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Supplements for Chronic Pain: What the Trials Show, and What to Check With Your Pain Medicines

For chronic pain, no supplement comes close to the exercise and psychological therapies guidelines recommend. The best-supported option, willow bark extract, eased flare-ups of low back pain for a few weeks in two trials (grade B), but it is a salicylate like aspirin: not for anyone under 18, or with an aspirin allergy, a stomach ulcer or a blood thinner. Vitamin D did not consistently ease chronic pain (grade C). Check supplements with your pain-medicine prescriber.

Published How we grade evidenceEditorial policy

Supplements are a small add-on at best for chronic pain, meaning pain that lasts or keeps coming back for more than 3 months. When a condition causes the pain, treating it comes first, and some have their own guides: fibromyalgia, arthritis and joint pain, period pain and migraine. This guide covers chronic pain in general, low back pain, diabetic nerve pain and key medicine pairs.

The short version

  • Willow bark extract for flare-ups of low back pain: less pain than placebo for a few weeks in two trials (moderate-quality evidence). It is a salicylate, like aspirin: not for anyone under 18, or with an aspirin allergy, a stomach ulcer or a blood thinner. Grade B (Oltean 2014; Chrubasik 2000).
  • Devil's claw for back pain flare-ups: may ease pain for a few weeks, from two low-quality trials by one research group. Grade C (Oltean 2014).
  • Vitamin D: no consistent benefit in many kinds of chronic pain, including back pain, on low-quality evidence from trials that differ. Grade C for no consistent benefit (Straube 2015; Lee 2024).
  • PEA (palmitoylethanolamide): lower pain scores in small, very mixed trials, several funded or supplied by makers. Grade C (Lang-Illievich 2023).
  • Alpha-lipoic acid for diabetic nerve pain: fewer symptoms in short trials, little or no change at 6 months. Grade B, mixed (Baicus 2024; Hsieh 2023).
  • Check these pairs first: sleep and calming herbs with opioids or pregabalin; St John's wort, SAMe or tryptophan with duloxetine, amitriptyline or tramadol; willow bark with NSAIDs or blood thinners (tramadol label; duloxetine label).
Option (who, compared with what)What trials foundSize of effectGrade
Willow bark extract (back pain flare-ups, 2 trials, 261 people, vs placebo)Less pain and rescue painkiller for a few weeks39% vs 6% pain-free in the larger trial's last weekB
Devil's claw extract (back pain flare-ups, 2 trials, 315 people, vs placebo)May ease pain for a few weeksSmall; low-quality evidenceC
Vitamin D (chronic pain, 10 trials, 811 adults, vs placebo)No consistent benefit; low-quality evidenceNone consistentC for no consistent benefit
PEA (11 small trials, 774 people, vs placebo or another treatment)Lower pain scores, very uneven resultsUnclearC
Alpha-lipoic acid (diabetic nerve damage, vs placebo)Fewer symptoms in short oral trials; little or no difference at 6 monthsSmallB, mixed
Omega-3s (41 trials, 3,759 people, vs placebo or other treatments)Less pain overall, mostly in rheumatoid arthritisSmall and unevenB

What helps chronic pain most?

Exercise, psychological therapy and treating the cause. For pain without a clear cause, the UK's NICE guideline recommends a supervised group exercise programme, and suggests considering cognitive behavioural or acceptance and commitment therapy, one course of acupuncture, or certain antidepressants, which may help pain, sleep and quality of life even without depression (NICE NG193; Carville 2021). It advises against starting opioids, NSAIDs (ibuprofen-type painkillers), paracetamol or gabapentin-type medicines for this kind of pain. If you already take one, don't stop it on your own: NICE asks prescribers to review it with you, because stopping can cause withdrawal problems. No supplement is among NICE's recommendations.

Does vitamin D help chronic pain?

Grade C for no consistent benefit (low-quality evidence; trials differ). Across 10 trials with 811 adults, a Cochrane review found no consistent pattern of vitamin D beating placebo in any chronic painful condition, on low-quality evidence; the trials differed in conditions, doses and added treatments (Straube 2015). In chronic low back pain, a 2024 analysis of 10 trials found no clear drop in pain, whatever the starting level; some trials used prescription forms (Lee 2024). A 2016 analysis found a small extra fall in pain from the start in 8 trials, larger in people already in pain, but no difference in final scores across 14 (Wu 2016). Our chronic pain page says vitamin D has moderate support but lists no vitamin D trial; on these reviews we disagree.

If a blood test shows you're low, your clinician can treat it. The adult upper limit is 4,000 IU a day; more can raise blood calcium (NIH ODS). Take more only with blood tests or your clinician's advice.

Does PEA (palmitoylethanolamide) help chronic pain?

Grade C: lower pain scores in small, very mixed trials. PEA is a fat-like compound the body makes. A 2023 review pooled 11 double-blind trials (774 people) and found lower pain scores than in the comparison groups, but results varied widely between trials (Lang-Illievich 2023). They covered 11 different pain conditions; four added another compound (polydatin), one compared PEA with ibuprofen instead of placebo, two gave it under the tongue, and four were funded or supplied by a maker. Alone by mouth against placebo, PEA eased pain in 3 of 4 trials, including knee arthritis and diabetic nerve pain, but not in carpal tunnel syndrome (Lang-Illievich 2023; Steels 2019; Pickering 2022); the knee trial was funded by the maker. An earlier review of 8 trials against an inactive control also found less pain, in often poor-quality trials (Artukoglu 2017).

The trials used 300 to 1,200 mg a day, usually in two doses, for 2 weeks to 12 months, and reported few side effects; there is no set upper limit. Ask your pharmacist before adding it to prescribed pain medicines.

Does alpha-lipoic acid help diabetic nerve pain?

Grade B, mixed: fewer symptoms in short trials, little or no difference in longer ones. Alpha-lipoic acid (ALA) is an antioxidant sold for diabetic nerve damage (neuropathy), which causes burning pain and numbness in the feet.

  • Mostly short trials: in SYDNEY 2, 181 adults took ALA by mouth or a placebo for 5 weeks; on 600 mg once a day, symptom scores fell 51%, against 32% on placebo (Ziegler 2006). A 2023 analysis of 10 oral trials (1,242 people) found lower symptom scores, more at higher doses, but no difference on a pain rating scale (Hsieh 2023).
  • Longer trials: a 2024 Cochrane review of 3 trials of 6 months to 4 years (816 people) found, in the one trial that measured symptoms at 6 months (330 people; it began with 3 weeks of drips into a vein), that ALA probably makes little or no difference (moderate certainty); all three trials lost many participants (Baicus 2024).

Nausea, vomiting and dizziness rose with the dose, and SYDNEY 2's authors judged 600 mg once a day the best balance. There is no set upper limit. Rarely, ALA triggers an immune reaction to the body's own insulin: in 37 published cases it caused low blood sugar, often at night or early morning (Li 2021). On insulin or other diabetes medicines, check your blood sugar more often when you start it.

Do willow bark or devil's claw help back pain?

Willow bark: grade B for short-term relief. Devil's claw: grade C. A Cochrane review of herbal medicines for low back pain (14 trials, 2,050 adults) found willow bark extract, standardised to 120 or 240 mg of salicin a day, probably eases pain and cuts rescue painkiller use for a few weeks better than placebo (2 trials, 261 people, moderate quality) (Oltean 2014). In the larger trial (210 adults with a flare-up, 4 weeks), 39% on the higher dose were pain-free without rescue tramadol by the last week, against 6% on placebo; one person had a severe allergic reaction, perhaps to the extract (Chrubasik 2000).

The catch: 240 mg of salicin can give about 113 mg of salicylic acid, more than the 62 mg from an 81 mg low-dose aspirin, yet supplements don't have to carry aspirin's warnings (Oketch-Rabah 2019). Europe's medicines agency rules it out under 18 (Reye's syndrome, a rare brain and liver illness), with an allergy to aspirin or NSAIDs or asthma they trigger, an active stomach ulcer, a bleeding disorder, G6PD deficiency, severe liver or kidney disease, and late in pregnancy. It may strengthen warfarin-type blood thinners and shouldn't be combined with aspirin or NSAIDs without medical advice (EMA willow bark monograph). If you bruise easily or see blood in your urine or black or bloody stools, stop it and get checked.

Devil's claw extract, standardised to give 50 or 100 mg of harpagoside daily, may ease pain for a few weeks better than placebo (2 trials, 315 people, low quality) (Oltean 2014). Both came from one German research group. In the larger trial, 10 people on the higher dose had no pain in its last week, against 3 on placebo, though subgroup analyses disagreed on who benefited most (Chrubasik 1999). Our devil's claw page grades back pain relief A and B, based on a 2004 review that called the evidence strong (Gagnier 2004); the newer Cochrane review rated it low quality, which is why this guide gives it a C.

Trial side effects were mostly minor stomach upsets, in about 3% of people (Vlachojannis 2008). Europe's medicines agency says not to take it with an active stomach or duodenal ulcer, to see a doctor first if you have gallstones, and not to use it in pregnancy or while breastfeeding (EMA devil's claw monograph). That monograph lists no interactions, but a review of herbs and warfarin counted devil's claw among products with reported interactions, based mostly on case reports or lab studies (Heck 2000), so ask first if you take a blood thinner.

Do fish oil, turmeric or magnesium help?

  • Fish oil and other omega-3s: grade B, small and uneven. A 2025 analysis of 41 trials (3,759 people) found less pain than in comparison groups, including in the 21 placebo-controlled trials, with clear results in rheumatoid arthritis and some other conditions, but not osteoarthritis (Xie 2025). Results varied widely; 11 trials used combination products (some with herbal extracts), several changed diet rather than giving a supplement, and 20 compared omega-3 with another treatment. In heart trials, omega-3 made atrial fibrillation, an irregular heartbeat, more likely, especially above 1 g a day (Gencer 2021). See our fish oil guide.
  • Turmeric (curcumin): our joint pain guide grades its knee arthritis results B. It has caused rare, serious liver injury: 10 US registry cases, 1 of them fatal (Halegoua-DeMarzio 2023). Stop it and get checked if your skin or eyes turn yellow or your urine darkens.
  • Magnesium: grade C, no benefit shown. In 45 people with nerve pain, a month of magnesium by mouth eased pain no more than placebo (Pickering 2011). The adult upper limit from supplements is 350 mg a day; diarrhoea is the usual first sign of too much (NIH ODS).

What we'd skip

  • SAMe: in four poor-quality placebo trials in knee or hip arthritis (656 people), pain was not clearly different from placebo (Rutjes 2009). It also adds to serotonin and can contribute to serotonin syndrome (Bodner 1995).
  • NAC: in the main pooled analysis of 3 trials across mixed pain conditions, it did not lower pain (Mohiuddin 2021).
  • Vitamin B12 pills for back pain: the positive trial gave B12 by injection, not pills (Mauro 2000).
  • CBD oils and gummies: across 32 trials of medical cannabis or cannabinoid medicines, not shop CBD oils, 10% more people had a meaningful drop in pain than on placebo, with more drowsiness, dizziness and nausea (Wang 2021). In the US, the FDA says CBD can't be sold as a dietary supplement and has warned companies illegally selling CBD products for pain relief (FDA).

Safety and interactions

  • Opioids and pregabalin: their labels warn that other drugs causing drowsiness can slow breathing dangerously (pregabalin label; tramadol label). Valerian and kava should not be taken with sedatives, melatonin can cause sleepiness, and cannabis products caused drowsiness in trials (Wang 2021; NCCIH valerian; NCCIH kava; NCCIH melatonin). Ask before adding any sleep or calming supplement.
  • Duloxetine, amitriptyline and tramadol: the duloxetine and amitriptyline labels warn of serotonin syndrome with St John's wort and tryptophan, and the tramadol label with other drugs that raise serotonin (duloxetine label; amitriptyline label); the same goes for SAMe and for 5-HTP, which the body makes from tryptophan (5-HTP with SSRIs). Agitation, shivering, muscle jerks and a fever need urgent help (Bodner 1995). Duloxetine also raises bleeding risk with aspirin, NSAIDs and blood thinners, so treat willow bark like aspirin alongside it.
  • NSAIDs (ibuprofen, naproxen): no willow bark without medical advice (EMA willow bark monograph); on a blood thinner, see our blood thinners guide.
  • Kava: linked to rare, sometimes fatal, liver injury (NCCIH kava); skip it, especially if you take paracetamol regularly (liver guide).
  • Pregnancy: no willow bark (ruled out late in pregnancy and advised against earlier) or devil's claw; any supplement amount is as advised by your midwife or obstetric team.
  • Breastfeeding? Don't use willow bark: salicylates pass into breast milk. For anything else, ask your midwife, doctor or a lactation specialist, who can check what passes into breast milk.
  • Children and teenagers: no willow bark under 18; for anything else, the amount is set by the child's doctor.

When to see a doctor

  • Call emergency services if back pain comes with numbness or weakness in both legs, loss of feeling around your genitals or bottom, new trouble peeing or controlling your bladder or bowels, chest pain, or after a serious accident (NHS).
  • Get an urgent appointment if pain comes with a fever or feeling hot, cold or shivery, or is severe, sudden or getting worse quickly.
  • See your doctor if pain stops your daily activities, you've lost weight without trying, there's a lump or swelling in your back, it's worse at night or rest doesn't help, or you're struggling.
  • On alpha-lipoic acid with diabetes: if you feel shaky, sweaty or confused, check your blood sugar.
  • Don't stop a prescribed medicine on your own; ask the prescriber or pharmacist.

FAQ

What is the best supplement for chronic pain? None has strong evidence. Willow bark eased flare-ups of low back pain for a few weeks (grade B), but it acts like aspirin. Exercise programmes and psychological therapies have more support.

Does vitamin D help chronic pain? Not consistently: trials in many kinds of chronic pain, including back pain, found no reliable benefit over placebo. If a blood test shows you're low, your clinician can treat it.

Can I take willow bark with ibuprofen? Not without medical advice. Both can irritate the stomach and affect bleeding, and Europe's medicines agency advises against the pair unless a doctor agrees.

Sources

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