No Benefit of Curcumin in Abdominal Aortic Aneurysm Repair

Megan Brooks

November 01, 2018

Perioperative curcumin given orally has no beneficial anti-inflammatory effects and may be harmful in patients undergoing elective abdominal aortic aneurysm repair, results of a randomized, placebo-controlled trial show.

"Neither curcumin nor placebo significantly altered any of four biomarkers of injury and inflammation and there was no benefit of curcumin on the rate of perioperative complications or the length of hospital stay and we potentially saw a signal of a higher risk of kidney injury with curcumin," Amit Garg, MD, Western University and Lawson Health Research Institute, London, Ontario, Canada, noted in a CMAJ podcast.

The study was published online October 29 in CMAJ.

Curcumin, a popular herbal supplement from the spice turmeric with antioxidant and anti-inflammatory effects, has been shown to reduce the risk for ischemic reperfusion and toxin-induced injury to the kidney in multiple animal studies, including animal models of abdominal aorta cross-clamping and contrast-induced injury.

In a randomized controlled single-center trial of 121 patients undergoing coronary artery bypass graft surgery in Thailand, oral curcumin reduced the risk for postoperative myocardial infarction and lowered concentrations of plasma biomarkers for inflammation, oxidation, and injury, compared with placebo.

Garg and colleagues investigated whether perioperative oral curcumin alters biomarkers of injury and inflammation or the risk for postrepair complications after elective abdominal aortic aneurysm repair, a setting where kidney injury is common.

They enrolled 606 patients (median age, 76 years) scheduled for elective surgery for unruptured abdominal aortic aneurysm repair at 10 Canadian hospitals and randomly assigned 304 to perioperative high-dose oral curcumin and 302 to matching placebo.

The curcumin dose was 4000 mg per day in two divided doses for 2 days before surgery, followed by 2000 mg the morning of the repair, 2000 mg on call to the operating room, 2000 mg 6 hours after surgery, and 2000 mg the following morning. The two groups were well balanced on all baseline and procedural characteristics.

The primary outcomes were median concentrations in the hours and days after surgery of four biomarkers of tissue injury and inflammation: postoperative urine interleukin (IL)-18, perioperative rise in serum creatinine, plasma N-terminal pro–B-type natriuretic peptide (NT-pro-BNP), and plasma high-sensitivity C-reactive protein (hsCRP).

For the two groups combined, there was a 202% rise in the mean perioperative concentration of plasma NT-pro-BNP (postoperative minus preoperative value) and an 1846% rise in the mean perioperative concentration of plasma hsCRP, the researchers report.

Relative to placebo, curcumin did not significantly alter any of the biomarker concentrations.

Biomarker Concentrations by Treatment Group
End Point Curcumin Placebo P Value
Median postop urine IL-18, pg/mL 13 16 .2
Median perioperative rise in:      
Serum creatinine, μmol/L 1 1 .2
Plasma NT-pro-BNP, mesoscale pg/mL 221 184 .1
Plasma hsCRP, μg/mL 58 58 .9

 

In secondary analyses, there was a higher risk of postsurgical acute kidney injury with curcumin than with placebo (17% vs 10%; P = .01).

"We don't have a good biological reason to explain why that occurred but it's something we noted and suggests that that should be considered in future studies," said Garg.

There was no difference in median length of hospital stay or risk for a composite of clinical events, such as death, myocardial infarction, and stroke, or in safety outcomes, such as change in hemoglobin, clinically important bleeding, peptic ulcer, hypoglycemia, diarrhea, or nausea.

"We went into this trial thinking that curcumin would be beneficial, and so seeing the totality of the results, we think at least in this setting with the formulation we used, there is no indication that we should test it any further," said Garg.

Disappointing but Not Surprising

In a related editorial, Kirsten Patrick and, MBBCh, and Matthew Stanbrook, MD, PhD, deputy editors, CMAJ, say, "No one should be shocked by the findings of the study by Garg and colleagues. This is how science works. It's deeply disappointing when a promising compound is shown to be no better than nothing. But it happens every day."

"Unsurprisingly," they write, "the findings of this large multicentre randomized controlled trial don't support the widespread claims of powerful anti-inflammatory properties of curcumin, highlighting the importance of studying natural health products like this."

"With natural health products, the marketing most often comes first — usually based on few small, nonrandomized and unblinded studies at best — and the good science usually fails to follow," they state.

" We need lots more studies like the linked trial by Garg and colleagues. We need to know when a substance that offers much hope and, through poor regulation, benefits from premature hype is actually useless or harmful," they add.

The study was funded by the Canadian Institutes of Health Research. The authors and editorial writers have no relevant disclosures.

CMAJ. Published online October 29, 2018. Article, Editorial

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