Joanna Cosgrove, Online Editor09.13.12
Omega 3 fatty acid supplements have had a long-standing reputation as being beneficial for cardiovascular and cognitive health but it’s been a tough couple of weeks for the category. First, ConsumerLab.com issued critical findings from its own independent testing of retail omega 3 supplement products, and then the Journal of the American Medical Association (JAMA) published a meta-analysis that panned the use of omega 3 supplements for heart health. The story was subsequently picked up and publicized by the national media, much to the dismay of the supplement industry.
Late last month, ConsumerLab went public with results of its laboratory analyses of 35 fish oil/omega 3 supplements and declared problems 11, or 31.4%, of the products, with problems ranging from contamination to excessive PCBs and mislabeling.
According to the group, four supplements (including one of the contaminated products) contained 20% to 30% less than the claimed amounts of EPA, DHA or other omega 3 fatty acids. Three products contained two to three times the claimed amounts of EPA or other fatty acids, and one supplement incorrectly claimed to contain 1 mg of fat but actually contained 1000 mg (1 gram).
Also, mercury was not detected in any of the products however trace levels of PCBs were found in every product, and two supplements were found to exceed contaminations limits for PCBs. One softgel product also contained spoiled fish oil.
Adam Ismail, executive director of The Global Organization for EPA and DHA (GOED), poked holes in ConsumerLab’s tests and its findings, pointing out that in past ConsumerLab tests most of the products that failed did so because of contaminant or spoilage issues. “It’s a positive sign that such a small number failed for these reasons this time, although of course we need to continue to be vigilant about labeling and GMP issues,” he said. “Companies should be testing each batch of product to make sure it meets the spec, which is a requirement under GMP's, and they should use labs that participate in lab proficiency programs to make sure they measure EPAs and DHA’s proficiently. An example would be the AOCS/GOED Lab Proficiency Program.”
Mr. Ismail went on to note that from a safety perspective, at the “overage” levels of omega 3s according to ConsumerLab, there are no safety concerns. “In fact, GOED recently commissioned a safety study that found no upper limit for EPA and DHA could be set; EFSA also last month agreed that they could not determine a tolerable upper limit.
A factor worth noting was that although ConsumerLab’s worrisome headline statistic proclaimed 30% of the products failed its testing protocols (11 out of 35), the group actually tested a total of 68 products—including those from companies who paid to have their products tested—yet the “fail” designation was still limited to the aforementioned 11 products, bringing the failure rate down to 16%. Also worth noting was that two of the failed products were from the pet nutrition market; so nine out of the 65 human products failed, or 13%. Though a failure rate of 13% is still unacceptable, the more inclusive picture of the testing tells a different story than the bold headline of ConsumerLab’s press release.
Taking JAMA to Task
While the ConsumerLab report might’ve given omega 3 consumers pause for thought in the supplement aisle, the effect of the media take away on the JAMA findings might be far more detrimental.
The study, “Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events: A Systematic Review and Meta-Analysis” a team led by Evangelos C. Rizos, MD, PhD, of the University Hospital of Ioannina in Greece, assessed “the role of omega 3 supplementation on major cardiovascular outcomes” by reviewing 20 studies that included more than 68,000 patients and reported 7044 deaths, 3993 cardiac deaths, 1150 sudden deaths, 1837 myocardial infarctions and 1490 strokes. They reported finding no statistically significant association with all-cause mortality, cardiac death, sudden death, heart attack and stroke when all supplement studies were considered, and concluded that “omega 3 PUFAs are not statistically significantly associated with major cardiovascular outcomes across various patient populations,” and panned the use of omega 3 supplements for those purposes.
The findings have been met with ongoing opposition from the industry, including GOED and CRN.
GOED criticized the “flawed design” of the meta-analysis because it looked at people who had already suffered heart attacks or strokes rather than the general healthy population, thus failing to account for the effect of cardiovascular disease medications consumed by subjects in the studies analyzed.
"Consider that cardiac patients today are prescribed multiple cardio drugs (such as cardiac glycosides, antiarrhythmics, antihypertensives, hypolipidemics, antianginals, anticoagulants, beta-blockers, calcium channel blockers, diuretics and/or vasodilators),” asserted Harry Rice, PhD, GOED’s vice president-regulatory and scientific affairs. “There is a significant challenge in trying to determine if omega 3s can reduce cardiovascular disease risks if you are already giving patients a handful of other drugs that contribute to achieving that objective.
"We know from the studies that have shown a benefit that future research in this area should only analyze studies that do not include confounding medications, are longer than two years in duration, and use dosages greater than 1-2 grams of omega 3s per day," Dr. Rice continued. "Very few of the studies included in this meta-analysis met these criteria."
Loren Israelsen, executive director, United Natural Products Alliance (UNPA), agreed with GOED and added that he himself takes fish oil regularly and to stop taking it because of this study would be as “foolhardy” and “unwise” as discontinuing other medications. “This is the disservice of this study. The average consumer will not understand this critical distinction and may be discouraged from continuing omega 3 consumption, both through consumption of fish or use of supplements,” he said. “It is disheartening (literally) that a meta-analysis of this sort and subsequent media news surrounding it would fail to provide the essential background story so that the public is able to make informed and smart choices with respect to their heart health.”
Duffy MacKay ND, vice president, scientific and regulatory affairs, CRN, also hit upon the nature of the studies included in the review. “Many of the studies included in the meta-analysis were conducted on diseased individuals already undergoing treatment with one or more drugs (e.g., statins), which may mask the less potent and more long-term effects of omega 3 fats,” he said, and pointed to the existing published body of evidence that contradicted the JAMA findings. “The attraction of doing a meta-analysis is to combine comparable smaller clinical studies to assess whether similarities in the combined results exist,” he said. “The problem is that this meta-analysis combined studies that were not comparable in their design (e.g., studies on healthy individuals were combined with those targeting diseased individuals), which makes the results more skew.”
Mr. MacKay also questioned why the researchers apparently did not examine whether or not study subjects had sufficient dietary intake of omega 3 fats. “Without that information, they could not have controlled for this variable,” he said. “In this regard, studies on drugs are far simpler than those of nutrients (the treatment group gets the drug and the placebo group does not); with nutrients, if participants in the control group already have a diet sufficient in that substance, then it will be that much harder to demonstrate any benefit among the treatment participants. It is impossible for five researchers to control the diet of almost 70,000 patients over several years (particularly as a retrospective meta-analysis), as omega 3 fats are widespread throughout a variety of foods.”
Mr. Israelsen did acknowledge what he considered to be the meta-analysis’ singular useful aspect. “It clearly points out the growing problem of studying patients who take both medicines and supplements on a daily basis for the same health objectives—thus making it increasingly difficult to understand the effects of binary medicine/nutritional co-therapy benefits,” he said. “I fear that in the fog of science the first one to get shot is the dietary supplement.”
In conclusion, CRN, GOED and UNPA felt consumers should take the JAMA findings with a metaphorical grain of salt. GOED affirmed the importance “for doctors and consumers to understand that the totality of the scientific evidence justifies the use of omega 3s for both people with diagnosed cardiovascular disease and those trying to prevent cardiovascular disease,” the group said. “Researchers from Harvard University have estimated that 84,000 deaths a year could be prevented by adequate omega 3 consumption and governments and scientific groups around the world have established minimum recommended intakes based on this evidence.”
Late last month, ConsumerLab went public with results of its laboratory analyses of 35 fish oil/omega 3 supplements and declared problems 11, or 31.4%, of the products, with problems ranging from contamination to excessive PCBs and mislabeling.
According to the group, four supplements (including one of the contaminated products) contained 20% to 30% less than the claimed amounts of EPA, DHA or other omega 3 fatty acids. Three products contained two to three times the claimed amounts of EPA or other fatty acids, and one supplement incorrectly claimed to contain 1 mg of fat but actually contained 1000 mg (1 gram).
Also, mercury was not detected in any of the products however trace levels of PCBs were found in every product, and two supplements were found to exceed contaminations limits for PCBs. One softgel product also contained spoiled fish oil.
Adam Ismail, executive director of The Global Organization for EPA and DHA (GOED), poked holes in ConsumerLab’s tests and its findings, pointing out that in past ConsumerLab tests most of the products that failed did so because of contaminant or spoilage issues. “It’s a positive sign that such a small number failed for these reasons this time, although of course we need to continue to be vigilant about labeling and GMP issues,” he said. “Companies should be testing each batch of product to make sure it meets the spec, which is a requirement under GMP's, and they should use labs that participate in lab proficiency programs to make sure they measure EPAs and DHA’s proficiently. An example would be the AOCS/GOED Lab Proficiency Program.”
Mr. Ismail went on to note that from a safety perspective, at the “overage” levels of omega 3s according to ConsumerLab, there are no safety concerns. “In fact, GOED recently commissioned a safety study that found no upper limit for EPA and DHA could be set; EFSA also last month agreed that they could not determine a tolerable upper limit.
A factor worth noting was that although ConsumerLab’s worrisome headline statistic proclaimed 30% of the products failed its testing protocols (11 out of 35), the group actually tested a total of 68 products—including those from companies who paid to have their products tested—yet the “fail” designation was still limited to the aforementioned 11 products, bringing the failure rate down to 16%. Also worth noting was that two of the failed products were from the pet nutrition market; so nine out of the 65 human products failed, or 13%. Though a failure rate of 13% is still unacceptable, the more inclusive picture of the testing tells a different story than the bold headline of ConsumerLab’s press release.
Taking JAMA to Task
While the ConsumerLab report might’ve given omega 3 consumers pause for thought in the supplement aisle, the effect of the media take away on the JAMA findings might be far more detrimental.
The study, “Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events: A Systematic Review and Meta-Analysis” a team led by Evangelos C. Rizos, MD, PhD, of the University Hospital of Ioannina in Greece, assessed “the role of omega 3 supplementation on major cardiovascular outcomes” by reviewing 20 studies that included more than 68,000 patients and reported 7044 deaths, 3993 cardiac deaths, 1150 sudden deaths, 1837 myocardial infarctions and 1490 strokes. They reported finding no statistically significant association with all-cause mortality, cardiac death, sudden death, heart attack and stroke when all supplement studies were considered, and concluded that “omega 3 PUFAs are not statistically significantly associated with major cardiovascular outcomes across various patient populations,” and panned the use of omega 3 supplements for those purposes.
The findings have been met with ongoing opposition from the industry, including GOED and CRN.
GOED criticized the “flawed design” of the meta-analysis because it looked at people who had already suffered heart attacks or strokes rather than the general healthy population, thus failing to account for the effect of cardiovascular disease medications consumed by subjects in the studies analyzed.
"Consider that cardiac patients today are prescribed multiple cardio drugs (such as cardiac glycosides, antiarrhythmics, antihypertensives, hypolipidemics, antianginals, anticoagulants, beta-blockers, calcium channel blockers, diuretics and/or vasodilators),” asserted Harry Rice, PhD, GOED’s vice president-regulatory and scientific affairs. “There is a significant challenge in trying to determine if omega 3s can reduce cardiovascular disease risks if you are already giving patients a handful of other drugs that contribute to achieving that objective.
"We know from the studies that have shown a benefit that future research in this area should only analyze studies that do not include confounding medications, are longer than two years in duration, and use dosages greater than 1-2 grams of omega 3s per day," Dr. Rice continued. "Very few of the studies included in this meta-analysis met these criteria."
Loren Israelsen, executive director, United Natural Products Alliance (UNPA), agreed with GOED and added that he himself takes fish oil regularly and to stop taking it because of this study would be as “foolhardy” and “unwise” as discontinuing other medications. “This is the disservice of this study. The average consumer will not understand this critical distinction and may be discouraged from continuing omega 3 consumption, both through consumption of fish or use of supplements,” he said. “It is disheartening (literally) that a meta-analysis of this sort and subsequent media news surrounding it would fail to provide the essential background story so that the public is able to make informed and smart choices with respect to their heart health.”
Duffy MacKay ND, vice president, scientific and regulatory affairs, CRN, also hit upon the nature of the studies included in the review. “Many of the studies included in the meta-analysis were conducted on diseased individuals already undergoing treatment with one or more drugs (e.g., statins), which may mask the less potent and more long-term effects of omega 3 fats,” he said, and pointed to the existing published body of evidence that contradicted the JAMA findings. “The attraction of doing a meta-analysis is to combine comparable smaller clinical studies to assess whether similarities in the combined results exist,” he said. “The problem is that this meta-analysis combined studies that were not comparable in their design (e.g., studies on healthy individuals were combined with those targeting diseased individuals), which makes the results more skew.”
Mr. MacKay also questioned why the researchers apparently did not examine whether or not study subjects had sufficient dietary intake of omega 3 fats. “Without that information, they could not have controlled for this variable,” he said. “In this regard, studies on drugs are far simpler than those of nutrients (the treatment group gets the drug and the placebo group does not); with nutrients, if participants in the control group already have a diet sufficient in that substance, then it will be that much harder to demonstrate any benefit among the treatment participants. It is impossible for five researchers to control the diet of almost 70,000 patients over several years (particularly as a retrospective meta-analysis), as omega 3 fats are widespread throughout a variety of foods.”
Mr. Israelsen did acknowledge what he considered to be the meta-analysis’ singular useful aspect. “It clearly points out the growing problem of studying patients who take both medicines and supplements on a daily basis for the same health objectives—thus making it increasingly difficult to understand the effects of binary medicine/nutritional co-therapy benefits,” he said. “I fear that in the fog of science the first one to get shot is the dietary supplement.”
In conclusion, CRN, GOED and UNPA felt consumers should take the JAMA findings with a metaphorical grain of salt. GOED affirmed the importance “for doctors and consumers to understand that the totality of the scientific evidence justifies the use of omega 3s for both people with diagnosed cardiovascular disease and those trying to prevent cardiovascular disease,” the group said. “Researchers from Harvard University have estimated that 84,000 deaths a year could be prevented by adequate omega 3 consumption and governments and scientific groups around the world have established minimum recommended intakes based on this evidence.”
