Chronic pain is not simply pain that lasts longer. It can reshape sleep, movement, mood, appetite, work and daily life. In 2021, an estimated 20.9% of U.S. adults—about 51.6 million people—experienced chronic pain, while 6.9% experienced high-impact chronic pain that substantially limited work or daily activities.[1]
Pain can arise from many different sources. Osteoarthritis, autoimmune disease, nerve injury, fibromyalgia, past trauma and persistent musculoskeletal problems do not have one identical cause. Yet they can share amplifying factors: inflammation, oxidative stress, disrupted glucose regulation, excess visceral fat, poor sleep, reduced physical activity and increased sensitivity within the nervous system.
This is where metabolic health may matter. A growing group of human intervention studies suggests that improving food quality and reducing carbohydrate intake can improve pain in some patients. In ketogenic trials and a broader randomized-trial synthesis, those clinical improvements have appeared alongside selective changes in markers such as high-sensitivity C-reactive protein (hsCRP), oxidative stress, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23) and other inflammatory signals.[2–9]
These findings do not mean that every form of chronic pain is caused by inflammation or that one diet will resolve every pain condition. They do support a practical clinical idea: nutrition can be one meaningful part of a broader pain-management plan, especially when chronic pain occurs alongside insulin resistance, obesity, elevated inflammatory markers or other signs of metabolic dysfunction.
Why metabolic health may influence pain
Pain is produced through interactions among injured or irritated tissues, the immune system, the brain and spinal cord, hormones, sleep, mood and prior experience. Metabolic dysfunction can affect several of those systems at once.
Inflammation can increase pain sensitivity
Inflammatory signaling is necessary for healing, but persistently elevated signaling can sensitize pain pathways. Cytokines such as IL-6, IL-17 and IL-23 help coordinate immune activity. In inflammatory diseases, they can also contribute to tissue irritation and disease activity. CRP is a broader blood marker that may rise when systemic inflammation is present.
Reducing an inflammatory marker does not automatically prove that inflammation caused a person’s pain. However, when pain scores and inflammatory markers improve during the same intervention, it raises a biologically plausible connection worth studying.
Insulin resistance can create an unfavorable metabolic environment
Insulin resistance often travels with elevated glucose, high insulin levels, visceral fat accumulation, fatty liver, higher triglycerides and vascular dysfunction. Adipose tissue is metabolically active and can produce inflammatory signals. Repeated large glucose excursions may also contribute to oxidative stress.
A therapeutic low-carbohydrate diet can reduce glucose exposure and insulin demand, while a ketogenic diet also raises circulating ketones such as beta-hydroxybutyrate. At the same time, these approaches frequently reduce ultra-processed food intake and promote loss of excess fat mass. Any combination of these changes could contribute to improvements in pain or inflammation.
Oxidative stress may amplify pain signaling
Oxidative stress refers to an imbalance between reactive molecules and the systems that control them. It has been implicated in tissue damage and pain sensitization. In a randomized knee-osteoarthritis trial, a low-carbohydrate diet reduced oxidative stress and leptin, and the fall in oxidative stress was associated with less functional pain.[3]
Sleep, mood and movement are part of the same system
Pain can disturb sleep and mood, while poor sleep, depression and anxiety can intensify the experience of pain. Pain can also reduce movement, which can worsen strength, mobility, insulin sensitivity and confidence. A useful intervention does not need to act through only one pathway. Better metabolic health may help interrupt several parts of this cycle at once.
What direct clinical trials have found
Chronic musculoskeletal pain: whole-food ketogenic diet
In a 12-week pilot randomized clinical trial, adults with chronic musculoskeletal pain first completed a three-week run-in period that removed ultra-processed foods. They were then assigned either to a whole-food, well-formulated ketogenic diet or to continue a minimally processed whole-food diet.[2]
Average weekly pain improved in both groups. The average reduction was 17.9 mm on a 100-mm visual analog scale in the ketogenic group and 11.0 mm in the whole-food comparison group. Both groups also reported better quality of life. The ketogenic group additionally experienced significant improvements in pain interference, weight, depression, anxiety and hsCRP. The improvement in average pain remained present at the three-month follow-up.
This study offers two useful lessons. First, removing ultra-processed foods may itself help people living with chronic pain. Second, the ketogenic intervention produced a broader pattern of improvement that included pain interference, mood, weight and a commonly used marker of systemic inflammation.
Knee osteoarthritis: low-carbohydrate versus low-fat diet
In a 12-week randomized pilot trial of adults ages 65 to 75 with knee osteoarthritis, participants followed a low-carbohydrate diet, a low-fat diet or their usual diet.[3] The low-carbohydrate group reported less pain intensity and unpleasantness during several functional tasks and less self-reported pain compared with the other groups.
The low-carbohydrate diet also reduced oxidative stress and leptin. Importantly, the reduction in oxidative stress was associated with the reduction in functional pain. That relationship supports the possibility that the benefit was not explained only by carrying less body weight across the knee joint.
A newer six-week prospective pilot study evaluated a carbohydrate-restricted diet in non-Hispanic Black women with knee osteoarthritis.[5] Participants received groceries designed to keep total carbohydrate intake at or below 40 grams per day. The study reported a clinically meaningful 3.8-point reduction in WOMAC pain, along with improvements in daily pain, pain interference, stiffness, physical function, energy and general health.
Fibromyalgia: symptoms improved during a ketogenic intervention
Fibromyalgia involves widespread pain along with symptoms that can include fatigue, impaired sleep and cognitive difficulty. In a 2023 pilot intervention, 20 women with fibromyalgia and obesity began a very-low-calorie ketogenic diet; 18 completed the full study period.[6]
The average Fibromyalgia Impact Questionnaire score fell from 61.7 at baseline to 37.0 after four weeks and 38.7 after eight weeks of the ketogenic phase. Improvements were also reported in anxiety, depression and quality-of-life measures, and much of the improvement remained after carbohydrates were progressively reintroduced. Changes in body mass index were not significantly associated with changes in the patient-reported outcomes, suggesting that weight loss alone may not fully explain the response.
Psoriatic arthritis: disease activity and inflammatory cytokines moved together
The research includes a randomized crossover trial in 26 people with obesity and psoriasis or psoriatic arthritis.[4] Participants completed eight weeks of a Mediterranean diet and eight weeks of a ketogenic diet, separated by a washout period.
Both diets improved weight and body-composition measures. After the ketogenic phase, participants also had significant reductions in the Disease Activity Index for Psoriatic Arthritis (DAPSA), psoriasis severity and the inflammatory cytokines IL-6, IL-17 and IL-23. Those disease-activity and cytokine changes were not significant after the Mediterranean-diet phase.
Because psoriatic arthritis is an inflammatory condition, this study provides an especially clear example of a ketogenic intervention improving clinical disease activity while inflammatory signaling changed in the same direction.
What other ketogenic trials show about inflammatory markers
Trials outside conventional musculoskeletal pain add to the biological picture. They do not prove that every inflammatory change translates into pain relief, but they show that the same dietary intervention can alter inflammatory markers across more than one clinical setting.
Migraine: CRP and inflammatory blood-cell indexes declined
In the EMIKETO randomized controlled trial, 57 adults with high-frequency episodic migraine and overweight or obesity were assigned to a very-low-calorie ketogenic diet or a hypocaloric balanced diet.[7] The ketogenic group experienced a greater reduction in monthly migraine days. By week 12, CRP, the neutrophil-to-lymphocyte ratio and total white blood cell count had also declined significantly in the ketogenic group.
Migraine is neurologic rather than a musculoskeletal pain disorder, but it is still a pain condition involving metabolic, vascular and neuroinflammatory pathways. The simultaneous improvement in migraine frequency and inflammatory indexes strengthens the case that ketogenic interventions may influence pain through more than weight loss alone.
Obesity: selective changes in cytokine signaling
The 2026 KETO-MINOX randomized trial assigned 80 women with overweight or class I obesity to either an energy-restricted Mediterranean-style ketogenic diet or an isocaloric standard diet.[8] Both groups improved body composition and reduced inflammation-related biomarkers. The ketogenic group achieved greater reductions in total and truncal fat and showed additional short-term changes in IL-5, GM-CSF, IL-8 and MCP-1. At the one-year follow-up, IL-10—an immune-regulating cytokine—was higher in the ketogenic group, although most other long-term between-group differences were no longer present.
This trial is useful because calories were standardized. Its findings suggest that macronutrient composition and ketosis may selectively influence immune signaling in addition to the effects produced by energy restriction and weight loss.
Across randomized trials: the response is selective, not uniform
The Disciple Inflammation resource highlighted a systematic review and meta-analysis of 44 randomized controlled trials evaluating ketogenic diets and inflammatory markers.[9] Compared with control diets, ketogenic interventions produced pooled reductions in TNF-α and IL-6. The pooled estimates for CRP, IL-8 and IL-10 did not significantly differ from controls.
This pattern is more informative than a blanket claim that ketosis is simply anti-inflammatory. Different immune pathways can respond differently, and the response may depend on study duration, age, adiposity, underlying condition, calorie intake and the comparison diet. The subgroup findings were also biologically interesting: TNF-α reductions were greater in shorter trials and participants aged 50 or younger, while IL-6 declined more among participants with a BMI above 30 kg/m².
How the inflammatory findings may relate to chronic pain
Taken together, these trials suggest a connected, testable model:
- A low-carbohydrate or ketogenic intervention lowers glucose exposure and insulin demand.
- Many participants lose visceral and truncal fat, which can reduce an important source of inflammatory signaling.
- Removing ultra-processed foods changes the overall inflammatory and nutritional environment.
- Ketone production may have direct signaling effects on oxidative stress, immune activity and nervous-system excitability.
- Improvements in sleep, mood, energy and mobility may further reduce pain amplification.
The strongest support for this model comes from trials in which clinical symptoms and biological markers moved together: pain and hsCRP in chronic musculoskeletal pain; knee pain and oxidative stress in osteoarthritis; disease activity and IL-6, IL-17 and IL-23 in psoriatic arthritis; and migraine days together with CRP and inflammatory blood-cell indexes.[2,3,6,7]
The likely explanation is not one single marker. Chronic pain is a systems problem, and the dietary effect may also be systemic. Glucose regulation, body composition, inflammation, oxidative stress, brain excitability, sleep and mood can all change at the same time. This is precisely why chronic pain belongs within a metabolic-health framework while still being displayed alongside Exercise, Strength & Mobility.
What this can look like in practice
A therapeutic nutrition plan for chronic pain should be individualized. The intervention used in a research trial may not be the right starting point for every patient. Useful principles can include:
- Build meals around adequate protein and minimally processed foods.
- Reduce refined starches, added sugars and ultra-processed snack foods.
- Choose a carbohydrate target that matches the condition, goals, medications and ability to sustain the plan.
- Include nonstarchy vegetables and whole-food fats as tolerated and clinically appropriate.
- Maintain hydration and address sodium, potassium and magnesium needs with clinical guidance when necessary.
- Track more than a scale number: pain intensity, pain interference, sleep, energy, mood, mobility and medication use are meaningful outcomes.
- Pair nutrition with an individualized movement plan, strength training, physical therapy, sleep treatment and appropriate medical care.
The goal is not to use diet in place of a thorough diagnosis. The goal is to identify metabolic factors that may be making pain harder to manage and to address them as part of a comprehensive plan.
Medication and safety considerations
People using insulin, sulfonylureas, blood-pressure medications or diuretics may need active monitoring and medication adjustment when substantially reducing carbohydrates. Glucose and blood pressure can improve quickly, creating a risk of hypoglycemia, low blood pressure or dehydration if medications are not adjusted appropriately.
Anyone with kidney disease, liver disease, a history of pancreatitis or gallbladder complications, pregnancy, an active eating disorder or another condition requiring specialized nutrition should work with a qualified clinician before beginning a ketogenic intervention.
Do not abruptly stop pain medication, anti-inflammatory treatment, steroids, disease-modifying antirheumatic drugs or other prescribed therapy because dietary symptoms improve. Medication changes should be planned with the prescribing clinician.
New severe pain, rapidly worsening pain, fever, a red or swollen joint, chest pain, new weakness or numbness, loss of bowel or bladder control, unexplained weight loss or pain after significant trauma requires prompt medical evaluation.
The practical takeaway
Nutrition is not peripheral to chronic pain. In human intervention studies, whole-food low-carbohydrate and ketogenic diets have improved pain, pain interference, physical function or disease activity in chronic musculoskeletal pain, knee osteoarthritis, fibromyalgia, psoriatic arthritis and migraine.[2–7]
The accompanying reductions in hsCRP, oxidative stress, leptin, IL-6, IL-17, IL-23, CRP and other immune signals provide a plausible explanation for part of that response. The benefit may also reflect better glucose regulation, less visceral fat, fewer ultra-processed foods, altered nervous-system signaling, better mood and improved energy.
For a person living with chronic pain—particularly one who also has insulin resistance, obesity or another metabolic condition—a well-formulated low-carbohydrate or ketogenic diet can be considered as part of a medically supervised, multimodal treatment plan.
References
Updated prevalence source
- Rikard SM, Strahan AE, Schmit KM, Guy GP Jr. Chronic Pain Among Adults—United States, 2019–2021. MMWR Morb Mortal Wkly Rep. 2023;72(15):379–385. doi: 10.15585/mmwr.mm7215a1. PubMed
Source references
- Field R, Pourkazemi F, Rooney K. Effects of a Low-Carbohydrate Ketogenic Diet on Reported Pain, Blood Biomarkers and Quality of Life in Patients with Chronic Pain: A Pilot Randomized Clinical Trial. Pain Med. 2022;23(2):326–338. doi: 10.1093/pm/pnab278. Original PubMed link
- Strath LJ, Jones CD, George AP, et al. The Effect of Low-Carbohydrate and Low-Fat Diets on Pain in Individuals with Knee Osteoarthritis. Pain Med. 2020;21(1):150–160. doi: 10.1093/pm/pnz022. Original PubMed link
- Lambadiari V, Katsimbri P, Kountouri A, et al. The Effect of a Ketogenic Diet versus Mediterranean Diet on Clinical and Biochemical Markers of Inflammation in Patients with Obesity and Psoriatic Arthritis: A Randomized Crossover Trial. Int J Mol Sci. 2024;25(5):2475. doi: 10.3390/ijms25052475. Original article link
Additional primary clinical studies
- Wiggins AM, Strath LJ, McPherson GE, et al. The effect of a low-carbohydrate diet on evoked pain and quality of life in Non-Hispanic Black women with knee osteoarthritis: a pilot study. BMC Musculoskelet Disord. 2024;25:1043. doi: 10.1186/s12891-024-08170-x. PubMed
- Ciaffi J, Lisi L, Mari A, et al. Efficacy, safety and tolerability of very-low-calorie ketogenic diet in obese women with fibromyalgia: a pilot interventional study. Front Nutr. 2023;10:1219321. doi: 10.3389/fnut.2023.1219321. PubMed
- Caprio M, Moriconi E, Camajani E, et al. Very-low-calorie ketogenic diet vs hypocaloric balanced diet in the prevention of high-frequency episodic migraine: the EMIKETO randomized, controlled trial. J Transl Med. 2023;21:692. doi: 10.1186/s12967-023-04561-1. PubMed
- Drabińska-Fois N, Ogrodowczyk AM, Bauer W, et al. Immune-modulating effects of energy-restricted ketogenic diet in women with overweight and obesity: KETO-MINOX study. Eur J Nutr. 2026;65(3):83. doi: 10.1007/s00394-026-03935-7. PubMed
Further reading
- Ji J, Fotros D, Sohouli MH, Velu P, Fatahi S, Liu Y. The effect of a ketogenic diet on inflammation-related markers: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2025;83(1):40–58. doi: 10.1093/nutrit/nuad175. Original PubMed link
