Have you heard that curcumin supplements offer a slew of health benefits but are not sure why? Curcumin, a polyphenol found in turmeric, is a spice used in traditional Indian cuisine and in other areas of Asia as a drink. Turmeric is harvested from the rhizome of Curcuma longa, which is a member of the ginger family. It has a long history of use both as a spice and in traditional Ayurvedic medicine.
Curcumin is anti-inflammatory and decreases oxidative stress. It inhibits TNF-alpha and decreases NF-kB.
Benefits of curcumin:
Curcumin is a well-studied polyphenol, with randomized, placebo-controlled trials as well as tons of animal and cell studies.
The main effect of curcumin is a decrease in inflammation through a reduction in inflammatory cytokines. This decrease in inflammation impacts a variety of different chronic conditions such as arthritis, diabetes, NAFLD, and cognitive function.
Clinical trials using curcumin:
Hundreds of randomized, placebo-controlled clinical trials have investigated the efficacy of curcumin for a variety of different conditions. Here are just a few of the trials:
Diabetes prevention: A clinical trial that included 240 participants assessed the efficacy of curcumin for preventing diabetes. The participants all had prediabetes, and half of the group took a curcumin supplement (500 mg/3 times a day) After 9 months, almost 1/5 of the control group had diabetes but none of the curcumin group had progressed. The curcumin treated group had a decrease in HOMA-IR.[ref]
COVID-19: A clinical trial with 80 participants tested nano-curcumin for the effect on cytokine production in COVID-19 patients. Nano-curcumin decreased IL-6 and IL-1B secretion, which may be important in severe cases of COVID-19.[ref]
Depression: A randomized clinical trial showed curcumin (500 mg/2x per day) to be more effective than placebo for improving depression.[ref]
Related article: Depression and Inflammation
Osteoarthritis: A curcumin-phosphatidylcholine complex (Meriva) was effective in decreasing inflammatory markers and in decreasing joint pain.[ref] Another clinical trial found that curcumin (500mg / 3x per day) was as effective as diclofenac for osteoarthritis – but with fewer side effects.[ref]
NAFLD: A clinical trial with 50 fatty liver disease patients found that 1500mg/day of curcumin significantly decreased liver fibrosis and inflammatory markers.[ref]
Related article: Fatty Liver Disease Genetic Risk Factor
PCOS: The trial included women with PCOS who were taking metformin. The addition of curcumin additionally decreased blood glucose levels as well as LDL cholesterol.[ref]
Related article: PCOS genes
Gulf War Illness: A clinical trial looked at the effect of curcumin and several other natural supplements on the symptoms of Gulf War Illness. Only curcumin significantly reduced symptoms of GWI.[ref]
Related article: Genetic risk factors for Gulf War Illness
Schizophrenia: As an adjunct to regular antipsychotic medication, the addition of nanocurcumin significantly improved psychiatric symptom scores.[ref]
Sarcopenia: Muscle mass decline is a serious problem in the elderly. Curcumin supplementation increased handgrip strength and weight lifting strength compared to placebo.[ref]
Cognitive Performance: Curcumin supplementation improved cognitive performance in middle-aged, overweight people.[ref]
Neuroinflammation: A trial of curcumin plus fish oil showed a significant reduction in IL-1β levels.[ref]
Muscle pain after exercise: In a clinical trial, curcumin supplementation reduced delayed-onset muscle pain after exercise.[ref]
Curcumin decreases chronic inflammation:
While the many human clinical trials show that curcumin is effective at reducing symptoms in chronic inflammatory conditions, cell and animal studies elucidate the mechanism of action:
IL-17 reduction: Curcumin reduces IL-17 production through the induction of IDO (tryptophan enzyme in the kynurenine pathway).[ref]
Inflammatory cytokines: A randomized clinical trial of curcumin (1g/day) in people with metabolic syndrome showed statistically significant reductions in TNF-α, IL-6, TGF-β, and MCP-1.[ref]
What are the side effects of curcumin?
Phase I clinical trials show that curcumin is safe at high doses of 12 g/day.[ref]
Anecdotally, curcumin at higher doses may give some people intestinal issues. Thus, keep an eye out for gastrointestinal side effects and cut back if needed.
Absorption and metabolism of curcumin:
Curcumin is not very bioavailable – poorly absorbed, rapidly metabolized, and quickly excreted.[ref]
Many studies point to the fact that it is quickly metabolized and that the parent curcumin compound doesn’t stick around long in the bloodstream.
Of note, though, is that recent research shows that some of the anti-inflammatory effects of curcumin are due to the curcumin metabolites, rather than curcumin itself. Research showed that the inhibition of NF-κB is due to the metabolite rather than the parent compound.[ref][ref]
Helping curcumin stick around longer:
Piperine, a compound found in black pepper, is sometimes combined with curcumin. Piperine interferes with glucuronidation, which is a route of curcumin metabolism. By slowing down glucuronidation, curcumin can remain in the system longer.[ref]
One clinical trial showed that 20 mg of piperine increase serum concentrations of curcumin for 1-2 hours after ingestion. The bioavailability of 2g doses of curcumin increased by 2000% (in humans).[ref]
Related article: UGTs: Glucuronidation genes
Increasing absorption of curcumin:
In the intestines, curcumin must cross the intestinal barrier for absorption. The gut bacteria in the intestines actually metabolize some of the oral curcumin that you take.
Using a surfactant that decreases the intestinal mucosa is effective in animal studies for increasing curcumin absorption.[ref] But surfactants or emulsifiers can cause intestinal inflammation and are not a good idea on a daily basis.
Related article: Emulsifiers and IBD
Combining curcumin with a fat is one way to boost absorption. Many of the different supplemental curcumin options take advantage of this option.
Curcumin nanoparticles: Theracurmin, a formulation with colloidal nano-particles, has a 27-fold higher bioavailability than powdered curcumin.[ref]
Curcumin phospholipid complex: A formulation of lecithin with curcumin increased absorption by about 29-fold in human trials. The brand used was Meriva, which is available from Thorne.[ref]
CURCUGEN: A patent-pending formula of curcumin and turmeric essential oil shows increased absorption ability in randomized trials. The CURCUGEN formulation increased free curcumin serum concentration by 16-fold compared to a standard powdered curcumin extract. CURCUGEN contains 50% curcuminoids, and it was compared to a 95% curcuminoid extract. The study used doses of each product that were equivalent to 2g of curcuminoids, so approximately 4g of CURCUGEN vs 2g of the 95% curcuminoid extract.
Curcumin metabolites: Some companies are creating metabolite versions of curcumin, with the focus on tetrahydrocurcumin as an active metabolite.
Cost-benefit analysis: Are more expensive curcumin supplements worth it?
Keep in mind that curcumin powder is fairly inexpensive, and turmeric is fairly cheap. Thus, it may be less expensive to take more powdered curcumin (or curcumin with piperine) than the more expensive, patented formulations with better bioavailability. You’ll need to do the math…
You should also consider that some of the benefits of curcumin are derived from its metabolites, as opposed to the free curcumin being studied in absorption studies.
Genes that interact with curcumin:
GSTP1: Curcumin induces the expression of GSTP1 (glutathione S-transferase P1).[ref] GSTP1 is part of the body’s detoxification system, responsible for getting rid of certain toxicants through conjugation with glutathione. GSTP1 is important in cancer prevention through its elimination of carcinogens.[ref]
Some people have GSTP1 variants that cause the enzyme not to function as well as normal:
Check your genetic data for rs1695 (23andMe v4, v5; AncestryDNA):
- A/A: typical; possibly higher IL-6 in men who take vitamin E[ref]
- A/G: typical risk of breast cancer
- G/G: reduced function, increased risk of breast cancer[ref][ref] increased risk of prostate cancer[ref] increased risk of nasal polyps[ref]
Members: Your genotype for rs1695 is —.
TNF-alpha: Curcumin decreases TNF-alpha levels. TNF-alpha is an inflammatory cytokine, important in the cellular defense against pathogens. Too much TNF-alpha can cause chronic inflammation and the downstream effects resulting in chronic disease.
Some people have genetic variants that increase their cellular production of TNF-alpha.
Check your genetic data for rs1800629 -308A/G (23andMe v4, v5; AncestryDNA):
- A/A: Higher TNF-alpha levels. Increased risk of: ulcerative colitis[ref] celiac disease[ref] (note – must have HLA type also), septic shock[ref], diabetic foot ulcers[ref], asthma[ref] , Hashimoto’s thyroiditis[ref], skin infections[ref], periodontitis[ref], asthma[ref] in children, COPD[ref], stroke[ref], gum disease[ref], heart disease[ref]; nasal polyps[ref] Lower risk of: Malaria (half the risk)[ref], osteoporosis[ref], stroke[ref]
- A/G: somewhat higher TNF-alpha levels – see above
- G/G: typical, better response to high protein/low carb diet
Members: Your genotype for rs1800629 is —.
p53 (tumor suppressor): The TP53 gene encodes a tumor suppressor, called p53, which is important in preventing cancer. Studies have shown that curcumin increases p53 in colon cancer patients.[ref][ref] It is being studied as an adjuvant to chemotherapy.[ref]
Nrf2 and Keap1: Studies show that curcumin decreases inflammation through modulating Nrf2. The Nrf2 pathway regulates the expression of antioxidants created in the cells and counteracts cellular oxidative stress. Keap1 is a protein that has been identified as a repressor of Nrf2 activation. Recent research shows that curcumin inhibits Keap1 expression, thus repressing the repressor of Nrf2.[ref]
Nrf2 levels are partly impacted by genetics:
Check your genetic data for rs6721961 (23andMe v4):
- G/G: typical
- G/T: typical
- T/T: significantly diminished Nrf2 expression, increased risk of lung cancer[ref]
Members: Your genotype for rs6721961 is —.
Epigenetics and curcumin:
Epigenetics is the changing of gene expression. These aren’t inherited changes to your DNA, but rather the increases or decreases in gene expression.
One way that genes turn ‘off or on’ is through histone modification. Histones control how your DNA is packaged up so that a gene can’t be translated into a protein. Modifying histones, therefore, allows a gene to ‘express’ or turn into its encoded protein.
Curcumin has been shown in studies to be a potent inhibitor of histone deacetylases. This means that curcumin inhibits the enzymes that control how histones package up DNA and prevent it from being read. In fact, curcumin seems to be more effective at inhibiting histone deacetylases than drugs, such as valproic acid or sodium butyrate, which are well known for this function. The key, though, is that this occurs at levels similar to pharmacological drugs only when curcumin concentrations are fairly high.[ref] (Higher than through regular supplement levels, if I’m understanding the research right).
Let me give you an example…
One way that curcumin may help as an adjunct in cancer treatments is through acting as a histone modifier to increase p53. The tumor suppressor p53 often ‘turns off’ in cancer cells, and studies show that curcumin is one molecule that may be able to turn it back on.[ref]
Curcumin is a well-studied natural supplement that has been tested in a myriad of clinical trials. It offers anti-inflammatory properties that may help with chronic diseases. There are many options for curcumin supplements, and you may find that experimenting with several types is the best way to find out what works for you.
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