- Is Curcumin bioavailable?
- Benefits and Effects in human studies
- Genes and SNPs
- Dosing Advice
- Any described side effects?
Curcumin is the darling of the supplement world, but many of the studies touting its benefits are based on animal studies. While there is nothing wrong with citing animal studies, we wanted to answer the question: what are Curcumin’s proven health benefits based on human studies?
Our research found that, based on human studies, curcumin has shown the most efficacy as an anti-inflammatory and for treating IBS, ulcerative colitis and other digestive disorders, as well as arthritis. There are also human studies to support curcumin’s use as an antioxidant, but the data isn’t as established.
Before we dive into the data, first a little background on the bioavailability of curcumin. One of the challenges with curcumin supplementation is bioavailability. Without bioavailable curcumin (curcumin the body can use), its health benefits cannot be realized.
See also: How to choose a curcumin supplement
Is Curcumin bioavailable?
Curcumin is typically isolated from the herbaceous turmeric plant (Curcuma longa) which is part of the ginger family, with the roots being a particularly rich source.
When processed, approximately 5% of turmeric root extract is made up of curcuminoids. Of these curcuminoids approximately 80% is curcumin (the one of most interest to us) with the rest comprising of other curcuminoids, such as demethoxycurcumin or bisdemethoxycurcumin, which are seemingly less bio-active than curcumin (R).
This raises an interesting issue about standardisation between plants and processing, and then, for end users, the content of their nutritional supplements. It is possible to both purify and standardise curcumin content in supplements, and many supplements are manufactured to contain at least 95% curcumin, known as 95% curcuminoid standardization, to maximise bio-availability. Pairing curcumin with black pepper extract has also been shown to increase bioavailability (R).
Interestingly a more recent study has found that an alternative preparation, which contains refined curcumin extract coupled with a water soluble carrier molecule (Polyvinylpyrrolidone or PVP) to increase absorption, and fat soluble forms of vitamin C and E as antioxidants, showed an even large improvement in bioavailability (R). As part of this study the authors compared the efficacy of several curcumin supplements which I’ve summarised in the table below.
CS = standardized curcumin mixture, CTR = curcumin with volatile oils to aid absorption, CP = curcumin with lipophilic phytosomes (lipid loving molecules to aid absorption), CHC = curcumin with PVP and natural antioxidants. Values are relative absorption of various curcuminoids into the blood, actual values are available in the paper (R). Red colored values are the worst performing for each type of curcuminoid, greens the best.
As you can clearly see in the table above the CHC preparation (which features PVP and vitamin C and E) significantly outperforms all other preparations, especially pure curcumin alone. This is particularly apparent when the level of curcumin and total curcuminoids present in the blood were measured where a 136 x and 46 x increase in absorption was observed.
For more information on how curcumin formulas aimed at increasing bioavailability could be detrimental to your health, see Curcumin and phospholipids: cause for concern?
Benefits and Effects in human studies
Many beneficial effects have been ascribed to curcumin, including in those with no existing health conditions (R); below we cover some areas where repeated studies have demonstrated a significant positive effect in those with chronic conditions. To give you the best insight into turmeric and curcumin I’ll run through some of the best quality human studies performed to date, and the various potential targets.
In case you’re wondering what the grades next to each topic represent, we rated the various health claims of curcumin based on the strength of the science on that topic. This is a new feature we are rolling out at Gene Food called Science Grade.
It remains unclear exactly how curcumin induces its anti-inflammatory response. Both inhibition of immune-cell activity and blocking of key inflammatory cell-signalling pathways, such as the NF-κB pathway, have been demonstrated. The exact mechanism of action in both instances has not been described and requires further research.
This anti-inflammatory response links in with several disorders including irritable bowel syndrome (IBS) (R), the more severe inflammatory bowel disease (IBD) (R – in conjunction with standard medication), osteoarthritis (R) and psoriasis (R). In all instances patient outcomes were improved with significant reductions in inflammatory markers. However, as discussed above a mechanism to describe curcumins potent anti-inflammatory mechanism remains unknown.
Digestive disorders impose a significant health burden on individuals worldwide, ranging from the milder end of the spectrum and IBS (although sufferers are unlikely to class it as mild) through to the clinical disorders such as IBD and various ulcerous diseases such as ulcerative colitis. In the UK such digestive disorders were estimated to cost the national health service in excess of £8 billion (~$11 billion) in 1997 (R), and these costs are only likely to have increased.
Tumeric shown to protect digestive health
In pre-clinical trials, turmeric demonstrated ability to protect the digestive system through its anti-inflammatory effects, and also by secreting enzymes to promote proper digestion, and overall digestive health (R). In a randomized control trial (the best quality trial where individuals are randomized into treatment groups, and researchers are blinded to results) significantly more patients who received turmeric displayed reduced digestive disorder symptoms compared to patients in the placebo group (R).
Taking this further, another study investigated the activity of purified curcumin compared to two standard ulcerative colitis (UC) treatments. In this instance no difference in effect was observed as between the medication and curcumin, suggesting that curcumin is performing as well as current therapeutics. However, the authors reported a reduction in rate of relapse with curcumin users, a particularly important factor in disorders of the gut (R). A further systematic review of all available studies reported a beneficial effect for curcumin as a co-therapy with established drugs in UC (R).
Figure adapted from Hanai et al. Curcumin Maintenance Therapy for Ulcerative Colitis: Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial. Clinical Gastroenterology and Hepatology. 2006. The top line shows patients receiving curcumin remained in remission for longer, and to a greater extent than patients receiving a placebo.
A full review of the role of curcumin in all digestive disorders is currently underway, and should be available shortly (R).
A similar anti-inflammatory effect is hypothesized to describe the protective effect of curcumin in several studies investigating both rheumatoid and osteoarthritis. Arthritis is a disorder affecting the joints often associated with chronic pain and reduction in motility, the incidence of both is increasing significantly due to increases in lifespan and changes in lifestyle.
In both rheumatoid, which is an autoimmune disorder, and osteoarthritis, which is associated with long term mechanical damage; an inflammatory environment in the joint leads to the breakdown of both cartilage and bone, giving rise to the disease symptoms.
Other members of the ginger family have traditionally been used as medicines for arthritis, inhibiting inflammation (R) and leading to reductions in reported pain (R), but with little effect on actual disease progression. Therefore investigating turmeric and curcumin was of obvious interest.
Curcumin performed on par with standard drug therapy
A study on rheumatoid arthritis demonstrated a beneficial effect following treatment with 500 mg/day of curcumin with or without a standard anti-inflammatory drug (diclofenac sodium). Curcumin performed as well as the standard therapy alone, and significant improvements were observed following co-treatment (R).
Figure adapted from Chandran et al. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother Research. 2012. Disease activity score was improved in all instances, with a slightly better response seen for curcumin and curcumin + standard therapy. Disease activity measures not just pain, but also motility so improvements can be functional as well, although the authors do not specify an effect.
Again, another systematic review has been performed, and in this instance the authors state that a dose of approximately 1000 mg/day of curcumin was effective in the treatment of arthritis (R). It should be noted that this dose was recommended for those currently suffering with severe arthritis and was delivered under the supervision of medical personnel. While below the maximum levels observed in some studies, starting supplementation at a lower dose to check tolerance is always to be recommended.
Another major positive aspect of curcumin is its anti-oxidative capacity. Oxidising agents generated in the body, or ingested, can rapidly induce cellular and genetic damage with lasting impacts. The body maintains anti-oxidative pathways, however in some individuals these pathways can demonstrate reduced activity, or due to chronic exposure to environmental oxidising agents (heavy metals, some pesticides and herbicides) these systems can become overwhelmed.
Curcumin has been shown to increase total anti-oxidant activity in both healthy individuals (R) and in those with a chronic environmental exposure, as in the following study performed in a population exposed to environmental arsenic (R).
Figure adapted from Biswas et al. Curcumin protects DNA damage in a chronically arsenic-exposed population of West Bengal. Human & Experimental Toxicology. 2010. In the first figure treatment with curcumin was initiated at point a) following three months exposure to arsenic. The occurrence of doubled stranded DNA, a measure of DNA breakdown, was reduced suggesting DNA was being protected from oxidative damage. A similar effect was seen in a confirmatory experiment.
In animal and human cell studies curcumin has been shown to both increase the expression and activity of key anti-oxidant enzymes. However, and in contrast to the positive effects observed in inflammatory disorders, confirmatory clinical trials have not yet been reported.
Turmeric and curcumin have been linked with a beneficial effect for a variety of other disorders, although the evidence supporting some of these claims is less robust than for the examples discussed above.
Several early studies demonstrated that curcumin exhibited potent anti-cancer properties for a wide variety of cancers including colorectal (R), pancreatic (R), breast (R), lung (R) and prostate cancer (R). These effects were modulated by altering cell signaling pathways typically associated with cancer development and also by promoting anti-oxidative effects. These promising results led researchers to undertake wide-ranging clinical trials in patients, however results were rather poor (R,R,R), often failing to meet primary outcomes. In part this is likely due to the relative complexity and time-courses of each disease. Identifying what may be quite small beneficial effects in either disease population will likely be difficult, and may require large scale studies. Ongoing, completed and withdrawn trials can be observed at the clinicaltrials.gov website.
Asthma and rhinitis
Due to its potent anti-inflammatory effect in disorders such as IBS or arthritis other disorders with an inflammatory aspect were also investigated. Asthma was of particular interest due the occurrence of inflammation but also a dysregulated immune response. Some studies in animal models have demonstrated a positive effect (R,R), but to date no clinical trials have been performed.
However, an early pre-clinical trial in patients suffering from perennial allergic rhinitis (PAR) (allergy to things such as dust mites, animal furs or fungi and molds present all year round) did show a positive effect (R). Inflammatory markers were reduced in PAR suffers following an oral dose of **** curcumin for 2 months. Importantly those taking curcumin also reported a reduction in symptom frequency and severity. As a relatively recent study (December 2016), a larger trial is unlikely to be available for a few more years.
A major concern in the majority of papers was the lack of bioavailability associated with curcumin. It is possible that more advanced formulations as discussed at the start of this post may improve outcomes. Another distinct possibility is that certain patients subgroups carrying particular SNPs that put them at risk, or promote a beneficial effect, may be present. However, there is currently no data available describing any such groups. This is a perfect example of watch this space.
Cardiovascular disease and diabetes
In a study of healthy individuals a dose of 80 mg/day curcumin was associated with markers potentially associated with good health (R). Following on from this no beneficial effect for those at risk of, or already suffering from, cardiovascular disorders has been reported. In a small study of pre-diabetic patients (i.e. those at a high risk of developing type 2 diabetes [T2D]) a protective effect following curcumin supplementation was observed (R), a later study also demonstrated improvements in the metabolic profile of patients with T2D but did not report on improved health outcomes (R).
There are a few studies reporting on the potential use of curcumin as a contraceptive due to its ability to kill, or impair the movement of sperm (R,R). No clinical trials have been performed to date with existing studies either using human sperm outside the body, or mouse models. Due to issues surrounding application methodology and timing, and the relatively poor contraceptive action (compared to existing contraceptives) this finding seems more like an interesting quirk of curcumin rather than something that will be used clinically or commercially.
To provide a balanced review of curcumin and turmeric it is important to discuss some caveats associated with the research. Whilst some beneficial effects are repeatable, numerous others are not. Some researchers put this down to the relative reactivity of curcumin and its lack of bio-availability (R) making it difficult to identify its true activity. This has led some researchers to term curcumin a PAIC, a compound which regularly flags up in drug screens, but whose mechanisms of action cannot be determined.
Genes and SNPs
There are several genes and SNPs which may be of interest for those considering curcumin supplementation.
The risk ‘A’ allele of rs4073 in the IL8 gene is associated with an increased risk of bacterial infections of the gut (R), leading to the potential for stomach ulcers to form (R), impaired nutrient uptake and development of IBS (R). As an inflammatory disorder there is some evidence that turmeric/curcumin can alleviate the development of the more severe symptoms (R, R). Results for IBS were more confusing with one study reporting no effect (R), whereas another reported a significant beneficial effect (R).
Several SNPs in the AOC1 gene (rs10156191, rs1049742, rs1049793, rs45558339 and rs35070995) are associated with reductions in the breakdown of histamine (R). Histamine plays a major role in the immune response generating inflammation to fight infection, however its incorrect release is associated with severe allergic reactions. Those carrying the risk alleles for the above SNPs demonstrate a prolonged inflammatory response following histamine release. Several trials have demonstrated that curcumin can reduce the inflammatory response associated with histamine release (R,R), meaning supplementation may be of interest to those at risk.
The superoxide dismutase 2 and 3 (SOD2, SOD3) genes are potent antioxidants. The risk ‘T’ allele of rs4880 in SOD2 and the risk ‘G’ allele of rs1799895 in SOD3 are both associated with impaired antioxidant capacity putting carries at risk of cardiovascular disease (R,R), diabetes (R) and cancer (R).
Animal studies have shown that curcumin supplementation can increase SOD2 expression and activity (R) in rats, and increase total SOD activity in human cells cultured in the lab (R). However, to date no trials have been performed in humans which directly assess the impact of curcumin on SOD activity, although a general improvement to antioxidant response has been observed (R).
See also: SOD2A16V: the oxidative stress gene?
There are no firm guidelines on dosing, however in clinical studies, individuals ingesting doses of up to 8g per day for extended periods without any adverse effects (R). However, as with all supplementation a much lower dose is to be recommended if starting supplementation
Any described side effects?
As above there are no serious side effects when ingested even at doses as high as 8g per day (R). However, in the same study some participants did report mild nausea or diarrhoea. Some practitioners offer intravenous injections of curcumin/turmeric extract however the evidence supporting this delivery method is poor and is associated with much higher risks (R).
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