Pharma-supplement showdown: CRN refutes findings of AstraZeneca-funded study, authors clap back

08 Nov 2022 --- The US-based Council for Responsible Nutrition (CRN) has issued a statement disparaging a recent study that demonstrated the efficacy of pharmaceutical statin drugs compared to that of supplements commonly consumed for lowering cholesterol – the latter found to be 35.2% less effective. The CRN argues that the study is flawed and potentially biased. 

Delving into this issue, NutritionInsight speaks directly with two of the study’s authors, Dr. Luke Laffin, co-director of the Center for Blood Pressure Disorders and the medical director of cardiac rehabilitation at Cleveland Clinic and Dr. Karol Watson, professor of medicine and co-director of the program in preventive cardiology at the University of California Los Angeles.

“This topic is too important to get wrong,” assures Watson. “For cardiovascular risk reduction, we need to prioritize agents that have documented, proven cardiovascular risk reduction as evidenced by large scale randomized, controlled cardiovascular outcomes trials.”

“We know definitively what works,” she stresses. “We should use the agent with proven benefit.”

Dr. Laffin’s comments are slightly more to the point. “CRN is a trade association paid to promote supplements,” he says.

NutritionInsight also reached out to the CRN for comment, but the organization has not responded. 

Meanwhile, the American Heart Association (AHA), which hosted the conference where the study’s findings were presented maintains that: “Statements and conclusions of studies that are presented at the AHA’s scientific meetings are solely those of the study authors and do not necessarily reflect the Association’s policy or position.”

Supplements standoff
The Supplements, Placebo or Rosuvastatin (SPORT) study pitted six supplements – Nature Made’s fish oil for omega 3 fatty acids (2400 mg), Nutriflair’s branded cinnamon (2,400mg), Garlique brand garlic (5,000 mcg), Bio Schwartz’s brand turmeric curcumin (4,500 mg), Nature Made’s plant sterol supplement CholestOff Plus (1,600 mg) and Arazo Nutrition’s Red Yeast Rice (2,400 mg) – against a placebo and the statin drug Rosuvastatin.

The CRN underscores that supplements are not intended to be used in place of medication.The study, published in the Journal of the American College of Cardiology, studied the effects of the seven active ingredients and placebo over the course of 28 days. 

During this time, the 190 participants were monitored for low-density lipoprotein (LDL) cholesterol, commonly referred to as “bad” cholesterol, as well as overall cholesterol. 

It found that Rosuvastatin decreased LDL by 35.2%, total cholesterol reduced by 24% and triglycerides in the bloodstream decreased by 19%. None of the other nutritional supplements performed any better than the placebo.

A SPORTing chance
According to the CRN, the underperformance of certain supplements was the result of three main factors: inadequate time span of the study, poor supplement selection and potential biases.

“SPORT completely misses the point of supplementation by comparing the effects of a prescription drug to dietary supplements in a short-term study,” argues Andrea Wong, senior vice president of scientific and regulatory affairs at CRN. 

“Dietary supplements are not intended to be quick fixes,” she adds. “Their effects may not be revealed during the course of a study that only spans four weeks, particularly on a multifactorial condition like high cholesterol.”

Moreover, she holds that even if the supplements had been paired with diet and exercise, results would likely not be seen in such a small time frame.

Laffin also speaks in defense of his studies findings. “The trial duration is consistent with widely accepted cardiovascular society-endorsed guidelines,” he points out.

“The most recent AHA and American College of Cardiology lipid guidelines state, ‘assess adherence and percentage response to LDL lowering medications and lifestyle changes with repeat lipid measurement in four to 12 weeks.’”Six common supplements were found to have no more effect than the placebo over a 28 day period.

"The study was short term – we acknowledge that,” states Watson. “That being said, there is absolutely no data to suggest that cholesterol lowering would be different if the study continued for longer.”

Wrong choice of supplements?
Wong at CRN argues that many of the supplements used in the study are not actually marketed for their cholesterol-lowering abilities, which she considers “perplexing.”

“It’s as if the study was set up for misdirection and failure of the supplements,” she remarks. “While all the supplements included in the study are well-recognized for their benefits related to heart health, only three are marketed for their cholesterol lowering benefits.” 

However, Laffin insists that it is clear from clinical practice and market research that patients do take the studied supplements with the hopes of improving their heart health or cholesterol health.

“We are committed to high-quality clinical research, and the SPORT trial was performed under a US Food and Drug Administration (FDA) Investigational New Drugs application for the supplements,” he says. 

Laffin further notes that an FDA Investigational New Drug Application was not needed for Rosuvastatin since it was already approved by the FDA.

Watson sheds further light on the decision to include these specific supplements.

“As a co-author of the study, I can tell you our rationale,” she says. “The members of the steering committee are all busy, practicing cardiologists and we chose the supplements based on what we see in clinical practice.”

“All of these supplements are commonly taken by patients with the hopes of lowering their cholesterol – all of them,” she underscores. “We designed the study in response to actual clinical realities.”

Unrealistic expectations?
The main portion of the CRN statement suggests that there is “potential researcher bias and unrealistic expectations plague results.” The latter argument is clearly made in that the organization repeatedly calls out the study for expecting too much from the supplements in too short of a timeframe.Dr. Watson stresses that patients and doctors should only use supplements that have been proven through research to work.

Furthermore, CRN argues that supplements are not intended to be used in place of pharmaceuticals. 

“Both prescription drugs and dietary supplements have beneficial roles to play in achieving better health,” Wong stresses. “Supplements are not intended to replace medications or other medical treatments.” 

“Instead, they support and maintain health. In conjunction with a healthy diet, physical activity and regular check-ups with a healthcare professional, they can help reduce disease risk.”

CRN’s argument suggesting researcher bias is less evidenced, other than the organization’s statement that the study was funded by AstraZeneca, the maker of the statin used in the trial.

“This was an investigator-initiated study supported by an unrestricted grant from the sponsor,” highlights Laffin, in defense of the study. 

“The entirety of the trial, including methodology, statistical analysis and conclusions, were performed independently by C5Research, the academic research organization of the Heart, Vascular and Thoracic Institute of the Cleveland Clinic.”

By William Bradford Nichols