable. Although plaque accumulation is gradual, rupture events are often triggered by acute neuro-immuno-hormonal and inflammatory responses.

Roberto Veiga Giraldez, MD, PhD, director of the Acute Coronary Care Unit at the Heart Institute, Hospital das Clínicas, University of São Paulo, cited research linking acute myocardial infarction to external stressors such as natural disasters or high-stakes sporting events. During these situations, sympathetic nervous system activation and systemic inflammation intensify, raising the risk of acute coronary syndromes.

One study cited by Giraldez was conducted in South Korea, where cities vulnerable to earthquakes experienced a significant spike in acute coronary syndrome cases immediately following seismic events. Incidence peaked shortly after the quakes and gradually declined over time.

Another analysis focused on the 2006 FIFA World Cup. In several German cities, rates of myocardial infarction rose during high-stakes national team matches — especially during tense or decisive games. The highest incidence occurred in the early minutes of play, when fan anxiety was likely at its peak.

“These data illustrate how acute stress can influence outcomes in patients with coronary artery disease,” said Giraldez. “Spirituality can help mitigate this impact. Resignation and faith — whatever form they take — can help individuals face stressful situations with greater composure.”

How Should Clinicians Address Spirituality?

According to Nunes, spirituality should be systematically integrated into clinical practice — always with sensitivity to the patient’s values, preferences, and boundaries. “We should approach spirituality with the same seriousness we apply to mental health and lifestyle habits. Understanding what matters to the patient and why they seek care can shape the therapeutic journey,” he said.

He advocated for incorporating spiritual assessment into palliative care and broader multidisciplinary strategies, particularly in advanced stages of heart failure. “Nutritionists, nurses, psychologists — everyone can play a role in listening,” he added.

Nobre emphasized that addressing spirituality doesn’t have to be complex — just intentional. “During the medical history, when we ask about lifestyle, why not also ask how the illness is affecting them emotionally? Or whether they believe in something greater? For some, spirituality may be irrelevant, and that’s fine. But if it matters to the patient, it can become a powerful ally — especially in supporting treatment adherence.”

“We’re not necessarily talking about religion,” he continued. “A person might be Catholic, Evangelical, Umbandist, or have no religion at all. The point is: Does it matter to them? When we make that connection, care moves beyond the physical body. It becomes whole-person care — addressing mind, emotions, and values. And that’s when medicine reaches its fullest potential,” Nobre concluded.