Curcumin & Liver Health: Benefits, Research & Safety Guide

Curcumin’s history begins in Far Eastern medicine and dates back 5,000 years for Ayurveda and 2,000 for Atharveda. Curcumin, the most active curcuminoid, was isolated in 1815 and described by Vogel and Pelletier. It is a yellow-orange diferuloylmethane molecule.

We examined several sources in the peer-reviewed literature. The sources highlight curcumin's potential as a hepatoprotective agent, meaning it may help shield the liver from damage. Here's a breakdown:

• Curcumin shows promise in reducing liver enzyme levels: A meta-analysis of 14 clinical trials indicated that curcumin significantly reduced total triglyceride levels and waist circumference in patients with NAFLD. While the effects on liver enzymes like ALT, AST, and ALP were not statistically significant in the overall analysis, the authors noted that curcumin did significantly reduce liver enzymes in specific subgroups.
• The hepatoprotective effects of curcumin are attributed to a multifaceted approach: 
• Antioxidant activity: Curcumin acts as a potent antioxidant, counteracting the damaging effects of free radicals in the liver. This is achieved through various mechanisms, including scavenging free radicals, donating hydrogen atoms and electrons to neutralize them, and boosting the levels of endogenous antioxidants.
• Anti-inflammatory action: Curcumin effectively reduces inflammation by inhibiting the activity of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. It accomplishes this by suppressing NF-κB activation, a key player in the inflammatory response.
• Antifibrotic effects: Curcumin may help protect against liver fibrosis, a condition where scar tissue builds up in the liver. Studies suggest that curcumin disrupts pathways involved in fibrosis development, including the PDGF-R/ERK and mTOR pathways. It also appears to activate PPAR-g, a receptor known to have anti-fibrotic effects, and modulate the expression of certain microRNAs and genes involved in fibrosis.
• Modulation of metabolic pathways: Curcumin may positively impact liver health by influencing metabolic processes. For instance, research indicates that it can inhibit ethanol-induced pathways, modulate antioxidant signaling pathways, and regulate genes involved in detoxification.
• Bioavailability: Curcumin's low bioavailability remains a significant challenge. It's poorly absorbed, rapidly metabolized, and quickly eliminated from the body.
• Despite promising preclinical and in vitro findings, the sources emphasize the need for more human trials to confirm curcumin's efficacy in treating liver disease. In our opinion, there is always a need for more studies of natural products and we wish that the major funding sources would provide the ability to complete such work. 
• The safety, tolerability, and nontoxicity of curcumin at high doses are well established by human clinical trials. For instance, it has been found that curcumin at 8 g/day in combination with gemcitabine was safe and well-tolerated in patients with pancreatic cancer. The clinical trials conducted thus far have indicated the therapeutic potential of curcumin against a wide range of human diseases. It has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. 
• Concerning paracetamol-induced hepatotoxicity, curcumin administration attenuated mitochondrial dysfunction by scavenging free radicals, induced antioxidant enzymes expression, and inhibited NF-kB and transient receptor potential melastatin 2 (TRPM2) channels.
• In mice with alcoholic fatty liver, curcumin administration attenuated hepatocyte necroptosis, suppressed the ethanol-induced pathway, inhibited glyoxylate, dicarboxylate, and pyruvate metabolisms, modulated antioxidant signaling pathways and upregulated detoxifying genes expression via the ERK/p38-MAPK pathway.
• It has also been demonstrated that curcumin can attenuate liver fibrosis and cirrhosis. Curcumin administration in Sprague-Dawley rats with CCl4-induced hepatic fibrosis led to a decrease in liver fibrosis through: i) reducing extracellular matrix overproduction in HSCs; ii) disrupting PDGF-R/ERK and mTOR pathways; iii) activating PPAR-g; iv) upregulating PTEN and miR-29b expression; and v) downregulating cannabinoid receptors (CBR) type 1 and DNA methyltranferase 3b.
• Hepatoprotective Effect: Several agents, such as alcohol, drugs, pollutants, parasites, and dietary components (fructose, added sugars), among others, can trigger acute and chronic liver injuries, including liver fibrosis, non-alcoholic steatohepatitis, non-alcoholic liver disease, and even cirrhosis. Curcumin has been extensively studied for its hepatoprotective effects in the face of such agents. Even though our prior work and the general body of research indicates that the long and safe history use of curcumin has been established and that curcumin is actually hepatoprotective, we searched diligently for any adverse events. This is what we found:
• Although turmeric and curcumin are generally safe, some adverse effects have been reported, including: 
• Nausea
• Diarrhea
• Headache
• Rash
• Yellow stool
• Increased levels of serum alkaline phosphatase
• Increased levels of lactate dehydrogenase
• People with allergies to plants in the Curcuma genus may be more likely to have an allergic reaction to turmeric or its constituents.
• Turmeric should be used cautiously by people taking anticoagulants, as it has antithrombotic properties that could increase the risk of bleeding.
• Turmeric may stimulate uterine contractions, so it is not recommended for use during pregnancy. We have never recommended the use of any supplement in pregnancy beyond prescribed prenatal supplements. We still recommend against taking any medication or supplement if pregnant, unless fully cleared by the treating physician.
• Turmeric may stimulate gallbladder contractions and should be used cautiously by people with gallstones.

We believe that this physician who was concerned about turmeric affecting the liver may have considered the ability of turmeric to utilize an enzyme in the liver for processing that is also used by coumadin to be damaging to the liver. However, this is simply an interaction. A similar interaction happens with grapefruit juice and coumadin. For some people, taking a supplement (such as turmeric) can change how the liver enzymes work and alter serum concentrations of other drugs. 

Turmeric’s beneficial effects are undeniable; however, its consumption may interact with certain drugs and lead to several risks. For example, turmeric exerts an anticoagulant activity and inhibitory effects on platelet aggregation due to its antithrombotic properties; therefore, it is essential to consider this effect, given the fact that it potentiates the action of antiplatelet drugs.

Coupled with Ginkgo biloba or garlic or with an anticoagulant, such as aspirin (acetylsalicylic acid), clopidogrel (Plavix), dipyridamole (Persantine), ticlopidine (Ticlid), warfarin (Coumadine), or enoxaparin (Lovenox), turmeric can intensify its action, leading to serious consequences, such as hemorrhages. Moreover, according to animal studies, turmeric can lower the blood sugar and, as a result, have additive effects with oral glycemic modifiers. If you are on a blood thinner or a diabetes drug, discuss this with your physician of course. 

In short, turmeric and curcumin appear to be extremely safe and well-tolerated, even at high doses (up to 8 g per day), without toxic effects. Moreover, epidemiological data have shown a low incidence of several types of cancer in individuals who regularly consume curcumin. However, the safety of curcumin should be further explored, and long-term studies are needed for a better evaluation of possible adverse effects and to fully determine its toxic potential. Again, we would love to see large pharmaceutical companies, foundations, or the government fund such work.