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Curcumin · diferuloylmethane
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In one pass Curcumin is the source of the yellow in curry, and in recent years it has become a popular anti-inflammatory supplement.
Educational content, not medical advice — consult a clinician.
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Chapter 1
What curcumin is
Curcumin is the source of the yellow in curry, and in recent years it has become a popular anti-inflammatory supplement. One reality first: eating curry will not get you to the doses used in trials, because turmeric root contains too little of it.
Curcumin is a yellow polyphenol pigment extracted from the rhizome of turmeric (Curcuma longa). The pigments of this family in turmeric are called curcuminoids; curcumin itself makes up about 77%, and two close relatives make up about 17% and 3%.
Turmeric root itself contains only 3–5% curcuminoids, so getting curcumin from curry is not realistic in terms of dose. A serving of curry uses about 5 g of turmeric powder, which holds only 150–250 mg of curcuminoids, while clinical trials commonly use 500–1500 mg a day.
Curcumin is a yellow polyphenol pigment extracted from the rhizome of turmeric (Curcuma longa). The pigments of this family in turmeric are called curcuminoids; curcumin itself makes up about 77%, and two close relatives make up about 17% and 3%.
Turmeric root itself contains only 3–5% curcuminoids, so getting curcumin from curry is not realistic in terms of dose. A serving of curry uses about 5 g of turmeric powder, which holds only 150–250 mg of curcuminoids, while clinical trials commonly use 500–1500 mg a day.
Background · Kitchen to clinic, and a chemists' warning
Turmeric has been used in Indian and Chinese traditional medicine for more than 4000 years: Indian Ayurvedic medicine calls it Haridra, and traditional Chinese medicine calls it jianghuang (warming, said to move qi and blood). Curcumin's chemical name is diferuloylmethane, with a molecular weight of 368 Da.Modern biomedical interest in it began between 1995 and 2005:
Cell experiments repeatedly reported that it can inhibit , a master switch for inflammation (a series of papers from the Aggarwal lab at MD Anderson)A wave of research into it as a natural anti-inflammatory drug followedClinical trials multiplied from the 2010s on, covering arthritis, depression, cancer, Alzheimer's disease, diabetes, fatty liver, ulcerative colitis, skin inflammation, and more; by the count in Nelson 2017, more than 120 clinical trials of curcuminoids had been run
But there is one key reflection. In 2017, Nelson and colleagues published a review in the Journal of Medicinal Chemistry, The Essential Medicinal Chemistry of Curcumin, that placed curcumin in two categories: PAINS (pan-assay interference compounds, molecules that show activity in all sorts of tests) and IMPS (invalid metabolic panaceas). It shows activity in almost any lab test, and that all-purpose reactivity makes screening results look too good. Their own words go further: no double-blind, placebo-controlled clinical trial of curcumin has truly succeeded, and it is an unstable, reactive compound that is hard to absorb.
This is one of the rare cases in nutrition where a popular supplement was explicitly flagged by a top chemistry journal. Every positive trial described later should be read against this background: there is a signal, and it is far from settled.
Chapter 2
How it dampens inflammation
In cell experiments curcumin is reported to bind more than 100 proteins, which sounds remarkable. The three lines lab studies report most often are these:
Holding down , the master switch for inflammation: once NF-κB enters the cell nucleus, it switches on inflammatory genes such as and (more than 100 of them) in bulk; curcumin keeps it out in the cytoplasm.Releasing Nrf2, the antioxidant switch: Nrf2 runs the body's own antioxidant system (glutathione, for example), and curcumin lets it loose.Holding down COX-2, which makes inflammatory mediators: the action resembles that of ibuprofen-type painkillers, but it barely touches COX-1, the version that protects the stomach.
Know its limits: all of this was seen in cells, and curcumin is precisely a molecule that looks active at almost anything in a dish, so whether these pathways really run in the human body is not established. The real bottleneck is that too little of an oral dose ever reaches the tissues.
Holding down , the master switch for inflammation: once NF-κB enters the cell nucleus, it switches on inflammatory genes such as and (more than 100 of them) in bulk; curcumin keeps it out in the cytoplasm.Releasing Nrf2, the antioxidant switch: Nrf2 runs the body's own antioxidant system (glutathione, for example), and curcumin lets it loose.Holding down COX-2, which makes inflammatory mediators: the action resembles that of ibuprofen-type painkillers, but it barely touches COX-1, the version that protects the stomach.
Know its limits: all of this was seen in cells, and curcumin is precisely a molecule that looks active at almost anything in a dish, so whether these pathways really run in the human body is not established. The real bottleneck is that too little of an oral dose ever reaches the tissues.
Mechanism · Why so little reaches the blood
This is the key to the whole curcumin story.The oral bioavailability of plain curcumin (the share of a swallowed dose that actually enters the circulation) is estimated at below 1%, for several reasons:
It barely dissolves in waterIt is poorly absorbed in the gut, and most of it passes out unchangedThe liver and gut wall quickly attach glucuronic acid or sulfate groups, turning it into forms that are easy to excrete (phase II metabolism), so its half-life is under 2 hoursEfflux pumps in the gut wall (P-glycoprotein, P-gp) push it back into the gut
The result: after a gram-scale oral dose, free curcumin in the plasma often reaches only the nanomolar range (about 50 nmol/L), while most cell experiments use effective concentrations of 1–10 μmol/L, 20–200 times higher than what is in the blood. And 8 g of turmeric powder is not 8 g of curcumin. That is the physical reason for strong activity in the dish, unstable effect in the body.
Ways to raise absorption (the form matters more than a quoted multiple):
Adding piperine from black pepper (5–20 mg): it blocks efflux and glucuronidation in the gut wall. Shoba 1998 was a small pharmacokinetic study in healthy volunteers: 2 g of curcumin alone was barely detectable in the blood, while taking it with 20 mg of piperine raised bioavailability about 20-foldPhospholipid complexes (Meriva, a phytosome): bound to lecithin to cross cell membranes better, giving higher plasma exposure than plain powder; how much higher depends on the assay and on whether doses were matchedNanoparticles and liquid microemulsions (Theracurmin, NovaSOL, Longvida): these also raise plasma exposure; do not multiply 50 nmol/L by a cross-product multipleTaking it with food that contains fat: helps a little, not by much
In practice, plain curcumin and enhanced forms reach very different plasma levels, and that is one reason so many studies disagree: they used different forms. Before reading any clinical study of curcumin, check which form it used.
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Chapter 3
Which conditions have evidence
Curcumin can hold down inflammatory pathways in cells, but that does not mean it treats every disease linked to inflammation. The human evidence differs sharply from condition to condition. For knee osteoarthritis pain, a set of small randomized trials points the same way. For depression there is only one trial of 56 people, which gave partial support. A pooled analysis of blood lipids found no effect. Fatty liver and colitis are still at the stage of small trials. Cancer prevention, Alzheimer's disease, and anti-aging have almost no human support.
The reason was set up earlier: a pathway you can shut down in a test tube often never sees that concentration in a person. So when you read curcumin is anti-inflammatory, ask one more question: for which disease, in which form, and in how large a trial?
The reason was set up earlier: a pathway you can shut down in a test tube often never sees that concentration in a person. So when you read curcumin is anti-inflammatory, ask one more question: for which disease, in which form, and in how large a trial?
Evidence · The evidence, condition by condition
The strength of the evidence for curcumin differs by condition, and only looking at each one separately keeps the single word anti-inflammatory from leading you astray.A set of small randomized trials pointing the same way:
Knee osteoarthritis pain: the by Daily 2016 pooled 8 randomized trials. Compared with placebo, pain and function scores improved; compared with painkillers, there was no significant difference. The authors themselves state that the number of trials, the total sample size, and the methodological quality were not enough for a definitive conclusion.
A single trial with partial support:
Depression, as an add-on: Lopresti 2014 was a double-blind, placebo-controlled trial in 56 people with major depressive disorder, 500 mg twice a day for 8 weeks. Both groups improved in the first 4 weeks; between weeks 4 and 8, the curcumin group improved more on a self-rated depression scale, just past the line for statistical significance. The authors concluded it offered only partial support and that larger, longer trials are needed.
A pooled analysis that found no effect:
Blood lipids: the meta-analysis by Sahebkar 2014 (5 trials, 133 people on curcumin and 90 controls) found no significant effect on total cholesterol, low-density lipoprotein cholesterol (), high-density lipoprotein cholesterol, or ; the pooled change in triglycerides was only -1.29 mg/dL. The author recommends longer trials of better-absorbed forms in people with abnormal lipids.
Small trials awaiting replication:
Metabolic dysfunction-associated steatotic liver disease, (formerly NAFLD), with trials enrolled by the definitions of their time: several small trials saw the liver enzyme fallKeeping ulcerative colitis in remission: 1 positive trial, awaiting replicationSkin inflammation and psoriasis
Not enough evidence to recommend:
Preventing or treating cancer: strong activity in the dish, and clinical translation has almost always failedPreventing Alzheimer's disease: no human trial has shown a benefitLongevity and anti-aging: no long-term human dataDetox: a marketing word with no scientific meaning
This sorting exposes a common mistake: curcumin is anti-inflammatory is true in cells, but anti-inflammatory does not mean treats every disease linked to inflammation.
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Evidence · Reading the knee arthritis trials
Daily 2016 (J Med Food) is a systematic review and that ended up including 8 randomized trials comparing turmeric or curcumin with placebo or painkillers in arthritis (mainly knee osteoarthritis).Main results:
Pain: pooling 3 placebo-controlled trials, the pain visual analogue score was 2.04 points lower on averageFunction: pooling 4 trials, the WOMAC osteoarthritis index (lower is better) was 15.36 points lower on averageVersus painkillers: pooling 5 trials, pain scores did not differ significantly. That is not proof that it works as well as an anti-inflammatory painkiller: small trials struggle to detect a difference, and failing to find one is not the same as showing equivalenceSide effects: the paper listed them trial by trial and did not pool them
Dose: the authors summarize it as about 1000 mg of curcumin a day; individual trials mostly used 500–1500 mg of curcuminoids a day (less for enhanced forms), for 4–12 weeks.
Discounts to apply as you read:
1. Most trials were small (< 100 people) and short (< 3 months)
2. The forms differed: some used plain powder with piperine, some Meriva, some BCM-95
3. Blinding is hard: curcumin is intensely yellow, so participants may guess what they are taking
4. Some trials were funded by manufacturers
Add the chemists' statement that no double-blind, placebo-controlled trial has truly succeeded, and the reasonable reading of both together is: there is a signal, but not a settled answer.
Practical inference: for mild to moderate knee osteoarthritis, curcumin is a fairly low-risk option to try. But if there is no clear improvement after 6–8 weeks, the answer is not take it for a few more months but that you do not respond to it. Physical therapy, weight control, and strength training have stronger evidence in osteoarthritis.
Chapter 4
Who benefits
The people who might benefit are a narrow group: those with mild to moderate knee or hip osteoarthritis who want to use fewer anti-inflammatory painkillers; people using it, with a doctor's agreement, as an add-on to depression treatment; or anyone treating it as one small tool in a healthy eating pattern. Arthritis, depression, and abnormal blood lipids all have mainstream treatments with firmer evidence, and curcumin is an add-on, not the main therapy. For healthy people taking it for wellness or anti-aging, there is no evidence.
It can also interfere with anticoagulants, glucose-lowering drugs, chemotherapy, and iron supplements. Eating curry in normal food amounts is safe during pregnancy and breastfeeding, but there are no data on high-dose supplements. Natural does not mean safe, and that applies here too.
It can also interfere with anticoagulants, glucose-lowering drugs, chemotherapy, and iron supplements. Eating curry in normal food amounts is safe during pregnancy and breastfeeding, but there are no data on high-dose supplements. Natural does not mean safe, and that applies here too.
In practice · Who may benefit, who should skip
May benefit:People with mild to moderate knee or hip osteoarthritis who want to avoid the long-term stomach, gut, and kidney risks of nonsteroidal anti-inflammatory drugs (): a 6–8 week trial is reasonableAn add-on to depression treatment (not a replacement for antidepressants), agreed with a doctorPeople with long-standing low-grade inflammation, whose C-reactive protein (, a blood test for inflammation) stays high without a clear disease: it can go into the dietary toolbox, though a Mediterranean diet plus regular exercise is more solid
No need:
Healthy people taking it for wellness or anti-aging: no evidence, wasted moneyTreating cancer or preventing Alzheimer's disease: the evidence does not support itLowering blood lipids: a pooled analysis found no effectReplacing standard care: arthritis, depression, and abnormal lipids all have evidence-based mainstream treatments, and curcumin is an add-on, not the main therapy
Drug interactions (watch for these):
Anticoagulant and antiplatelet drugs (warfarin, aspirin, clopidogrel): curcumin has a weak antiplatelet effect, so high doses together with an anticoagulant raise the risk of bleeding; tell your doctorGlucose-lowering drugs: curcumin may lower blood sugar slightly, so people on insulin or sulfonylureas should monitor their glucoseChemotherapy drugs (irinotecan, paclitaxel): curcumin may change how these drugs are metabolized, so do not add it on your own during chemotherapyIron supplements: curcumin can bind non-heme iron, so if you are iron-deficient or taking iron, keep the two at least 2 hours apart
Pregnancy and breastfeeding: curry in normal food amounts is safe; high-dose supplements (> 500 mg a day) have no data, so avoid them as a precaution.
Safety · Why natural does not mean safe
Curcumin is a good example of natural does not mean safe. Here are the common misconceptions, set one by one against the data:Misconception 1: anything from a plant has no side effects
At high doses over long periods (> 1500 mg a day), a minority of people get diarrhea, nausea, or headacheRare but reported: worsening of bile-duct obstruction (curcumin increases bile secretion, so people with gallstones or cholangitis are at risk)The European Food Safety Authority (EFSA) sets the acceptable daily intake (ADI) for curcumin as a food coloring at 0–3 mg/kg of body weight, about 180 mg a day for a 60 kg person. That line is a conservative value for a food additive eaten every day for life, not a safety ceiling for supplements. Trials have used 500–1500 mg a day for weeks to months, usually well tolerated. But that is several times the ADI, so long-term continuous use should be treated the way you would treat a drug
Misconception 2: purer is better, and more is better
At very high doses (> 8 g a day), the absorbed share actually falls, because absorption in the gut is already saturatedEnhanced forms (Meriva, Theracurmin) cannot be compared milligram for milligram with plain curcumin
Misconception 3: it protects the liver
Most small trials in fatty liver () saw a mild improvement in the liver enzyme . But there are also a very small number of case reports of drug-induced liver injury linked to curcumin supplements (Lukefahr 2018 and other individual cases)LiverTox, the US database of drug-induced liver injury, lists turmeric as a rare cause of liver injury. This is not an absolute contraindication, but people whose liver tests are already abnormal should avoid it or use it only under a doctor's monitoringIf you are taking a curcumin supplement and notice yellowing of the skin or the whites of the eyes, urine the color of strong tea, pain in the upper right abdomen, or marked fatigue, stop taking it and seek medical care promptly to have your liver checked
Misconception 4: it has nothing to do with kidney stones
Turmeric powder (the spice) contains a fair amount of oxalate. The oxalate comes from the turmeric plant, not from the curcumin molecule. People with a history of calcium oxalate kidney stones should avoid eating large amounts of turmeric powder, or supplements made from it, over the long term
Conclusion: curcumin is safe overall, but safe overall is not the same as safe for everyone at every dose. Its safety data are more complete than those of most supplements, but it is not zero-risk.
Chapter 5
How much, and which form
The form matters more than the dose. Plain curcumin barely gets into the blood; adding piperine, or making it into a phospholipid complex or nanoparticles, is what raises plasma exposure. What differs between enhanced forms is how much reaches the blood, so do not multiply a test-tube concentration by some factor and call it a human level.
It dissolves in fat and has a short half-life, so take it with a meal that contains some fat, split the dose, and give it a few weeks: the effects in trials showed up only after several weeks of continuous use, not on the same day. Doses differ between the enhanced forms, so read the label for that particular form rather than converting between forms milligram for milligram.
It dissolves in fat and has a short half-life, so take it with a meal that contains some fat, split the dose, and give it a few weeks: the effects in trials showed up only after several weeks of continuous use, not on the same day. Doses differ between the enhanced forms, so read the label for that particular form rather than converting between forms milligram for milligram.
In practice · Form matters more than milligrams
Choosing the form matters most, more than the dose, because plasma exposure differs a lot between enhanced forms.The main enhanced forms (by evidence and how common they are):
Curcumin plus piperine (5–20 mg): the cheapest, and the form used in the classic research; in the small pharmacokinetic study by Shoba 1998, bioavailability rose about 20-foldMeriva (a phospholipid complex patented by Indena): mid-priced and used in several clinical trials; plasma exposure is higher than plain powder, and how much higher depends on the assay and on whether doses were matchedTheracurmin (nanoparticles): more expensive, developed in Japan, and used in several trials; it also raises plasma exposure, but do not multiply 50 nmol/L by some factor and call the result micromolarLongvida (solid lipid particles, SLCP): designed to reach the brain better, and often used in Alzheimer's-related researchBCM-95 (mixed with turmeric essential oil): the form used in Lopresti's depression trial
Usual doses (adjusted by form):
Plain curcumin plus piperine: 500–1500 mg of curcuminoids a day, split into 2–3 doses with mealsMeriva: 500–1000 mg a dayTheracurmin: 180–360 mg a day (a lower dose, but a higher plasma level)
Timing:
Take it with a meal that contains fat; it dissolves in fat, so absorption is betterSplit it into 2–3 doses a day rather than one, because the half-life is shortUse it continuously for 4–8 weeks before judging: the effects in trials built up over time and were not immediate
In practice · What to avoid when buying
Only buy products like this:The first ingredient is turmeric root extract, labeled with a purity of curcuminoids ≥ 95%The enhancement method is stated clearly: added piperine (BioPerine®), or a trademark such as Meriva®, Theracurmin®, or Longvida®Third-party testing: certification from USP, NSF, Informed Sport, ConsumerLab, or similar
Do not buy products like this:
Turmeric powder taken as a supplement: the dose is too low and impurities are common (see lead contamination below)Products that just say curcumin without an enhancement method: most likely the plain form, with bioavailability under 1%Products that loudly claim to treat cancer, fight Alzheimer's disease, detox, or boost immunity: the claims themselves break the rules and signal a manufacturer you cannot trustLoose turmeric powder cut with wheat flour, rice flour, or coloring: a high risk of lead contamination
Lead contamination is a real problem:
The US FDA has repeatedly recalled loose turmeric from South Asia after finding lead far above permitted levels; there is no safe level of lead intakeThe cause: some cheap producers use lead chromate to brighten dull-colored turmeric rootsMajor-brand supplements with third-party testing are unlikely to have this problem, but for loose kitchen turmeric the origin matters; in spot checks by consumer organizations, most supplements were within lead limits and a few exceeded them
Price guide (China market): plain curcumin with piperine is the cheapest, Meriva is in the middle, and Theracurmin is the most expensive.
Storage: keep it dry and away from light; heat degrades curcumin (it turns deep brown).
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Chapter 6
How to judge any supplement
Curcumin is a good textbook for learning how to judge supplements. In cells it can hold down and switch on Nrf2, and for knee pain a set of small trials points the same way. But the plain form barely gets into the blood, chemists warn that it looks active at almost anything in a dish, and the market still sells it as anti-cancer and anti-aging. Natural does not mean zero risk either.
So activity in a test tube is not usefulness in your body. Pick up any bottle of supplements and you can ask it the same set of questions: does the mechanism hold in people, how much of it is absorbed, which disease is the evidence about, and is the form you are buying the one the trials used?
So activity in a test tube is not usefulness in your body. Pick up any bottle of supplements and you can ask it the same set of questions: does the mechanism hold in people, how much of it is absorbed, which disease is the evidence about, and is the form you are buying the one the trials used?
In practice · Using curcumin to judge any supplement
Curcumin is a good case for learning how to judge a supplement, because both its strengths and its problems are clear.The good part:
The mechanism in cells is clear (, Nrf2, COX-2)For knee osteoarthritis pain, a set of small randomized trials points the same wayThe safety profile is good overall (limited side effects, known interactions that can be managed)How to take it is well defined (an enhanced form, with meals)
The part to be wary of:
Plain forms have an estimated bioavailability below 1%, which is close to not taking it at allActivity in the dish badly overstates the clinical effect (the chemists' PAINS and IMPS warning)For depression there is only one trial with partial support, and a pooled analysis of blood lipids found no effectThe market over-promises it for cancer, Alzheimer's prevention, and anti-aging, none of which has evidenceNatural does not mean zero risk (drug-induced liver injury, oxalate in turmeric powder, interactions with anticoagulants)
Next time you pick up any bottle of supplements, you can ask it the questions curcumin taught you, one by one:
1. Is the mechanism clear? Does activity in a test tube actually mean it is useful in your body?
2. Are there bioavailability data? Without them, whatever dose is printed on the label counts for nothing.
3. Split the evidence by condition: working for knees does not mean it works for the problem you want to solve.
4. Is the form you are buying the one the studies tested, or just a marketing variant?
5. Does it have side effects? Could it interfere with medicines you already take?
6. For the same goal, is there something more reliable than a supplement?
The final framework: supplements are tools on top of diet, exercise, sleep, and necessary medical care, not replacements for them. Transparent evidence, a clear form, a reasonable dose, and no over-promising: these four yardsticks apply to any supplement.
Evidence · Anti-inflammatory habits that beat a pill
A more reliable anti-inflammatory strategy than taking curcumin alone is your overall diet and lifestyle; curcumin is at most one tool within it.Dietary patterns (large randomized trials):
Mediterranean diet: in PREDIMED, a large randomized trial in adults at high cardiovascular risk, the groups on a Mediterranean diet with extra-virgin olive oil or nuts had about 30% fewer major cardiovascular events in relative terms (see cardiovascular)DASH diet: lowers blood pressure in randomized trials
Single foods (mostly observational studies plus cell and animal mechanisms):
Oily sea fish: and are the raw material the body uses to make resolvins and protectins, anti-inflammatory molecules that help wind down inflammationBlueberries and other berries: flavonoids such as anthocyaninsGreen tea: the catechin , which in cells has antioxidant and weak -inhibiting effectsExtra-virgin olive oil: contains several polyphenolsGarlic and onion: sulfur compoundsCruciferous vegetables (broccoli, kale): in cells, sulforaphane is a strong activator of Nrf2
Exercise:
Regular exercise: during a session, muscle releases (a myokine), yet people who exercise regularly have lower everyday levels of chronic inflammatory markers such as IL-6, so the net effect is anti-inflammatory
Sleep:
In laboratory studies, a night of no sleep or short sleep raises inflammatory markers such as IL-6 and in the blood the next dayIn observational studies, people who regularly sleep less than 6 hours a night more often have chronic low-grade inflammation (an association)
Practical inference: for I want to fight inflammation, a sensible order is:
1. Adjust your eating pattern (Mediterranean diet, DASH)
2. Exercise regularly and get enough sleep
3. Add a single item such as curcumin or omega-3 only when needed
Conversely, one curcumin capsule a day on top of sitting all day, short sleep, and a high-sugar diet does almost nothing, and that is the context most easily overlooked when people learn about supplements.
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References · 5
- Hewlings, S. J., & Kalman, D. S. (2017). Curcumin: a review of its effects on human health. Foods, 6(10), 92. 10.3390/foods6100092
- Anand, P., et al. (2007). Bioavailability of curcumin: problems and promises. Molecular Pharmaceutics, 4(6), 807–818. 10.1021/mp700113r
- Daily, J. W., Yang, M., & Park, S. (2016). Efficacy of turmeric extracts and curcumin for alleviating the symptoms of joint arthritis: a systematic review and meta-analysis of randomized clinical trials. Journal of Medicinal Food, 19(8), 717–729. 8 RCTs met the criteria (29 articles screened): pain VAS mean difference -2.04 (-2.85 to -1.24) vs placebo in 3 RCTs; WOMAC -15.36 (-26.9 to -3.77) in 4; no significant difference in pain VAS between turmeric/curcumin and pain medicine in 5 studies (a non-significant difference, not a tested equivalence). Typical dose about 1000 mg/day curcumin; the authors say trial number, sample size and quality are not sufficient for definitive conclusions (abstract, PMID 27533649). 10.1089/jmf.2016.3705
- Lopresti, A. L., et al. (2014). Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study. Journal of Affective Disorders, 167, 368–375. 56 people with major depressive disorder, curcumin 500 mg twice daily or placebo for 8 weeks. Both groups improved from baseline to week 4; from weeks 4 to 8 curcumin beat placebo on IDS-SR30 total score (p = .045) and mood score (p = .014), with only a trend on trait anxiety; greater effect in atypical depression; the authors call it partial support (abstract, PMID 25046624). 10.1016/j.jad.2014.06.001
- Nelson, K. M., et al. (2017). The essential medicinal chemistry of curcumin. Journal of Medicinal Chemistry, 60(5), 1620–1637. Abstract: curcumin is classified as both a PAINS and an IMPS candidate; its likely false activity in vitro and in vivo has led to more than 120 clinical trials of curcuminoids, and no double-blinded, placebo-controlled clinical trial of curcumin has been successful; the authors argue curcumin is unstable, reactive and non-bioavailable, a highly improbable lead (abstract, PMID 28074653). 10.1021/acs.jmedchem.6b00975