Vitamin D and B12 Deficiency Linked to Chronic Pain

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Researchers found a two-way relationship between some vitamin and mineral deficiencies and chronic pain, which could lead to personalized treatments for people with chronic pain.

University of Arizona Health Sciences researchers hope to use findings on micronutrient levels in people with chronic pain to inform personalized nutritional strategies to help manage chronic pain. 

Top takeaways:

• A new study from the University of Arizona Health Sciences, published in Pain Practice, explored the intricate link between micronutrient deficiencies and chronic pain.
• Researchers discovered a reciprocal relationship where lower levels of essential vitamins and minerals, specifically D, B12, folate, and magnesium, were more prevalent in individuals experiencing severe chronic pain, and conversely, those with severe deficiencies were more likely to suffer from severe chronic pain.
• This study, utilizing data from the National Institutes of Health’s All of Us Research Database, emphasizes the potential for personalized nutritional interventions as a holistic approach to pain management, aiming to improve quality of life and potentially reduce opioid reliance.

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.

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.

They found that for vitamin D, vitamin B12, folate and magnesium, people with severe deficiencies were more likely to have severe chronic pain. Conversely, lower levels of vitamin D, vitamin B12, folate and magnesium – and a greater incidence of those low levels – were seen in 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.

Morris and Pilitsis collaborated with researchers at Florida Atlantic University, Florida International University, Grigore T. Popa in Romania, and Vrije Universiteit Brussel in Belgium.

Reference: Goon M, Schmidt N, Berwal D, et al. Micronutrients and chronic pain: A cross-sectional analysis. Pain Prac. 2025. doi: 10.1111/papr.70053

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