Curcumin Supplements: Decreasing Inflammation

Key takeaways:
~ Curcumin is anti-inflammatory and decreases oxidative stress.
~ It inhibits TNF-alpha and decreases NF-kB.
~ Curcumin has been studied in a lot of human clinical trials.
~ It is not well absorbed, but absorption can be boosted in a couple of ways

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Benefits of curcumin:

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.

As a supplement, curcumin is well-studied, 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.

Safety of Curcumin:

A new study looked into the reported liver injuries from 2004 to 2022 in the US. The researchers found that 10 of the liver injury cases over the last decade were attributed to turmeric combined with black pepper. Genetically, the researchers found that half of those 10 with liver injuries also carried a specific HLA type, HLA-B*35:01 (not found in 23andMe or AncestryDNA data). [ref]

While clinical trial data shows that curcumin is relatively safe, always keep in mind that any supplement could cause problems for some people.

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 progressed to diabetes, but none of the curcumin group had progressed. In fact, the curcumin-treated group had a decrease in HOMA-IR.[ref]

Related article: Read about diabetes and blood glucose genes

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]

A randomized clinical trial showed curcumin (500 mg/2x per day) to be more effective than placebo for improving depression. The benefits were shown at 4 to 8 weeks after starting the supplement.[ref]

Related article: Depression and Inflammation (check to see if your genes make you more susceptible to depression or anxiety due to inflammatory cytokines)

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]

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

This clinical 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

As an adjunct to regular antipsychotic medication, the addition of nanocurcumin significantly improved psychiatric symptom scores.[ref]

Sarcopenia (muscle loss):
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]

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.


Curcumin Genotype Report:

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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] For women, GSTP1 is important in the way estrogen is metabolized, and promoting better GSTP1 function may help to decrease the risk of breast cancer.[ref]

Related article: Estrogen metabolism 

Some people have GSTP1 variants that cause the enzyme not to function as well as normal, and curcumin may help to increase expression.

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[refLower 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]

Absorption and metabolism of curcumin:

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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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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.