Copyright Eric Yarnell, ND, RH(AHG), 2023
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last updated 22 Aug 2023
To prove that a medicinal agent is clinically superior to another medicinal agent, it is necessary to do a head-to-head, double-blind, randomized, controlled trial comparing the two agents. I have scoured the literature for years and never found any such clinical trial that has been published comparing curcumin to whole turmeric. Until and unless this occurs, any statement that curcumin, a recently (in the last 50 years)-identified constituent mixture from turmeric should not be considered superior, especially given that turmeric has a history of use longer than recorded history!
Most of the arguments favoring curcumin are marketing hype, and seem to rest on pharmacokinetic research. The gist of this argument starts from several false premises then attempts to dazzle with human pharmacokinetic research. It goes like this: 1. curcumin is the "active" ingredient in turmeric (this is a categorically false starting premise). 2. Curcumin is present in small concentrations in whole turmeric, and is poorly absorbed, thus limiting the effectiveness of whole turmeric (this is also false). 3. Isolated curcumin, especially in one of several proprietary extracts with added ingredients for absorption enhancement, is better absorbed than from whole turmeric (not true). 4. Therefore, you should use isolated curcumin from one of these proprietary extracts (and generally whatever company is selling this whole line of malarky is touting their specific extract).
It is easy to prove that curcumin is not the "active" ingredient in turmeric. It is one set of constituents among many that contribute to turmeric's medicinal activity. Numerous studies show that curcumin-free extracts of turmeric have a wide range of relevant therapeutic activities (Nair, et al. 2019; Aggarwal, et al. 2013).
The contention that curcumin is poorly absorbed from whole turmeric compared to isolated forms or simple co-formulations is not clear. One clinical trial (in 45 healthy adult Indian men) compared a whole turmeric extract (somewhat bizarrely, all the different fractions of turmeric rhizome were extracted then mixed back together, clearly so they can market this product as something special when they should have just used the crude rhizome powder and saved a lot of time, money, and trouble) to 86% curcumin mixed with turmeric steam-distilled volatile oil and a product with 20% curcumin mixed with 40% phospholipids and 40% microcrystalline cellulose (Gopi, et al. 2017). In one 500 mg capsule of each, there was 180, 351, and 80.5 mg of the curcumin mixture (subjects took a single capsule dose). The Cmax was 3.6 times higher after the whole turmeric extract product compared to the curcumin/volatile oil product, and 2.44 times higher than the curcumin/phospholipid product. The Tmax was also significantly higher with the whole turmeric vs. either of the other two products. Most studies on bioavailability of curcumin products fail to describe what formulation is even being studied, and do not compare them to other forms or whole turmeric, further limiting the relevance of such research (Mimica, et al. 2022). Another study (in just 4 English subjects) looking at absorption of curcumin from a standardized meal providing 3 g turmeric (and ~100 mg curcumin total) could readily identify curcumin and its metabolites in serum, albeit in concentrations lower than those reported with curcumin formulations (Mahale, et al. 2018). It is important though, because a prior study found no absorption of curcumin from whole turmeric, and these researchers proved this was actually because they of poor methodological sensitivity (Sharma, et al. 2001).
"...it remains to be determined as to what is the minimum dose of curcumin required to see its beneficial effects in each disease condition, and whether there is a linear relationship between its bioavailability and bioefficacy. In view of the overwhelming body of compelling data for curcumin in thousands of studies, it is very possible that curcumin bioavailability may actually not even be a serious issue, if only a very small amount of this compound, its metabolites and/or conjugates are sufficient to exert their beneficial effect. After all we need to remind ourselves that the ultimate goal is not simply delivering the most curcumin/curcumin metabolites in circulation, but to prevent, mitigate, or treat a specific disease." —Toden and Goel 2017 (emphasis added)
Traditionally turmeric was often combined with Piper longum (long pepper) or P. nigrum (black pepper), which we now know may be because it improves absorption of curcuminoids and other compounds. Modern clinical trials have shown that adding the alkaloid piperine from these two species can enhance the efficacy of whole turmeric in clinical trials in people with type 2 diabetes mellitus or those on hemodialysis (Neta, eta l. 2021; Freitas E Silva-Santana, et al. 2022). This goes above and beyond showing that either of these peppers increases absorption, but actually contributes to turmeric's efficacy.
Regardless, the point of therapy with anything is not to optimize absorption but to get patients better! So at the end of the day, if all that can be shown is some form of curcumin is better absorbed, it doesn't matter. The implication is curcumin absorption = clinical efficacy, but this is false. There are many factors that determine whether a treatment will be effective, and absorption of a mixture of three compounds is not the main one. If truly isolated curcumin is all that matters for clinical efficacy, then clinical trials on whole turmeric supplying far lower levels of curcumin should all fail.
Clinical trials have in fact shown that low doses of whole turmeric rhizome powder, from 400 mg tid to 1000 mg bid, are effective at treating people with conditions including lupus nephritis, type 2 diabetes mellitus, diabetic nephropathy, metabolic liver disease, and obesity (Khajehdehi, et al. 2012; Srinivasan, et al. 2019; Adab, et al. 2019; Khajehdehi, et al. 2011; Jarhahzadeh, et al. 2021; Navekar, et al. 2017; Uchio, et al. 2021).
Coming close to a head-to-head comparison are trials looking at curcumin vs. whole turmeric in cancer patients being treated with paclitaxel. A study with intravenous curcumin 300 mg once weekly found it had almost no benefit in 150 Armenian women undergoing paclitaxel chemotherapy with breast cancer compared to placebo (Saghatelyan, et al. 2020). There was a reduction in fatigue with curcumin and an arguably pointless improvement in objective response (i.e. tumor shrinkage), but no change in survival or overall quality of life. On the other hand, 60 Indian women undergoing paclitaxel chemotherapy for breast cancer who took whole turmeric powder 1 g bid between chemotherapy infusions found found improved hemoglobin, white blood cell and neutrophil counts compared to baseline without turmeric (Kalluru, et al. 2020). Treatment did not interfere with paclitaxel pharmacokinetics (Kalluru, et al. 2022). While these trials had many differences, the whole turmeric outcomes were better. A true head-to-head, double-blind, randomized trial is still the only way to be certain, but the evidence doens't look good for isolated curcumin.
There is one situation in which curcumin extracts really could be argued to be preferred over whole turmeric, yet it is almost never mentioned. This stems from the fact that whole turmeric is extremely high in soluble oxalates (Ghosh Das and Savage 2012). It has been shown in a clinical trial that eating turmeric significantly increases urinary oxalate output (Tang, et al. 2008). This could obviously be a problem for anyone with hyperoxaluria and a history of kidney stones, or any other problem triggered by high intake of soluble oxalates. Various extracts of turmeric without oxalates could get around this problem, but should still include as much of the rhizome's other constituents as possible and not just curcumin. Taking whole turmeric with milk, other calcium-rich foods, or a calcium supplement should also greatly limit oxalate absorption. One study found that intake of 1200 mg of calcium in the diet daily limited oxalate absorption to 2.6%, compared to 17% with a diet providing only 200 mg calcium daily (von Unruh, et al. 2004). This may in part explain why it is so traditional for whole turmeric to be consumed with cow's milk in India.
Summary
Most of the arguments favoring curcumin are marketing hype, and seem to rest on pharmacokinetic research. The gist of this argument starts from several false premises then attempts to dazzle with human pharmacokinetic research. It goes like this: 1. curcumin is the "active" ingredient in turmeric (this is a categorically false starting premise). 2. Curcumin is present in small concentrations in whole turmeric, and is poorly absorbed, thus limiting the effectiveness of whole turmeric (this is also false). 3. Isolated curcumin, especially in one of several proprietary extracts with added ingredients for absorption enhancement, is better absorbed than from whole turmeric (not true). 4. Therefore, you should use isolated curcumin from one of these proprietary extracts (and generally whatever company is selling this whole line of malarky is touting their specific extract).
It is easy to prove that curcumin is not the "active" ingredient in turmeric. It is one set of constituents among many that contribute to turmeric's medicinal activity. Numerous studies show that curcumin-free extracts of turmeric have a wide range of relevant therapeutic activities (Nair, et al. 2019; Aggarwal, et al. 2013).
The contention that curcumin is poorly absorbed from whole turmeric compared to isolated forms or simple co-formulations is not clear. One clinical trial (in 45 healthy adult Indian men) compared a whole turmeric extract (somewhat bizarrely, all the different fractions of turmeric rhizome were extracted then mixed back together, clearly so they can market this product as something special when they should have just used the crude rhizome powder and saved a lot of time, money, and trouble) to 86% curcumin mixed with turmeric steam-distilled volatile oil and a product with 20% curcumin mixed with 40% phospholipids and 40% microcrystalline cellulose (Gopi, et al. 2017). In one 500 mg capsule of each, there was 180, 351, and 80.5 mg of the curcumin mixture (subjects took a single capsule dose). The Cmax was 3.6 times higher after the whole turmeric extract product compared to the curcumin/volatile oil product, and 2.44 times higher than the curcumin/phospholipid product. The Tmax was also significantly higher with the whole turmeric vs. either of the other two products. Most studies on bioavailability of curcumin products fail to describe what formulation is even being studied, and do not compare them to other forms or whole turmeric, further limiting the relevance of such research (Mimica, et al. 2022). Another study (in just 4 English subjects) looking at absorption of curcumin from a standardized meal providing 3 g turmeric (and ~100 mg curcumin total) could readily identify curcumin and its metabolites in serum, albeit in concentrations lower than those reported with curcumin formulations (Mahale, et al. 2018). It is important though, because a prior study found no absorption of curcumin from whole turmeric, and these researchers proved this was actually because they of poor methodological sensitivity (Sharma, et al. 2001).
"...it remains to be determined as to what is the minimum dose of curcumin required to see its beneficial effects in each disease condition, and whether there is a linear relationship between its bioavailability and bioefficacy. In view of the overwhelming body of compelling data for curcumin in thousands of studies, it is very possible that curcumin bioavailability may actually not even be a serious issue, if only a very small amount of this compound, its metabolites and/or conjugates are sufficient to exert their beneficial effect. After all we need to remind ourselves that the ultimate goal is not simply delivering the most curcumin/curcumin metabolites in circulation, but to prevent, mitigate, or treat a specific disease." —Toden and Goel 2017 (emphasis added)
Traditionally turmeric was often combined with Piper longum (long pepper) or P. nigrum (black pepper), which we now know may be because it improves absorption of curcuminoids and other compounds. Modern clinical trials have shown that adding the alkaloid piperine from these two species can enhance the efficacy of whole turmeric in clinical trials in people with type 2 diabetes mellitus or those on hemodialysis (Neta, eta l. 2021; Freitas E Silva-Santana, et al. 2022). This goes above and beyond showing that either of these peppers increases absorption, but actually contributes to turmeric's efficacy.
Regardless, the point of therapy with anything is not to optimize absorption but to get patients better! So at the end of the day, if all that can be shown is some form of curcumin is better absorbed, it doesn't matter. The implication is curcumin absorption = clinical efficacy, but this is false. There are many factors that determine whether a treatment will be effective, and absorption of a mixture of three compounds is not the main one. If truly isolated curcumin is all that matters for clinical efficacy, then clinical trials on whole turmeric supplying far lower levels of curcumin should all fail.
Clinical trials have in fact shown that low doses of whole turmeric rhizome powder, from 400 mg tid to 1000 mg bid, are effective at treating people with conditions including lupus nephritis, type 2 diabetes mellitus, diabetic nephropathy, metabolic liver disease, and obesity (Khajehdehi, et al. 2012; Srinivasan, et al. 2019; Adab, et al. 2019; Khajehdehi, et al. 2011; Jarhahzadeh, et al. 2021; Navekar, et al. 2017; Uchio, et al. 2021).
Coming close to a head-to-head comparison are trials looking at curcumin vs. whole turmeric in cancer patients being treated with paclitaxel. A study with intravenous curcumin 300 mg once weekly found it had almost no benefit in 150 Armenian women undergoing paclitaxel chemotherapy with breast cancer compared to placebo (Saghatelyan, et al. 2020). There was a reduction in fatigue with curcumin and an arguably pointless improvement in objective response (i.e. tumor shrinkage), but no change in survival or overall quality of life. On the other hand, 60 Indian women undergoing paclitaxel chemotherapy for breast cancer who took whole turmeric powder 1 g bid between chemotherapy infusions found found improved hemoglobin, white blood cell and neutrophil counts compared to baseline without turmeric (Kalluru, et al. 2020). Treatment did not interfere with paclitaxel pharmacokinetics (Kalluru, et al. 2022). While these trials had many differences, the whole turmeric outcomes were better. A true head-to-head, double-blind, randomized trial is still the only way to be certain, but the evidence doens't look good for isolated curcumin.
There is one situation in which curcumin extracts really could be argued to be preferred over whole turmeric, yet it is almost never mentioned. This stems from the fact that whole turmeric is extremely high in soluble oxalates (Ghosh Das and Savage 2012). It has been shown in a clinical trial that eating turmeric significantly increases urinary oxalate output (Tang, et al. 2008). This could obviously be a problem for anyone with hyperoxaluria and a history of kidney stones, or any other problem triggered by high intake of soluble oxalates. Various extracts of turmeric without oxalates could get around this problem, but should still include as much of the rhizome's other constituents as possible and not just curcumin. Taking whole turmeric with milk, other calcium-rich foods, or a calcium supplement should also greatly limit oxalate absorption. One study found that intake of 1200 mg of calcium in the diet daily limited oxalate absorption to 2.6%, compared to 17% with a diet providing only 200 mg calcium daily (von Unruh, et al. 2004). This may in part explain why it is so traditional for whole turmeric to be consumed with cow's milk in India.
Summary
- Curcumin has never been tested in a head-to-head clinical trial with whole turmeric, so their relative clinical efficacy is unknown.
- Studies showing better absorption of whole curcumin are irrelevant: the goal of medicine is clinical efficacy not absorption.
- Whole turmeric has such a long history of use (likely tens of thousands of years), it is illogical to switch to using just one tiny subset of compounds from it that have only been used for ~50 years without head-to-head research.
- Studies in similar populations (e.g. breast cancer) show whole turmeric has better clinical benefits than curcumin.
- Most sources promoting curcumin over whole turmeric are based on marketers trying to sell curcumin products.
References
Adab Z, Eghtesadi S, Vafa MR, et al. (2019) "Effect of turmeric on glycemic status, lipid profile, hs-CRP, and total antioxidant capacity in hyperlipidemic type 2 diabetes mellitus patients" Phytother Res 33(4):1173–81.
Aggarwal BB, Yuan W, Li S, Gupta SC (2013) "Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric" Mol Nutr Food Res 57(9):1529–42.
Freitas E Silva-Santana NC, Rodrigues HCN, Pereira Martins TF, et al. (2022) "Turmeric supplementation with piperine is more effective than turmeric alone in attenuating oxidative stress and inflammation in hemodialysis patients: A randomized, double-blind clinical trial" Free Radic Biol Med 193(Pt 2):648–55.
Ghosh Das S, Savage GP (2012) "Total and soluble oxalate content of some Indian spices" Plant Foods Hum Nutr 67(2):186–90.
Gopi S, Jacob J, Varma K, et al. (2017) "Comparative oral absorption of curcumin in a natural turmeric matrix with two other curcumin formulations: An open-label parallel-arm study" Phytother Res 31(12):1883–91.
Jarhahzadeh M, Alavinejad P, Farsi F, et al. (2021) "The effect of turmeric on lipid profile, malondialdehyde, liver echogenicity and enzymes among patients with nonalcoholic fatty liver disease: A randomized double blind clinical trial" Diabetol Metab Syndr 13(1):112.
Kalluru H, Kondaveeti SS, Telapolu S, Kalachaveedu M (2020) "Turmeric supplementation improves the quality of life and hematological parameters in breast cancer patients on paclitaxel chemotherapy: A case series" Complement Ther Clin Pract 41:101247.
Kalluru H, Mallayasamy SR, Kondaveeti SS, et al. (2022) "Effect of turmeric supplementation on the pharmacokinetics of paclitaxel in breast cancer patients: A study with population pharmacokinetics approach" Phytother Res 36(4):1761–9.
Khajehdehi P, Pakfetrat M, Javidnia K, et al. (2011) "Oral supplementation of turmeric attenuates proteinuria, transforming growth factor-β and interleukin-8 levels in patients with overt type 2 diabetic nephropathy: A randomized, double-blind and placebo-controlled study" Scand J Urol Nephrol 45(5):365–70.
Khajehdehi P, Zanjaninejad B, Aflaki E, et al. (2012) "Oral supplementation of turmeric decreases proteinuria, hematuria, and systolic blood pressure in patients suffering from relapsing or refractory lupus nephritis: A randomized and placebo-controlled study" J Ren Nutr 22(1):50–7.
Mahale J, Singh R, Howells LM, et al. (2018) "Detection of plasma curcuminoids from dietary intake of turmeric-containing food in human volunteers" Mol Nutr Food Res 62(16):e1800267.
Mimica B, Bučević Popović V, et al. (2022) "Methods used for enhancing the bioavailability of oral curcumin in randomized controlled trials: A meta-research study" Pharmaceuticals (Basel) 15(8):939.
Nair A, Amalraj A, Jacob J, et al. (2019) "Non-curcuminoids from turmeric and their potential in cancer therapy and anticancer drug delivery formulations" Biomolecules 9(1):13.
Navekar R, Rafraf M, Ghaffari A, et al. (2017) "Turmeric supplementation improves serum glucose indices and leptin levels in patients with nonalcoholic fatty liver diseases" J Am Coll Nutr 36(4):261–7.
Neta JFF, Veras VS, Sousa DF, et al. (2021) "Effectiveness of the piperine-supplemented Curcuma longa L in metabolic control of patients with type 2 diabetes: A randomised double-blind placebo-controlled clinical trial" Int J Food Sci Nutr 72(7):968–977.
Saghatelyan T, Tananyan A, Janoyan N, et al. (2020) "Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial" Phytomedicine 70:153218.
Sharma RA, McLelland HR, Hill KA, et al. (2001) "Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer" Clin Cancer Res 7(7):1894–900.
Srinivasan A, Selvarajan S, Kamalanathan S, et al. (2019) "Effect of Curcuma longa on vascular function in native Tamilians with type 2 diabetes mellitus: A randomized, double-blind, parallel arm, placebo-controlled trial" Phytother Res 33(7):1898–911.
Tang M, Larson-Meyer DE, Liebman M (2008) "Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects" Am J Clin Nutr 87(5):1262–7.
Uchio R, Kawasaki K, Okuda-Hanafusa C, et al. (2021) "Curcuma longa extract improves serum inflammatory markers and mental health in healthy participants who are overweight: A randomized, double-blind, placebo-controlled trial" Nutr J 20(1):91.
von Unruh GE, Voss S, Sauerbruch T, Hesse A (2004) "Dependence of oxalate absorption on the daily calcium intake" J Am Soc Nephrol 15(6):1567–73.
Aggarwal BB, Yuan W, Li S, Gupta SC (2013) "Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric" Mol Nutr Food Res 57(9):1529–42.
Freitas E Silva-Santana NC, Rodrigues HCN, Pereira Martins TF, et al. (2022) "Turmeric supplementation with piperine is more effective than turmeric alone in attenuating oxidative stress and inflammation in hemodialysis patients: A randomized, double-blind clinical trial" Free Radic Biol Med 193(Pt 2):648–55.
Ghosh Das S, Savage GP (2012) "Total and soluble oxalate content of some Indian spices" Plant Foods Hum Nutr 67(2):186–90.
Gopi S, Jacob J, Varma K, et al. (2017) "Comparative oral absorption of curcumin in a natural turmeric matrix with two other curcumin formulations: An open-label parallel-arm study" Phytother Res 31(12):1883–91.
Jarhahzadeh M, Alavinejad P, Farsi F, et al. (2021) "The effect of turmeric on lipid profile, malondialdehyde, liver echogenicity and enzymes among patients with nonalcoholic fatty liver disease: A randomized double blind clinical trial" Diabetol Metab Syndr 13(1):112.
Kalluru H, Kondaveeti SS, Telapolu S, Kalachaveedu M (2020) "Turmeric supplementation improves the quality of life and hematological parameters in breast cancer patients on paclitaxel chemotherapy: A case series" Complement Ther Clin Pract 41:101247.
Kalluru H, Mallayasamy SR, Kondaveeti SS, et al. (2022) "Effect of turmeric supplementation on the pharmacokinetics of paclitaxel in breast cancer patients: A study with population pharmacokinetics approach" Phytother Res 36(4):1761–9.
Khajehdehi P, Pakfetrat M, Javidnia K, et al. (2011) "Oral supplementation of turmeric attenuates proteinuria, transforming growth factor-β and interleukin-8 levels in patients with overt type 2 diabetic nephropathy: A randomized, double-blind and placebo-controlled study" Scand J Urol Nephrol 45(5):365–70.
Khajehdehi P, Zanjaninejad B, Aflaki E, et al. (2012) "Oral supplementation of turmeric decreases proteinuria, hematuria, and systolic blood pressure in patients suffering from relapsing or refractory lupus nephritis: A randomized and placebo-controlled study" J Ren Nutr 22(1):50–7.
Mahale J, Singh R, Howells LM, et al. (2018) "Detection of plasma curcuminoids from dietary intake of turmeric-containing food in human volunteers" Mol Nutr Food Res 62(16):e1800267.
Mimica B, Bučević Popović V, et al. (2022) "Methods used for enhancing the bioavailability of oral curcumin in randomized controlled trials: A meta-research study" Pharmaceuticals (Basel) 15(8):939.
Nair A, Amalraj A, Jacob J, et al. (2019) "Non-curcuminoids from turmeric and their potential in cancer therapy and anticancer drug delivery formulations" Biomolecules 9(1):13.
Navekar R, Rafraf M, Ghaffari A, et al. (2017) "Turmeric supplementation improves serum glucose indices and leptin levels in patients with nonalcoholic fatty liver diseases" J Am Coll Nutr 36(4):261–7.
Neta JFF, Veras VS, Sousa DF, et al. (2021) "Effectiveness of the piperine-supplemented Curcuma longa L in metabolic control of patients with type 2 diabetes: A randomised double-blind placebo-controlled clinical trial" Int J Food Sci Nutr 72(7):968–977.
Saghatelyan T, Tananyan A, Janoyan N, et al. (2020) "Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial" Phytomedicine 70:153218.
Sharma RA, McLelland HR, Hill KA, et al. (2001) "Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer" Clin Cancer Res 7(7):1894–900.
Srinivasan A, Selvarajan S, Kamalanathan S, et al. (2019) "Effect of Curcuma longa on vascular function in native Tamilians with type 2 diabetes mellitus: A randomized, double-blind, parallel arm, placebo-controlled trial" Phytother Res 33(7):1898–911.
Tang M, Larson-Meyer DE, Liebman M (2008) "Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects" Am J Clin Nutr 87(5):1262–7.
Uchio R, Kawasaki K, Okuda-Hanafusa C, et al. (2021) "Curcuma longa extract improves serum inflammatory markers and mental health in healthy participants who are overweight: A randomized, double-blind, placebo-controlled trial" Nutr J 20(1):91.
von Unruh GE, Voss S, Sauerbruch T, Hesse A (2004) "Dependence of oxalate absorption on the daily calcium intake" J Am Soc Nephrol 15(6):1567–73.